‘Slight’ increase in breast cancer risk with recent progestogen-only contraceptive use
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Key takeaways :
- Relative risk for breast cancer rises about 20% to 30% with recent use of any oral contraceptives.
- Current or recent progestogen-only contraceptive use increases breast cancer risk regardless of delivery mode.
Current or recent use of progestogen-only contraceptives was associated with a “slight” increase in breast cancer risk, according to findings from a nested case-control study and meta-analysis published in PLOS Medicine.
“In England, for example, prescriptions for oral progestogen-only contraceptives almost doubled in the last decade; and in 2020, there were almost as many prescriptions for oral progestogen-only contraceptives as for oral combined contraceptives,” Danielle Fitzpatrick, MA, from the cancer epidemiology unit at Nuffield department of population health at the University of Oxford, U.K., and the Adelaide Medical School at the University of Adelaide, South Australia, and colleagues wrote. “Given the trend towards increasing use of progestogen-only contraceptives, it is important to reliably quantify their effects on breast cancer risk.”
Researchers compared hormonal contraceptive prescriptions recorded in a U.K. primary care database for 9,498 women younger than 50 years with incident invasive breast cancer diagnosed between 1996 and 2017 and 18,171 matched controls. Each case and their matched controls had an average of 7.3 years of clinical records before the diagnosis date.
Researchers observed hormonal contraceptive prescriptions an average of 3.1 years before diagnosis among 44% of women with breast cancer and 39% of matched controls. Nearly half of the prescriptions were for progestogen-only contraceptives.
Compared with women who used no hormonal contraceptive during the study period, those who did use hormonal contraception had an increased risk for breast cancer if their last prescription was for oral combined (OR = 1.23; 95% CI, 1.14-1.32; P < .001), oral progestogen-only (OR = 1.26; 95% CI, 1.16-1.37; P < .001), injected progestogen (OR = 1.25; 95% CI, 1.07-1.45; P = .004) or progestogen-releasing IUDs (OR = 1.32; 95% CI, 1.17-1.49; P < .001).
Current or recent progestogen-only contraceptive use resulted in significantly increased risk for breast cancer for oral (RR = 1.29; 95% CI, 1.21-1.37), injected (RR = 1.18; 95% CI< 1.07-1.3), implanted (RR = 1.28; 95% CI, 1.08-1.51) and IUDs (RR = 1.21; 95% CI, 1.14-1.28).
When researchers combined the U.K. primary care database results with previously published findings, they observed an estimated eight cases per 100,000 users from age 16 to 20 years and 265 cases per 100,000 users from age 35 to 39 years in resulting 15-year absolute excess breast cancer risk associated with 5 years’ use of oral combined progestogen-only contraceptives in high-income countries, they wrote.
“This study provides important new evidence that current or recent use of progestogen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives,” the researchers wrote.
“Further research is ... needed to elucidate the mechanisms behind the similar associations of recent use of combined and progestogen-only contraceptives with breast cancer risk observed here,” the researchers wrote.
Perspective
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The study published in PLoS by Reeves and collegues examines whether progestin-only contraceptives carry similar increased risks for breast cancer to combined estrogen and progestin oral contraceptives. Some, but not all, previous studies have shown that combined oral contraceptives convey a slight increased risk for breast cancer proximate to the time of use. This paper demonstrates a slight but statistically significant risk with progestin-only methods. Of note, they show an increased risk with all progestin-only methods, including the progestin-containing IUDs.
Several factors are notable in reading this paper. Progestin-only oral contraceptives are far more widely used in the U.K. compared to the U.S., where only 4% of contraception users use progestin-only pills; in the U.K. progestin-only pills are used just as frequently as combined oral contraceptives.
Progestin-only IUDs promote a high concentration of progestin in the uterus, but not systemically. There is no obvious explanation for why a minimal increase in the serum progestin levels would affect the breast.
From the data collected on the participants, we do not know stratification of risk factors for breast cancer in the patients; complete family histories are not known. One possible explanation is that perhaps providers when hearing of a significant family history, with a perception of estrogen as problematic for breast cancer risk, might suggest that that patient use a progestin-only contraceptive.
In deciding on contraception, especially in the post-Dobbs era in the United States, women need to use highly reliable contraception, provided by many of the methods here under consideration. Women also need to be reminded that combined oral contraceptives significantly decrease the incidence of both ovarian and endometrial cancers (even in women with high-risk mutations). Given that the increased risk for breast cancer demonstrated in this study is very small, this needs to be just one small part of the choosing in deciding on the best contraceptive method for them.
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