Hormone Replacement Therapy Linked to Increase in Breast Cancer Risk

In a possible case of the cure being worse than the ailment, hormone replacement therapy—a common treatment for severe menopause symptoms—has been linked to an increase in breast cancer risk, according to a new study conducted by Yana Vinogradova, PhD, senior research fellow in medical statistics in the division of primary care at the University of Nottingham, and colleagues. The October study was published in the British Medical Journal. 

Once a woman reaches the end of her reproductive lifetime, her body stops producing estrogen and progesterone—sex hormones that regulate a variety of physical processes associated with puberty, pregnancy, and birth—and in turn, can experience a range of adverse symptoms.

If severe, these symptoms have the potential to significantly decrease her quality of life, according to the study. In such cases, hormone replacement therapy (HRT), also known as menopausal hormone therapy, is often prescribed to relieve the corresponding physical discomfort by boosting estrogen and progesterone levels. But it's not without risk. 

Researchers found that women who had used HRT were slightly more likely to develop breast cancer. In total, 34% of women who participated in the study with a breast cancer diagnosis and 31% of women without a breast cancer diagnosis had used HRT—a difference of about 3%. 

“This large observational study found that exposure to most HRT drugs is associated with an increased risk of breast cancer,” the researchers wrote. 

HRT and Breast Cancer Risk

By combing through patient records stored in two U.K. primary care databases, researchers identified 98,611 women ages 50 to 79 who had been diagnosed with breast cancer between January 1, 1998 and December 31, 2018.

The study broke down HRT use by:

• Type: estrogen-only or estrogen plus progestogen
• Duration: short-term, meaning fewer than five years, or long-term, meaning more than five years
• Recency: recent, meaning between one and five years prior to participation in the study, and past, meaning more than five years prior to participation in the study

Vinogradova and colleagues then compared their rates of HRT use to those of 457,498 women of similar ages who had not been diagnosed with breast cancer.

Although she adds the disclaimer that “I am a medical statistician, not a doctor,” lead author Vinogradova speculates that HRT may increase breast cancer risk by causing changes at the cellular level.

“The breast is a different organ, and if you think of it, it develops during pregnancy and continues to develop during breastfeeding,” she tells Verywell. “So you can say this organ, not like others, is dependent on hormones, hugely. That's why when we have quite a fine balance in our body and we add extra hormones, it might affect the processes in breasts.” 

The study builds on earlier research on the correlation between HRT and increased breast cancer risk. Several previous studies on HRT use among postmenopausal women found that women who used estrogen-progestogen therapy were more likely to be diagnosed with breast cancer and die of lung cancer than either women who used estrogen-only therapy or women who did not use HRT at all. 

Several Factors Influence Risk

The effects of HRT use on breast cancer risk varied by type of HRT and duration of use.

Researchers found women who were at higher risk were those who:

• Used estrogen-progestogen therapy rather than estrogen-only therapy
• Used HRT long-term rather than short-term
• Used HRT within the past five years rather than earlier

“The levels of risks varied between types of HRT, with higher risks for combined [estrogen-progestogen] treatments and for longer duration of use,” the researchers wrote. 

Essentially, “when you use just one hormone, the risk is much lower than when you use both of them," Vinogradova says.

Risk level also seemed to be dependent on age and body type. Younger women and overweight or obese women experienced a smaller increase in breast cancer risk associated with HRT use than older women and thin women did—one of many findings with the potential to affect clinical practice. 

“Our results add more evidence to the existing knowledge base and should help doctors and women to identify the most appropriate HRT formulation and treatment regimen, and provide more consistently derived information for women’s health experts, healthcare researchers, and treatment policy professionals,” the researchers say.