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Certain birth control methods may increase breast cancer risk
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Women who currently use or recently used hormonal contraception demonstrated a 20% higher relative risk for breast cancer than those who had never used hormonal contraceptives, according to results of a prospective study of women in Denmark.
“An estimated 140 million women worldwide use hormonal contraception; this number accounts for approximately 13% of women between the ages of 15 and 49 years,” Lina S. Mørch, PhD, of Juliane Marie Centre — part of Rigshospitalet, one of the largest hospitals in Denmark — and colleagues wrote. “Previous, mainly case-control studies that showed positive associations between the use of oral contraceptives and breast cancer risk were generally conducted when the estrogen dose in combined (estrogen-progestin) hormonal contraceptives was higher than it is today, and before the availability of products with new progestins and new routes of delivery.”
Mørch and colleagues used data from Danish national registries on more than 1.79 million females (age range, 15 to 49 years) to evaluate associations between various preparations of hormonal contraceptives and breast cancer risk.
Study criteria excluded those who had a history of cancer other than nonmelanoma skin cancer, those who had venous thromboembolism and those who received treatment for infertility.
Mean follow-up was 10.9 years, equating to 19.6 million person-years.
During that time, 11,517 breast cancer cases occurred in the study population.
Women who were current or recent users of hormonal contraception exhibited a 20% higher risk (RR = 1.2; 95% CI, 1.14-1.26) for breast cancer than women who had never used hormonal contraception.
The risk increased with duration of use. Women who used hormonal contraception for more than 10 years (RR = 1.38; 95% CI, 1.26-1.51) exhibited a greater risk than those who used hormonal contraception for less than 1 year (RR = 1.09; 95% CI, 0.96-1.23).
Even after discontinuation of hormonal contraception, women who had used it for 5 years or more still exhibited higher breast cancer risk than those who had not used hormonal contraceptives.
Because of the large population size, the researchers were able to study the risks associated with different preparations of hormonal contraceptives.
When adjusting for estrogen dose in each product, the researchers found the RR for breast cancer was attenuated; however, the risk remained elevated for products with gestodene products.
Women who currently or recently used a levonorgestrel-releasing intrauterine system also exhibited elevated risk for breast cancer (RR = 1.21; 95% CI, 1.11-1.33).
Breast cancer risk appeared lowest among users of a progestin-only implant and depot medroxyprogesterone acetate.
Researchers acknowledged study limitations, including their inability to adjust for potential confounders due to missing data for older women, lack of information about contraceptive use prior to the study period, and uncertainty about prescription adherence and duration.
“The estimated number of additional breast cancers that were associated with hormonal contraception did not include extra cases diagnosed after the discontinuation of long-term use,” Mørch and colleagues wrote. “Even so, the estimated number of additional breast cancers among premenopausal women that were attributable to hormonal contraception is likely to be low. This risk should be weighed against important benefits of hormonal contraceptives.”
David J. Hunter, MD, BS, ScD, Richard Doll professor of epidemiology and medicine and director of the translational epidemiology unit at University of Oxford in the United Kingdom, expressed a similar sentiment in an accompanying editorial.
“The approximately 20% higher risk of breast cancer among women who currently use hormonal contraceptives and those who do not must be placed in the context of the low incidence rates of breast cancer among younger women,” he wrote.
Women in their 40s are more than five times as likely as women in their 30s to develop breast cancer and, as the researchers noted, the excess number of breast cancer cases associated with hormonal contraceptive use increases rapidly with age, Hunter wrote.
According to Mørch and colleagues, the absolute overall increase in risk is 13 per 100,000 women overall, but only 2 per 100,000 women aged younger than 35 years.
“Most of the cases that occurred I this analysis occurred among women who were using oral contraceptives in their 40s,” Hunter wrote.
Hunter also discussed the potential benefits for oral contraceptives. They often are used for women with dysmenorrhea and menorrhagia, and oral contraceptive use also has been linked to reduced risks for ovarian, endometrial and colorectal cancers.
“Some calculations have suggested that the net effect of the use of oral contraceptives for 5 years or longer is a slight reduction in the total risk [for] cancer,” Hunter wrote. “The higher excess risk as women move into their 40s — [for] breast cancer, as well as [for] other uncommon risks, such as myocardial infarction and stroke — suggests careful consideration of alternative methods of contraception, such as nonhormonal, long-acting, reversible contraceptives (eg, intrauterine devices) in this age group.”
Although results revealed some differences in RR for various formulations of hormonal contraception, all confidence intervals overlapped the consensus estimate of 1.2.
“These results do not suggest that any particular preparation is free of risk,” Hunter wrote. “The search for an oral contraceptive that does not elevate the risk [for] breast cancer needs to continue.” -- by Cassie Homer
Disclosures: A grant from Novo Nordisk Foundation supported this study. Mørch and another researcher report becoming employed by Novo Nordisk after the manuscript was accepted for publication. Hunter reports no relevant financial disclosures.
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