Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study

Abstract

and International BRCA1/2 Carrier Cohort Study BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependenteweighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5e9 years [hazard ratio, 0.67; 95% confidence interval, 0.40e1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19e0.73]; P trend ¼.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of !10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14e0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18e0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associ...

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

“…Collectively, these data demonstrate that oral contraceptives reduce the risk of ovarian cancer by 45% to 50% in carriers of a BRCA1 mutation and 50% in carriers of a BRCA2 mutation 236,238,239 .…”

“…In a recent meta-analysis of six studies conducted among women with a BRCA1 or BRCA2 mutation, Moorman et al reported that a history of oral contraceptive use was associated with a 42% reduction in risk (OR = 0.58; 95% CI 0.46-0.73) in women with either mutation, consistent with risk estimates observed in the general population 237 . Moreover, this protective effect appears to increase with long-term use and persists over 20 years after discontinuation of use 238 .…”

“…With respect to patterns of oral contraceptive use, two reports based on data from the International BRCA1/2 Carrier Cohort study have investigated associations between year of initiation, age of initiation and time since last use and ovarian cancer 75,238 . The most recent retrospective cohort analysis involved 1,989 BRCA1 mutation carriers and 2,445 BRCA2 mutation carriers 238 . Authors took a left-truncated approach to minimize survival bias and accounted for related aspects of oral contraceptive use.…”

“…Moreover, these effects are apparent after relatively short-term use, increase with longer durations of use and persist at least 20 years following cessation of use 238 Women who inherit a deleterious BRCA1 or BRCA2 germline mutation face an increased lifetime risk of developing ovarian and fallopian tube cancer (referred to as ovarian cancer hereafter). Based on prospective studies, the cumulative risk of ovarian cancer to age 80 is estimated between 44% to 49% for BRCA1 mutation carriers and between 17% to 21% for BRCA2 mutation carriers 11,12 .…”

Evolución de la ginecología peruana al Bicentenario, y el futuro

“…La duración media del uso fue de 7 años para las portadoras de BRCA1 y BRCA2 que desarrollaron cáncer de ovario y de 9 y 8 años para las portadoras no afectadas de BRCA1 y BRCA2 con cáncer de ovario, respectivamente. En el caso de las portadoras de la mutación BRCA1, una mayor duración del uso de anticonceptivos orales se ha asociado con mayor reducción del riesgo de cáncer de ovario, y la protección es a largo plazo(64) .…”