Longer Use of Hormone Replacement Therapy Linked to Greater Breast Cancer Risk in Study

The longer women use hormone therapy after menopause the higher is their breast cancer risk over time, and this risk persists for more than a decade after stopping this replacement therapy, a new meta-analysis suggests.

“Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence” was published in The Lancet.

Menopausal hormone therapy (MHT) involves taking hormones — usually estrogen, sometimes also progesterone — that the body makes less of after menopause. This can help alleviate some of the unpleasant effects of menopause, but studies have suggested it can increase the risk of some types of cancer, most notably breast cancer.

In this meta-analysis, researchers in the U.K. looked at 58 different scientific studies, published between 1992 and 2018, to analyze this risk based on the most available data. They used patient data covering 128,435 women who developed breast cancer after menopause (the cases) and 366,965 who did not (the controls). About half of women in the cases group had used MHT.

Importantly, most of the data included are from prospective studies, where participants were actively followed over time (as opposed to retrospective studies, where researchers review hospital records to look for trends). Prospective studies are generally better indicators of cause-and-effect relationships, because investigators can control for more variables.

The researchers found that every type of MHT, with the sole exception of vaginally applied topical estrogen, increased breast cancer risk.

To illustrate this, they estimated the rate of breast cancer in women ages 50 to 70, a timeframe chosen because the most common age at menopause is 50 years old. Mean age at first MHT use in this study was also 50.

Among people who had never used MHT, the estimated rate was 6.3%. For those who used estrogen and progesterone daily for five years, the estimated rate was 8.3% — an increase that would correspond statistically to 1 in every 50 users getting breast cancer.

For those who used estrogen daily and progesterone sometimes, this rate was 7·7%, an increase corresponding to 1 in 70 users. For users of daily estrogen alone, it was 6.8%, an increase corresponding to 1 in 200 users.

When MHT was taken for twice as long (i.e., 10 years), these estimated risks doubled. By the researchers’ estimation, MHT has caused 1 million cases of breast cancer in the last 30 years – a full 5% of all breast cancer cases worldwide.

“Users of systemic hormone therapy who started around the time of menopause were at greater risk of invasive breast cancer than apparently similar never users,” the researchers wrote, adding that “some risk persisted for more than a decade after MHT use ceased.”

Importantly, these associations remained stable after other variables were accounted for, including age at menarche (a first period), ethnicity, education, and use of oral contraceptives. The researchers did note a lesser increase in breast cancer risk among MHT users with higher body mass indexes (BMIs).

The associations were strongly linked to length of time on MHT. “There was little excess risk after use of MHT for less than 1 year,” the researchers wrote, “but there were definite excess risks associated with just 1–4 years of use, and progressively greater risks with longer use.”

Overall, the available data suggest that women who decide to use MHT should work with their doctors to minimize the length of time that they are on it, and those who use MHT — along with people who do not — should get regularly screened.