ORCID Profile
0000-0003-4891-1199
Current Organisations
University of Aberdeen
,
Memorial Sloan Kettering Cancer Center
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Publisher: Wiley
Date: 04-04-2022
DOI: 10.1002/IJC.34001
Abstract: Mammographic dense area (MDA) is an established predictor of future breast cancer risk. Recent studies have found that risk prediction might be improved by redefining MDA in effect at higher‐than‐conventional intensity thresholds. We assessed whether such higher‐intensity MDA measures gave stronger prediction of subsequent contralateral breast cancer (CBC) risk using the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population‐based CBC case‐control study of ≥1 year survivors of unilateral breast cancer diagnosed between 1990 and 2008. Three measures of MDA for the unaffected contralateral breast were made at the conventional intensity threshold (“ Cumulus ”) and at two sequentially higher‐intensity thresholds (“ Altocumulus” and “ Cirrocumulus” ) using the CUMULUS software and mammograms taken up to 3 years prior to the first breast cancer diagnosis. The measures were fitted separately and together in multivariable‐adjusted logistic regression models of CBC (252 CBC cases and 271 unilateral breast cancer controls). The strongest association with CBC was MDA defined using the highest intensity threshold, Cirrocumulus (odds ratio per adjusted SD [OPERA] 1.40, 95% CI 1.13‐1.73) and the weakest association was MDA defined at the conventional threshold, Cumulus (1.32, 95% CI 1.05‐1.66). In a model fitting the three measures together, the association of CBC with Cirrocumulus was unchanged (1.40, 95% CI 0.97‐2.05), and the lower brightness measures did not contribute to the CBC model fit. These results suggest that MDA defined at a high‐intensity threshold is a better predictor of CBC risk and has the potential to improve CBC risk stratification beyond conventional MDA measures.
Publisher: American Association for Cancer Research (AACR)
Date: 13-07-2023
DOI: 10.1158/1078-0432.23676032
Abstract: Supplementary Tables S1-S5
Publisher: Wiley
Date: 20-01-2019
DOI: 10.1002/IJC.32029
Publisher: American Association for Cancer Research (AACR)
Date: 13-07-2023
DOI: 10.1158/1078-0432.23676035
Abstract: Supplementary Figures S1-S4
Publisher: American Association for Cancer Research (AACR)
Date: 13-07-2023
DOI: 10.1158/1078-0432.23676035.V1
Abstract: Supplementary Figures S1-S4
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488651
Abstract: Supplementary Methods
Publisher: American Association for Cancer Research (AACR)
Date: 21-01-2022
DOI: 10.1158/1055-9965.EPI-21-1091
Abstract: Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small s le sizes. Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype. During the mean follow-up of 6.34 years (SD = 4.80), 6,418 patients passed away (57.4%). There was no evidence of associations between the reproductive factors and survival among patients with ovarian cancer overall or by histotype. This study found no association between reproductive factors and survival after an ovarian cancer diagnosis. Reproductive factors are well-established risk factors for ovarian cancer, but they are not associated with survival after a diagnosis of ovarian cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 20-06-2023
DOI: 10.1158/1078-0432.CCR-22-3815
Abstract: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%–20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited. We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC. Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (POLEmut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival P & 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the no specific molecular profile (NSMP) subtype, where immune infiltrates lacking B cells (TILB minus) had inferior outcome (disease-specific survival: HR, 4.0 95% confidence interval, 1.1–14.7 P & 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes. Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488654
Abstract: Supplementary Figures S1-S13
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
DOI: 10.1158/1078-0432.C.6740546
Abstract: AbstractPurpose: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%–20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited. Experimental Design: We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC. Results: Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden ( i POLE /i mut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival i P /i 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the i no specific molecular profile /i (NSMP) subtype, where immune infiltrates lacking B cells (TIL sub B minus /sub ) had inferior outcome (disease-specific survival: HR, 4.0 95% confidence interval, 1.1–14.7 i P /i 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes. Conclusions: Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study. /
Publisher: American Association for Cancer Research (AACR)
Date: 13-07-2023
DOI: 10.1158/1078-0432.C.6740546.V1
Abstract: AbstractPurpose: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%–20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited. Experimental Design: We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC. Results: Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden ( i POLE /i mut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival i P /i 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the i no specific molecular profile /i (NSMP) subtype, where immune infiltrates lacking B cells (TIL sub B minus /sub ) had inferior outcome (disease-specific survival: HR, 4.0 95% confidence interval, 1.1–14.7 i P /i 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes. Conclusions: Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study. /
Publisher: American Association for Cancer Research (AACR)
Date: 07-10-2022
DOI: 10.1158/1078-0432.CCR-22-1206
Abstract: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 02-2022
DOI: 10.1158/1055-9965.EPI-21-0977
Abstract: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use aspirin use other nonsteroidal anti-inflammatory drug use body mass index environmental tobacco smoke exposure history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis menopausal hormone therapy use physical inactivity smoking status and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data. There was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09 95% confidence interval (CI), 1.03–1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11–1.54). A higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival. Given that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 22-02-2021
DOI: 10.1158/1055-9965.EPI-20-1355
Abstract: Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered. The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case–control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted. Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65 95% confidence interval, 0.50–0.85). There was a statistically significant trend of decreasing risk with increasing duration of use (Ptrend & 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk. DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted. The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488651.V1
Abstract: Supplementary Methods
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488654.V1
Abstract: Supplementary Figures S1-S13
Publisher: American Association for Cancer Research (AACR)
Date: 15-10-2020
DOI: 10.1158/1078-0432.CCR-20-0103
Abstract: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of in idual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with & % accuracy that was maintained in all analytic and biological validations. We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271
Publisher: Wiley
Date: 17-11-2020
DOI: 10.1002/IJC.33360
Abstract: A full‐term pregnancy is associated with reduced endometrial cancer risk however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy‐related factors and endometrial cancer risk are less clear. We pooled in idual participant data from 11 cohort and 19 case‐control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one‐ and two‐stage meta‐analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full‐term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full‐term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56‐0.63). The risk reduction appeared the greatest for the first full‐term pregnancy (OR = 0.78, 95% CI 0.72‐0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14‐0.28) that was independent of age at last full‐term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%‐9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full‐term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full‐term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
Publisher: American Association for Cancer Research (AACR)
Date: 13-07-2023
DOI: 10.1158/1078-0432.23676032.V1
Abstract: Supplementary Tables S1-S5
Publisher: Wiley
Date: 12-11-2020
DOI: 10.1002/IJC.32731
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488645
Abstract: Supplementary Tables S1-S11
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532782
Abstract: AbstractPurpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC ( i n /i = 333), mucinous borderline ovarian tumors (MBOT, i n /i = 151), and upper GI ( i n /i = 65) and lower GI tumors ( i n /i = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, i P /i = 0.042]. Increased expression of i THBS2 /i and i TAGLN /i was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, i P /i = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, i P /i = 0.043), respectively. i ERBB2 /i (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of i THBS2 /i and i TAGLN /i in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies. /
Publisher: American Association for Cancer Research (AACR)
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488645.V1
Abstract: Supplementary Tables S1-S11
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532782.V1
Abstract: AbstractPurpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC ( i n /i = 333), mucinous borderline ovarian tumors (MBOT, i n /i = 151), and upper GI ( i n /i = 65) and lower GI tumors ( i n /i = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, i P /i = 0.042]. Increased expression of i THBS2 /i and i TAGLN /i was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, i P /i = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, i P /i = 0.043), respectively. i ERBB2 /i (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of i THBS2 /i and i TAGLN /i in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies. /
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Malcolm Pike.