Contraceptive use and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation

Xia, Yue; Gronwald, Jacek; Karlan, Beth Y.; Lubiński, Jan; McCuaig, Jeanna; Brooks, Jennifer; Møller, Pål; Eisen, Andrea; Sun, Sophie; Senter, Leigha; Bordeleau, Louise; Neuhausen, Susan L.; Singer, Christian F.; Tung, Nadine; Foulkes, William D.; Sun, Ping; Narod, Steven A.; Kotsopoulos, Joanne

doi:10.1016/j.ygyno.2022.01.014

Cited by 16 publications

(6 citation statements)

References 202 publications

(317 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…copper IUD, LR-IUD, transdermal contraceptive patch, vaginal ring, contraceptive injection, progestogen-only contraceptive pill and contraceptive implant) on cancer risks among women at high inherited risk for breast and ovarian cancer at the time we performed our systematic search. Nevertheless, in early 2022, the first study that investigated progestin only contraceptives including the implant, the injection and the IUD among BRCA1/2 -PV carriers was published ( Xia et al , 2022 ), revealing a preventive effect of the implant on ovarian cancer risk but no significant effects on ovarian cancer risk were found for the injection, the hormonal IUD and the non-hormonal IUD. As we found comparable results in the general population and the BRCA1/2 -PV population regarding OCP and TL, one could imagine that other contraceptives may similarly impact cancer risks as well ( Madsen et al , 2015 ; Mørch et al , 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Bommel¹,

IntHout²,

Veldmate

et al. 2022

Human Reproduction Update

View full text Add to dashboard Cite

BACKGROUND Increasing numbers of BReast CAncer (BRCA) 1 or 2 pathogenic variant (PV) carriers, who have an inherited predisposition to breast and ovarian cancer, are being identified. Among these women, data regarding the effects of contraception on cancer risks are unclear and various guidelines provide various recommendations. OBJECTIVE AND RATIONALE We aim to optimize counselling regarding contraception for BRCA1/2-PV carriers. Therefore, we performed a systematic review and meta-analysis. We investigated the risk ratio for developing breast cancer or ovarian cancer in BRCA1/2-PV carriers who have used any form of contraception versus non-users. Second, we analysed breast and ovarian cancer risk among BRCA1/2-PV carriers as influenced by the duration of contraceptive use and by the time since last use. In addition, we provide an overview of all relevant international guidelines regarding contraceptive use for BRCA1/2-PV carriers. SEARCH METHODS A systematic search in the Medline database and Cochrane library identified studies describing breast and/or ovarian cancer risk in BRCA1/2-PV carriers as modified by contraception until June 2021. The search included medical subject headings, keywords and synonyms related to BRCA and contraceptives (any kind). PRISMA guidance was followed. Risk Of Bias In Non-randomized Studies of Interventions and Grading of Recommendations, Assessment, Development and Evaluations assessments were performed. Random-effects meta-analyses were used to estimate pooled effects for breast and ovarian cancer risk separately. Subgroup analyses were conducted for BRCA1 versus BRCA2 and for the various contraceptive methods. OUTCOMES Results of the breast cancer risk with oral contraceptive pill (OCP) analysis depended on the outcome measure. Meta-analyses of seven studies with 7525 women revealed a hazard ratio (HR) of 1.55 (95% CI: 1.36–1.76) and of four studies including 9106 women resulted in an odds ratio (OR) of 1.06 (95% CI: 0.90–1.25), heterogeneity (I2) 0% and 52%, respectively. Breast cancer risk was still increased in ever-users compared with never-users >10 years after last OCP use. In contrast, ovarian cancer risk was decreased among OCP users: HR 0.62 (95% CI: 0.52–0.74) based on two studies including 10 981 women (I2: 0%), and OR 0.49 (95% CI: 0.38–0.63) based on eight studies including 10 390 women (I2: 64%). The protective effect vanished after cessation of use. Tubal ligation also protects against ovarian cancer: one study including 3319 women (I2: 0%): HR: 0.44 (95% CI: 0.26–0.74) and three studies with 7691 women (I2: 44%): OR: 0.74 (95% CI: 0.53–1.03). Data regarding other contraceptives were unavailable. No differences were observed between BRCA1 and BRCA2-PV carriers. The quality of evidence was either low or very low. WIDER IMPLICATIONS The OCP potentially increases breast cancer risk, while ovarian cancer risk decreases with either the OCP and tubal ligation in BRCA1/2-PV carriers. Counselling of BRCA1/2-PV carriers should be personalized; the genetic and non-genetic factors (like prior risk-reducing surgeries, prior breast cancer and age) and patients’ preferences (reversibility, ease of use, reliability and effect on menstrual cycle) should be balanced. To further optimize counselling for high-risk women, future research should focus on other (commonly used) contraceptive methods and cancer risks in this specific population, and on the potential impact of changing formulations over time.

show abstract

Section: Discussionmentioning

confidence: 99%

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Bommel¹,

IntHout²,

Veldmate

et al. 2022

Human Reproduction Update

View full text Add to dashboard Cite

show abstract

“…It is well-established that use of oral contraceptive pill (OCP), pregnancy, breastfeeding, and tubal ligation are protective factors of ovarian cancer; other factors including use of aspirin and non-aspirin non-steroidal anti-inflammatory drugs may also reduce the risk of ovarian cancer ( 25 , 26 ). For the moderate-to-high risk population (people with genetic predispositions), risk-reduction surgery and chemoprevention (such as OCPs and aspirin) can be beneficial ( 25 , 27 ). Therefore, it is important to perform risk stratification and further personalize individual risk, so targeted prevention and management strategies can be implemented to reduce the life loss and relieve overall ovarian cancer disease burden.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study

Zhang

Chen³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

ObjectivesIt is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women’s health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China.Materials and MethodsCo-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi’s world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method.ResultsA total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P < 0.001), respectively.ConclusionsPopulation ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.

show abstract

“…In this field, the protective role of OC use is well known and supported by studies and meta-analyses both in general [ 60 ] and in BRCA-mutated population [ 61 ]. In January 2022, a case control study was published [ 62 ] with an in-depth analysis of 1733 matched pairs of BRCA1 or BRCA2 mutated women that confirmed the protective impact of OC. Cases were less likely to have a history of OC use (with a p -value < 0.0001) and even implant use ( p = 0.001).…”

Section: Discussionmentioning

confidence: 99%

Pathologic Findings at Risk Reducing Surgery in BRCA and Non-BRCA Mutation Carriers: A Single-Center Experience

et al. 2022

View full text Add to dashboard Cite

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers.

show abstract

Contraceptive use and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation

Cited by 16 publications

References 202 publications

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis

Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study

Pathologic Findings at Risk Reducing Surgery in BRCA and Non-BRCA Mutation Carriers: A Single-Center Experience

Contact Info

Product

Resources

About