ORCID Profile
0000-0002-4946-2789
Current Organisations
University of Sydney
,
Royal Prince Alfred Hospital
,
Garvan Institute of Medical Research
,
Chris O'Brien Lifehouse
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Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/07357900802392667
Abstract: Radiation recall dermatitis (RRD) is a rare cutaneous reaction occurring within a previously irradiated field, precipitated by certain drugs. We report a case of RRD occurring after pre-sensitization with pegylated liposomal doxorubicin (PLD) in a woman with Stage IV breast cancer. The RRD occurred in one of the patient's four previous radiotherapy fields. We discuss the time/dose factors of radiation exposure and measure the corresponding skin dose. In our case the radiation dose was low and below previously reported thresholds, and illustrates that there is a more complex interaction between the radiotherapy and the trigger agent than has previously been considered.
Publisher: SAGE Publications
Date: 03-2016
DOI: 10.2217/WHE.15.105
Abstract: This article provides an overview of the main controversies in a number of key areas of breast cancer management. Relevant studies that have contributed to guide the treatment of this heterogeneous disease in the field of breast screening, surgery, chemotherapy and radiotherapy are highlighted. Mammography and ultrasound are the main methods of breast screening. MRI and tomosynthesis are emerging as new screening tools for a selected group of breast cancer patients. From a surgical perspective, oncoplastic techniques and neoadjuvant chemotherapy are improving cosmetic results in breast-conserving surgery. For high-risk patients, controversies still remain regarding prophylactic mastectomies. Finally, the appropriate management of the axilla continues evolving with the increasing role of radiotherapy as an alternative treatment to axillary dissection.
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: Springer Science and Business Media LLC
Date: 22-03-2013
Abstract: Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole. This was a prospective open-label cross-over study in 60 women with early stage breast cancer taking either tamoxifen, anastrozole or letrozole (n=20/group). Participants received ginkgo biloba (EGb 761) for 3 weeks (120 mg twice daily). Trough concentrations of drugs were measured before and after ginkgo biloba treatment using LC-MS/MS. Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Trough concentrations before and after treatment with ginkgo biloba were not significantly different for tamoxifen (93.5 ± 29.0, 86.5 ± 25.3 ng/mL p=0.16), letrozole (91.1 ± 50.4, 89.6 ± 52.14 ng/mL p=0.60) or anastrozole (29.1 ± 8.6, 29.1 ± 7.6 ng/mL p=0.97). Ginkgo biloba was well tolerated, with no difference in toxicity during ginkgo biloba. Co-administration of ginkgo biloba does not significantly affect the pharmacokinetics of tamoxifen, anastrozole or letrozole. There was no difference in the toxicity profile of hormone therapy with ginkgo biloba use in women with early stage breast cancer.
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: Springer Science and Business Media LLC
Date: 02-07-2014
DOI: 10.1007/S11764-014-0378-Y
Abstract: This study aimed to explore differences in physical activity and fitness between women with metastatic breast cancer compared to healthy controls and factors associated with their physical activity levels. Seventy-one women with metastatic breast cancer, aged (mean (SD)) 57.7 (9.5) and 2.9 (3.1) years after the onset of metastatic disease, and 71 healthy controls aged 55.0 (9.4) years participated. Of those with metastatic disease, 27% had bone-only metastases, 35% visceral-only metastases and 38% bone and visceral metastases. Patient-reported outcomes and physical measures of muscle strength and aerobic fitness assessments were obtained. Participants wore a SenseWear® physical activity monitor over 7 days, and the average steps/day and the time spent in moderate-to-vigorous intensity physical activity were determined. Women with metastases were significantly (i) less aerobically fit than the control group (25.3 (5.4) vs. 31.9 (6.1) mL • kg(-1) • min(-1) P < 0.001) (ii) weaker (e.g. lower limb strength for the metastatic and control groups was 53.5 (23.7) vs. 76.0 (27.4) kg, respectively P < 0.001) (iii) less active, with the metastatic group attaining only 56% of the mean daily step counts of the healthy women and (iv) more symptomatic, reporting higher levels of fatigue and dyspnoea (P < 0.001). Women living in the community with metastatic breast cancer possessed lower aerobic fitness, reduced muscular strength and less daily physical activity compared to healthy counterparts. They also experienced poorer functioning and higher symptom burden. Women living with metastatic breast cancer may benefit from a physical activity programme to address their physical impairments.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2009
Publisher: Wiley
Date: 23-08-2013
DOI: 10.1002/PON.3348
Abstract: Fear of cancer recurrence (FCR) is a common problem amongst survivors. Past research has shown that young women with breast cancer are particularly vulnerable to FCR, yet few previous studies have specifically examined FCR in this subgroup. The aim of the study is to explore the relationship between FCR, psychological morbidity and social factors. A secondary aim was to explore the relationship between clinical levels of FCR and generalised anxiety disorder (GAD) and hypochondriasis. Two hundred eighteen breast cancer survivors (aged 18-45 years at diagnosis) diagnosed at least 1 year prior were recruited through seven metropolitan oncology clinics and two breast cancer consumer groups. Participants completed a web-based questionnaire, which assessed FCR, psychological functioning, generalised anxiety, hypochondriasis and items exploring past cancer-related experiences, attitudes to future childbearing, social support and correlates were identified using linear regression. Psychological morbidity scales measuring anxiety and psychological functioning and stressful life events were significantly associated with FCR in adjusted and unadjusted models (p < 0.0001). Past cancer experiences, children, social support and attitudes to childrearing were not associated with FCR. Among those with clinical levels of FCR (n = 152), 43% met screening criteria for hypochondriasis, and 36% met screening criteria for GAD. This study shows psychological morbidity is associated with FCR, but the majority of women with high levels of FCR do not also meet the criteria for a clinical level of GAD or hypochondriasis. Understanding the factors that make young women vulnerable to FCR is important to help guide the development of FCR-specific interventions for this subgroup.
Publisher: Wiley
Date: 07-10-2009
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.PEC.2008.02.021
Abstract: Preferences of women who had completed adjuvant chemotherapy for early breast cancer were compared with those of their partners by determining the smallest benefits they judged sufficient to make adjuvant chemotherapy worthwhile. Forty-six women and their partners were interviewed separately, 3-34 months after completing adjuvant chemotherapy. Preferences were elicited using four sets of validated, hypothetical trade-off scenarios about the possible benefits of adjuvant chemotherapy on survival times (5 and 15 years) and survival rates (65% and 85% at 5 years). Agreement within couples was assessed with the intraclass correlation coefficient (ICC). Associations between baseline characteristics, preferences, and agreement within couples were assessed with linear regression after normal score transformation. The mean age of the women was 57 years and of their partners' was 60. Most couples were married (91%). Benefits of an extra 1 day or 0.1% were judged sufficient to make adjuvant chemotherapy worthwhile by 59-72% of women and 54-59% of partners. Agreement was exact in 35-41% of couples and approximate in 59-83%. Agreement was better for scenarios with a worse prognosis (ICC 0.67 and 0.35) than for scenarios with a better prognosis (ICC 0.13 and 0.05). Having dependent children was associated with partners requiring larger benefits but patients requiring smaller benefits to make adjuvant chemotherapy worthwhile (interaction P=0.001). Patients' and partners' preferences for adjuvant chemotherapy differed and were influenced by considerations other than length and quality of life. Clinicians who are aware of these differences can tailor discussions to ensure that all interested parties understand and agree on the goals and benefits of treatment.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2007
DOI: 10.1007/S10549-007-9710-9
Abstract: The aim of this systematic review was to identify the prevalence and severity of upper limb problems following surgery and radiation for early breast cancer. Additionally, the independent prognostic contribution of radiation, type of breast surgery, type of axillary surgery, age and body mass index (BMI) was evaluated. Searches of electronic databases were conducted to identify articles that reported upper limb and quality of life outcomes after breast cancer surgery and external radiation. Eligible studies for prognosis were longitudinal in design, with > or =95% of patients treated by surgery and radiation that excluded the axilla. Cross-sectional studies were also included for identification of prognostic factors. Where possible, the contribution of independent prognostic factors was analyzed. The review identified 32 relevant studies. Shoulder restriction was reported in between <1% and 67% of participants, lymphedema was reported in between 0 and 34% of participants, shoulder/arm pain was reported in between 9 and 68% of participants and arm weakness was reported in between 9 and 28% of participants. Quality of life was high across studies. Irradiated patients had slightly increased odds of lymphedema (OR = 1.46, 95% CI 1.16-1.84) and shoulder restriction (OR = 1.67, 95% CI 0.98-2.86) compared with non-irradiated patients. For patients undergoing surgery and radiation for breast cancer, the prognosis is good in terms of the upper limb and quality of life. Radiation that excludes the axilla does not appear to be a strong prognostic indicator of adverse upper limb outcomes.
Publisher: John Wiley & Sons, Ltd
Date: 08-10-2008
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: Wiley
Date: 12-2009
Publisher: Wiley
Date: 28-08-2011
Publisher: Wiley
Date: 03-2016
DOI: 10.1111/AJCO.12491
Abstract: Endocrine therapy for the treatment of hormone receptor positive, HER2 negative, metastatic breast cancer is continually evolving. We systematically reviewed phase 2 and 3 randomized controlled trials (RCTs) of agents used in this setting to assess the effectiveness and safety of these agents for postmenopausal women. Across the 32 studies in more than 10,000 patients, the greatest improvement in progression-free survival (PFS) was seen with the addition of a cyclin-dependent kinase (CDK)4/6 inhibitor to standard endocrine therapy. Treatment with a mammalian target of rapamycin (mTOR) inhibitor, phosphoinositol-3-kinase (Pi3K) inhibitor, vascular endothelial growth factor (VEGF) inhibitor and with a selective estrogen receptor degrader (SERD) also showed benefit in PFS for selected trials. Overall survival (OS) improved with the use of mTOR inhibitors and a SERD however, studies were not powered for an OS endpoint. Encouraging results from early studies of histone deacetylase (HDAC) and B-cell lymphoma (BCL2) inhibitors are yet to be confirmed in phase III clinical trials. Study discontinuation rates and toxicity-related deaths were highest with VEGF inhibitors in combination with endocrine therapy, limiting their use in hormone receptor positive breast cancer. CDK4/6 inhibitors and mTOR inhibitors appeared to have activity in both first and second line settings, but required additional monitoring for common toxicities. The activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors was limited to the first-line setting and treatment discontinuation rates were higher than with mTOR inhibitors and SERDs. Overall, PFS benefit appears to be greatest when agents acting on CDK4/6, mTOR and Pi3K pathways, and SERDs are added to standard endocrine therapy. If these early results persist in further studies, these data are likely to change the way we treat hormone receptor positive, HER2 negative metastatic breast cancer. In the follow-up article to this review, we will consider the potential future treatment options for these patients.
Publisher: Wiley
Date: 03-2015
DOI: 10.1111/AJCO.12492
Abstract: Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is lost over time due to evolving changes in tumor biology and the development of endocrine resistance. Many agents targeting the intracellular signaling pathways associated with endocrine resistance are in development. Encouraging early results have been seen for agents which directly target the estrogen receptor (ER), inhibitors of co-signaling pathways, inhibitors of ER chaperones, ER antagonists able to inhibit mutated or otherwise activated ERs, and modulators of histone acetylation restoring synthesis of ER signaling components. Following our systematic review of treatments with established benefits in this supplement, we review some of the more promising new strategies for overcoming endocrine resistance, looking at the impact on disease control and quality of life for women with hormone receptor positive, HER2 negative breast cancer. We also examine the biomarkers that may guide selection of the best therapy for the in idual.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2021
Publisher: SAGE Publications
Date: 09-2013
DOI: 10.1136/ACUPMED-2012-010309
Abstract: Aromatase inhibitors (AIs) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer. A substantial proportion of women taking AIs experience joint pain and stiffness. Studies have suggested that acupuncture may be effective in treating joint pain. A pilot study was conducted to evaluate the feasibility, safety and efficacy of using acupuncture to treat AI-induced arthralgia. A total of 32 patients were randomised to receive either sham or real electroacupuncture (EA) twice weekly for 6 weeks. Outcomes of joint pain, stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), overall pain severity and interference with the BPI-SF and quality of life (QOL) with the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Hand strength was assessed by a grip test, and a serum marker of inflammation (C reactive protein (CRP)) was also measured. All assessments were performed at baseline, 6 weeks and 12 weeks, except for blood s les at baseline and 6 weeks only. No serious adverse events were reported during or after acupuncture treatments. There were no significant differences in outcome measures. However, positive trends were observed in stiffness and physical function at week 12 in favour of real EA. Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI. A larger study with adequately powered to confirm these results and detect clinically relevant effects is needed.
Publisher: Wiley
Date: 2007
DOI: 10.1002/PON.1045
Abstract: Many women who have had adjuvant chemotherapy for early breast cancer judge small benefits sufficient to make it worthwhile despite significant side effects and inconvenience. The rationality of these preferences has been questioned. We sought to better understand such preferences by assessing associations between preferences and psychosocial factors, and by asking women who judged negligible benefits sufficient to explain why. We recruited 83 consecutive consenting women who had completed adjuvant chemotherapy for early breast cancer 3-34 months earlier. Preferences were elicited during a structured, scripted interview using four sets of validated, hypothetical trade-off scenarios about the possible benefits of adjuvant chemotherapy on survival times (5 and 15 years) and rates (65 and 85% at 5 years). Women completed questionnaires measuring anxiety, depression, optimism, quality and quantity of social support, and illness perceptions. More than half the women judged benefits of 1 day or 0.1% sufficient to make adjuvant chemotherapy worthwhile. The most important factors in multivariable models were whether the woman had dependants and number of non-specific symptoms attributed to breast cancer and adjuvant chemotherapy since completing treatment. The proportion of variance explained was modest. Preferences were not associated with: scores for anxiety, optimism, and perceived quality and quantity of social support. Explanations for judging negligible benefits sufficient included minimising regret, parenting concerns, doubts about the information provided and feeling that they had no choice. Preferences were highly variable and influenced by women's unique circumstances and attitudes, but not by their anxiety or optimism scores.
Publisher: Wiley
Date: 12-01-2012
DOI: 10.1111/J.1743-7563.2011.01462.X
Abstract: To explore the incidence of subclinical cardiotoxicity in women treated with adjuvant trastuzumab in the early breast cancer setting using cardiac magnetic resonance imaging (cMRI). The cardiac function and myocardial tissue characteristics of 25 women who had completed adjuvant trastuzumab therapy greater than 6 months previously was evaluated using MRI and comparing this with symptoms and routine echocardiography. Evidence of myocardial tissue damage was seen in two women in the absence of functional change or previous cardiac symptoms. Tissue characterization using cMRI may provide a useful tool in defining trastuzumab induced cardiotoxicity.
Publisher: BMJ
Date: 12-12-2015
DOI: 10.1136/JCLINPATH-2014-202331
Abstract: The diagnosis of intraductal papillary lesions of the breast on core biopsy remains challenging in pathology, with most patients requiring formal surgical excision for a definitive diagnosis. The aim of this study was to determine whether a representative panel of proliferative cell cycle immunohistochemical markers (cyclin A2, cyclin B1 and cyclin D1) could improve the specificity of pathological diagnosis of these lesions. A series of 68 surgically excised intraductal papillary lesion cases were retrospectively selected, and immunohistochemistry for cyclin A2, cyclin B1 and cyclin D1 was performed. Cyclin B1 (OR 1.80, 95% CI 1.01 to 3.2, p=0.046) and cyclin D1 (OR 1.13, 95% CI 1.05 to 1.22, p=0.002) expression was independently associated with a diagnosis of malignancy in papillary lesions, although expression was frequently heterogeneous and only focal. Cyclin A2 expression (OR 0.76, 95% CI 0.41 to 1.4, p=0.38) was not associated with a malignant diagnosis in multivariable logistic regression models. All three cyclins displayed high sensitivity (80%-95%) for a diagnosis of malignancy, although cyclin B1 showed a superior specificity of 72.7% compared with the low specificity of cyclins A2 and D1. Our study has identified for the first time that the expression of key cell cycle markers differs between benign and malignant papillary breast lesions and identified changes to the mitotic marker, cyclin B1, as particularly significant. However, given the low level and heterogeneous nature of expression of these markers, there remains a significant risk of unders ling in core biopsies and thus they are unlikely to be useful in routine clinical practice.
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: BMJ
Date: 22-02-2013
DOI: 10.1136/JCLINPATH-2012-201361
Abstract: Outcomes have improved significantly for many women diagnosed with breast cancer. For the heterogeneous group of tumours lacking expression of the oestrogen, progesterone and HER2 receptors, 'triple negative' breast cancers (TNBC), the prognosis overall has remained quite poor. When TNBC recurs, there is often little response to chemotherapy, and there are a few treatment options in this setting. Thus, there is an urgent clinical need to identify new therapeutic targets in order to improve the outlook for these patients. This review highlights the most promising therapeutic targets identified through new sequencing technologies, as well as through studies of apoptosis. We also present mounting evidence that the developmental signalling pathways Wnt/β-catenin, NOTCH and Hedgehog play an important role in the pathogenesis and progression of TNBC with new therapeutic approaches inhibiting these pathways in advanced preclinical studies or early clinical trials.
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.BREAST.2005.02.001
Abstract: There is increasing use of luteinising hormone-releasing hormone (LHRH) agonists in the adjuvant treatment of breast cancer (J. Clin. Oncol. 19(2) (2001) 343). However, few mature studies are available and there is uncertainty regarding the optimal use of these agents. We performed a systematic review to address the role of LHRH agonists in the adjuvant treatment of pre-menopausal women with early breast cancer. As ovarian suppression is unlikely to benefit women with ER-negative tumours, the review is limited to women with ER-positive disease. The objectives of this review were to address the following issues the role of LHRH agonists compared to tamoxifen (TAM), LHRH agonists in place of chemotherapy and LHRH agonists integrated into chemo-hormonal regimens. We identified 11 randomised trials. In three trials, adjuvant suppression of ovarian function using LHRH agonists, with or without TAM, had similar benefits at 5-6 years follow-up in terms of disease-free survival (DFS) and overall survival (OS) to adjuvant CMF chemotherapy (J. Clin. Oncol 20(24) (2002) 4628 J. Natl. Cancer Inst. 95(24) (2003) 1833 Anticancer Res. 22 (2002) 2325 In: San Antonio Breast Cancer Symposium, San Antonio, TX, 2003, Abstr 40). These findings suggest that ovarian suppression using LHRH agonists (+/-TAM) is a reasonable alternative to CMF chemotherapy in women with oestrogen receptor (ER) positive tumours. The role of chemotherapy in addition to LHRH agonists is not clearly defined and mature results of four trials are awaited (J. Clin. Oncol. 20(24) (2002) 4621 J. Clin. Oncol. 18(14) (2000) 2718 Proc. Am. Soc. Clin. Oncol. 2000, Abstr 279 Proc. Am. Soc. Clin. Oncol. 20 (2001) Abstr 104 Proc. Am. Soc. Clin. Oncol. 2001, Abstr. 1777). Data is also inadequate at the time of publication to inform decisions about the efficacy of LHRH agonists in comparison with TAM for the treatment of ER-positive early breast cancer (Proc. Am. Soc. Clin. Oncol. 21 (2001) Abstr. 103 Eur. J. Surg. Oncol. 28(5) (2002) 505 Proc. Am. Soc. Clin. Oncol. 22 (2003), Abstr. 15).
Publisher: Elsevier BV
Date: 08-2005
Publisher: Elsevier BV
Date: 03-1996
DOI: 10.1016/0959-8049(95)00608-7
Abstract: The toxicity and efficacy of concomitant chemotherapy and radiotherapy as induction therapy was evaluated in patients with previously untreated small cell carcinoma of the lung (SCLC), and in responding patients the value of maintenance chemotherapy was examined. 202 patients received induction chemotherapy with cisplatin and etoposide (EP), in combination with cranial and local radiotherapy. 85 patients (42%) developed grades III and IV myelosuppression, the main toxicity of induction treatment. Of the 154 responding patients, 129 were randomised to maintenance chemotherapy with vincristine, doxorubicin and cyclophosphamide (VAC) or no further treatment. The response rate for the limited disease patients (LD) was 87%, 62% achieving a complete response (CR) and the response rate for extensive disease patients (ED) was 68%, with 26% achieving a CR. 17 patients (11%) completed 10 courses of maintenance chemotherapy. 32 patients (57%) developed grade III and IV neutropenia. Median survival for all patients was 53 weeks (LD, 70 weeks ED, 42.5 weeks). There was no significant difference in overall survival (OS) or disease-free survival (DFS) in the two randomisation arms. This study shows that EP combined with radiotherapy is an effective induction regimen in SCLC. Maintenance chemotherapy with VAC is not associated with increased survival but has significant toxicity after such induction treatment.
Publisher: Mary Ann Liebert Inc
Date: 09-2011
Publisher: Springer Science and Business Media LLC
Date: 29-01-2012
DOI: 10.1007/S10549-012-1964-1
Abstract: The aim of this study was to determine whether an exercise program, commencing 4-6 weeks post-operatively, reduces upper limb impairments in women treated for early breast cancer. Women (n = 160) were randomized to either an 8-week exercise program (n = 81) or to a control group (n = 79) following stratification for axillary surgery. The exercise program comprised a weekly session and home program of passive stretching and progressive resistance training for shoulder muscles. The control group attended fortnightly assessments but no exercises were provided. The primary outcome was self-reported arm symptoms derived from the EORTC breast cancer-specific questionnaire (BR23), scored out of 100 with a low score indicative of fewer symptoms. The secondary outcomes included physical measures of shoulder range of motion, strength, and swelling (i.e., lymphedema). Women were assessed immediately following the intervention and at 6 months post-intervention. The change in symptoms from baseline was not significantly different between groups immediately following the intervention or at 6 m post-intervention. The between group difference immediately following the intervention was 4 (95% CI -1 to 9) and 6 months post-intervention was 4 (-2 to 10). However, the change in range of motion for flexion and abduction was significantly greater in the exercise group immediately following the intervention, as was change in shoulder abductor strength. In conclusion, a supervised exercise program provided some, albeit small, additional benefit at 6 months post-intervention to women who had been provided with written information and reminders to use their arm. Both the groups reported few impairments including swelling immediately following the intervention and 6 months post-intervention. Notably, resistance training in the post-operative period did not precipitate lymphedema.
Publisher: Wiley
Date: 25-08-2015
DOI: 10.1002/PON.3659
Abstract: Fear of cancer recurrence (FCR) is a common and severe problem amongst cancer survivors, but mechanisms to explain its development and maintenance are still lacking. The self-regulatory executive function (S-REF) model suggests that metacognitions and attentional bias to cancer-related words may explain high FCR. Thus, this study aimed to explore relationships between FCR, metacognitions and attentional bias in a mixed group of cancer survivors. Sixty-three early-stage breast or prostate cancer survivors, diagnosed within 6 months to 5 years prior to participation and who had completed all hospital-based treatment with no evidence of cancer recurrence were recruited through two metropolitan oncology clinics. Participants completed a questionnaire battery and the dot-probe task. Survivors with clinical FCR had significantly greater positive beliefs about worry (10.1 vs 7.4, p = 0.002) and beliefs about the uncontrollability and danger of worry (12.0 vs 7.7, p = 0.000) than those with non-clinical FCR, whereas the total metacognition score significantly predicted FCR in multiple regression analysis (β = 0.371, p = 0.001). No significant differences were detected between participants scoring above and below clinical FCR levels in attention bias indices. This study found partial support for the S-REF model of FCR, with metacognitions but not attentional bias found to be related to FCR. Further research is needed to explore attentional biases in more detail.
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.2165/00003088-200645060-00004
Abstract: To determine the safety profile of 40 mg/m(2) docetaxel administered weekly to a mixed population of advanced cancer patients and identify predictors of toxicity and survival following treatment with weekly docetaxel in this population. 68 patients with advanced cancer were enrolled into the study. Various patient characteristics, including inflammatory and nutritional status, docetaxel pharmacokinetics and liver function were investigated. Predictors of treatment-related toxicity and survival were analysed using multivariate logistic regression and Cox proportional hazards analysis, respectively. 27 patients (40%) experienced grade 3 or 4 toxicity, mainly gastrointestinal toxicities (20%), leukopenia (16%) and neutropenia (12%), during the first 8 weeks of docetaxel treatment. Docetaxel pharmacokinetics were the only predictive factor for haematological toxicity. The odds of severe haematological toxicity were approximately 9-fold higher for patients with reduced docetaxel clearance (e.g. 1.5 g/L or C-reactive protein >10 mg/L). Multivariate analysis indicated that weight loss, liver dysfunction and elevated levels of AAGP were independently significant predictors of survival. This is the first description of factors predictive of the toxicity and survival following weekly administration of docetaxel. Patients with reduced clearance of docetaxel and elevated markers of inflammation experienced worse adverse effects, while patients with weight loss, liver dysfunction and elevated markers of inflammation had worse survival.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.CCT.2011.04.012
Abstract: Aromatase inhibitors (AIs) have improved the prognosis for breast cancer survivors and are now standard of care for postmenopausal women with hormone receptor positive early stage breast cancer. One side-effect, however, is a decrease in bone mineral density (BMD) and increased fracture risk. Since hormone replacement therapy (HRT) is contraindicated in these women, one prevention option is exercise combined with vitamin D and calcium. The effect of this intervention on drug-induced osteoporosis is unknown. A single-blind randomized controlled trial will be undertaken to test the hypothesis that exercise combined with vitamin D and calcium can prevent the decrease in BMD associated with the use of AIs. Sixty postmenopausal women prescribed an AI for the treatment of breast cancer will be randomized into either an exercise or control group. Participants randomized to the exercise group will undertake a 12-month gym-based exercise program, 3 times per week involving resistance and impact training. Participants in the control group will be advised on the benefits of exercise for preventing osteoporosis, but not prescribed exercise. Both groups will receive vitamin D and calcium supplements. The primary outcome will be total hip bone mineral density measured via dual energy X-ray absorptiometry (DXA). Study outcomes will be compared between groups at baseline, 6months and 12months. This study will investigate the effect of exercise in combination with vitamin D and calcium on prevention of drug-induced osteoporosis in postmenopausal women prescribed AIs for the treatment of breast cancer.
Publisher: Elsevier BV
Date: 11-2005
Abstract: Studies of women who had adjuvant chemotherapy for early breast cancer 10-20 years ago showed that many judged small benefits sufficient to make it worthwhile. Indications, regimens and supportive care have changed. We sought the preferences of contemporary women who received similar chemotherapy. Ninety-seven consecutive consenting women who completed adjuvant chemotherapy for early breast cancer 3-34 months previously were interviewed. Preferences were elicited with a structured, scripted interview using the trade-off method. Women were presented with four hypothetical scenarios based on known life expectancies (5 and 15 years) and survival rates (65% and 85% at 5 years) without adjuvant chemotherapy. Improvements of an additional year in life expectancy or 3% in survival rates were judged sufficient to make adjuvant chemotherapy worthwhile by 68-84% of women. Half the women judged 1 day or 0.1% sufficient to make adjuvant chemotherapy worthwhile. Recollections of better well-being during adjuvant chemotherapy, having dependants and having a friend or relative who died from cancer were independently associated with judging smaller benefits sufficient to make adjuvant chemotherapy worthwhile (all P < 0.05). Preferences were highly variable, but the benefits judged sufficient to make adjuvant chemotherapy worthwhile were even smaller than those found in previous studies. Preferences were influenced by factors other than direct benefits and harms of chemotherapy.
Publisher: Elsevier BV
Date: 02-2011
Publisher: Springer Science and Business Media LLC
Date: 15-03-2013
DOI: 10.1007/S00520-013-1770-2
Abstract: The aim was to better understand the incidence, time course and risk factors for swelling in the arm on the side of surgery over the first year following surgery for breast cancer. Women (n = 160) were assessed 1 month following surgery and then randomised to the exercise or control group. Reassessment occurred 3, 9 and 15 months following surgery. Potential risk factors for swelling included age, body mass index, side of surgery and surgical and medical treatments for their breast cancer, physical measures of shoulder range of motion and strength, inter-limb arm circumference difference and the group to which they were randomised. Swelling was determined using bioimpedance spectroscopy with reference to previously established cut-offs for lymphoedema. The number of women with swelling at 3, 9 and 15 months was 15, 15 and 13, respectively however, at 15 months only 5/13 presented with swelling in either of the preceding assessments. The risk of swelling increased at 3, 9 and 15 months for each centimetre increase in the baseline inter-limb difference in sum of arm circumferences by 1.30, 1.17 and 1.14. In addition, risk of swelling at 3 months was 2.6 times greater for women in the control group at 9 months, 7 times greater for women who had taxane-based chemotherapy and at 15 months, the risk increased 1.16 times for each day the drain was in situ. Swelling in the first year is likely to be transient, and factors including exercise and taxane chemotherapy affect the risk of developing swelling.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2006
DOI: 10.1007/S10637-006-9014-7
Abstract: There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study assessed the effects of bosentan monotherapy (500 mg oral tablets, bid) on tumor response in patients with stage IV metastatic melanoma. Patients were treated until disease progression, death or serious adverse event leading to premature study drug discontinuation. Tumor response was assessed at 6-weekly intervals using the Response Evaluation Criteria in Solid Tumors (RECIST). Among the 35 patients included in this study with stage IV metastatic melanoma, 21 (60%) were stage M1C, 10 (29%) stage M1B and 4 (11%) stage M1A (American Joint Committee on Cancer [AJCC] classification). Nine patients (26%) had received prior therapy for stage IV melanoma. Disease stabilization was observed in 6 of the 32 patients analyzed per protocol at week 6 with confirmatory evaluation at week 12, 5 of whom were still stable at > or =24 weeks. Of the 6 patients with disease stabilization, 2 were stage M1A, 1 was stage M1B and the remaining 3 were stage M1C. Partial or complete response was not observed. Progressive disease was observed in 17 (49%) patients at week 12 and in 25 (71%) patients at the end of the study (data base closure). The most frequent adverse events were typical for the underlying disease or known to be associated with bosentan: headache (43%), fatigue (34%), nausea (31%), back pain (23%) and abnormal hepatic function (23%). Bosentan might have benefit in disease stabilization in certain patients with metastatic melanoma and deserves further investigation in combination with other anticancer drugs.
Publisher: Wiley
Date: 06-05-2014
DOI: 10.1111/AJCO.12206
Abstract: We aimed to systematically review and summarize data from the available clinical trials that examined the treatment of HER2-positive metastatic breast cancer. We reviewed phase 2 and 3 studies in which an anti-HER2 agent was used in one or both arms of the study. While formal meta-analysis was not possible for such a heterogeneous group of trials, resulting forest plots outline some generalizable findings. There is strong evidence that the addition of an anti-HER2 agent to standard chemo- or endocrine therapy improves clinically relevant measurable outcomes. There is also consistent evidence that initial treatment with trastuzumab alone (and subsequent use of a cytotoxic) is inferior to the initial combination of trastuzumab plus chemotherapy, and that either T-DM1 or dual anti-HER2 agents are superior to single anti-HER2 agent regimens. There is no strong evidence that the use of more than one cytotoxic agent together with an anti-HER2 agent confers any benefit over a single cytotoxic, anti-HER2 combination. This review provides a strong evidence base for current clinical practice with a discussion of treatment in the Australian setting.
Publisher: American Chemical Society (ACS)
Date: 20-05-2022
Abstract: Keypads constructed from fabric materials are the ideal input devices for smart clothing applications. However, multi-modal reaction problems have to be addressed before they can be of practical use on apparels, i.e., the fabric-based keypads need to distinguish between the legitimate actions by the fingertips and the illegitimate deformations and stresses caused by human movements. In this paper, we propose to use the humidity sensor functionalized from graphene oxide (GO)-coated polyester fibers to construct the e-textile keypads. As the moisture level in the proximity of human fingertips is much higher (over 70%) than other parts of the human body, humidity sensing has many advantages over other tactility mechanisms. Experiments have demonstrated that the GO-functionalized fabric keypad has a stable uni-modal tactility only to fingertip touches, and it is not sensitive to deformation, pressure, temperature variation, and other ambient interferences. With biasing and sensing circuits, the keypad exhibits a quick response and recovery time (around 0.1 s), comparable to mechanical keyboards. To demonstrate its application on smart clothing, the keypad was sewn on a sweater and embroidered conductive yarns were used to control an MP3 player in the pocket.
Publisher: Wiley
Date: 06-05-2014
DOI: 10.1111/AJCO.12207
Abstract: Improvements in the treatment of metastatic HER2-positive breast cancer constitute one of the great advances in breast cancer medicine of the last generation. From being a highly aggressive fatal condition, the use of anti-HER2-targeted therapies, in particular trastuzumab, has led to significant improvements in disease outcomes. There are reports of increasing numbers of patients alive and well more than 5 years from diagnosis of metastatic disease. Nevertheless, there remain many complex and clinically difficult scenarios where there is little in the way of randomized evidence or published guidelines to guide decision making. As a companion piece to our review of HER2-targeted therapies in the metastatic setting, we decided to focus on a series of clinical scenarios that fell outside of the standard trial-based settings and where opinions and guidance from experienced clinicians and experts in the field would be considered useful to help develop safe and effective treatment strategies. The following eight cases were put forward by our panel of experts, voted on by their peers to select the most relevant and interesting cases, and the discussions worked on by teams of two followed by review and commentary by another team of two.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-06-2007
Abstract: To evaluate tumor response, pharmacodynamic effects, and safety of a combination of lomeguatrib (LM), an O 6 -methylguanine DNA-methyltransferase (MGMT) inactivator, and temozolomide (TMZ), TMZ alone, and LM/TMZ after disease progression on TMZ alone in patients with advanced melanoma. Patients with unresectable stage III or IV cutaneous melanoma who had no prior systemic chemotherapy were randomly assigned to receive either 40 to 80 mg LM and 125 mg/m 2 TMZ or 200 mg/m 2 TMZ on days 1 through 5 of each 28-day treatment cycle. Drugs were administered orally for up to six cycles of treatment. Patients on TMZ alone were offered LM/TMZ at progression, if fit enough to receive treatment. One hundred four patients were enrolled, with 52 in each trial arm. Twenty-seven TMZ-treated patients received LM/TMZ after progression on TMZ. Unexpectedly, analysis of tumor biopsies showed rapid recovery of MGMT after LM/TMZ with 40 mg/d LM. Therefore, doses of LM were escalated to 60 then 80 mg/d. Tumor response rates were 13.5% with LM/TMZ and 17.3% with TMZ alone. No patient responded to LM/TMZ having progressed through TMZ. Median time to disease progression was 65.5 days for LM/TMZ and 68 days for TMZ. All treatments were well tolerated, although hematologic and gastrointestinal adverse events were common. A higher incidence of hematological adverse events was observed in the LM/TMZ combination arm. The efficacy of LM and TMZ in the current dosing schedule is similar to that of TMZ alone. To maintain MGMT depletion in tumor dosing of LM needs to be continued beyond that of TMZ.
Publisher: Springer Science and Business Media LLC
Date: 04-2009
Publisher: Elsevier BV
Date: 05-2001
DOI: 10.1016/S0169-5002(00)00218-X
Abstract: The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30% 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2007
Publisher: Springer Science and Business Media LLC
Date: 31-03-2009
Publisher: Wiley
Date: 22-04-2008
DOI: 10.1002/IJC.23448
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.IJROBP.2015.08.046
Abstract: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series of 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers--TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1--were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy-treated patients but not in untreated matched control in iduals (n=107 P<.05). Biomarkers of DNA repair and cell cycle control can identify patients at high risk of treatment failure in those receiving radiation therapy for early breast cancer in independent cohorts. These should be further investigated prospectively, especially TOP2A and SKP2, for which targeted therapies are available.
Publisher: Springer Science and Business Media LLC
Date: 12-2006
Publisher: Springer Science and Business Media LLC
Date: 11-02-2012
DOI: 10.1007/S00520-011-1371-X
Abstract: Fear of cancer recurrence (FCR) is common and associated with younger age. This study aimed to explore the prevalence and correlates of FCR amongst younger survivors of early breast cancer. A total of 218 women aged 18-45 were diagnosed with stage 0-2 breast cancer at least 1 year earlier. The participants completed a web-based survey including a validated measure of FCR and items exploring medical surveillance practices and health care use. A total of 70% of participants reported clinical levels of FCR. Higher FCR was associated with higher frequency of unscheduled visits to the GP, higher frequency of breast self-examination and other forms of self-examination for cancer, not having mammograms or ultrasounds or other forms of cancer screening in the past year, more complementary therapy use and the use of counselling and support groups. Young women with breast cancer are particularly vulnerable to FCR. The present study provides preliminary evidence that FCR is associated with higher health costs and lower surveillance rates which may compromise health outcomes. Routine screening for FCR in follow-up care is recommended.
Publisher: Frontiers Media SA
Date: 20-01-2017
Publisher: Springer Science and Business Media LLC
Date: 02-12-2006
DOI: 10.1007/S10549-006-9339-0
Abstract: Surgery and radiotherapy commonly cause adverse musculoskeletal problems, particularly loss of strength and range of motion, in the upper quadrant of breast cancer patients. Few well-designed studies have investigated whether these impairments can be prevented. Stretching is an effective technique for increasing range of motion, hence the aim of this study was to investigate whether a stretching program reduced acute musculoskeletal impairments in patients undergoing radiotherapy for breast cancer. Sixty-four women were recruited prior to commencement of radiotherapy following breast cancer surgery. Participants were randomised to either a control or stretch group. Participants in both groups were reviewed by the physical therapist on a weekly basis for approximately 6 weeks, and were given general information about skin care and lymphedema. The control group received no advice about exercise. The stretch group received instruction on low-load, prolonged pectoral stretches, which were to be performed daily and were checked at weekly visits. Shoulder range of motion, strength, arm circumference, and quality of life measurements were taken prior to, and at completion of radiotherapy, and at 7 months after radiotherapy. There was no difference in any outcome between groups. Breast symptoms increased for both groups during radiotherapy, without loss of strength or range of movement. The incidence of lymphedema during the study was low for both groups and did not differ between groups. The pectoral stretching program did not influence the outcomes measured because the symptoms reported by patients were not a consequence of contracture.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2014
DOI: 10.1038/SREP04669
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CLBC.2014.12.012
Abstract: The adjuvant trastuzumab trials largely excluded women with small, node-negative, HER2-positive breast cancers. Accordingly, limited data exist regarding the effect of trastuzumab in the management of these patients. Our aim was to assess the outcomes of, and treatments administered to, women with small (≤ 2 cm), node-negative, HER2-positive breast cancer in 4 Australian cancer centers. A retrospective analysis of data on all women with node-negative, HER2-positive breast cancers ≤ 2 cm diagnosed between 1 January 2001 and 31 December 2011 and treated at 4 cancer centers in Sydney, Australia was undertaken. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS). In total, 128 patients with node-negative, HER2-positive breast cancers ≤ 2 cm were identified. Of these, 83 women (65%) received adjuvant trastuzumab which, in 96% of cases, was in addition to adjuvant chemotherapy. At 3-year follow-up, the RFS was 100% and 79.2% and the OS was 100% and 92.6% for women treated with, and without, trastuzumab, respectively. There were 14 recurrence events and 6 deaths in the study population. There were no significant differences in RFS and OS for the 46 women treated with, or without, trastuzumab for those with tumors ≤ 1 cm. There is a growing body of evidence to support the use of adjuvant trastuzumab therapy in the management of small, node-negative, HER2-positive breast cancers. However, future studies with longer follow-up and prospective biomarker analysis might assist in clinical decision-making for this patient group.
Publisher: Frontiers Media SA
Date: 09-04-2020
Publisher: Informa UK Limited
Date: 16-11-2010
DOI: 10.3109/07357900902918494
Abstract: To determine the relationship between physical methods of measuring lymphedema and self-reported swelling, their reliability, and standard error of measurement. Lymphedema in each arm of women with (n = 33) and without (n = 18) unilateral arm lymphedema, secondary to breast cancer was measured by self-report, bioimpedance spectroscopy (BIS), perometer, and the truncated cone method. The physical measurement tools were highly reliable (ICC((2,1)): 0.94 to 1.00) with high concordance (r(c): 0.89 to 0.99). Self-report correlated moderately with physical measurements (r = 0.65 to 0.71) and was moderately reliable (ICC((2,1)): 0.70). Lymphedema assessment methods are concordant and reliable but not interchangeable.
Publisher: Mary Ann Liebert Inc
Date: 06-2013
Abstract: To explore what factors affect volume of extracellular fluid (ECF) in the arm on the side of surgery pre- and postoperatively and to determine the value of knowing preoperative ECF volume for diagnosis of lymphedema postoperatively. Women (N=516) with early breast cancer were assessed preoperatively and within 4 weeks postoperatively. Baseline measures included inter-arm ECF ratio, side of cancer, number of nodes involved, and other in idual characteristics. Postoperative assessment included inter-limb ECF ratio and details from surgery. The postoperative ECF ratio was categorized as to whether it exceeded previously established thresholds, and the change in ECF was categorized as to whether it exceeded 0.1. Linear regression identified which factors explained the variance for preoperative ECF ratio and the change in ratio. Chi square analysis compared whether women categorized using thresholds were the same as those whose ratio increased >0.1 postoperatively. Postoperative ECF ratio was significantly higher than the preoperative ratio (p 0.1 postoperatively (p<0.001). Only the side of surgery explained the preoperative ECF measure extent of surgery and actual weight explained the change in ECF ratio. The ECF ratio preoperatively is not affected by nodal involvement. The change in ECF ratio is affected by the extent of surgery and body mass. Change from preoperative ECF ratio did identify more women at risk for lymphedema than reliance postoperatively on thresholds, supporting preoperative measures.
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: Mary Ann Liebert Inc
Date: 12-2012
Publisher: Oxford University Press (OUP)
Date: 05-2010
DOI: 10.2522/PTJ.20090104
Abstract: Shoulder movement impairment is a commonly reported consequence of surgery for breast cancer. The aim of this study was to determine whether shoulder girdle kinematics, including those of the scapula, spine, and upper limb, in women who have undergone a unilateral mastectomy for breast cancer are different from those demonstrated by an age-matched control group. An observational study using 3-dimensional kinematic analysis was performed. Women who had a unilateral mastectomy on their dominant-arm side (n=29, mean [±SD] age=62.4±8.9 years) or nondominant-arm side (n=24, mean [±SD] age=59.8±9.9 years), as well as a control group of age-matched women without upper-limb, shoulder, or spinal problems (n=22, mean [±SD] age=58.1±11.5 years), were measured while performing bilateral arm movements in the sagittal, scapular, and coronal planes. All of the women were free of shoulder pain at the time of testing. Data were collected from the glenohumeral joint, the scapulothoracic articulation, and the spine (upper and lower thoracic and lumbar regions) using an electromagnetic tracking system. Women following mastectomy displayed altered patterns of scapular rotation compared with controls in all planes of movement. In particular, the scapula on the mastectomy side rotated upward to a markedly greater extent than that on the nonmastectomy side, and women following mastectomy displayed greater scapular excursion than controls. The findings suggest that altered motor patterns of the scapula are associated with mastectomy on the same side. Whether these changes are harmful or not is unclear. Investigation of interventions designed to restore normal scapulohumeral relationships on the affected side following unilateral mastectomy for breast cancer is warranted.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.BREAST.2016.04.011
Abstract: A prospective study was conducted to identify women at increased risk for lymphoedema (LE) based on axillary surgery. Assessment occurred prior to surgery, within 4 weeks, and at 6, 12 and 18 months following surgery. Following post-surgery assessment, women were asked to complete weekly diaries regarding events that occurred in the previous week. Risk factors were grouped into demographic, lifestyle, breast cancer treatment-related, arm swelling-related, and post-surgical activities. Bioimpedance spectroscopy thresholds were used to determine presence of LE. At 18-months, 241 women with <5 nodes removed and 209 women with ≥5 nodes removed were assessed. For those with <5 nodes removed, LE was present in 3.3% compared with 18.2% for those with ≥5 nodes removed. There were insufficient events to identify risk factors for those with 5 nodes removed, independent risk factors included presence of arm swelling at 12-months (Odds Ratio (OR): 13.5, 95% CI 4.8, 38.1 P < 0.01), at 6-months (5.6 (2.0, 16.9) P 5 nodes removed and who maintained weekly diaries, only blood drawn from the 'at-risk' arm was identified as a potential risk (OR 2.0 0.8, 5.2). For women with ≥5 nodes removed, arm swelling in the first year poses a very strong risk for presence of LE at 18-months.
Publisher: Wiley
Date: 24-02-2009
Publisher: Mary Ann Liebert Inc
Date: 12-2014
Abstract: Taxanes can cause fluid accumulation by increasing extracellular fluid (ECF). Taxane-based regimens are standard of care for early breast cancer, but it is unknown whether they increase the risk of lymphedema. The aim of this study was to describe the incidence of lymphedema, generalized limb edema, and associated symptoms in women receiving adjuvant taxane-based chemotherapy. Women (n=63) recruited after axillary surgery for early breast cancer were assessed prior to anthracycline-based, prior to taxane-based chemotherapy, and 3 weeks and 6 months after completing taxane-based chemotherapy. At each assessment, the inter-limb ECF ratios and intra-limb intracellular fluid to ECF ratios were determined using bioimpedance spectroscopy. Inter-limb arm volume ratios were calculated from arm circumferences measurements. Self-rated symptoms of swelling and pain in the arm on the side of surgery were recorded. In the 53 women who completed assessments, taxane-based chemotherapy increased the ECF volume in both upper and lower limbs, which was not observed after anthracycline-based chemotherapy. The arm on the side of surgery was preferentially affected, indicated by elevated ECF ratios at 3 weeks and 6 months after completing taxane-based chemotherapy with 32% and 23% meeting the criteria for lymphedema at these time-points, respectively. Edema resolved by 6 months following completion of chemotherapy except in the arm on the side of surgery. The incidence of lymphedema in the arm on the side of surgery following taxane-based chemotherapy was increased persisting at least 6 months after ceasing chemotherapy. However, generalized swelling in the legs and opposite arm resolved by 6 months after chemotherapy.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2013
Publisher: Springer Science and Business Media LLC
Date: 15-05-2011
DOI: 10.1007/S00520-010-0896-8
Abstract: To determine if bioimpedance spectroscopy (BIS) could detect localised lymphoedema of the arm and to compare BIS measurements with equivalent measures of limb volume by perometry. Women with mild to severe upper limb lymphoedema (n = 29) and women with no history of lymphoedema (n = 11) participated. Commencing at the ulnar styloid of the wrist, 4 × 10 cm segment measurements were made of each arm using both BIS and perometry. Average BIS inter-limb ratios for the total arm and each arm segment were higher than comparable perometry measures in women with lymphoedema, but similar to perometry measures for women without lymphoedema. Limits of agreement analysis showed that the mean difference between methods varied according to segment measured, ranging from 8.5% for the uppermost segment of the arm to 16.6% for the forearm segment just below the elbow. For all limb segments, there was a positive bias towards BIS measurements, which increased as lymphoedema severity increased. BIS can be used for localised measurement of lymphoedema. Because it is specific to extracellular fluid, BIS is more sensitive to localised lymphoedema than perometry.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2007
DOI: 10.1007/S00520-007-0328-6
Abstract: Radiotherapy is routinely used in the treatment of early breast cancer, particularly in women who have undergone lumpectomy. Its impact on the quality of life of patients is important and is taken into consideration when making informed choices about treatment from both a patient's and health professional's point of view. This study reports on the quality of life of women at baseline, the completion of radiotherapy and 7 months after the completion of radiotherapy. European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C-30 and BR-23 questionnaires were used to evaluate quality of life of 61 women treated with radiotherapy for breast cancer. Additionally, demographic and treatment variables were analysed in relation to quality of life outcomes to determine if there were any significant predictors of quality of life. There was no difference in quality of life of women at baseline, completion and 7 months after completion of radiotherapy. Fatigue and breast symptoms increased during radiotherapy but returned to baseline levels at 7 months. Fatigue was the strongest predictor of poor quality of life in women after radiotherapy. Women retain a high quality of life and return to baseline function by 7 months after radiotherapy. Treatment may best be targeted to alleviate fatigue and breast symptoms during radiotherapy.
Publisher: Wiley
Date: 18-09-2012
DOI: 10.1111/J.1445-2197.2012.06254.X
Abstract: Delays in commencing adjuvant chemotherapy for early breast cancer beyond 12 weeks are associated with increased mortality. The aim of this study was to identify factors delaying chemotherapy in an inner metropolitan, outer metropolitan, small rural and large rural cancer centre in New South Wales, Australia. We retrospectively reviewed 400 consecutive patients that received adjuvant chemotherapy for stages I-III breast cancer. We evaluated factors affecting time from primary and definitive surgery until commencing chemotherapy. The primary factor associated with chemotherapy delays was the geographic location of the cancer centre. The median time from primary surgery to chemotherapy was longer for the large rural centre (median 58 days), compared with the outer metropolitan (45 days), small rural (39 days) and inner metropolitan centre (33 days). Treatment delays in the large rural centre were associated with higher rates of multiple operations (43% versus 31% elsewhere), mainly because of more staged axillary dissections (34% versus 19%), and longer time from definitive surgery to oncology assessment. Patients in the large rural centre, who are served by fly-in medical oncology services, are more likely to experience delays in receiving adjuvant chemotherapy for early breast cancer. Strategies to reduce delays include use of intraoperative frozen section analysis, multidisciplinary meetings, improving efficiency in pathology reporting and employment of a breast cancer care coordinator and an on-site medical oncologist.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 03-2011
Publisher: Wiley
Date: 10-09-2019
DOI: 10.1002/PON.5218
Abstract: To develop and evaluate the usability of iConquerFear, an online self-management adaptation of an efficacious face-to-face therapist-delivered treatment for fear of cancer recurrence (FCR). iConquerFear development was theory based and person based. Development was guided by Ritterband et al's behaviour change model for internet interventions. iConquerFear end users (cancer survivors) provided iterative feedback in accordance with Yardley et al's person-based approach to maximise engagement and usability. Online focus groups and cognitive interviews were conducted to evaluate the usability of iConquerFear. Discussions were recorded, transcribed verbatim, and thematically analysed. Five online FCR modules were developed. Twenty-three cancer survivors (47% of those eligible) participated 11/23 (58%) were breast cancer survivors, and average age was 53 years (SD = 10.8). Thematic saturation was reached after six focus groups (n = 16) and seven in idual think-aloud interviews. Thematic analysis produced five overarching themes: easy navigation essential satisfaction and engagement with content flexible access is key normalising and empowering and a useful first step. Online self-management interventions like iConquerFear have the potential to address the unmet supportive care needs reported by burgeoning numbers of cancer survivors. However, that potential may not be realised unless interventions are rigorously developed and user tested, as benefits are constrained by limited engagement. Themes from the usability testing of iConquerFear highlight the importance of developing flexible, tailored, interactive, and contextual online self-management interventions for people with cancer.
No related grants have been discovered for Jane Beith.