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. 2022 Apr 11;114(4):540-552.
doi: 10.1093/jnci/djac004.

Oral Contraceptive Use in BRCA1 and BRCA2 Mutation Carriers: Absolute Cancer Risks and Benefits

Lieske H Schrijver  1 , Thea M Mooij  1 , Anouk Pijpe  1 , Gabe S Sonke  2 , Marian J E Mourits  3 , Nadine Andrieu  4   5   6   7 , Antonis C Antoniou  8 , Douglas F Easton  8   9 , Christoph Engel  10 , David Goldgar  11 , Esther M John  12 , Karin Kast  13 , Roger L Milne  14   15   16 , Håkan Olsson  17 , Kelly-Anne Phillips  15   18   19 , Mary Beth Terry  20 , John L Hopper  15 , Flora E van Leeuwen  1 , Matti A Rookus  1
Affiliations

Oral Contraceptive Use in BRCA1 and BRCA2 Mutation Carriers: Absolute Cancer Risks and Benefits

Lieske H Schrijver et al. J Natl Cancer Inst. .

Abstract

Background: To help BRCA1 and 2 mutation carriers make informed decisions regarding use of combined-type oral contraceptive preparation (COCP), absolute risk-benefit estimates are needed for COCP-associated cancer.

Methods: For a hypothetical cohort of 10 000 women, we calculated the increased or decreased cumulative incidence of COCP-associated (breast, ovarian, endometrial) cancer, examining 18 scenarios with differences in duration and timing of COCP use, uptake of prophylactic surgeries, and menopausal hormone therapy.

Results: COCP use initially increased breast cancer risk and decreased ovarian and endometrial cancer risk long term. For 10 000 BRCA1 mutation carriers, 10 years of COCP use from age 20 to 30 years resulted in 66 additional COCP-associated cancer cases by the age of 35 years, in addition to 625 cases expected for never users. By the age of 70 years such COCP use resulted in 907 fewer cancer cases than the expected 9093 cases in never users. Triple-negative breast cancer estimates resulted in 196 additional COCP-associated cases by age 40 years, in addition to the 1454 expected. For 10 000 BRCA2 mutation carriers using COCP from age 20 to 30 years, 80 excess cancer cases were estimated by age 40 years in addition to 651 expected cases; by the age of 70 years, we calculated 382 fewer cases compared with the 6156 cases expected. The long-term benefit of COCP use diminished after risk-reducing bilateral salpingo-oophorectomy followed by menopausal hormone therapy use.

Conclusion: Although COCP use in BRCA1 and BRCA2 mutation carriers initially increases breast, ovarian, and endometrial cancer risk, it strongly decreases lifetime cancer risk. Risk-reducing bilateral salpingo-oophorectomy and menopausal hormone therapy use appear to counteract the long-term COCP-benefit.

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Figures

Figure 1.
Figure 1.
Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 women (general population, BRCA1 and BRCA2 mutation carriers, attributable to 10 years of continuous COCP use starting at age 20 years with no uptake of prophylactic surgeries (scenario B). The numbers in the chart do not always add up because of rounding. COCP = combined-type oral contraceptive preparations. aThese are the values displayed in Figures 3 (BRCA1) and (BRCA2).
Figure 2.
Figure 2.
Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA1 (A) or BRCA2 (B) mutation carrier, attributable to 10-year continuous COCP use and no prophylactic surgeries and stratified by type of cancer. COCP = combined-type oral contraceptive preparations; RRM = risk-reducing bilateral mastectomy; RRSO = risk-reducing bilateral salpingo-oophorectomy.
Figure 3.
Figure 3.
Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer attributable to COCP use per 10 000 BRCA1 mutation carriers. A) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA1 mutation carriers, attributable to 10 years COCP use at age 20 years, varying uptake of prophylactic surgeries. B) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA1 mutation carriers, attributable to COCP use, varying both use of COCP and uptake of prophylactic surgeries. The numbers in the chart do not always add up because of rounding. COCP = combined-type oral contraceptive preparations; RRM = risk-reducing bilateral mastectomy; RRSO = risk-reducing bilateral salpingo-oophorectomy. aThese are the values displayed in Figure 3, B.
Figure 3.
Figure 3.
Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer attributable to COCP use per 10 000 BRCA1 mutation carriers. A) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA1 mutation carriers, attributable to 10 years COCP use at age 20 years, varying uptake of prophylactic surgeries. B) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA1 mutation carriers, attributable to COCP use, varying both use of COCP and uptake of prophylactic surgeries. The numbers in the chart do not always add up because of rounding. COCP = combined-type oral contraceptive preparations; RRM = risk-reducing bilateral mastectomy; RRSO = risk-reducing bilateral salpingo-oophorectomy. aThese are the values displayed in Figure 3, B.
Figure 4.
Figure 4.
Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer attributable to COCP use per 10 000 BRCA2 mutation carriers. A) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA2 mutation carriers, attributable to 10 years of COCP use at age 20 years, varying uptake of prophylactic surgeries. B) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA2 mutation carriers, attributable to COCP use, varying both use of COCP and uptake of prophylactic surgeries. The numbers in the chart do not always add up because of rounding. COCP = combined-type oral contraceptive preparations; RRM = risk-reducing bilateral mastectomy; RRSO = risk-reducing bilateral salpingo-oophorectomy. aThese are the values displayed in Figure 4, B.
Figure 4.
Figure 4.
Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer attributable to COCP use per 10 000 BRCA2 mutation carriers. A) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA2 mutation carriers, attributable to 10 years of COCP use at age 20 years, varying uptake of prophylactic surgeries. B) Increased or decreased absolute cumulative incidence of breast, ovarian, and endometrial cancer per 10 000 BRCA2 mutation carriers, attributable to COCP use, varying both use of COCP and uptake of prophylactic surgeries. The numbers in the chart do not always add up because of rounding. COCP = combined-type oral contraceptive preparations; RRM = risk-reducing bilateral mastectomy; RRSO = risk-reducing bilateral salpingo-oophorectomy. aThese are the values displayed in Figure 4, B.
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References

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