Toniolo, P., & Whittemore, A. S. (1992). Re: "Polycystic ovaries and the risk of breast cancer". American journal of epidemiology, 136(3), 372-373. https://doi.org/10.1093/oxfordjournals.aje.a116506
Toniolo P, Whittemore AS. Re: "Polycystic ovaries and the risk of breast cancer". Am J Epidemiol. 1992;136(3):372-373. doi:10.1093/oxfordjournals.aje.a116506
Toniolo, P., and A. S. Whittemore. "Re: "Polycystic ovaries and the risk of breast cancer"." American journal of epidemiology, vol. 136, no. 3, 1992, pp. 372-373.
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Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California;00f54p054
Gammon and Thompson (1) recently reported in the Journal the results of an analysis of data from the Center for Disease Control's Cancer and Steroid Hormones Study to examine the association between a history of physician-diagnosed polycystic ovaries and the risk of breast cancer. Despite the small number of exposed cases (n =23) and controls (nm 44), their data strongly support the conclusion that a history of polycystic ovaries protects against premenopausal and carly postmenopausal breast cancer. These results are in apparent conflict with those reported in a previous cohort study by Coulam et al. (2), who found a threefold increase in postmenopausal breast cancer in women with polycystic ovaries. Such discrepancy may reflect real, albeit unexplained differences between premenopausal and postmenopausal women in the influence of endogenous hormones on breast cancer.
Manolio TA et al., 2009·Nature·Free full text on PubMed Central
Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Haile RW et al., 2006·Cancer Epidemiol Biomarkers Prev
Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice. We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years. For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P(trend) = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (OR(trend) per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later. We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue.
Milne RL et al., 2005·Cancer Epidemiol Biomarkers Prev
Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear. Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls. After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001). There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.
Data collected from 2,197 white ovarian cancer patients and 8,893 white controls in 12 US case-control studies conducted in the period 1956-1986 were used to evaluate the relation of invasive epithelial ovarian cancer to reproductive and menstrual characteristics, exogenous estrogen use, and prior pelvic surgeries. Clear trends of decreasing risk were evident with increasing number of pregnancies (regardless of outcome) and increasing duration of breast feeding and oral contraceptive use. Ovarian dysfunction leading to both infertility and malignancy is an unlikely explanation for these trends for several reasons: 1) The trends were evident even among the highly parous; 2) risk among nulliparous women did not vary by marital status or gravidity; and 3) risk among ever-married women showed little relation to length of longest pregnancy attempt or history of clinically diagnosed infertility. Risk was increased among women who had used fertility drugs and among women with long total duration of premenopausal sexual activity without birth control; these associations were particularly strong among the nulligravid. No consistent trends in risk were seen with age at menarche, age at menopause, or duration of estrogen replacement therapy. A history of tubal ligation or of hysterectomy with ovarian conservation was associated with reduced ovarian cancer risk. These observations suggest that pregnancy, breast feeding, and oral contraceptive use induce biological changes that protect against ovarian malignancy, that, at most, a small fraction of the excess ovarian cancer risk among nulliparous women is due to infertility, and that any increased risk associated with infertility may be due to the use of fertility drugs.
Collaborative Group on Hormonal Factors in Breast Cancer, 2012·Lancet Oncol·Free full text on PubMed Central
Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. Findings: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons). Interpretation: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. Cancer Research UK.
Breast cancer incidence rates are high in societies with a Western lifestyle characterized by low levels of physical activity, and by an energy-dense diet rich in total and saturated fat and refined carbohydrates. Epidemiologic studies, so far mostly on postmenopausal women, have shown that breast cancer risk is increased in hyperandrogenic women, with decreased levels of plasma sex-hormone binding globulin, and with increased levels of testosterone and of free estrogens. This paper describes the role of hyperinsulinemia as a physiologic link between nutritional lifestyle factors, obesity, and the development of a hyperandrogenic endocrine profile, and reviews evidence that may or may not support the theory that chronic hyperinsulinemia is an underlying cause of breast cancer. An hypothesis is presented, stipulating that breast cancer risk is increased not only in hyperandrogenic postmenopausal women, but also in premenopausal women with mild hyperandrogenism and normal (ovulatory) menstrual cycles. The author suggests further investigation as to whether there is a positive association between risk of breast cancer before menopause and subclinical forms of the polycystic ovary syndrome (PCOS), and to what extent diet and physical activity during childhood, by modulating the degree of insulin resistance during adolescence, may or may not be determinants of a PCO-like hyperandrogenic endocrine profile persisting into adulthood.
Ye J et al., 2022·BMC women's health·Free full text on PubMed Central
Endometriosis (EMS) is confirmed pathophysiologically to be an estrogen-dependent disease, similar to endometrial hyperplasia/cancer and breast cancer. Epidemiological and biological data on endometriosis might explain links between endometriosis and these cancers. We sought to identify the differences in the risk of endometrial cancer and breast cancer between women with and women without endometriosis. We searched PubMed, EMBASE, the Cochrane Library, and four Chinese databases (CNKI, VIP, WanFang, CBM) to identify relevant studies published online between January 2011 and March 2021. In our meta-analysis, we used the Newcastle-Ottawa Scale (NOS) to evaluate the design and quality of all studies, and we calculated the pooled risk ratio (RR) using the random model. The Q test and I2 were used to evaluate the degree of heterogeneity of eligible studies. We used funnel plots and Begg's and Egger's tests to assess publication bias. Of the 1369 articles, we finally included 14 cohort studies and seven case-control studies. Data from large cohort and case-control studies indicate that women with endometriosis had an increased risk of both endometrial cancer [RR, 1.662; 95% CI, (1.148-2.407)] and breast cancer [RR, 1.082; 95% CI, (1.001-1.169)]. Endometriosis can increase the risk of endometrial cancer and breast cancer, and women with endometriosis are recommended to receive routine screening in long-term management.
Several randomized trials and observational studies show that the use of hormone therapy (HT) increases the risk of breast cancer (BC). The aim of this study was to assess the effects of exposure to both HT and oral contraceptives (OCs) on BC risk in postmenopausal women, all residing in the same metropolitan area. Data regarding a series of 238 consecutive postmenopausal women with infiltrating ductal carcinoma (cases) and 255 randomly selected age-matched healthy women (controls) were reviewed. Odds ratios for no breast-feeding and HT and OC use were 1.82 (95% CI, 1.20-2.77), 2.49 (95% CI, 1.73-3.58), and 2.06 (95% CI 1.14-3.70), respectively. Four independent variables (years between menarche and menopause, breast-feeding, OC use, and HT use) were included in the final multivariate analysis using logistic regression. The cumulative odds ratio calculated from the observed versus predicted values, obtained using the logistic regression function, was 4.55 (95% CI, 2.13-9.71), whereas the cumulative risk of common exposure to both OCs and HT was 2.77 (95% CI, 1.44-5.32). The logistic model correctly classified 67.5% (95% CI, 63.2-71.5) of cases. The receiver operating characteristic (ROC) curve of the complete logistic function showed a fair area of accuracy (0.77; 95% CI, 0.72-0.81). Our results show that the risk of common exposure to both OCs and HT increases in women with other risk factors. However, several parameters traditionally considered in epidemiological studies do not have the same weight in each local community, suggesting the need to create different models to correctly select the high-risk population.
General Gynecology › Breast Health › Breast Cancer Risk · Reproductive Endocrinology › Ovarian Hormones › Estrogen
Alice S Whittemore
A Whittemore
PMID 1415155 1415155 DOI 10.1093/oxfordjournals.aje.a116506 10.1093/oxfordjournals.aje.a116506 Toniolo et al. 1992, Toniolo 1992
Cite this article
Toniolo, P., & Whittemore, A. S. (1992). Re: "Polycystic ovaries and the risk of breast cancer". American journal of epidemiology, 136(3), 372-373. https://doi.org/10.1093/oxfordjournals.aje.a116506
Toniolo P, Whittemore AS. Re: "Polycystic ovaries and the risk of breast cancer". Am J Epidemiol. 1992;136(3):372-373. doi:10.1093/oxfordjournals.aje.a116506
Toniolo, P., and A. S. Whittemore. "Re: "Polycystic ovaries and the risk of breast cancer"." American journal of epidemiology, vol. 136, no. 3, 1992, pp. 372-373.
Keywords
Breast Neoplasms/epidemiology, Confounding Factors, Epidemiologic, Female, Humans, Polycystic Ovary Syndrome/complications/therapy
