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0000-0002-0475-1771
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Peter MacCallum Cancer Centre
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Publisher: American Association for Cancer Research (AACR)
Date: 06-2009
DOI: 10.1158/1055-9965.EPI-08-1014
Abstract: Studies have examined the prognostic relevance of reproductive factors before breast cancer diagnosis, but most have been small and their overall findings inconclusive. Associations between reproductive risk factors and all-cause mortality after breast cancer diagnosis were assessed with the use of a population-based cohort of 3,107 women of White European ancestry with invasive breast cancer (1,130 from Melbourne and Sydney, Australia 1,441 from Ontario, Canada and 536 from Northern California, United States). During follow-up with a median of 8.5 years, 567 deaths occurred. At recruitment, questionnaire data were collected on oral contraceptive use, number of full-term pregnancies, age at first full-term pregnancy, time from last full-term pregnancy to breast cancer diagnosis, breastfeeding, age at menarche, and menopause and menopausal status at breast cancer diagnosis. Hazard ratios for all-cause mortality were estimated with the use of Cox proportional hazards models with and without adjustment for age at diagnosis, study center, education, and body mass index. Compared with nulliparous women, those who had a child up to 2 years, or between 2 and 5 years, before their breast cancer diagnosis were more likely to die. The unadjusted hazard ratio estimates were 2.75 [95% confidence interval (95% CI), 1.98-3.83 P & 0.001] and 2.20 (95% CI, 1.65-2.94 P & 0.001), respectively, and the adjusted estimates were 2.25 (95% CI, 1.59-3.18 P & 0.001) and 1.82 (95% CI, 1.35-2.46 P & 0.001), respectively. When evaluating the prognosis of women recently diagnosed with breast cancer, the time since last full-term pregnancy should be routinely considered along with other established host and tumor prognostic factors, but consideration of other reproductive factors may not be warranted. (Cancer Epidemiol Biomarkers Prev 2009 (6):1792–7)
Publisher: Elsevier BV
Date: 12-2001
Publisher: American Association for Cancer Research (AACR)
Date: 2020
DOI: 10.1158/0008-5472.CAN-19-1847
Abstract: These findings suggest that physical activity might reduce breast cancer risk by about 20% for women across the risk continuum, including women at higher-than-average risk due to their family history or genetic susceptibility. See related commentary by Niehoff et al., p. 23
Publisher: Wiley
Date: 30-04-2008
DOI: 10.1002/IJC.23509
Abstract: Different subtypes of ovarian cancer appear to have different causes however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8 1.1-2.8) but not mucinous tumors (1.1 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer.
Publisher: Wiley
Date: 21-08-2021
DOI: 10.5694/MJA2.51226
Publisher: Oxford University Press (OUP)
Date: 05-11-2008
DOI: 10.1093/JNCI/DJN345
Abstract: X chromosome inactivation, which silences gene expression from one of the two X chromosomes in females, is usually random. Skewed X inactivation has been implicated in both the expression and the suppression of X-linked disease phenotypes and has been reported to occur more frequently in breast and ovarian cancer patients, including BRCA1 or BRCA2 mutation carriers, than in control subjects. We assessed the pattern of X chromosome inactivation using methylation-specific polymerase chain reaction lification of the exon 1 microsatellite region of the X-linked androgen receptor (AR) gene in DNA from blood s les obtained from control subjects without a personal history of breast or ovarian cancer (n = 735), ovarian cancer patients (n = 313), familial breast cancer patients who did not carry mutations in BRCA1 or BRCA2 (n = 235), and affected and unaffected carriers of mutations in BRCA1 (n = 260) or BRCA2 (n = 63). We defined the pattern of X chromosome inactivation as skewed when the same X chromosome was active in at least 90% of cells. The association between skewed X inactivation and disease and/or BRCA mutation status was assessed by logistic regression analysis. The association between skewed X inactivation and age at cancer diagnosis was assessed by Cox proportional hazards regression analysis. All statistical tests were two-sided. The age-adjusted frequency of skewed X inactivation was not statistically significantly higher in ovarian cancer or familial breast cancer case subjects compared with control subjects. Skewed X inactivation was higher in BRCA1 mutation carriers than in control subjects (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.1 to 6.2 P = .02), particularly among unaffected women (OR = 6.1, 95% CI = 1.5 to 31.8 P = .005). Among BRCA1 mutation carriers, those with skewed X inactivation were older at diagnosis of breast or ovarian cancer than those without skewed X inactivation (hazard ratio [HR] of breast or ovarian cancer = 0.37, 95% CI = 0.14 to 0.95 P = .04). Among BRCA2 mutation carriers, skewed X inactivation also occurred more frequently in unaffected carriers than in those diagnosed with breast or ovarian cancer (OR = 5.2, 95% CI = 0.5 to 28.9 P = .08) and was associated with delayed age at onset (HR = 0.59, 95% CI = 0.37 to 0.94 P = .03). Skewed X inactivation occurs at an increased frequency in BRCA1 (and possibly BRCA2) mutation carriers compared with control subjects and is associated with a statistically significant increase in age at diagnosis of breast and ovarian cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 02-2020
DOI: 10.1158/1055-9965.EPI-19-0546
Abstract: Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer, but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high breast cancer risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with breast cancer risk is essential. Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers and 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers and 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models. For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with breast cancer risk, except smoking for more than 5 years before a first full-term pregnancy (FFTP) when compared with parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HRR) was 1.19 [95% confidence interval (CI), 1.02–1.39] and the HR from prospective analysis (HRP) was 1.36 (95% CI, 0.99–1.87). For BRCA2 mutation carriers, smoking for more than 5 years before an FFTP showed an association of a similar magnitude, but the confidence limits were wider (HRR = 1.25 95% CI, 1.01–1.55 and HRP = 1.30 95% CI, 0.83–2.01). For both carrier groups, alcohol consumption was not associated with breast cancer risk. The finding that smoking during the prereproductive years increases breast cancer risk for mutation carriers warrants further investigation. This is the largest prospective study of BRCA mutation carriers to assess these important risk factors.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6511532
Abstract: Abstract Although physical activity is associated with lower breast cancer risk for average-risk women, it is not known if this association applies to women at high familial/genetic risk. We examined the association of recreational physical activity (self-reported by questionnaire) with breast cancer risk using the Prospective Family Study Cohort, which is enriched with women who have a breast cancer family history ( i N /i = 15,550). We examined associations of adult and adolescent recreational physical activity (quintiles of age-adjusted total metabolic equivalents per week) with breast cancer risk using multivariable Cox proportional hazards regression, adjusted for demographics, lifestyle factors, and body mass index. We tested for multiplicative interactions of physical activity with predicted absolute breast cancer familial risk based on pedigree data and with i BRCA1 /i and i BRCA2 /i mutation status. Baseline recreational physical activity level in the highest four quintiles compared with the lowest quintile was associated with a 20% lower breast cancer risk (HR, 0.80 95% confidence interval, 0.68–0.93). The association was not modified by familial risk or i BRCA /i mutation status ( i P /i interactions .05). No overall association was found for adolescent recreational physical activity. Recreational physical activity in adulthood may lower breast cancer risk for women across the spectrum of familial risk. Significance: These findings suggest that physical activity might reduce breast cancer risk by about 20% for women across the risk continuum, including women at higher-than-average risk due to their family history or genetic susceptibility. i See related commentary by Niehoff et al., p. 23 /i /
Publisher: Wiley
Date: 09-09-2007
DOI: 10.1007/S10897-007-9105-4
Abstract: Some women at increased familial risk of breast cancer experience elevated levels of cancer-specific worry, which can possibly act as a barrier to screening, and may be a significant factor in decisions regarding risk-reducing surgery. The aim of this study was to comprehensively examine predictors of cancer-specific worry in high risk women and to test a model which proposes that perceived breast cancer risk mediates the impact of other factors on worry. 1,437 unaffected women from high risk breast cancer families completed questionnaires and interviews. Path analysis was used to test the model of potential predictors of cancer worry, including familial, personal and psychological variables, mediated via perceived cancer risk. Levels of cancer-specific worry were generally low despite an average perceived risk of 50.3%. The goodness-of-fit of the proposed model was poor, explaining only 9% of the variance for perceived risk and 10% of the variance for cancer specific worry. An alternative model of a direct relationship between all of the predictor variables and cancer worry, explained 24% of the variation in cancer worry. General anxiety, perceived risk, the stressful impact of recent cancer related events, a relative risk greater than 10, being closer in age to the youngest breast cancer diagnosis in family, and knowledge of personal mutation status, all independently contributed to cancer worry. Addressing general affective responses, experiences of recent cancer related events, in addition to education about personal risk, should be considered in counselling women with elevated cancer worry. Risk perception appears to act independently of other factors in its formulation and impact on cancer worry. Further research on the way in which women come to perceive their risk is indicated.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2012
Abstract: To compare breast cancer prognosis in BRCA1 and BRCA2 mutation carriers with that in patients with sporadic disease. An international population-based cohort study was conducted in Canada, the United States, and Australia of 3,220 women with incident breast cancer diagnosed between 1995 and 2000 and observed prospectively. Ninety-three had BRCA1 mutations 71, BRCA2 mutations one, both mutations 1,550, sporadic breast cancer and 1,505, familial breast cancer (without known BRCA1 or BRCA2 mutation). Distant recurrence and death were analyzed. Mean age at diagnosis was 45.3 years mean follow-up was 7.9 years. Risks of distant recurrence and death did not differ significantly between BRCA1 mutation carriers and those with sporadic disease in univariable and multivariable analyses. Risk of distant recurrence was higher for BRCA2 mutation carriers compared with those with sporadic disease in univariable analysis (hazard ratio [HR], 1.63 95% CI, 1.02 to 2.60 P = .04). Risk of death was also higher in BRCA2 carriers in univariable analysis (HR, 1.81 95% CI, 1.15 to 2.86 P = .01). After adjustment for age, tumor stage and grade, nodal status, hormone receptors, and year of diagnosis, no differences were observed for distant recurrence (HR, 1.00 95% CI, 0.62 to 1.61 P = 1.00) or death (HR, 1.12 95% CI, 0.70 to 1.79 P = .64). Outcomes of BRCA1 mutation carriers were similar to those of patients with sporadic breast cancer. Worse outcomes in BRCA2 mutation carriers in univariable analysis seem to reflect the presence of more adverse tumor characteristics in these carriers. Similar outcomes were identified in BRCA2 carriers and those with sporadic disease in multivariable analyses.
Publisher: Wiley
Date: 31-10-2002
DOI: 10.1002/CNCR.10949
Abstract: The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population. The Ontario Familial Breast Cancer Registry collects clinical and family history data in familial breast carcinoma cases, and unselected Ashkenazi breast carcinomas, and acts as a tumor tissue repository. Using this resource, we examined the tumor morphology, hormone receptor status, and HER-2/neu protein overexpression in Canadian Ashkenazi breast carcinoma patients whose germline BRCA1 mutation status is known. Thirty-eight tumors from 32 BRCA1 carriers and 354 tumors from 334 noncarriers were analyzed. The tumors in BRCA1 mutation carriers were more likely to be high grade (P < 0.0001) and estrogen receptor negative (P < 0.004). There was an increased frequency of typical medullary carcinomas in mutation carriers when all tumors were analyzed. However, this difference did not remain statistically significant when only the first tumor diagnosed in each patient was included in the analysis. There was no difference in HER-2/neu protein overexpression between the two groups overall (P = 0.07). However, when the analysis was restricted to Grade III tumors, there were significantly fewer HER-2/neu-positive tumors in the mutation carriers versus noncarriers (3.1% vs. 21.5%, P = 0.012). No significant differences were found in the incidence of lymph node status, progesterone receptor status, lymphatic vessel invasion, degree of lymphocytic infiltration, or in the presence of ductal carcinoma in situ associated with the invasive tumors. Increasing awareness of the morphologic and immunophenotypic features more commonly found in BRCA1-associated breast carcinomas may lead to a wider use of these characteristics in genetic screening programs and provide further clues to their pathogenesis.
Publisher: Springer Science and Business Media LLC
Date: 13-08-2013
DOI: 10.1038/BJC.2013.382
Publisher: Springer Science and Business Media LLC
Date: 17-06-2014
DOI: 10.1038/NCOMMS5051
Publisher: Oxford University Press (OUP)
Date: 10-12-2021
DOI: 10.1093/JNCI/DJAA178
Abstract: Clinical guidelines often use predicted lifetime risk from birth to define criteria for making decisions regarding breast cancer screening rather than thresholds based on absolute 5-year risk from current age. We used the Prospective Family Cohort Study of 14 657 women without breast cancer at baseline in which, during a median follow-up of 10 years, 482 women were diagnosed with invasive breast cancer. We examined the performances of the International Breast Cancer Intervention Study (IBIS) and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk models when using the alternative thresholds by comparing predictions based on 5-year risk with those based on lifetime risk from birth and remaining lifetime risk. All statistical tests were 2-sided. Using IBIS, the areas under the receiver-operating characteristic curves were 0.66 (95% confidence interval = 0.63 to 0.68) and 0.56 (95% confidence interval = 0.54 to 0.59) for 5-year and lifetime risks, respectively (Pdiff & .001). For equivalent sensitivities, the 5-year incidence almost always had higher specificities than lifetime risk from birth. For women aged 20-39 years, 5-year risk performed better than lifetime risk from birth. For women aged 40 years or older, receiver-operating characteristic curves were similar for 5-year and lifetime IBIS risk from birth. Classifications based on remaining lifetime risk were inferior to 5-year risk estimates. Results were similar using BOADICEA. Our analysis shows that risk stratification using clinical models will likely be more accurate when based on predicted 5-year risk compared with risks based on predicted lifetime and remaining lifetime, particularly for women aged 20-39 years.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2007
DOI: 10.1158/1055-9965.EPI-07-0566
Abstract: It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n = 1,269) or borderline (n = 311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n = 1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results from observational studies suggest that a modest inverse association exists between level of recreational physical activity and the risk of ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2007 (11):2321–30)
Publisher: BMJ
Date: 2003
DOI: 10.1046/J.1525-1438.2003.13018.X
Abstract: This paper reviews changes that have occurred within and without the medical profession that have fostered an increasing demand for decision aids as adjuncts to practitioners' counseling to prepare patients for decision making. In the absence of data on the efficacy of ovarian cancer screening and prophylactic strategies, decisions about optimal care are difficult for both women and their doctors. Because surveillance and preventive options are an area of great uncertainty, a decision aid has been developed specifically aimed at facilitating decisions involving ovarian cancer risk management options. This was achieved by reviewing and integrating the available literature on models of medical decision making, patient preferences for information and involvement in decision making, the utility of decision aids, and management options for ovarian cancer risk. Findings indicate that patients wish to be informed participants in the decision-making process and that decision aids are an acceptable and effective method of providing quality information in a format that facilitates an inclusive model of shared decision making. A decision aid designed for women at increased risk of ovarian cancer that facilitates informed decision making may be a valuable addition to patient support. A randomized controlled trial of this type of educational material will provide timely and much needed evidence on its acceptability and efficacy.
Publisher: Elsevier BV
Date: 10-2010
Publisher: Springer Science and Business Media LLC
Date: 06-2005
DOI: 10.1007/S10689-004-6129-X
Abstract: Prospective collection of epidemiological, psychosocial and outcome data in large breast cancer family cohorts should provide less biased data than retrospective studies regarding penetrance of breast cancer and modifiers of genetic risk. The Kathleen Cuningham Foundation for Research into Breast Cancer (kConFab) recently commenced 3-yearly follow-up on over 750 families with multiple cases of breast cancer. Clinical follow-up was by mailed self-report questionnaire to all participants, while psychosocial follow-up was only of unaffected women and consisted of two components: a mailed questionnaire and an interview regarding stressful life events. To date, 1928 of 2748 (70%) participants returned the clinical follow-up questionnaire (10% opted out, 16% were non-responders, and 4% were not contactable). Of the unaffected females who returned the clinical follow-up questionnaire, 91% participated in the psychosocial follow-up. In multivariate analyses, sex, personal cancer status, marital status, age and educational status were independent predictors of response to the clinical follow-up questionnaire, and number of female children, age, and family history of breast cancer were independent predictors of response to the psychosocial follow-up. A first round of 3-yearly clinical and psychosocial follow-up using a mailed questionnaire was feasible in this cohort. High response rates were achieved by employing intensive tracing and reminder strategies. The predictors of response for the clinical and psychosocial follow-up components of this study should be considered in designing similar follow-up strategies for other family cancer cohorts.
Publisher: Springer Science and Business Media LLC
Date: 06-04-2016
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423589
Abstract: e Table1 contains the minimum number of average metabolic equivalents (METs) per week required to be classified as physically active at baseline and in adolescence for a given age at baseline. eTable 2 presents the association of baseline and adolescent strenuous and moderate recreational physical activity with breast cancer risk in the Prospective Family Study Cohort (N=15,500).
Publisher: Wiley
Date: 10-07-2003
DOI: 10.1034/J.1399-0004.2003.00097.X
Abstract: Prophylactic mastectomy (PM) is a risk-management option for women at high familial risk of breast cancer (BC). This study describes the PM experience of women enrolled in a large observational cohort study involving families with a history of hereditary breast cancer. Within 357 multiple-case BC families [119 (33%) BRCA1 or BRCA2 mutation positive], identified via family cancer clinics, 49 cases of PM [21 (43%) BRCA1 or BRCA2 mutation positive] were identified and their clinical, pathological and genetic features reviewed. Families with at least one incidence of PM displayed stronger breast/ovarian cancer histories than did families without PM. Median age at time of PM was 45 years (range 28-58). Ten cases (21%) were bilateral PMs in unaffected women and 39 cases were contralateral PMs in women with prior invasive BC (71%) or ductal carcinoma in situ (DCIS) (8%). Most (88%) underwent total mastectomy. Unnecessary axillary surgery occurred in eight subjects (16%). Malignant histology was found in three PM specimens (6%). Prior to genetic testing, PM was performed in two women who were subsequently shown not to carry the mutation specific to their family. Optimal utilization of genetic testing to guide surgical decision making, appropriate surgical technique and careful pathology examination of PM specimens, are important issues to consider prior to PM in women at high familial risk of BC.
Publisher: Springer Science and Business Media LLC
Date: 28-06-2007
DOI: 10.1038/NATURE05887
Publisher: SAGE Publications
Date: 07-2006
Abstract: Purpose. To carry out a randomized controlled trial of a decision aid for women at increased risk of developing ovarian cancer to facilitate decision making regarding risk management options. Methods. This randomized trial, conducted through 6 familial cancer centers, compared the efficacy of tailored decision aid to that of a general educational p hlet in preparing women for decision making. Participants. 131 women with a family history of breast and/or ovarian cancer or of hereditary nonpolyposis colorectal cancer. Outcome measures. Decisional conflict, knowledge about ovarian cancer risk management options, and psychological adjustment were reassessed at 3 time points. Results. Compared to those who received the p hlet (control), women who received the decision aid (intervention) were significantly more likely to report a high degree of acceptability of the educational material at both follow-up assessment time points. Findings indicate neither group experienced significant increases in psychological distress at either follow-up assessment time points relative to baseline. Two weeks postintervention, the intervention group demonstrated a significant decrease in decisional conflict compared to the control group (t = 2.4, P 0.025) and a trend for a greater increase in knowledge about risk management options (t = 2.1, P = 0.037). No significant differences were found 6 months postintervention. Conclusion. This form of educational material is successful in increasing knowledge about risk management options and in reducing decisional conflict in the shorter term. The decision aid is an effective and acceptable strategy for patient education to facilitate an inclusive and informed decision-making process about managing ovarian cancer risk.
Publisher: American Association for Cancer Research (AACR)
Date: 03-2022
DOI: 10.1158/1940-6207.CAPR-21-0164
Abstract: Our results suggest that the relationship between BMI and breast cancer could be due to a relationship between weight and breast cancer, downgraded by inappropriately adjusting for height potential importance of anthropometric measures other than total body fat breast cancer risk associations with BMI and weight are across a continuum.
Publisher: Oxford University Press (OUP)
Date: 13-07-2015
DOI: 10.1093/IJE/DYV118
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22534607
Abstract: Supplementary Data from Weight is More Informative than Body Mass Index for Predicting Postmenopausal Breast Cancer Risk: Prospective Family Study Cohort (ProF-SC)
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533914
Abstract: Survey sent to clincians
Publisher: Wiley
Date: 17-05-2001
DOI: 10.1046/J.1440-1673.2001.00903.X
Abstract: The role of breast conservation therapy (limited surgery and irradiation of the breast with/without axilla) in the approximately 5% of breast cancer patients who harbour a germline mutation in BRCA1 or BRCA2, is a largely unexplored area and is seen by some as controversial. The relatively high cumulative risk of second primary cancers in such patients and concern about a possible decreased ability of mutation carriers to repair DNA damage caused by radiation has fuelled this controversy. Published studies of breast conservation therapy in carriers of a mutation in BRCA1 or BRCA2 are reviewed, with particular attention to their methodology. These studies have not demonstrated any increase in radiation sensitivity of normal tissues in mutation carriers, either in terms of increased early or late toxicity or tumourigenesis. Likewise, tumour sensitivity to radiotherapy, which might be expected based on the known functions of the BRCA1 and BRCA2 genes, has not been documented to date in mutation carriers. Further, methodologically rigorous studies of large numbers of breast cancer patients who carry a mutation in BRCA1 or BRCA2 are required to fully elucidate these issues.
Publisher: Elsevier BV
Date: 08-2005
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533911
Abstract: Strongest barriers to and facilitators of risk reducing medication use for kConFab women
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Publisher: Springer Science and Business Media LLC
Date: 04-05-2009
Abstract: Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention. Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically. Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers), practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it), and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments). The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-2008
Abstract: Most women with early-stage breast cancer believe that psychosocial factors are an important influence over whether their cancer will recur. Studies of the issue have produced conflicting results. A population-based s le of 708 Australian women diagnosed before age 60 years with nonmetastatic breast cancer was observed for a median of 8.2 years. Depression and anxiety, coping style, and social support were assessed at a median of 11 months after diagnosis. Hazard ratios for distant disease-free survival (DDFS) and overall survival (OS) associated with psychosocial factors were estimated separately using Cox proportional hazards survival models, with and without adjustment for known prognostic factors. Distant recurrence occurred in 209 (33%) of 638 assessable patients, and 170 (24%) of 708 patients died during the follow-up period. There were no statistically significant associations between any of the measured psychosocial factors and DDFS or OS from the adjusted analyses. From unadjusted analyses, associations between greater anxious preoccupation and poorer DDFS and OS were observed (P = .02). These associations were no longer evident after adjustment for established prognostic factors greater anxious preoccupation was associated with younger age at diagnosis (P = .03), higher tumor grade (P = .02), and greater number of involved axillary nodes (P = .008). The findings do not support the measured psychosocial factors being an important influence on breast cancer outcomes. Interventions for adverse psychosocial factors are warranted to improve quality of life but should not be expected to improve survival.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 15-02-2004
Abstract: The time interval between last childbirth and subsequent breast cancer diagnosis is emerging as an important prognostic factor for premenopausal women. We studied, prospectively, 750 women diagnosed with primary invasive breast cancer before age 45 years who participated in the population-based Australian Breast Cancer Family Study (ABCFS). Median follow-up time was 4.9 years (range, 0.8 to 10.8 years). Compared with nulliparous women, women who gave birth within 2 years prior to diagnosis were more likely to have axillary node-positive (58% v 41% P = .01), and estrogen receptor-negative (58% v 39% P = .005) tumors. The unadjusted hazard ratios for death were 2.3 (95% CI, 1.3 to 3.8 P = .002), 1.7 (95% CI, 1.1 to 2.6 P = .03), and 0.9 (95% CI, 0.6 to 1.5 P = .8) for patients who gave birth less than 2 years, 2 to 5 years, and 5 or more years before diagnosis, respectively. After adjusting for tumor characteristics, these hazard ratios were reduced to 1.9 (95%CI, 1.1 to 3.2 P = .02), 1.3 (95% CI, 0.8 to 2.1 P = .3), and 0.9 (95%CI, 0.5 to 1.4 P = .5). Modeling showed that, compared with nulliparous women, the mortality hazard ratio in parous women was 1.9, decreasing by 8% (95%CI, 4% to 13% P .001) for each year between last birth and breast cancer diagnosis. Proximity of last childbirth to subsequent breast cancer diagnosis is a predictor of mortality independent of histopathological tumor characteristics. Clinicians should be aware that women diagnosed with breast cancer within a few years following childbirth may have a worse outcome than that suggested solely by the standard histopathological prognostic factors of their cancer.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-2013
Abstract: To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases). This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
Publisher: Springer Science and Business Media LLC
Date: 11-06-2020
DOI: 10.1038/S41568-020-0266-X
Abstract: Despite decades of laboratory, epidemiological and clinical research, breast cancer incidence continues to rise. Breast cancer remains the leading cancer-related cause of disease burden for women, affecting one in 20 globally and as many as one in eight in high-income countries. Reducing breast cancer incidence will likely require both a population-based approach of reducing exposure to modifiable risk factors and a precision-prevention approach of identifying women at increased risk and targeting them for specific interventions, such as risk-reducing medication. We already have the capacity to estimate an in idual woman's breast cancer risk using validated risk assessment models, and the accuracy of these models is likely to continue to improve over time, particularly with inclusion of newer risk factors, such as polygenic risk and mammographic density. Evidence-based risk-reducing medications are cheap, widely available and recommended by professional health bodies however, widespread implementation of these has proven challenging. The barriers to uptake of, and adherence to, current medications will need to be considered as we deepen our understanding of breast cancer initiation and begin developing and testing novel preventives.
Publisher: Elsevier BV
Date: 09-2010
Publisher: Oxford University Press (OUP)
Date: 20-01-2022
DOI: 10.1093/JNCI/DJAC004
Abstract: To help BRCA1 and 2 mutation carriers make informed decisions regarding use of combined-type oral contraceptive preparation (COCP), absolute risk-benefit estimates are needed for COCP-associated cancer. For a hypothetical cohort of 10 000 women, we calculated the increased or decreased cumulative incidence of COCP-associated (breast, ovarian, endometrial) cancer, examining 18 scenarios with differences in duration and timing of COCP use, uptake of prophylactic surgeries, and menopausal hormone therapy. COCP use initially increased breast cancer risk and decreased ovarian and endometrial cancer risk long term. For 10 000 BRCA1 mutation carriers, 10 years of COCP use from age 20 to 30 years resulted in 66 additional COCP-associated cancer cases by the age of 35 years, in addition to 625 cases expected for never users. By the age of 70 years such COCP use resulted in 907 fewer cancer cases than the expected 9093 cases in never users. Triple-negative breast cancer estimates resulted in 196 additional COCP-associated cases by age 40 years, in addition to the 1454 expected. For 10 000 BRCA2 mutation carriers using COCP from age 20 to 30 years, 80 excess cancer cases were estimated by age 40 years in addition to 651 expected cases by the age of 70 years, we calculated 382 fewer cases compared with the 6156 cases expected. The long-term benefit of COCP use diminished after risk-reducing bilateral salpingo-oophorectomy followed by menopausal hormone therapy use. Although COCP use in BRCA1 and BRCA2 mutation carriers initially increases breast, ovarian, and endometrial cancer risk, it strongly decreases lifetime cancer risk. Risk-reducing bilateral salpingo-oophorectomy and menopausal hormone therapy use appear to counteract the long-term COCP-benefit.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6511532.V1
Abstract: Abstract Although physical activity is associated with lower breast cancer risk for average-risk women, it is not known if this association applies to women at high familial/genetic risk. We examined the association of recreational physical activity (self-reported by questionnaire) with breast cancer risk using the Prospective Family Study Cohort, which is enriched with women who have a breast cancer family history ( i N /i = 15,550). We examined associations of adult and adolescent recreational physical activity (quintiles of age-adjusted total metabolic equivalents per week) with breast cancer risk using multivariable Cox proportional hazards regression, adjusted for demographics, lifestyle factors, and body mass index. We tested for multiplicative interactions of physical activity with predicted absolute breast cancer familial risk based on pedigree data and with i BRCA1 /i and i BRCA2 /i mutation status. Baseline recreational physical activity level in the highest four quintiles compared with the lowest quintile was associated with a 20% lower breast cancer risk (HR, 0.80 95% confidence interval, 0.68–0.93). The association was not modified by familial risk or i BRCA /i mutation status ( i P /i interactions .05). No overall association was found for adolescent recreational physical activity. Recreational physical activity in adulthood may lower breast cancer risk for women across the spectrum of familial risk. Significance: These findings suggest that physical activity might reduce breast cancer risk by about 20% for women across the risk continuum, including women at higher-than-average risk due to their family history or genetic susceptibility. i See related commentary by Niehoff et al., p. 23 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533917
Abstract: Survey sent to kConFab women
Publisher: Oxford University Press (OUP)
Date: 11-01-2006
DOI: 10.1093/HMG/DDI459
Abstract: A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.
Publisher: Elsevier BV
Date: 05-2016
Publisher: American Association for Cancer Research (AACR)
Date: 07-2005
DOI: 10.1158/1055-9965.EPI-05-0042
Abstract: Purpose: Obesity is associated with adverse outcomes in postmenopausal women with breast cancer. In premenopausal women, the association is less clear. Methods: A population-based s le of 1,360 Australian women with breast cancer before the age of 60 years, 47% diagnosed before age 40, and 74% premenopausal, was studied prospectively for a median of 5 years (range, 0.2-10.8 years). Obesity was defined as a body mass index of ≥30 kg/m2. The hazard ratio (HR) for adverse clinical outcome associated with obesity was estimated using Cox proportional hazard survival models. Results: Obesity increased with age (P & 0.001) and was associated with increased breast cancer recurrence (P = 0.02) and death (P = 0.06), larger tumors (P = 0.002), and more involved axillary nodes (P = 0.003) but not with hormone receptor status (P ≥ 0.6) or with first cycle adjuvant chemotherapy dose reductions (P = 0.1). Adjusting for number of axillary nodes, age at diagnosis, tumor size, grade, and hormone receptor status, obese women of all ages were more likely than nonobese women to have disease recurrence [HR, 1.57 95% confidence interval (95% CI), 1.11-2.22 P = 0.02] and to die from any cause during follow-up (HR, 1.56 95% CI, 1.01-2.40 P = 0.05). In premenopausal women, the adjusted HRs were 1.50 (95% CI, 1.00-2.26 P = 0.06) and 1.71 (95% CI, 1.05-2.77 P = 0.04), respectively. Conclusions: Obesity is independently associated with poorer outcomes in premenopausal women, as it is in postmenopausal women, and this is not entirely explained by differences in tumor size or nodal status. Given the high and increasing prevalence of obesity in western countries, more research on improving the treatment of obese breast cancer patients is warranted.
Publisher: Wiley
Date: 30-08-2001
DOI: 10.1046/J.1445-5994.2001.00075.X
Abstract: The identification of two breast cancer predisposition genes, BRCA1 and BRCA2, in the mid-1990s has led to a better understanding of the molecular pathogenesis of hereditary breast cancer and to a new era in breast cancer research. The present article reviews the current state of knowledge regarding the biology of BRCA1 and BRCA2, the cancer risks associated with carrying a pathogenic mutation in either of these genes and the possible genetic and environmental risk modifiers. The phenotypes of BRCA1- and BRCA2-associated hereditary breast cancers are reviewed. Research into BRCA1- and BRCA2-associated breast cancer is in its infancy and much remains to be learned, particularly about modifiers of genetic risk and the clinical implications of carrying a mutation in one of these two genes. Australia has an excellent research infrastructure in place, through the Australian Breast Cancer Family Study and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, to contribute substantially to future research in this area.
Publisher: Wiley
Date: 12-1998
DOI: 10.1002/(SICI)1097-0142(19981201)83:11<2251::AID-CNCR3>3.0.CO;2-6
Publisher: American Association for Cancer Research (AACR)
Date: 2021
DOI: 10.1158/1940-6207.CAPR-20-0369
Abstract: Despite its efficacy in reducing breast cancer incidence, chemoprevention is underutilised. This survey study of Australian women and their clinicians used behavioural change theory to identify modifiable barriers to chemoprevention uptake, and to suggest interventions such as policy change, educational resources and public c aigns, that may increase awareness and use. See related Spotlight by Vogel, p. 1
Publisher: Wiley
Date: 10-08-2006
DOI: 10.1111/J.1399-0004.2006.00665.X
Abstract: This study prospectively evaluated the utilization of cancer risk management strategies in a multi-institutional cohort of BRCA1 and BRCA2 mutation carriers using a self-report questionnaire. Of 142 unaffected female mutation carriers, 70 (49%) had elected to receive their mutation result. Of those who knew their mutation result, 11% underwent bilateral mastectomy (BM), 29% had bilateral oophorectomy (BO), 78% performed regular breast self-examination (BSE), and 80%, 89%, 67%, and 0% had at least annual clinical breast examination (CBE), mammography, transvaginal ultrasound (TVU), and CA125, respectively. A further 20%, 7%, 0%, 21%, and 75%, respectively, reported never having had these tests. For women who elected not to receive their mutation result, 0% underwent BM, 6% underwent BO, and 77%, 42%, 56%, 7%, and 0% had regular BSE, CBE, mammography, TVU, and CA125, respectively. Only one woman used chemoprevention outside a clinical trial. Uptake of prophylactic surgery and screening was associated with knowing one's mutation status (for all behaviors except BSE), age (for BO and CBE) and residence (for mammography). In this cohort, the minority of mutation carriers utilized risk-reducing surgery or chemoprevention and a substantial minority were not undergoing regular cancer-screening tests.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
Publisher: Oxford University Press (OUP)
Date: 19-09-2019
Abstract: iPrevent is an online breast cancer (BC) risk management decision support tool. It uses an internal switching algorithm, based on a woman’s risk factor data, to estimate her absolute BC risk using either the International Breast Cancer Intervention Study (IBIS) version 7.02, or Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 3 models, and then provides tailored risk management information. This study assessed the accuracy of the 10-year risk estimates using prospective data. iPrevent-assigned 10-year invasive BC risk was calculated for 15 732 women aged 20–70 years and without BC at recruitment to the Prospective Family Study Cohort. Calibration, the ratio of the expected (E) number of BCs to the observed (O) number and discriminatory accuracy were assessed. During the 10 years of follow-up, 619 women (3.9%) developed BC compared with 702 expected (E/O = 1.13 95% confidence interval [CI] =1.05 to 1.23). For women younger than 50 years, 50 years and older, and BRCA1/2-mutation carriers and noncarriers, E/O was 1.04 (95% CI = 0.93 to 1.16), 1.24 (95% CI = 1.11 to 1.39), 1.13 (95% CI = 0.96 to 1.34), and 1.13 (95% CI = 1.04 to 1.24), respectively. The C-statistic was 0.70 (95% CI = 0.68 to 0.73) overall and 0.74 (95% CI = 0.71 to 0.77), 0.63 (95% CI = 0.59 to 0.66), 0.59 (95% CI = 0.53 to 0.64), and 0.65 (95% CI = 0.63 to 0.68), respectively, for the subgroups above. Applying the newer IBIS version 8.0b in the iPrevent switching algorithm improved calibration overall (E/O = 1.06, 95% CI = 0.98 to 1.15) and in all subgroups, without changing discriminatory accuracy. For 10-year BC risk, iPrevent had good discriminatory accuracy overall and was well calibrated for women aged younger than 50 years. Calibration may be improved in the future by incorporating IBIS version 8.0b.
Publisher: JMIR Publications Inc.
Date: 07-11-2018
Publisher: Springer Science and Business Media LLC
Date: 04-04-2010
DOI: 10.1007/S10549-010-0868-1
Abstract: This study applied the self-regulation model to examine cognitive and emotional predictors of screening in unaffected women with a strong family history of breast cancer. 748 unaffected female members of an Australian registry of multiple-case breast cancer families formed the s le. Participants completed a baseline psychosocial questionnaire and a screening questionnaire 3 years later. Multinomial logistic regression was employed to determine predictors of under- and over-screening according to national guidelines. At follow-up 16% of women under-screened and 10% over-screened with mammography 55% under-screened with clinical breast examination (CBE) and 9% over-screened with breast self-examination (BSE). Of the women found screening according to guidelines for mammography 72% reported ever having received specific recommendations for mammography screening from a health professional. Compared to appropriate screeners, under-screeners on mammography were less likely to have received a screening recommendation (as were under-screeners on CBE), were younger and reported lower perceived breast cancer risk, but were at higher relative risk (RR) of breast cancer and were more likely to report elevated depression. Over-screeners on mammography were more likely to be younger and have a lower RR of breast cancer. Over-screeners on BSE reported elevated cancer-specific anxiety, were less likely to be university educated and more likely to have received a recommendation for BSE. Under- and over-screening is common in women with a strong family history of breast cancer. Evaluation of interventions targeting perceived risk of breast cancer, anxiety and depression are needed to ensure women obtain accurate advice from relevant specialists and enact screening recommendations.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1038/GIM.2016.43
Publisher: Wiley
Date: 22-04-2008
DOI: 10.1002/IJC.23448
Publisher: Springer Science and Business Media LLC
Date: 24-05-2014
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533908
Abstract: Strongest clinician barriers to and facilitators of discussing and prescribing risk reducing medication
Publisher: Massachusetts Medical Society
Date: 10-06-1999
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.EJON.2015.12.002
Abstract: Most women with unilateral breast cancer (BC) without BRCA1/2 gene mutations are at low risk of contralateral breast cancer (CBC). One CBC risk-management option is contralateral prophylactic mastectomy (CPM). While there is no evidence that CPM increases life-expectancy, its uptake is increasing. This study aimed to assess the validity of an extended social-cognition model, the Theory of Planned Behaviour (TPB), in predicting women's intentions to undergo CPM. Four hundred women previously treated for BC completed an online survey exploring demographic and disease factors, attitude, subjective norm, perceived behavioural control, anticipated regret, uncertainty avoidance, self-efficacy to not have CPM and intentions to undergo CPM in a common hypothetical decision-making scenario. The TPB uniquely explained 25.7% of intention variance. Greater anticipated regret, uncertainty avoidance and lower self-efficacy to cope with not having CPM were associated with stronger CPM intentions, explaining an additional 7.7%, 10.6% and 2.9% respectively, of variance over and above the TPB. Women who had undergone CPM, had not attended university, and had children reported stronger CPM intentions. A holistic understanding of CPM decision-making appears to require consideration beyond CBC risk, demographics and disease characteristics, exploring women's expectations about CPM outcomes, others' opinions, and avoidance of emotionality and difficulties associated with not undergoing surgery. This study provides a theoretical basis from which the complexity of CPM decision-making may be understood, and from which resources for patients and treating staff may be developed to support women's informed decision-making aligning with their personal values.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 08-2005
Abstract: The use of chemotherapy and endocrine therapies in the treatment of premenopausal women carries with it reproductive and gynecologic implications that young women may find distressing and discordant with plans for childbearing. This multicenter study aimed to investigate fertility- and menopause-related information needs among young women with a diagnosis of early-stage breast cancer. Two hundred twenty-eight women with a diagnosis of early-stage breast cancer who were aged 40 years or younger at diagnosis and who were 6 to 60 months after diagnosis were entered onto the trial. Participants completed a mailed self-report questionnaire that included a purposely designed fertility- and menopause-related information needs survey and standardized measures of distress, anxiety, quality of life, menopausal symptoms, and information-seeking style. Seventy-one percent of participants discussed fertility-related issues with a health professional as part of their breast cancer treatment, and 86% discussed menopause-related issues. Consultation with a fertility or menopause specialist was the most preferred method of obtaining this information. Receiving fertility-related information was rated as being significantly more important than receiving menopause-related information at time of diagnosis (P .001) and at treatment decision making (P = .058). Receiving menopause-related information was rated as being significantly more important than receiving fertility-related information during adjuvant treatment (P .05), at completion of adjuvant treatment (P .001), and during follow-up (P .001). Common questions, sources of information, and correlates of perceived importance were identified. The results of this study suggest that younger women have unmet needs for fertility- and menopause-related information and provide preliminary empirical data to guide the development of better fertility- and menopause-related patient education materials for younger women with a diagnosis of early breast cancer.
Publisher: Springer Science and Business Media LLC
Date: 03-2012
DOI: 10.1038/BJC.2012.61
Publisher: Oxford University Press (OUP)
Date: 03-11-2021
Abstract: Recreational physical activity (RPA) is associated with improved survival after breast cancer (BC) in average-risk women, but evidence is limited for women who are at increased familial risk because of a BC family history or BRCA1 and BRCA2 pathogenic variants (BRCA1/2 PVs). We estimated associations of RPA (self-reported average hours per week within 3 years of BC diagnosis) with all-cause mortality and second BC events (recurrence or new primary) after first invasive BC in women in the Prospective Family Study Cohort (n = 4610, diagnosed 1993-2011, aged 22-79 years at diagnosis). We fitted Cox proportional hazards regression models adjusted for age at diagnosis, demographics, and lifestyle factors. We tested for multiplicative interactions (Wald test statistic for cross-product terms) and additive interactions (relative excess risk due to interaction) by age at diagnosis, body mass index, estrogen receptor status, stage at diagnosis, BRCA1/2 PVs, and familial risk score estimated from multigenerational pedigree data. Statistical tests were 2-sided. We observed 1212 deaths and 473 second BC events over a median follow-up from study enrollment of 11.0 and 10.5 years, respectively. After adjusting for covariates, RPA (any vs none) was associated with lower all-cause mortality of 16.1% (95% confidence interval [CI] = 2.4% to 27.9%) overall, 11.8% (95% CI = -3.6% to 24.9%) in women without BRCA1/2 PVs, and 47.5% (95% CI = 17.4% to 66.6%) in women with BRCA1/2 PVs (RPA*BRCA1/2 multiplicative interaction P = .005 relative excess risk due to interaction = 0.87, 95% CI = 0.01 to 1.74). RPA was not associated with risk of second BC events. Findings support that RPA is associated with lower all-cause mortality in women with BC, particularly in women with BRCA1/2 PVs.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547571.V1
Abstract: Abstract We considered whether weight is more informative than body mass index (BMI) = weight/height sup /sup when predicting breast cancer risk for postmenopausal women, and if the weight association differs by underlying familial risk. We studied 6,761 women postmenopausal at baseline with a wide range of familial risk from 2,364 families in the Prospective Family Study Cohort. Participants were followed for on average 11.45 years and there were 416 incident breast cancers. We used Cox regression to estimate risk associations with log-transformed weight and BMI after adjusting for underlying familial risk. We compared model fits using the Akaike information criterion (AIC) and nested models using the likelihood ratio test. The AIC for the weight-only model was 6.22 units lower than for the BMI-only model, and the log risk gradient was 23% greater. Adding BMI or height to weight did not improve fit (ΔAIC = 0.90 and 0.83, respectively both i P /i = 0.3). Conversely, adding weight to BMI or height gave better fits (ΔAIC = 5.32 and 11.64 i P /i = 0.007 and 0.0002, respectively). Adding height improved only the BMI model (ΔAIC = 5.47 i P /i = 0.006). There was no evidence that the BMI or weight associations differed by underlying familial risk ( i P /i 0.2). Weight is more informative than BMI for predicting breast cancer risk, consistent with nonadipose as well as adipose tissue being etiologically relevant. The independent but multiplicative associations of weight and familial risk suggest that, in terms of absolute breast cancer risk, the association with weight is more important the greater a woman's underlying familial risk. Prevention Relevance: Our results suggest that the relationship between BMI and breast cancer could be due to a relationship between weight and breast cancer, downgraded by inappropriately adjusting for height potential importance of anthropometric measures other than total body fat breast cancer risk associations with BMI and weight are across a continuum. /
Publisher: Springer Science and Business Media LLC
Date: 02-07-2015
Publisher: Elsevier BV
Date: 05-2004
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423589.V1
Abstract: e Table1 contains the minimum number of average metabolic equivalents (METs) per week required to be classified as physically active at baseline and in adolescence for a given age at baseline. eTable 2 presents the association of baseline and adolescent strenuous and moderate recreational physical activity with breast cancer risk in the Prospective Family Study Cohort (N=15,500).
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1086/498455
Publisher: Oxford University Press (OUP)
Date: 17-01-2001
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.PEC.2015.11.012
Abstract: Most women diagnosed with unilateral breast cancer without BRCA1 or BRCA2 mutations are at low risk of contralateral breast cancer. Contralateral Prophylactic Mastectomy (CPM) decreases the relative risk of contralateral breast cancer, but may not increase life expectancy yet international uptake is increasing. This study applied protection motivation theory (PMT) to determine factors associated with women's intentions to undergo CPM. Three hundred eighty-eight women previously diagnosed with unilateral breast cancer and of negative or unknown BRCA1 or BRCA2 status were recruited from an advocacy group's research database. Participants completed measures of PMT constructs based on a common hypothetical CPM decision-making scenario. PMT constructs explained 16% of variance in intentions to undergo CPM. Response efficacy (CPM's advantages) and response costs (CPM's disadvantages) were unique in idual predictors of intentions. Decision-making appears driven by considerations of the psychological, cosmetic and emotional advantages and disadvantages of CPM. Overestimations of threat to life from contralateral breast cancer and survival benefit from CPM also appear influential factors. Patients require balanced and medically accurate information regarding the pros and cons of CPM, survival rates, and recurrence risks to ensure realistic and informed decision-making.
Publisher: Massachusetts Medical Society
Date: 05-03-2015
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2013
Abstract: Limited data suggest that germline BRCA1 mutations are associated with occult primary ovarian insufficiency and that BRCA1 and BRCA2 mutation carriers might have earlier natural menopause (NM) than their noncarrier relatives. Eligible women were mutation carriers and noncarriers from families segregating a BRCA1 or BRCA2 mutation. Data were self-reported using uniform questionnaires at cohort entry and every 3 years thereafter. NM was defined as the cessation of menses for 12 months without another cause. Cox proportional hazards analysis modeled time from birth to NM, adjusting for multiple potential confounders. Analysis time was censored at the earliest of the following: last follow-up, bilateral oophorectomy, hysterectomy, commencement of hormone therapy, insertion of intrauterine device, or any cancer diagnosis. Hazard ratios (HRs) were estimated as a measure of how likely mutation carriers are, relative to noncarriers, to reach NM at a given age. A total of 1,840 women were eligible for analysis. Overall only 19% reached NM. A lower proportion of BRCA1 and BRCA2 mutation carriers reached NM compared with noncarriers. Conversely, a higher proportion of mutation carriers were censored at cancer diagnosis or oophorectomy than noncarriers. The adjusted HR estimates for NM were 1.03 (95% CI, 0.75 to 1.40 P = .9) for 445 BRCA1 mutation carriers and 559 noncarrier relatives and 1.01 (95% CI, 0.71 to 1.42 P = .9) for 374 BRCA2 mutation carriers and 462 noncarrier relatives. We found no evidence that BRCA1 and BRCA2 mutation carriers are at higher risk of NM at a given age than their noncarrier relatives.
Publisher: Wiley
Date: 2005
DOI: 10.1002/PON.835
Abstract: There has been an ongoing debate in the literature on the extent to which women with a family history of breast cancer are at risk of psychological morbidity. This study compares psychological morbidity in 557 women participating in a large Australian registry of high-risk breast cancer families (kConFab) with 2 age and education matched s les, 1494 general practitioner attendees and 158 members of a twin registry. Participants completed the Somatic and Psychological Health Report (SPHERE). There were no significant differences between the three groups on psychological distress (F(2, 670) = 1.77, p = 0.17). Unsurprisingly, GP attendees reported more symptoms of somatic distress than the kConFab group (t411 = 2.89, p = 0.004) there were no differences between the twins and the kConFab group on somatic distress (t174 = 0.40, p = 0.687). Clinically significant anxiety/depression, a combination of psychological and somatic distress, therefore was significantly higher in GP attendees (28%) than the kConFab and twin s les (both 20%). These results refute the hypothesis that women with a family history of breast cancer are at greater psychological risk.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JOCN.2019.05.008
Abstract: We present a case of leptomeningeal metastatic disease to the cauda equina detected on Magnetic Resonance myelography. The heavy T2-weighting and small field-of-view of this MRI technique are designed to detect CSF leaks, but also provide exquisite detail of the cauda equina and any associated nodularity. Magnetic Resonance myelography thus shows promise as an adjunct to the MRI evaluation of patients with suspected leptomeningeal metastatic disease and other tumours affecting the cauda equina.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2023
Publisher: AMPCo
Date: 12-2011
DOI: 10.5694/MJA11.10830
Abstract: Selective oestrogen receptor modulators effectively reduce breast cancer in women at moderate to high risk, so why aren't they being discussed routinely?
Publisher: Springer Science and Business Media LLC
Date: 10-2014
DOI: 10.1007/S10689-013-9687-Y
Abstract: This study assessed the sociodemographic, medical and psychological predictors of accuracy of perceived risk in women at increased genetic risk for ovarian cancer. Women participating in a large cohort study who were at increased risk of ovarian and fallopian tube cancer, had no personal history of cancer and had ≥1 ovary in situ at cohort enrollment, were eligible. Women completed self-administered questionnaires and attended an interview at enrollment. Of 2,868 women unaffected with cancer at cohort enrollment, 561 were eligible. 335 women (59.8 %) overestimated their ovarian cancer risk, while 215 women (38.4 %) accurately estimated their risk, and 10 (1.8 %) underestimated it. Women who did not know their mutation status were more likely to overestimate their risk (OR 1.74, 95 % CI 1.10, 2.77, p = 0.018), as were those with higher cancer-specific anxiety (OR 1.05, 95 % CI 1.02, 1.08, p < 0.001) and/or a mother who had been diagnosed with ovarian cancer (OR 1.98, 95 % CI 1.23, 3.18, p = 0.005). Amongst the group of women who did not know their mutation status, 63.3 % overestimated their risk and the mean perceived lifetime risk of developing ovarian cancer was 42.1 %, compared to a mean objective risk of 6.4 %. A large number of women at increased risk for ovarian cancer overestimate their risk. This is of concern especially in women who are at moderately increased risk only for this sub-group of women, interventions are needed to reduce potentially unnecessary psychological distress and minimise engagement in unnecessary surgery or screening.
Publisher: Springer Science and Business Media LLC
Date: 22-02-2011
DOI: 10.1038/BJC.2011.41
Publisher: Springer Science and Business Media LLC
Date: 28-03-2015
DOI: 10.1007/S10865-015-9632-7
Abstract: Risk comprehension in in iduals at increased familial risk of cancer is suboptimal and little is known about how risk is understood and managed by at-risk in iduals who do not undergo genetic testing. We qualitatively studied these issues in 36 unaffected women from high-risk breast cancer families, including both women who had and had not undergone genetic testing. Data were collected through semi-structured interviews and data analysis was guided by Grounded Theory. Risk comprehension and risk management were largely influenced by the in idual's experience of coming from a high-risk family, with both tested and untested women relying heavily on their intuition. Although women's cognitive understanding of their risk appeared generally accurate, this objective risk information was considered of secondary value. The findings could be used to guide the development and delivery of information about risk and risk management to genetically tested and untested in iduals at increased risk of hereditary cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 02-2016
DOI: 10.1158/1055-9965.EPI-15-0838
Abstract: Background: The extent to which clinical breast cancer risk prediction models can be improved by including information on known susceptibility SNPs is not known. Methods: Using 750 cases and 405 controls from the population-based Australian Breast Cancer Family Registry who were younger than 50 years at diagnosis and recruitment, respectively, Caucasian and not BRCA1 or BRCA2 mutation carriers, we derived absolute 5-year risks of breast cancer using the BOADICEA, BRCAPRO, BCRAT, and IBIS risk prediction models and combined these with a risk score based on 77 independent risk-associated SNPs. We used logistic regression to estimate the OR per adjusted SD for log-transformed age-adjusted 5-year risks. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test. We also constructed reclassification tables and calculated the net reclassification improvement. Results: The ORs for BOADICEA, BRCAPRO, BCRAT, and IBIS were 1.80, 1.75, 1.67, and 1.30, respectively. When combined with the SNP-based score, the corresponding ORs were 1.96, 1.89, 1.80, and 1.52. The corresponding AUCs were 0.66, 0.65, 0.64, and 0.57 for the risk prediction models, and 0.70, 0.69, 0.66, and 0.63 when combined with the SNP-based score. Conclusions: By combining a 77 SNP-based score with clinical models, the AUC for predicting breast cancer before age 50 years improved by & %. Impact: Our estimates of the increased performance of clinical risk prediction models from including genetic information could be used to inform targeted screening and prevention. Cancer Epidemiol Biomarkers Prev 25(2) 359–65. ©2015 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2015
DOI: 10.1158/1538-7445.SABCS14-P1-12-06
Abstract: Background: Cognitive impairment is a potential side-effect of breast cancer (BC) treatment. Estrogen is an important neuromodulator that affects cognition. Estrogen depletion by oophorectomy or GnRH agonists may adversely affect cognition in non-oncological settings, but there are few data regarding the cognitive effects of ovarian function suppression (OFS) in women with breast cancer. Patients and Methods: Between November 2003 and January 2011, 3066 premenopausal women with hormone receptor-positive BC were randomised on the SOFT trial to 5 years of adjuvant endocrine therapy with tamoxifen alone, tamoxifen+OFS or exemestane+OFS. OFS was achieved by the GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Prior chemotherapy was allowed, provided women had premenopausal estradiol levels at enrolment. Women eligible for Co-SOFT must not have received any prior adjuvant endocrine therapy. At study entry (t1), and approximately 1 year after SOFT randomisation (t2), objective cognitive function was assessed with a brief computerized test battery comprising 7 tasks (CogState Ltd: cogstate.com). Subjective cognitive function, psychological distress, fatigue, insomnia and quality of life were also assessed. Co-SOFT recruited 86 of a planned 321 patients from 27 of 426 SOFT centres between November 2007 and January 2011, when Co-SOFT was closed as the SOFT trial completed accrual. The protocol-specified primary comparison was the change in the composite score of the CogState tasks over 1 year for women randomised to tamoxifen versus tamoxifen+OFS. However, due to low accrual this was modified, prior to any analysis, to compare the tamoxifen versus the pooled tamoxifen+OFS and exemestane+OFS groups. Cognitive test scores were standardized according to age-specific norms, averaged to compute the composite score and then change between t1 and t2 calculated a negative change in composite score indicates deterioration in cognitive function. Change in composite score was compared using Wilcoxon rank sum test. Results: Of 86 Co-SOFT enrolled patients, 74 underwent both t1 and t2 CogState testing and were included in the primary analysis (7 withdrew consent/declined assessment, 5 missed testing due to scheduling). Of these 74 women, 20 were randomised to tamoxifen and 54 to OFS+tamoxifen (28) or OFS+exemestane (26). Baseline characteristics were well balanced between the 2 groups. During the first year 49 women utilised GnRH alone for OFS, 4 had GnRH followed by oophorectomy and 1 had oophorectomy alone. There was no significant difference in the changes in the CogState composite scores from t1 and t2 for patients randomised to tamoxifen alone compared with OFS+oral endocrine therapy (median, -0.057 versus -0.146 respectively, p=0.51). There were no significant between-group differences in the changes from t1 and t2 for any of the 7 in idual cognitive tasks comprising the composite score. Conclusions: The results of this 1-year longitudinal substudy suggest that the addition of OFS to oral endocrine therapy does not significantly affect cognitive function in the setting of adjuvant BC treatment. Co-SOFT was limited by small s le size, so further investigation of the impact of OFS on cognitive function in BC patients is warranted. Citation Format: Kelly-Anne Phillips, Yang Feng, Karin Ribi, Jürg Bernhard, Fabio Puglisi, Meritxell Bellet, Simon Spazzapan, Per Karlsson, Daniel R Budman, Khalil Zaman, Ehtesham A Abdi, Susan M Domchek, Meredith M Regan, Alan S Coates, Richard D Gelber, Paul Maruff, Frances Boyle, John F Forbes, Gini F Fleming, Prudence A Francis. Co-SOFT: The cognitive function substudy of the suppression of ovarian function trial (SOFT) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13 San Antonio, TX. Philadelphia (PA): AACR Cancer Res 2015 (9 Suppl):Abstract nr P1-12-06.
Publisher: Massachusetts Medical Society
Date: 11-10-2007
DOI: 10.1056/NEJMC072301
Publisher: Springer Science and Business Media LLC
Date: 22-04-2010
Publisher: Springer Science and Business Media LLC
Date: 06-01-2009
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.PEC.2014.04.011
Abstract: Selective estrogen receptor modulators (SERMs) reduce breast cancer risk by 38%. However, uptake is low and the reasons are not well understood. This study applied protection motivation theory (PMT) to determine factors associated with intention to take SERMs. Women at increased risk of breast cancer (N=107), recruited from two familial cancer clinics in Australia, completed a questionnaire containing measures of PMT constructs. Hierarchical multiple linear regression analysis was used to analyze the data. Forty-five percent of women said they would be likely or very likely to take SERMs in the future. PMT components accounted for 40% of variance in intention to take SERMs. Perceived vulnerability, severity and response efficacy appeared the most influential in women's decisions to take or not take SERMs. Many women are interested in SERMs as a risk management option. Accurate risk estimation and an understanding of the benefits of SERMs are critical to women's decision making. Health professionals need to explore women's perceptions of their risk and its consequences, as well as providing clear evidence-based information about the efficacy of SERMs. Exploring the source and strength of beliefs about SERMs may allow more effective, tailored counseling.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533917.V1
Abstract: Survey sent to kConFab women
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1007/S10689-012-9585-8
Abstract: Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015) knowing one's mutation positive status (OR 2.9, p < 0.001) and having a mother and/or sister who died from ovarian cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and in idual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.
Publisher: AMPCo
Date: 11-2013
DOI: 10.5694/MJA13.10848
Abstract: To estimate the prevalence of the use of cancer risk-reducing measures among Australian BRCA1 and BRCA2 mutation carriers. Prospective follow-up of female carriers of BRCA1 or BRCA2 mutations who had no personal history of cancer and were enrolled in a multiple-case breast cancer family cohort study (kConFab). Data, including cancer events and uptake of risk-reducing surgery and medication were collected by self-report at cohort entry and 3 yearly thereafter. Surgery was confirmed from pathology and medical records. Women were followed up from enrolment until cancer diagnosis, date of last follow-up, or death. Data were collected from 3 November 1997 to 21 May 2012. Uptake of risk-reducing surgery and/or medication. Of 175 BRCA1 and 150 BRCA2 mutation carriers (median age, 37 years at cohort enrolment), 69 (21%) underwent risk-reducing mastectomy, 125 (38%) underwent risk-reducing bilateral salpingo-oophorectomy and nine (3%) participated in a clinical trial of risk-reducing medication, during 2447 person-years of follow-up (median follow-up, 9 years). Sixty-eight women (21%) reported incident cancers, including 52 breast cancers and nine ovarian cancers (defined in this article as high-grade serous cancers of the ovary, fallopian tube or peritoneum). There is considerable scope to increase the uptake of cancer risk-reducing measures in Australian BRCA1 and BRCA2 mutation carriers. These findings should drive (i) future research into the factors contributing to low uptake in Australia and (ii) changes to policy and practice to help better translate genetic knowledge into reductions in cancer incidence.
Publisher: Oxford University Press (OUP)
Date: 10-10-2019
Abstract: Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2), a finding that has recently been questioned. We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a BRCA1/2 pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group. Breast cancer hazard ratios (HRs) for time-dependent RRSO were estimated using Cox regression with age time-scale (4943 and 4990 women-years in RRSO and OCS cohorts, respectively). All statistical tests were two-sided. The RRSO cohort included 925 participants, and 1453 participants were in the OCS cohort (381 underwent RRSO during follow-up), with 88 incident breast cancers diagnosed. Among BRCA1/2 pathogenic variant carriers, a non-statistically significant lower breast cancer incidence was observed in the RRSO compared with the OCS cohort (HR = 0.86, 95% confidence interval = 0.45 to 1.67 P = .67). No difference was observed in the overall population or among subgroups stratified by prior breast cancer history or menopausal status. Seven fallopian tube and four ovarian cancers were prospectively diagnosed in the OCS cohort, and one primary peritoneal carcinoma occurred in the RRSO cohort. These data suggest that RRSO might be associated with reduced breast cancer incidence among women with a BRCA1/2 pathogenic variant, although the effect, if present, is small. This evolving evidence warrants a thorough discussion regarding the impact of RRSO on breast cancer risk with women considering this intervention.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.EJCA.2008.09.023
Abstract: Few data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer. Self-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression. Of 892 women, 55% (n=489) used CAM, 6% (n=53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83-3.58, p<0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00-1.10, p=0.049), greater anxiety (OR 1.92, 95% CI 1.16-3.16, p=0.01), not currently smoking (OR 0.64, 95% CI 0.42-0.97, p=0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72-0.94, p=0.005). The majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer.
Publisher: JMIR Publications Inc.
Date: 25-01-2018
Abstract: Prevent estimates breast cancer (BC) risk and provides tailored risk management information. he objective of this study was to assess the usability and acceptability of the iPrevent prototype. linicians were eligible for participation in the study if they worked in primary care, breast surgery, or genetics clinics. Female patients aged 18-70 years with no personal cancer history were eligible. Clinicians were first familiarized with iPrevent using hypothetical paper-based cases and then actor scenarios subsequently, they used iPrevent with their patients. Clinicians and patients completed the System Usability Scale (SUS) and an Acceptability questionnaire 2 weeks after using iPrevent patients also completed measures of BC worry, anxiety, risk perception, and knowledge pre- and 2 weeks post-iPrevent. Data were summarized using descriptive statistics. he SUS and Acceptability questionnaires were completed by 19 of 20 clinicians and 37 of 43 patients. Usability was above average (SUS score ) for 68% (13/19) clinicians and 76% (28/37) patients. The amount of information provided by iPrevent was reported as “about right” by 89% (17/19) clinicians and 89% (33/37) patients and 95% (18/19) and 97% (36/37), respectively, would recommend iPrevent to others, although 53% (10/19) clinicians and 27% (10/37) patients found it too long. Exploratory analyses suggested that iPrevent could improve risk perception, decrease frequency of BC worry, and enhance BC prevention knowledge without changing state anxiety. he iPrevent prototype demonstrated good usability and acceptability. Because concerns about length could be an implementation barrier, data entry has been abbreviated in the publicly available version of iPrevent.
Publisher: Wiley
Date: 2008
DOI: 10.1002/GCC.20526
Publisher: Wiley
Date: 26-10-2008
DOI: 10.1002/IJC.23017
Abstract: Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer.
Publisher: Wiley
Date: 05-2000
DOI: 10.1034/J.1399-0004.2000.570508.X
Abstract: The perceived benefits and risks of genetic testing may vary between groups of in iduals with different cultural, demographic, and family history features. This multicentre study examined the factors that influenced the decision to undergo genetic testing for BRCA1 and BRCA2 in Canadian Jewish women with breast cancer. A self-administered questionnaire was developed and distributed to 134 in iduals enrolled in a research-based testing program for Ashkenazi women. The questionnaire assessed demographic, social, and family history parameters, and the influence of medical, family, social, psychological, and cultural/religious factors on decision making about genetic testing. Seventy-six percent of women completed the questionnaire. Forty-one percent of study participants had no family history of breast or ovarian cancer. The most important factors influencing the decision to undergo testing were a desire to contribute to research, potential benefit to other family members, curiosity, and the potential for relief if not found to be a carrier (endorsed by 87, 78, 70, and 60% of participants, respectively). The main perceived risks of undergoing genetic testing related to insurance discrimination, confidentiality, accuracy and interpretability of results, potential impact on marriage prospects for family members, and focus on the Jewish community (endorsed by 28, 24, 30, 17, and 14% of participants, respectively). This study provides novel information on the motivating factors for BRCA1 and BRCA2 mutation testing in Canadian women of Ashkenazi Jewish descent. The focus on altruistic factors and those related to perceived psychological benefits of testing is notable.
Publisher: Springer Science and Business Media LLC
Date: 06-2013
Publisher: Elsevier BV
Date: 02-2012
Publisher: Springer Science and Business Media LLC
Date: 02-2006
DOI: 10.1186/BCR1377
Publisher: Future Medicine Ltd
Date: 03-2014
DOI: 10.2217/FON.13.278
Publisher: AMPCo
Date: 10-2014
DOI: 10.5694/MJA14.01203
Publisher: Oxford University Press (OUP)
Date: 28-05-2021
DOI: 10.1093/JNCI/DJAB111
Abstract: Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function. Eligible trials were phase III (neo)adjuvant trials of pharmacologic treatments for breast cancer, recruiting between June 2008 and October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, and EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were 2-sided. Of 2354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2 targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), cyclin-dependent kinase 4/6 inhibitors (5.0%), and poly-ADP-ribose polymerase inhibitors (2.8%). Ovarian function was a prespecified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected posttrial-intervention data. Common postintervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%), and follicle-stimulating hormone levels (8.5%). Only 4 (2.8%) trials collected postintervention anti-müllerian hormone levels, and 3 (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, cyclin-dependent kinase 4/6 inhibitors, or poly-ADP-ribose polymerase inhibitors, none specified ovarian function as an endpoint, but 4 (18.2%) collected postintervention ovarian function data. The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase III breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision making.
Publisher: Elsevier
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 21-06-2018
Publisher: American Association for Cancer Research (AACR)
Date: 07-2006
DOI: 10.1158/1055-9965.EPI-05-0986
Abstract: Background: Loss of heterozygosity (LOH) in breast ductal lavage (DL) fluid has been reported to be a potential biomarker of malignant change. Interpretation of LOH is reliant on sufficient quality and quantity of DNA. We investigated LOH of the BRCA1/2 loci in DL s les from BRCA1/2 mutation carriers, while also assessing the effect of DNA quantity. Methods: DNA yield was estimated using quantitative real-time PCR. Allelic status of DL DNA was determined using fluorescently tagged microsatellite markers with the subject's lymphocytic DNA serving as a control. S les were scored as consistently heterozygous or as demonstrating LOH if the same result was observed in replicate experiments. Additionally, s les were scored as “discordant LOH” if they initially showed LOH, but in replicate experiments either showed heterozygosity or LOH of the opposite allele. Results: In 11 BRCA1 carriers, 46 ducts were assessable, and 39 ducts from 14 BRCA2 carriers were assessable. LOH was observed in 17% and 18% of ducts from BRCA1 and BRCA2, respectively. Discordant results were seen in 23 BRCA1 (50%) and 15 BRCA2 (38%) s les. DNA yield was significantly greater in s les that were consistently heterozygous than those that were either discordant or showed LOH in replicate experiments for both BRCA1 (P = 0.003) and BRCA2 (P = 0.003). Conclusions: DNA quantity is highly variable between DL s les, with low yields likely to detrimentally affect the interpretation of LOH. In conclusion, LOH may not be an adequate method to detect the early stages of malignant change in s les obtained via DL. (Cancer Epidemiol Biomarkers Prev 2006 (7):1396–8)
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
DOI: 10.1038/NG.3521
Publisher: Springer Science and Business Media LLC
Date: 24-04-2012
DOI: 10.1038/BJC.2012.156
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533914.V1
Abstract: Survey sent to clincians
Publisher: BMJ
Date: 09-2001
DOI: 10.1046/J.1525-1438.2001.01047.X
Abstract: There are few reports in the literature of platinum-based chemotherapy administered in pregnancy. We present a case of serous adenocarcinoma of the ovary complicating pregnancy. Following laparotomy at 16 weeks of gestation, four cycles of cisplatin were administered prior to confinement at 32 weeks. There were no neonatal sequelae. We believe there is increasing evidence for the safe use of cisplatin in pregnancy.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.EJCA.2005.11.020
Abstract: This multicentre study examined uptake of bilateral risk-reducing mastectomy (BRRM) and bilateral risk-reducing oophorectomy (BRRO) in women at increased risk for breast and/or ovarian cancer who had attended a familial cancer clinic (FCC) between January 1999 and June 2000. Eligible women (N=396), were mailed a questionnaire assessing: BRRM and BRRO details risk perception and anxiety. Family history, genetic testing and risk assessment were abstracted from medical records. Surgery was cross-tabulated with demographics, risk perception and anxiety with either Fisher's exact test or the exact form of the Mantel-Haenszel test (for ordinal factors) used to investigate for associations. Ordinal logistic regression was used with continuous-scale covariates. In total, 130 women were lost to follow-up leaving 266 of these 182 (68.4%) responded. Mean follow-up time was 3.73 years. The BRRM rate was 4.4% with no difference found between moderate and high-risk groups. BRRM was associated with increasing numbers of affected relatives (P=0.025). BRRO was undertaken by 17.3%, more commonly in women older than 40 years of age (P=0.023) and with a BRCA1/2 mutation (P=0.017). Women who underwent BRRM (P=0.052) or BRRO (P<0.001) had a lower post-procedure risk perception than those who did not. During the timeframe of this study, risk-reducing surgery was undertaken by a small percentage of Australian women at increased risk for breast and/or ovarian cancer who attended FCCs. Family cancer history and mutation status were associated with uptake.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2016
DOI: 10.1038/BJC.2016.71
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533908.V1
Abstract: Strongest clinician barriers to and facilitators of discussing and prescribing risk reducing medication
Publisher: Springer Science and Business Media LLC
Date: 07-02-2010
Publisher: Springer Science and Business Media LLC
Date: 18-02-2021
Publisher: American Association for Cancer Research (AACR)
Date: 2010
DOI: 10.1158/1055-9965.EPI-09-0359
Abstract: Purpose: Genomic alterations (including gene hypermethylation) are likely to precede the phenotypic changes associated with breast tumorigenesis. From a prospective collection of ductal lavage (DL) s les from women with a known mutation in BRCA1 or BRCA2, we have assessed promoter methylation with a comparison of results with several variables, including breast cancer (BC) outcome. Experimental Design: Hypermethylation of p16, RASSF1A, twist, and RARβ was assessed using a qualitative, real-time, nested PCR assay. Associations between methylation status and variables were tested using Fisher's exact test or logistic regression. Analyses were done at three levels: a single breast, a single duct (both over time), and each DL s le in isolation. Results: A total of 168 s les from 93 ducts in 54 breasts have been analyzed in 34 women (16 BRCA1 and 18 BRCA2 mutation carriers). A median of 2 DL was done (range, 1–5), with 7 women developing BC on study, 1 bilateral. Methylation of p16 was associated with a known BRCA1 mutation (P = 0.001, P & 0.001, and P & 0.001 for breast, duct, and s le levels, respectively) and women with a history of contralateral BC (P = 0.001 and P & 0.001 for duct and s le levels, respectively). An association was seen for women who developed BC on study and RASSF1A methylation (P = 0.001 for s le level). Conclusions: Genetic methylation patterns could potentially be used to predict future BC risk. In addition, p16 methylation may be a predictor of BRCA1 mutation status. Further research is required to corroborate these findings. Cancer Epidemiol Biomarkers Prev 19(1) 265–74
Publisher: Elsevier BV
Date: 04-2016
Publisher: Wiley
Date: 09-03-2004
DOI: 10.1023/B:JOGC.0000018822.56297.A6
Abstract: Forty-seven unaffected women from high-risk breast cancer families who had received results for hereditary breast/ovarian predisposition genes between 1 month and 5 years ago were interviewed regarding their experiences. Women responded to open-ended questions. The initial emotional turmoil reported by most was generally short lived. However, the impact of genetic testing went beyond the in idual to the extended family and social context, particularly in the short-term. A common theme was the difficulty associated with ulging a result to family members, who were also adjusting to their own result. The majority of carriers reported advantages that were both physical (options for surveillance programs and prophylactic surgery) and emotional (reduced uncertainty, increased awareness of options and knowledge about risk, preparation time). Most carriers reported no change in lifestyle although some reported discovering their mutation status as a positive life-changing experience. Implications for genetic counseling and further research are discussed.
Publisher: Public Library of Science (PLoS)
Date: 04-2015
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1532-5415.2008.02130.X
Abstract: To assess whether there is an association between delivery of adjuvant chemotherapy to older women with breast cancer and development of dementia over time. Retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare claims data. Women residing in geographic areas included in the SEER registry. Women aged 66 to 80 diagnosed with non-metastatic invasive breast cancer from 1992 to 1999 were included. It was determined whether patients had undergone chemotherapy within 6 months of diagnosis. Whether women developed dementia over time was determined using diagnostic codes. The effect of adjuvant chemotherapy on development of dementia was evaluated, adjusting for confounders using a proportional hazards model stratified for age. Twenty-one thousand three hundred sixty-two women met selection criteria 2,913 received chemotherapy, and 18,449 did not. Women who received chemotherapy were younger than those who did not (median aged 70 vs 73 P<.001). Median follow-up time was 59 months. After controlling for other factors, it was found that chemotherapy was not associated with a greater risk of development of dementia over time for any age group (hazard ratio for dementia in women receiving chemotherapy: aged 66-70=0.83, 95% confidence interval (CI)=0.48-1.45, P=.5 aged 71-75=0.74, 95% CI=0.46-1.18, P=.2 aged 76-80=0.49, 95% CI=0.28-0.88, P=.02). Receipt of chemotherapy in older women with breast cancer was not associated with a greater risk of dementia diagnosis over time very elderly women who undergo chemotherapy may be at lower baseline risk. The use of a claims-based definition of dementia limited the study.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-01-2008
Abstract: Women from BRCA mutation–positive families who do not carry the family-specific mutation are generally at average cancer risk and therefore do not require intensive risk management. Participants were female noncarriers from BRCA mutation–positive families who had responded to 3 yearly follow-up questionnaires and had chosen to either receive or not receive their genetic test result. In the former group, undertaking mammography younger than age 40 years or more than once every 2 years, clinical breast examination (CBE) more than yearly, breast self-examination (BSE) more than monthly, or any transvaginal ultrasound (TVU) or CA-125 was considered overscreening. Screening behaviors of women who did and did not know their genetic test result were compared. Logistic regression and nonparametric analyses were performed to identify demographic and psychosocial factors (respectively) associated with overscreening. Of 325 eligible women, 116 knew their mutation status and 209 did not. For the first group, proportions overscreening were mammography, 53% CBE, 10% BSE, 11% TVU, 7% and CA-125, 10%. There were no significant differences in screening behaviors between the groups. In those aware of their mutation status, parous women were more likely to overuse mammography (odds ratio [OR] = 4.4 95% CI, 1.1 to 17 P = .03) and women with one or more first-degree relative with ovarian cancer (OC) were more likely to overuse OC screening (TVU: OR = 6.00 95% CI, 1.0 to 35.1 P = .047, and CA-125: OR = 6.50 95% CI, 1.49 to 28.4 P = .013). The reasons for overuse of screening (particularly mammography) by mutation noncarriers require additional elucidation given the potential for harm.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2014
DOI: 10.1038/SREP04669
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533911.V1
Abstract: Strongest barriers to and facilitators of risk reducing medication use for kConFab women
Publisher: American Medical Association (AMA)
Date: 07-04-2015
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.BANDC.2005.05.001
Abstract: Several studies have identified that adjuvant chemotherapy for breast cancer is associated with cognitive impairment however, the magnitude of this impairment is unclear. This study assessed the severity and nature of cognitive impairment associated with adjuvant chemotherapy by conducting a meta-analysis of the published literature to date. Six studies (five cross-sectional and one prospective) meeting the inclusion criteria provided a total of 208 breast cancer patients who had undergone adjuvant chemotherapy, 122 control participants and 122 effect sizes (Cohen's d) falling into six cognitive domains. First, the mean of all the effect sizes within each cognitive domain was calculated (separately for cross-sectional and prospective studies) second, a mean effect size was calculated for all of the effect sizes in each cross-sectional study and third, regression analyses were conducted to determine any relationships between effect size for each study and four different variables. For the cross-sectional studies, each of the cognitive domains assessed (besides attention) showed small to moderate effect sizes (-0.18 to -0.51). The effect sizes for each study were small to moderate (-0.07 to -0.50) and regression analysis detected a significant negative logarithmic relationship (R2 = .63) between study effect size and the time since last receiving chemotherapy. For the prospective study, effect sizes ranged from small to large (0.11-1.09) and indicated improvements in cognitive function from the beginning of chemotherapy treatment to 3 weeks and even 1 year following treatment. This meta-analysis suggests that cognitive impairment occurs reliably in women who have undergone adjuvant chemotherapy for breast cancer but that the magnitude of this impairment depends on the type of design that was used (i.e., cross-sectional or prospective). Thus, more prospective studies are required before definite conclusions about the effects of adjuvant chemotherapy on cognition can be made.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-06-2022
DOI: 10.1200/JCO.22.00325
Publisher: Springer Science and Business Media LLC
Date: 03-11-2010
Publisher: Springer Science and Business Media LLC
Date: 26-11-2009
Publisher: American Association for Cancer Research (AACR)
Date: 12-2007
DOI: 10.1158/1055-9965.EPI-07-0542
Abstract: Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148 r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation s les, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. (Cancer Epidemiol Biomarkers Prev 2007 (12):2557–9)
Publisher: Oxford University Press (OUP)
Date: 19-04-2016
Publisher: Massachusetts Medical Society
Date: 14-01-1999
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2021
DOI: 10.1158/1940-6207.CAPR-21-0141
Abstract: Without preventive interventions, women with germline pathogenic variants in BRCA1 or BRCA2 have high lifetime risks for breast cancer and tubo-ovarian cancer. The increased risk for breast cancer starts at a considerably younger age than that for tubo-ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (rrBSO) is effective in reducing tubo-ovarian cancer risk for BRCA1 and BRCA2 mutation carriers, but whether it reduces breast cancer risk is less clear. All studies of rrBSO and breast cancer risk are observational in nature and subject to various forms of bias and confounding, thus limiting conclusions that can be drawn about causation. Early studies supported a statistically significant protective association for rrBSO on breast cancer risk, which is reflected by several international guidelines that recommend consideration of premenopausal rrBSO for breast cancer risk reduction. However, these historical studies were h ered by the presence of several important biases, including immortal person-time bias, confounding by indication, informative censoring, and confounding by other risk factors, which may have led to overestimation of any protective benefit. Contemporary studies, specifically designed to reduce some of these biases, have yielded contradictory results. Taken together, there is no clear and consistent evidence for a role of premenopausal rrBSO in reducing breast cancer risk in BRCA1 or BRCA2 mutation carriers.
Publisher: Springer Science and Business Media LLC
Date: 07-07-2006
DOI: 10.1007/S10689-006-0006-8
Abstract: This multicenter study examined the adherence of high-risk women to screening recommendations for breast and ovarian cancer following consultation at a familial cancer clinic (FCC). Self-report questionnaires assessing recall of screening advice, tests undertaken, risk perception, anxiety (Impact of Events Scale) and demographics were mailed to 396 consecutive eligible women who had attended one of six FCCs a median of 3.6 years prior. Family history, genetic test results and screening recommendations were abstracted from medical records. 182/266 (68.4%) women responded with 130 lost to follow-up. The proportions of women undertaking at least the recommended frequency of screening tests were: breast self examination (BSE) 50.4%, clinical breast examination (CBE) 66.0%, mammography 82.2%, transvaginal ultrasound (TVUS) 70.0%, CA125 84.0%. Factors associated with adherence to screening were: higher anxiety for BSE and CBE, being BRCA1/2 positive for CBE, older age, method of arrangement and having at least one affected first degree relative for mammography. Factors significantly associated with over-adherence were higher scores for anxiety for BSE and CBE and younger age (< 40 years) for TVUS. Between 41.3% (BSE) and 57.6% (CBE) of women incorrectly recalled their screening recommendations. A substantial minority of high-risk women do not adhere to screening advice. Strategies to improve the accuracy of recall of recommendations and the uptake of recommended screening are required.
Publisher: Elsevier BV
Date: 04-2010
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-07-2005
Abstract: Although self-report data on treatment for breast cancer are collected in some large epidemiologic studies, their accuracy is unknown. As part of a population-based Breast Cancer Family Registry, questionnaires on initial breast cancer treatment and subsequent recurrence were mailed to Australian women diagnosed between 1991 and 1998. These self-report data were validated against medical records for 895 women. The median recall period was 3.2 years, mean age at diagnosis was 44 years, and 81% of women had early-stage breast cancer. Agreement between the two data sources was very high for general questions about type of treatment (100%, 99%, 99%, and 94% for surgery, radiotherapy, chemotherapy, hormonal therapy, respectively). For more specific questions about details of each treatment received, agreement was: for radiation therapy, 96% and 99% for radiation to the breast and chest wall, respectively for surgery, 83%, 97%, and 88% for lumpectomy, mastectomy, and lymph node dissection, respectively for hormonal therapy, 94% for tamoxifen and for chemotherapy, range between 76% and 93%. There was 97% agreement about whether there had been a recurrence, and agreement about the location of recurrence was at least 90% for all sites. Agreement regarding stage at diagnosis was 62%, with discrepancies mostly due to women with locoregional disease incorrectly reporting distant spread. This self-report questionnaire can be used to collect accurate data on broad categories of initial breast cancer treatment and recurrence, and even for more detailed information on specifics of treatment and site of recurrence.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2011
DOI: 10.1007/S10549-011-1733-6
Abstract: Published studies have reached contradictory conclusions regarding breast cancer risk for women from families segregating a BRCA1 or BRCA2 mutation who do not carry the family-specific mutation. Accurate estimation of breast cancer risk is crucial for appropriate counselling regarding risk management. The aim of this study is to prospectively assess whether breast cancer risk for mutation negative women from families segregating BRCA1 or BRCA2 mutations is greater than for women in the general population. Eligible women were 722 first-, second- and third-degree relatives of a BRCA1 or BRCA2 mutation carrier from 224 mutation positive (128 BRCA1, 96 BRCA2) families, had no personal cancer history at baseline, and had been tested and found not to carry the family-specific mutation. Self-reported family history of cancer, preventive interventions and verified cancer diagnoses were collected at baseline, and every 3 years thereafter. Median follow-up was 6.1 years (range 0.1-12.4 years). Time at risk of breast cancer was censored at cancer diagnosis or risk-reducing surgery. Standardised incidence ratios (SIR) were estimated by comparing observed to population incidences of invasive breast cancer using Australian Cancer Incidence and Mortality Books. Six cases of invasive breast cancer were observed. The estimated SIRs were 1.14 (95% CI: 0.51-2.53) overall (n = 722), 1.29 (95% CI: 0.58-2.88) when restricted to first- and second-degree relatives of an affected mutation carrier (n = 442) and 0.48 (95% CI: 0.12-1.93) when restricted to those with no family history of breast cancer in the non-mutation carrying parental lineage (n = 424). There was no evidence that mutation negative women from families segregating BRCA1 or BRCA2 mutations are at increased risk of breast cancer. Despite this being the largest prospective cohort to assess this issue, moderately increased breast cancer risk (2-fold) cannot be ruled out.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2009
DOI: 10.1007/S10549-009-0497-8
Abstract: The purpose of this study is to determine the prevalence and predictors of contralateral risk-reducing mastectomy (CRRM) in Australasian women at high familial risk of a second primary breast cancer (BC). Participants were women with unilateral BC and a strong family history of the disease, including BRCA1/2 mutation carriers. Data were collected through interview, self-administered questionnaire and review of pathology and surgical reports. Associations between CRRM and potential predictors were assessed using multivariate logistic regression. Of 1,018 women (median follow-up 11.1 years), 154 (15%) underwent CRRM, 43% of these within 12 months of initial BC surgery. More likely to undergo CRRM were women who were younger at BC diagnosis (odds ratio [OR] = 0.94 per year of age, P < 0.001), were diagnosed more recently (OR = 1.16 per calendar year, P < 0.001), underwent mastectomy as initial definitive BC treatment (OR = 5.2, P < 0.001) and underwent risk-reducing salpingo-oophorectomy (OR = 3.4, P < 0.001). BRCA1/2 mutation status, axillary nodal status and receipt of chemotherapy were not independently associated with CRRM uptake. A contralateral BC event (invasive or in situ) occurred in 177 (20.5%) of the 864 women who did not have CRRM, compared with one chest wall event (0.6%) in the 154 women post-CRRM. The contralateral event rate was 15.1 per 1,000 women-years for non-CRRM women and 0.7 per 1,000 women-years for CRRM women P < 0.0001. Younger women with more recently diagnosed BC treated with mastectomy are more likely to elect CRRM. Neither BRCA1/2 mutation status, nor the competing risk of BC recurrence and death, appears to influence decision making.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22534607.V1
Abstract: Supplementary Data from Weight is More Informative than Body Mass Index for Predicting Postmenopausal Breast Cancer Risk: Prospective Family Study Cohort (ProF-SC)
Publisher: Springer Science and Business Media LLC
Date: 17-07-2009
Publisher: Oxford University Press (OUP)
Date: 08-12-2021
Abstract: This study examined why women and doctors screen for ovarian cancer (OC) contrary to guidelines. Surveys, based on the Theoretical Domains Framework, were sent to women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer and family physicians and gynecologists who organized their screening. Of 1264 Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer women, 832 (65.8%) responded. In the past 2 years, 126 (15.1%) had screened. Most of these (n = 101, 80.2%) would continue even if their doctor told them it is ineffective. For women, key OC screening motivators operated in the domains of social role and goals (staying healthy for family, 93.9%), emotion and reinforcement (peace of mind, 93.1%), and beliefs about capabilities (tests are easy to have, 91.9%). Of 531 clinicians 252 (47.5%) responded a minority (family physicians 45.8%, gynecologists 16.7%) thought OC screening was useful. For gynecologists, the main motivators of OC screening operated in the domains of environmental context (lack of other screening options, 27.6%), and emotion (patient peace of mind, 17.2% difficulty discontinuing screening, 13.8%). For family physicians,, the strongest motivators were in the domains of social influence (women ask for these tests, 20.7%), goals (a chance these tests will detect cancer early, 16.4%), emotion (patient peace of mind, 13.8%), and environmental context (no other OC screening options, 11.2%). Reasons for OC screening are mostly patient driven. Clinician knowledge and practice are discordant. Motivators of OC screening encompass several domains, which could be targeted in interventions to reduce inappropriate OC screening.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547304.V1
Abstract: Abstract Guidelines endorse the use of chemoprevention for breast cancer risk reduction. This study examined the barriers and facilitators to chemoprevention use for Australian women at increased risk of breast cancer, and their clinicians. Surveys, based on the Theoretical Domains Framework, were mailed to 1,113 women at ≥16% lifetime risk of breast cancer who were enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer cohort study (kConFab), and their 524 treating clinicians. Seven hundred twenty-five women (65%) and 221 (42%) clinicians responded. Only 10 (1.4%) kConFab women had ever taken chemoprevention. Three hundred seventy-eight (52%) kConFab women, two (3%) breast surgeons, and 51 (35%) family physicians were not aware of chemoprevention. For women, the strongest barriers to chemoprevention were side effects (31%) and inadequate information (23%), which operate in the Theoretical Domains Framework domains of “beliefs about consequences” and “knowledge,” respectively. Strongest facilitators related to tamoxifen's long-term efficacy (35%, “knowledge,” “beliefs about consequences,” and “goals” domains), staying healthy for family (13%, “social role” and “goals” domains), and abnormal breast biopsy (13%, “environmental context” domain). The strongest barrier for family physicians was insufficient knowledge (45%, “knowledge” domain) and for breast surgeons was medication side effects (40%, “beliefs about consequences” domain). The strongest facilitators for both clinician groups related to clear guidelines, strong family history, and better tools to select patients (“environmental context and resources” domain). Clinician knowledge and resources, and beliefs about the side-effect consequences of chemoprevention, are key domains that could be targeted to potentially enhance uptake. Prevention Relevance: Despite its efficacy in reducing breast cancer incidence, chemoprevention is underutilised. This survey study of Australian women and their clinicians used behavioural change theory to identify modifiable barriers to chemoprevention uptake, and to suggest interventions such as policy change, educational resources and public c aigns, that may increase awareness and use. i See related Spotlight by Vogel, p. 1 /i /
Publisher: Informa UK Limited
Date: 20-03-2015
Publisher: Springer Science and Business Media LLC
Date: 22-03-2011
No related grants have been discovered for Kelly-Anne Phillips.