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

Schrijver, Lieske H ; Antoniou, Antonis C ; Olsson, Håkan LU ; Mooij, Thea M ; Roos-Blom, Marie-José ; Azarang, Leyla ; Adlard, Julian ; Ahmed, Munaza ; Barrowdale, Daniel and Davidson, Rosemarie , et al. (2021) In American Journal of Obstetrics and Gynecology
Abstract

BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.

OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better... (More)

BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.

OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better risk estimates.

STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using OCP data on 3,989 BRCA1 and 2,445 BRCA2 mutation carriers. Age-dependent weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as covariate. To minimize survival bias, analyses were left-truncated at 5 years before baseline questionnaire. Separate analysis were conducted for each of the aspects of OCP use and in a multivariate analysis including all these aspects. In addition, the analysis of duration of OCP use was stratified by recency of use.

RESULTS: OCPs were less often used by mutation carriers who were diagnosed with ovarian cancer (Ever use: BRCA1 58.6%, BRCA2 53.5%) than by unaffected carriers (Ever use: BRCA1 88.9%, BRCA2 80.7%. The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer, and 9 and 8 years for ovarian cancer unaffected BRCA1 and BRCA2 carriers, respectively. For BRCA1 mutation carriers univariate analyses showed that both a longer duration of OCP use and more recent use of OCPs were inversely associated with risk of ovarian cancer. However, in multivariate analyses including duration of use, age at first use and time since last use, duration of use proved to be the prominent protective factor (compared with <5 years, 5-9 years HR=0.67;95%CI 0.40-1.12, 10+ years HR=0.37;95%CI 0.19-0.73; ptrend=0.008). 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: HR=0.24 95%CI 0.14-0.43, 15+ years since last use: HR 0.56 95%CI 0.18-0.59). Univariate results for BRCA2 mutation carriers were similar, but due to limit sample size inconclusive.

CONCLUSION: For BRCA1 mutation carriers, a longer duration of OCP use is associated with a greater reduction of ovarian cancer risk and the protection is long term.

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American Journal of Obstetrics and Gynecology
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Elsevier
external identifiers
  • scopus:85101390784
  • pmid:33493488
ISSN
1097-6868
DOI
10.1016/j.ajog.2021.01.014
language
English
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yes
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0c73d8cf-dff9-4139-a293-0f815a550bbb
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2021-02-01 00:52:31
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2021-06-08 04:54:32
@article{0c73d8cf-dff9-4139-a293-0f815a550bbb,
  abstract     = {<p>BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.</p><p>OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better risk estimates.</p><p>STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using OCP data on 3,989 BRCA1 and 2,445 BRCA2 mutation carriers. Age-dependent weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as covariate. To minimize survival bias, analyses were left-truncated at 5 years before baseline questionnaire. Separate analysis were conducted for each of the aspects of OCP use and in a multivariate analysis including all these aspects. In addition, the analysis of duration of OCP use was stratified by recency of use.</p><p>RESULTS: OCPs were less often used by mutation carriers who were diagnosed with ovarian cancer (Ever use: BRCA1 58.6%, BRCA2 53.5%) than by unaffected carriers (Ever use: BRCA1 88.9%, BRCA2 80.7%. The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer, and 9 and 8 years for ovarian cancer unaffected BRCA1 and BRCA2 carriers, respectively. For BRCA1 mutation carriers univariate analyses showed that both a longer duration of OCP use and more recent use of OCPs were inversely associated with risk of ovarian cancer. However, in multivariate analyses including duration of use, age at first use and time since last use, duration of use proved to be the prominent protective factor (compared with &lt;5 years, 5-9 years HR=0.67;95%CI 0.40-1.12, 10+ years HR=0.37;95%CI 0.19-0.73; ptrend=0.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (Duration of ≥10 years; BRCA1: &lt;15 years since last use: HR=0.24 95%CI 0.14-0.43, 15+ years since last use: HR 0.56 95%CI 0.18-0.59). Univariate results for BRCA2 mutation carriers were similar, but due to limit sample size inconclusive.</p><p>CONCLUSION: For BRCA1 mutation carriers, a longer duration of OCP use is associated with a greater reduction of ovarian cancer risk and the protection is long term.</p>},
  author       = {Schrijver, Lieske H and Antoniou, Antonis C and Olsson, Håkan and Mooij, Thea M and Roos-Blom, Marie-José and Azarang, Leyla and Adlard, Julian and Ahmed, Munaza and Barrowdale, Daniel and Davidson, Rosemarie and Donaldson, Alan and Eeles, Ros and Evans, D Gareth and Frost, Debra and Henderson, Alex and Izatt, Louise and Ong, Kai-Ren and Bonadona, Valérie and Coupier, Isabelle and Faivre, Laurence and Fricker, Jean-Pierre and Gesta, Paul and VAN Engelen, Klaartje and Jager, Agnes and Menko, Fred H and Mourits, Marian J E and Singer, Christian F and Tan, Yen Y and Foretova, Lenka and Navratilova, Marie and Schmutzler, Rita K and Ellberg, Carolina and Gerdes, Anne-Marie and Caldes, Trinidad and Simard, Jacques and Olah, Edith and Jakubowska, Anna and Rantala, Johanna and Osorio, Ana and Hopper, John L and Phillips, Kelly-Anne and Milne, Roger L and Terry, Mary Beth and NoguÈs, Catherine and Engel, Christoph and Kast, Karin and Goldgar, David E and van Leeuwen, Flora E and Easton, Douglas F and Andrieu, Nadine and Rookus, Matti A},
  issn         = {1097-6868},
  language     = {eng},
  month        = {01},
  publisher    = {Elsevier},
  series       = {American Journal of Obstetrics and Gynecology},
  title        = {Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers : an international cohort study},
  url          = {http://dx.doi.org/10.1016/j.ajog.2021.01.014},
  doi          = {10.1016/j.ajog.2021.01.014},
  year         = {2021},
}