CATEGORY*: IARC known carcinogen, NTP known carcinogen
FOUND IN: Medications
THE GIST: Some studies suggest that birth control pills increase breast cancer risks, especially among women who have used them for more than five years, premenopausal women, and those with a history of breast cancer. However, risk levels return to normal after a decade-long hiatus from taking the pill. The pill also reduces risks for ovarian and endometrial cancers.
State of the Evidence on Oral Contraceptives
Numerous studies have demonstrated an increased risk of breast cancer in women using oral contraceptives (Althuis, 2003; Dai, 2009; Delort, 2007; Kumle, 2002; Rosenberg, 2009). This is not suprising given the long established link between lifetime exposure to steroid hormones and breast cancer. There are many different formulations of oral contraceptives, although the most common are a combination of the estrogenic hormone ethinyl estradiol and some form of synthetic progestin. Most studies examining effects of taking oral contraceptives and later risk for disease, including breast cancer, do not distinguish the particular formulations—either chemically or by dose—taken by women participating in the studies.
TIPS FOR PREVENTION
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A 2014 study of female enrollees in a large U.S. integrated health care delivery system looked at formulation differences (Beaber, 2014). This study reconfirmed that recent oral contraceptive use (within the prior year) was associated with an increased breast cancer risk. Three specific formulations of oral contraceptives were associated with particularly elevated risks. These included: 1) high-dose estrogen, 2) ethynodiol diacetate (a type of progestin); and 3) triphasic dosing (where the pills have three different doses of hormones in the three weeks of active pills) including norethindrone (a progesterone) at an average of 0.75 mg. Other types, including low-dose estrogen oral contraceptives, were not associated with elevated risks.
The risk for breast cancer is greatest among current and recent users, particularly those who have used them for more than five years and, especially, those who started using birth control pills earlier in life and took them for longer periods of time (Pasanisi, 2009; Rosenberg, 2009).
Women with BRCA1 or BRCA2 mutations (Haile, 2006; Narod 2002; Pasanisi, 2009, cf Figueiredo, 2010), as well as women with family histories of breast or ovarian cancer (Haile, 2006; Narod, 2002; cf Gaffield, 2009), have an increased susceptibility to the risk-inducing effects of oral contraceptive exposures. A recent study indicates that when the BRCA mutation comes from the father's genes, it confers greater risk for women with this genetic variation who also use oral contraceptives (Bernholtz, 2011). One mechanism by which the interaction between BRCA gene status and use of oral contraceptives may influence breast cancer risk, is alteration of the sensitivity and activity of progesterone in breast cancer cells, by increasing the synthesis of progesterone receptor (PR) in the cells and by enhancing the responsiveness of progesterone-regulated genes (Calvo, 2011).
One study compared the possible effects of oral contraceptive use on later risk for breast cancer in Hispanic and non-Hispanic white women. Statistically, Hispanic women have somewhat lower rates of breast cancer than do white women, but when they are diagnosed with the disease, it is more likely to be the estrogen-receptor-positive (ER+) type. Despite these group differences, use of oral contraceptives during the previous five years led to statistically significant increases in breast cancer incidence in both groups. The effect was magnified for women of both groups when oral contraceptive use continued for more than 20 years. Mirroring other study evidence, and again for both Hispanic and non-Hispanic white women, significant increases in ER+ tumors were observed (Sweeney, 2007).
Researchers in the Black Women’s Health Study, a large (more than 53,000 women) prospective study of women across the U.S., report that use of oral contraceptives by African American women was associated with a higher risk of receptor negative (ER−, PR−) cancer than women who did not use the pill. The risk for diagnosis of breast cancer increased as the duration of contraceptive use increased among women who took the pill within the past five years (Rosenberg, 2010).
Post-menopausal women who used oral contraceptives for eight or more years, but who had discontinued use for at least a decade, showed no significant increase in breast cancer rates (CGHFBC, 1996; Vessey, 2006).
Two recent studies have examined the relationship between use of injectable progestin-only contraceptives and breast cancer incidence. Both studies found statistically significant increases in breast cancer risk, but rates decreased to normal within a few years after stopping use of the drugs (Li, 2012; Urban, 2012).
*For chemicals that have been shown to be carcinogens, we provide classifications from two authoritative bodies: the International Agency for Research on Cancer (IARC, an international body) and the National Toxicology Program (NTP, a division of the U.S. Department of Health and Human Services). We have categorized endocrine-disrupting compounds where the body of peer-reviewed research indicates a strong foundation for doing so.