Oral contraceptives and risk of breast cancer and ovarian cancer in women with a <i>BRCA1</i> or <i>BRCA2</i> mutation: a meta-analysis of observational studies

Park, Junli; Huang, Dan; Chang, Yoon Jung; Lim, Myong Cheol; Myung, Seung‐Kwon

doi:10.1093/carcin/bgab107

Cited by 12 publications

(8 citation statements)

References 47 publications

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“…This theory would also explain the decreased risk of ovarian cancer associated with pregnancy and with COCP use, which results in reduced exposure to gonadotropins due to the steroid feedback on the pituitary. In the 2–3 years after menopause, gonadotropin levels are particularly high, such that concentrations of FSH and LH reach a peak of 10–20 times (50–100 mIU/ml) and 3–4 times (20–50 mIU/ml) the values recorded during the proliferative phase of the menstrual cycle, respectively, and after which there is a gradual but slight decline in both gonadotropins [ 15 , 16 ]. Thus, in support of the gonadotropin theory, the incidence of ovarian cancer climbs dramatically around the age at which most women reach menopause [ 45 ].…”

Section: Previously Proposed Mechanismsmentioning

confidence: 99%

“…For example, most epidemiological studies have shown that oral contraception is associated with a 1.5–3.3-fold higher relative risk of cervical cancer by promoting human papilloma virus—DNA integration into the host genome, but only in users for > 5 years [ 13 ]. There is also a slight increase in the incidence of breast cancer after prolonged intake of COCPs [ 14 – 16 ]. Meanwhile, COCPs exposure is associated with reduced risk of endometrial, ovarian, lymphatic, colorectal and hematopoietic cancers that persists after discontinuation [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use

Avramenko,

Flanagan

2023

Clin Epigenet

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Background Ovarian cancer is the second most common gynecological cancer type after uterine cancers. In 2020, according to worldwide statistics, there were more than 313,000 new cases of ovarian cancer. Most concerning with ovarian cancer is the poor overall survival, with only 30% of patients surviving for longer than 5 years after diagnosis. The reason for this poor outcome includes late diagnosis due to non-specific symptoms and a lack of any highly effective biomarkers of the early stages of ovarian carcinogenesis. However, it is important to note that some modifiable lifestyle factors can be preventative [pregnancy, breastfeeding and combined oral contraceptives pill (COCP) use]. Results There is now increasing data reporting the role of epigenetic changes, which are detectable in ovarian cancer tumors, suggesting the possibility that epigenetics may also play a key role in the mechanism of long-term effective prevention of ovarian cancer. To our knowledge, there is a lack of high-quality data on the molecular mechanisms of ovarian cancer prevention, although several hypotheses have been proposed. Conclusions This review focusses on the evidence for a proposed novel hypothesis—that COCPs act as a chemoprevention through the impact on the epigenome of the cells of origin of ovarian cancer—fallopian tubes epithelium.

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Section: Previously Proposed Mechanismsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use

Avramenko,

Flanagan

2023

Clin Epigenet

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“…BRCA1/2 mutation carriers also benefitted from the protective effects of COC use, which decreases the risk of ovarian cancer [ 97 ]. On the contrary, a new meta-analysis reported the elevated risk for breast cancer among long-term users (>5 years), while a protective effect for ovarian cancer was observed regardless of COC use [ 98 ]. Therefore, an elevation in BC risk cannot be ruled out.…”

Section: Brca1/2 Carriersmentioning

confidence: 99%

Review of the literature on combined oral contraceptives and cancer

Kamani¹,

Akgör²,

Gültekin³

2022

ecancer

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Millions of women have given preference to the use of combined oral contraceptives (COCs) since its introduction in the 1960s. Both oestrogens and progestogens can regulate proliferation and it is plausible these effects may contribute to carcinogenesis. We aimed to review the accumulated knowledge to date to appreciate the modifying effects combined oral contraceptives may have on carcinogenesis. Our methodology involved a review of the current published literature, paying attention to studies published in the last 20 years. It has been noted that the overall cancer odds do not change with the use of COCs. Increased risk for breast cancer with COC use is not consistently backed in the literature; the results range from no increase in risk to a 20%-30% elevation in risk, and the risk seems to be temporary, limited to recent or current regular COC use. Also, diagnosed breast cancer cases seem to be clinically advanced in ever-users compared to never-users. Data show that the ongoing and prolonged use of COCs may provide diminished risk for endometrial, colorectal and ovarian cancers. Although studies do not clearly support increased risk with COC use in high-risk groups, such as women with family history of cancer or BRCA carriers, local and international guidelines are available for clinical decision-making. For cervical cancer, COCs seem to enhance the risk with more than 5 years of use, and in many studies, this enhanced risk diminishes after discontinuation and restores to those of never-users within 10 years. The relationship between COC use and liver malignancy risk assessments has provided conflicting findings. Some studies have suggested that hormonal contraceptives may increase the risk of not only hepatocellular carcinoma but also intrahepatic cholangiocarcinoma. Combined oral contraceptives are safe and effective and the effects are reversible. Patients who pursue family planning should be warned of possible carcinogenic outcomes, but it should also be explained that-in addition to sexual health advantages-preferring COCs may also decrease the risks of endometrial, colorectal and ovarian cancers.

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“…Oral contraceptives have proven preventive efficacy for ovarian cancer with a family history. However, it is controversial whether oral contraceptives increase the risk of breast cancer in BRCA1/2 mutation carriers ( 123 ).…”

Section: Regular Surveillance Prevention and Treatment For ...mentioning

confidence: 99%

Overview on population screening for carriers with germline BRCA mutation in China

Lei

Zhang²,

Zhang³

et al. 2022

Front. Oncol.

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Carriers with BRCA1/2 germline pathogenic variants are associated with a high risk of breast and ovarian cancers (also pancreatic and prostate cancers). While the spectrum on germline BRCA mutations among the Chinese population shows ethnic specificity, the identification of carriers with germline BRCA mutation before cancer onset is the most effective approach to protect them. This review focused on the current status of BRCA1/2 screening, the surveillance and prevention measures, and discussed the issues and potential impact of BRCA1/2 population screening in China. We conducted literature research on databases PubMed and Google Scholar, as well as Chinese databases CNKI and Wangfang Med Online database (up to 31 March 2022). Latest publications on germline BRCA1/2 prevalence, spectrum, genetic screening as well as carrier counseling, surveillance and prevention were captured where available. While overall 15,256 records were retrieved, 72 publications using germline BRCA1/2 testing were finally retained for further analyses. Germline BRCA1/2 mutations are common in Chinese patients with hereditary breast, ovarian, prostate and pancreatic cancers. Within previous studies, a unique BRCA mutation spectrum in China was revealed. Next-generation sequencing panel was considered as the most common method for BRCA1/2 screening. Regular surveillance and preventive surgeries were tailored to carriers with mutated-BRCA1/2. We recommend that all Chinese diagnosed with breast, ovarian, pancreatic or prostate cancers and also healthy family members, shall undergo BRCA1/2 gene test to provide risk assessment. Subsequently, timely preventive measures for mutation carriers are recommended after authentic genetic counseling.

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Oral contraceptives and risk of breast cancer and ovarian cancer in women with a BRCA1 or BRCA2 mutation: a meta-analysis of observational studies

Cited by 12 publications

References 47 publications

An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use

An epigenetic hypothesis for ovarian cancer prevention by oral contraceptive pill use

Review of the literature on combined oral contraceptives and cancer

Overview on population screening for carriers with germline BRCA mutation in China

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