SummaryBackgroundEndometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.MethodsData from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models.Findings13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45).InterpretationClinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer.FundingOvarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

BackgroundBreast cancer patients with tumors that are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive have lower risks of mortality after their diagnosis compared to women with ER- and/or PR-negative disease. However, few studies have evaluated variations in the risks of breast cancer-specific mortality across ER/PR status by either demographic or clinical characteristics.MethodsUsing data from 11 population-based cancer registries that participate in the SEER (Surveillance, Epidemiology, and End Results) program, 155,175 women at least 30 years old with a primary diagnosis of invasive breast carcinoma from 1990 to 2001 were included in the study. Associations between joint hormone receptor status and breast cancer mortality risk within categories of diagnosis age, diagnosis year, race/ethnicity, histologic tumor type, stage, grade, size, and axillary lymph node status were evaluated using the Cox proportional hazards model.ResultsCompared to ER+/PR+ cases, elevations in risk of mortality were observed across all subcategories of age at diagnosis, ranging from 1.2- to 1.5-fold differences for ER+/PR- cases, 1.5- to 2.1-fold differences for ER-/PR+ cases, and 2.1- to 2.6-fold differences for ER-/PR- cases. Greater differences were observed in analyses stratified by grade; among women with low-grade lesions, ER-/PR- patients had a 2.6-fold (95% confidence interval [CI] 1.7 to 3.9) to 3.1-fold (95% CI 2.8 to 3.4) increased risk of mortality compared to ER+/PR+ patients, but among women with high-grade lesions, they had a 2.1-fold (95% CI 1.9 to 2.2) to 2.3-fold (95% CI 1.8 to 2.8) increased risk.ConclusionCompared to women with ER+/PR+ tumors, women with ER+/PR-, ER-/PR+, or ER-/PR- tumors experienced higher risks of mortality, which were largely independent of the various demographic and clinical tumor characteristics assessed in this study. The higher relative mortality risks identified among ER-/PR- patients with small or low-grade tumors raise the question of whether there may be a beneficial role for adjuvant chemotherapy in this population.

TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10 −7 ), reduced estrogen receptor negative (ER-negative) (P=1.0×10 −8 ) and BRCA1 mutation carrier (P=1.1×10 −5 ) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10 −14 ), increased low malignant potential ovarian cancer risk (P=1.3×10 −15 ) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10 −12 ) and BRCA1 mutation carrier (P=1.6×10 −14 ) breast and invasive ovarian (P=1.3×10 −11 ) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splicevariant.