Can Menopausal Hormone Therapy Increase the Risk of Breast Cancer?

Menopausal hormone therapy (MHT) was associated with an increased risk of breast cancer, according to data from more than 100,000 women with breast cancer taken from 58 epidemiological studies worldwide. Additionally, this increased risk may persist for more than 10 years after cessation of MHT, the study published in The Lancet showed.

“If the associations are largely causal, MHT use in western countries has already caused about 1 million breast cancers, out of a total of about 20 million since 1990,” wrote researchers from the Collaborative Group of Hormonal Factors in Breast Cancer.

To estimate these risks, the researchers analyzed data from all eligible prospective studies that looked at the type and timing of MHT use. Source studies were published between 1992 and 2018.

Of the postmenopausal women included in the studies, 108,647 were diagnosed with breast cancer. About half (51%) had used MHT. Among current users of MHT, the mean duration of use was 10 years. This decreased to 7 years among past users. The average age at starting MHT was 50 years.

According to the study, all types of MHT, except for vaginal estrogens, were associated with excess breast cancer risk. Increased risk for breast cancer was seen during years 1 to 4 of use (estrogen-progestagen RR=1.60, 95% CI 1.52–1.69; estrogen-only RR=1.17, 1.10–1.26), and doubled during years 5 to 14 (estrogen-progestagen RR=2.08, 2.02–2.15; estrogen-only RR=1.33, 1.28–1.37).

From age 50 years to 69 years for women with 5 years of use of the three main types of MHT, the 20-year breast cancer risk would increase from 6.3 per 100 in never-users to 8.3 per 100 in users of estrogen plus daily progestogen, 7.7 per 100 in users of estrogen plus intermittent progestogen, and 6.8 per 100 in users of estrogen-only.

This increased 20-year risk included increased risk not only during the 5 years when MHT was being used, but also during the 15 years after it had been stopped.

“Use of menopausal hormone therapy for 10 years results in about twice the excess breast cancer risk associated with 5 years of use,” according to Gillian Reeves, from University of Oxford, United Kingdom. “But there appears to be little risk from use of menopausal hormone therapy for less than one year, or from topical use of vaginal oestrogens that are applied locally as creams or pessaries and are not intended to reach the bloodstream.”

In an accompanying editorial, Joanne Kotsopoulos, of Women’s College Hospital, Toronto, noted that the study was complex, making it difficult to appraise the results.

“Most of us will take the results at face value,” she wrote. “However, it is often difficult to avoid biases in prospective studies in which the period of exposure (hormone replacement therapy use) overlaps with the period of risk (breast cancer incidence). Clinicians must heed the message of this study but also to take a rational and comprehensive approach to the management of menopausal symptoms, with careful consideration of the risks and benefits of initiating MHT for each woman.”

JoAnn Manson, MD, DrPH, of Brigham and Women’s Hospital in Boston, also emphasized the importance of shared decision0making between the physician and the patient.

“Women need to be informed about both the risks and the benefits so that they can make an informed choice,” she told Cancer Network.

This means that physicians and their patients should assess the severity of menopausal symptoms and underlying risk factors for breast cancer. For example, if the patient has moderate to severe hot flashes, night sweats, and a family history of breast cancer, and she is anxious about her risk, she may not be a good candidate, and she should consider non-hormonal options for her menopausal symptoms.

Manson also pointed out that breast cancer risk should not necessarily be looked at in isolation.

“In the Women’s Health Initiative, we did not see an increased risk of incidence of total cancer incidence or total cancer mortality,” she said. “Combination hormone therapy may increase breast cancer risk, but it was associated with lower risk of colorectal cancer and endometrial cancer in WHI and other studies.”

This emphasizes the need for individualized decision making, she said, because in some cases the overall net benefit of hormone therapy can be favorable.