February 04, 2021
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is "extremely small" and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and Extending Knowledge
"These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort," commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women's Hospital, both in Boston. "Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs."
The results "reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer," Keating said. "Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use."
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study "again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50," although the lifetime risk was not elevated, Keating said.
"The counseling regarding the effect on breast cancer is more complex," she said. "I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist."
For certain patients, the association may be more relevant.
"For most women, this risk is so small that it should be a limited factor in their decision to start OCPs," Keating said. "However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception)."
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
"Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation)," Badalian said. "Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk."
Data From the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. "However, we did not see a significant association between oral contraceptive use and breast cancer" for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
"Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation," Asa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. "Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk."
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Marta Beijers, the Marcus Borgstrom, the Ake Wiberg, and the A and M Rudbergs foundations. The authors, Keating, and Badalian had no conflicts of interest.