Oral contraceptive use is associated with somewhat increased breast cancer risk, especially among young women. The pill increases the risk of triple negative (ER-/PR-/HER2-) disease more than other types of breast cancer. Newer formulations have not eliminated the risk associated with hormonal contraceptives. In fact, contraceptive implants and birth control pills containing the progestin levonorgestrel might increase breast cancer risk even more than the old high-dose pills.
Birth control pills increase risk of triple negative breast cancer
Although not all studies are in agreement, use of birth control pills appears to increase the risk of triple negative (ER-/PR-/HER2-) breast cancer more than estrogen receptor positive (ER+) types, a finding that is perhaps surprising since triple negative disease is not considered estrogen responsive. One study reported that oral contraceptive use was associated with a 2.9-fold increased risk of triple-negative breast cancer among women of 45 to 64 years of age who had begun to use oral contraceptives before age 18. The same study found that oral contraceptive use was not associated with any other breast cancer subtype as defined by ER/PR/HER2/p53 status.
Another study found that oral contraceptive use of at least one year in duration was associated with a 4.2-fold increase in risk of triple-negative breast cancer among women 40 and younger. Longer oral contraceptive duration and more recent use increased the risk of triple-negative breast cancer. There was no significantly increased risk among women 41 to 45 years of age. Again, no significant associations with other subtypes of breast cancer were found.
Generally speaking, the relationship between oral contraceptive use and risk of breast cancer does not appear to differ between lobular and ductal breast cancer in young women. However, birth control use is associated with increased risk of both mucinous and medullary breast cancer, both of which rare breast cancer subtypes with comparatively favorable prognosis.
Age of birth control pill use and breast cancer risk
Birth control pill use before age 20 significantly increases the risk of breast cancer in later years. Women who start using birth control pills at an early age also develop breast cancer earlier than women who start using the pill later in life. One study reported that women who started using the pill at age 18 or earlier were four years younger at breast cancer diagnosis, on average, than women who started using the pill after age 30. The same study found that women who started using the pill between ages 22 and 25 were three years younger at diagnosis.
HRT plus the pill heightens breast cancer risk
Combined hormone replacement therapy (estrogen plus progestin HRT) has been shown to increase the risk of breast cancer. Among middle aged women, use of combined HRT amplifies the increased risk of breast cancer associated with taking birth control pills. Women who use HRT to find relief from perimenopausal symptoms should not use birth control pills for contraception. The elevated risks associated with using birth control pills, HRT, or both decline with age after menopause.
Effect of birth control pill use on BRCA carriers
Use of oral contraceptives reduces the risk of ovarian cancer among breast cancer susceptibility gene (BRCA) mutation carriers. However, birth control pills appear to increase the risk of breast cancer for BRCA carriers when used at a young age. The effect might be greater for BRCA2 carriers than BRCA1 carriers, although both are affected. A longer duration of use, especially before first full-term pregnancy, has been found to be associated with increased risk of breast cancer among both BRCA1 and BRCA2 mutation carriers. Studies have reported that each year of birth control use prior to age 20 confers a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 40. The effect of teenage birth control pill use confered increased breast cancer risk to age 36 in study participants. The risks appear to be similar for both low-dose and high-dose pills.
Increased breast density is a possible mechanism of action
High breast density is strongly associated with increased breast cancer risk. One study reported that percent mammographic breast density was 5.3% greater in past oral contraceptives users than in nonusers among premenopausal women who later developed breast cancer. The difference in breast density associated with birth control pill use was greater in women who later developed breast cancer than in cancer-free controls. In other words, the women who developed cancer appeared to be more vulnerable to the effects of the pill. Note that birth control pill use appears to be a risk factor for inflammatory breast cancer (IBC), a very aggressive form of the disease which is normally found in women with high breast density.
Impact of prior birth control pill use on prognosis
Few studies have examined the influence of birth control pill use on prognosis. Based on the available evidence, prior birth control use appears to be associated with increased recurrence of premenopausal breast cancer, but only among women who used the pill as teenagers. However, note that women should not use the pill or other hormonal contraception after a diagnosis of breast cancer.
One 2014 study reported that, compared to no use of oral contraceptives, birth control pill use at any age was associated with significantly lower risk of breast cancer recurrence among women diagnosed at age at least 50 who were treated with aromatase inhibitors. No such reduction in risk was observed for ever users of the pill who were treated with tamoxifen. This suggests that women with ER+ postmenopausal breast cancer who have used the pill at any point in their lives may be better off using an aromatase inhibitor rather than tamoxifen as endocrine treatment.
Type of birth control pill or hormonal contraceptive influences breast cancer risk
While newer oral contraceptives have lower hormone levels than those produced before 1975, the new formulations have not eliminated increased breast cancer risk. A 2010 study reported that the excess risk was substantially accounted for by one specific formulation: triphasic preparations with levonorgestrel as the progestin. Triphasic pills contain estrogen plus progestin concentrations that vary during the menstrual cycle. Levonorgestrel is also the active ingredient in the "morning after" pill. Intrauterine devices that release levonorgestrel have been found to be associated with increased risk of breast cancer. One major 2015 study found that levonorgestrel-releasing intrauterine system users had increased risks of both ductal breast cancer (20% increase compare to the general female population) and lobular breast cancer (33% increased risk). A 2017 Israeli study reported that use of levonorgestrel-releasing intrauterine system was associated with higher breast cancer risk among women in their early 40s but not in women closer to 50.
A 2012 study reported that recent use of birth control pills containing either the progestin ethynodiol diacetate or high dose estrogen were associated with more than double the risk of breast cancer compared to no use of hormonal contraceptives in the previous year. On the other hand, use of birth control with the progestin norgestimate or low dose estrogen was associated with modest or no increased risk of breast cancer.
Another 2012 study reported that use of the progestin-only injectable contraceptive depo-medroxyprogesterone acetate (Depo-Provera) for 12 months or longer was associated with a 2.2-fold increased risk of invasive breast cancer. The risk did not appear to vary by hormone receptor status.
Subdermal contraceptive implants (typically implanted under the skin of the arm) were found to be strongly associated with increased risk of breast cancer among the few women who used them in another study. These implants also normally contain levonorgestrel. However, there is some evidence that it might be the continuous nature of the drug administration (rather than the formulation) that is the source of heightened risk. More study is needed to determine the influence of use of contraceptive implants and vaginal rings on breast cancer risk.
Below are links to recent studies on this topic. For a more complete list of studies, please click on birth control pills.