Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review

Harris, Holly R.; Terry, Kathryn L.

doi:10.1186/s40738-016-0029-2

Cited by 110 publications

(80 citation statements)

References 107 publications

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“…However, the proportion of women who reported a history of PCOS was slightly lower for breast cancer cases (2.7%) than controls (3.4%, p = 0.36). This lack of association, which is in agreement with the results of the majority of studies that have examined the association of PCOS with breast cancer risk 6 , does not support the proposed hypothesis. It should be noted, though, that we cannot exclude that underdiagnosis contributed to the lack of association we observed.…”

supporting

confidence: 54%

Authors’ reply to: Anti‐Müllerian hormone and breast cancer risk: is the correlation possibly associated with PCOS

Clendenen

Dorgan

Zeleniuch‐Jacquotte

2018

Intl Journal of Cancer

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Dear Editor, Dr. Blumenfeld suggests that our observation of an increased risk of breast cancer with increasing anti-Müllerian hormone (AMH) concentration 1 could be due to a higher prevalence of polycystic ovary syndrome (PCOS), among women with high AMH concentration. This hypothesis is based on the observations that AMH concentration is elevated among women with PCOS 2,3 and that some studies have reported an association between PCOS and risk of breast cancer. 4,5 To explore the hypothesis proposed by Dr. Blumenfeld, we examined the association of PCOS with AMH and with risk of breast cancer in three cohorts (Breakthrough Generations Study, ORDET, and The Sister Study) that collected information on PCOS. We did observe higher AMH concentrations in women who reported PCOS than in women who did not, though differences were not statistically significant. In controls, the ageadjusted and cohort-adjusted geometric mean was 2.20 pmol/L (95% CI: 1.20, 4.04) for women with PCOS (n = 43) vs. 1.48 pmol/L (95% CI: 1.34, 1.64, p = .16) for women without. Similarly, in cases, the age-adjusted and cohort-adjusted geometric mean was 3.23 pmol/L (95% CI: 1.33, 7.86; n = 27) vs. 1.99 pmol/L (95% CI: 1.79, 2.21; p = .14). These observations are consistent with studies of AMH concentration in women diagnosed with PCOS. However, the proportion of women who reported a history of PCOS was slightly lower for breast cancer cases (2.7%) than controls (3.4%, p = .36). This lack of association, which is in agreement with the results of the majority of studies that have examined the association of PCOS with breast cancer risk, 6 does not support the proposed hypothesis. It should be noted, though, that we cannot exclude that underdiagnosis contributed to the lack of association we observed. The diagnosis of PCOS is difficult due to the heterogeneous nature of disease presentation and some women are asymptomatic or have nonspecific symptoms. 3,7 As a result, PCOS is often underdiagnosed, by up to 50% in some estimates, 8 with the overall prevalence estimated to be 6-10%. 9 The low prevalence of PCOS we observed suggests that underdiagnosis is indeed a possibility in our study.Another result of our study does not support the hypothesis of Dr. Blumenfeld. We observed a positive trend between AMH and breast cancer risk, with multivariate-adjusted odds ratios of 1.18, 1.34, and 1.62 for AMH quartiles 2, 3, and 4, respectively. Such a trend is not consistent with the association being driven by PCOS, even assuming a prevalence of 10%. Further, PCOS is often associated with hyperandrogenism, 10 yet the odds ratios for the AMH-risk association did not change appreciably when testosterone concentration was added to the multivariateadjusted model (AMH quartile 4 OR: 1.58).Given the lack of association between PCOS and risk of breast cancer and the positive trend of increasing risk with increasing AMH concentration we observed, our study does not support the hypothesis that the AMH-breast cancer risk association is explained by PCOS.Sincerely,

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supporting

confidence: 54%

Authors’ reply to: Anti‐Müllerian hormone and breast cancer risk: is the correlation possibly associated with PCOS

Clendenen

Dorgan

Zeleniuch‐Jacquotte

2018

Intl Journal of Cancer

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“…A systemic review involving eight studies and a meta-analysis found increased incidence of borderline serous cancer in patients with PCOS [155]. Proteomic biomarkers for identification of patients with PCOS who are at increased risk of ovarian cancer may be useful for early diagnosis but the clinical use of these markers need further verification [156].…”

Section: Polycystic Ovarian Syndromementioning

confidence: 99%

Risk Factors for Ovarian Cancer

Zayyan¹

2020

Tumor Progression and Metastasis

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Ovarian cancers remain a perplexing group of diseases that continue to raise questions over their etiology and clinical behavior. They are the most fatal of gynecological cancers. Despite a global lifetime risk of only 1-2%, they contribute the highest mortality and the lowest 5-year (overall) survival rate of just 35%. The three broad histological groups: epithelial, sex cord-stromal and germ cell cancers have different biologic behavior and may constitute different clinical disease entities. Of the eight subtypes in the epithelial group, high-grade serous are universally the most common and have the worst prognosis. Globally making 65-85% of all ovarian cancers, most of the focus on risk factors has been directed on the epithelial group but the importance of other primary malignancies cannot be overemphasized as a step towards understanding their etiology and clinical behavior. The normal ovary has none of the epithelia that produce the range of epithelial ovarian cancers or there is an obvious premalignant stage, symptoms are very vague, screening and early diagnosis are difficult and indeed unrewarding. No specific etiology is known for any of the histologic groups. However, commonly mentioned risk factors like increasing age, genetics, nulliparity, prolonged infertility, use of fertility drugs, high animal fat, obesity, endometriosis, polycystic ovary syndrome, previous history of cancer, use of hormone replacement therapy, pelvic inflammatory disease and smoking may not apply to all the subtypes, while factors like increasing parity, breast feeding, use of oral contraceptive pills, hysterectomy, tubal ligation and use of antioxidants may differ in the degree of protection they provide. There may also be geographical and probably racial variations in the relevance of some of the risk factors. Thorough understanding of the predisposing and protective factors of the various histologic subtypes is an important step understanding the disease and therefore improving treatment outcome or providing effective prevention.

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“…Since both causes and consequences of infertility could influence cancer risk, the relationship is complex. The associations between endometriosis and ovarian cancer, as well as between PCOS and endometrial cancer, are fairly well established [ 10 , 11 ]. Sustained estrogen stimulation to the endometrium without an opposed antiestrogenic effect of progesterone, which is the usual feature of chronic anovulation and PCOS, has a recognized carcinogenic effect in the development of some endometrial cancers.…”

Section: Introductionmentioning

confidence: 99%

The risk of breast and gynecological cancer in women with a diagnosis of infertility: a nationwide population-based study

et al. 2019

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Some studies have suggested that infertility is a risk factor for endometrial, ovarian and breast cancer. The study aimed to create a comprehensive picture of the association between infertility and the risk of ovarian, endometrial and breast cancer, and whether any association could be explained by ovulatory disturbances, endometriosis or nulliparity. In a population-based cohort of 2,882,847 women, cox regression analysis was used to investigate cancer incidence among infertile women. Overall, infertility was associated with a higher incidence rate of ovarian (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.38–1.71) and endometrial cancer (aHR 1.25, 95% CI 1.11–1.40), but not of breast cancer (aHR 0.96, 95% CI 0.92–1.01). Ovarian cancer incidence was higher in women diagnosed with endometriosis, and in nulliparous women with ovulatory disturbances, compared to women with none of the diagnoses. Endometrial cancer incidence was higher in women with ovulatory disturbances, but not in women with endometriosis. These findings suggest that infertility could have long-term consequences of importance to physicians and public health workers. Electronic supplementary material The online version of this article (10.1007/s10654-018-0474-9) contains supplementary material, which is available to authorized users.

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Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review

Cited by 110 publications

References 107 publications

Authors’ reply to: Anti‐Müllerian hormone and breast cancer risk: is the correlation possibly associated with PCOS

Authors’ reply to: Anti‐Müllerian hormone and breast cancer risk: is the correlation possibly associated with PCOS

Risk Factors for Ovarian Cancer

The risk of breast and gynecological cancer in women with a diagnosis of infertility: a nationwide population-based study

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