Long periods of hormone replacement therapy increase breast cancer risk, study says

Described colorfully by some women as a “personal summer,” the intense waves of heat and excessive sweating that come with menopause affect millions of women each year. An estimated 12 million women in Western countries are prescribed hormone replacement therapy (HRT) to combat the symptoms that happen with the decreasing levels of estrogen and progesterone associated with menopause.

But a new study from the Collaborative Group on Hormonal Factors in Breast Cancer published in The Lancet gives us the best evidence yet that the longer women use HRT, the higher their risk of breast cancer.

“This study is potentially going to change the way I prescribe hormones to my patients,” said Dr. Margaret Polaneczky, associate professor of Obstetrics and Gynecology at NYP-Weill Cornell who was not involved in the current research. While the study confirms long-held beliefs that the use of HRT leads to an increased risk of breast cancer, it distinguishes between different regimens of hormone therapy that are more likely to increase breast cancer risk than others.

Up to this point, data from the Women’s Health Initiative (WHI), the largest and most robust long-term study looking at HRT, have guided doctors' thinking about the risks and benefits of HRT. This new study deepens our understanding of the size of those risks.

“Women who use HRT for 10 years essentially double the risk of breast cancer caused by HRT than if they only use it for five years,” said Dr. Noah Kauff, an obstetrician and gynecologist and chief of Cancer Genetics at Northwell Health. He was not involved in the study.

The new data shows that the risk for breast cancer begins to increase with as little as one to four years of HRT use. For women taking five years of HRT starting at age 50, one in every 50 users of continuous estrogen-progestogen therapy develops breast cancer over a 20-year period than would have otherwise. Even after stopping HRT, that increased risk can persist for more than 10 years. On the brighter side, use of HRT for less than one year or use of vaginal estrogen creams alone were not associated with an increased risk of breast cancer.

On average, women use HRT for approximately two to three years, but the American College of Obstetrics and Gynecology recommends that women use the lowest dose of hormones for the shortest period of time to minimize both breast cancer risk and risk of blood clots. Determining what exactly the HRT doses and regimens should be is challenging, and this study gives doctors a bit more guidance.

“What’s new in this study compared to WHI is that it shows certain progestogen regimens might be more linked to breast cancer than others,” said Polaneczky.

Women who take HRT can either take estrogen alone or estrogen in combination with a progestogen. For women who still have their uterus, estrogen causes excess growth of the uterine lining as an unwanted side effect, so they need to take a progestogen to balance out this effect.

But there are different ways to take progestogens and there are different kinds. While some women take it daily with their estrogen, others take “cyclic” progestogen for only several days out of the month.

The study showed that women who take cyclic progestogens have a slightly lower risk of breast cancer compared to women taking progestogens every day. There were no substantial differences in cancer risk between the different types of progestogens used, including progestins and natural progesterone.

“This study has me rethinking going back to cycling progestogens with my patients,” said Polaneczky. She advises that women should be on progestogens for no fewer than 10-12 days per month to avoid the risk of endometrial cancer.

“These are really individualized discussions,” she added. “Many women don’t like progestogens as it is because they can cause mood swings and bloating. I don’t want women to take less and less of their progestogens as a result of this study and then risk getting endometrial cancer.”

In general, more women may prefer natural oral progesterone, which tends to have fewer side effects than the more potent progestins, she explained.

For women who have had their uterus surgically removed, estrogen-only regimens are preferred.

“There used to be controversy about whether estrogen alone increases breast cancer risk. That issue is put to rest in this study,” said Kauff. “Turns out that estrogen-only regimens are still associated with increased cancer risk, although it is less than those on combined HRT.”

Doctors say that women are understandably concerned about the potential for developing breast cancer in association with HRT use. It’s the most common malignancy in Western countries with almost 3% of women diagnosed with the disease in their 50s.

“While using HRT may increase your risk for developing breast cancer, it also has important benefits, like reducing osteoporotic fractures and potentially reducing risk of colon cancer,” said Kauff.

Those benefits may level out the risks, since there is no significant difference in death due to all causes in women taking HRT compared to those who are not taking it.

Polaneczky tells her patients that the risk is still minimal. “We know that using HRT increases breast cancer risk by about 1-2% over a 20-year period. It’s not a large risk, but I tell them that,” she said.

“If you don’t want the breast cancer risk, then don’t take hormones,” she noted. Instead, Polaneczky encourages her patients who are hesitant about HRT to try other medications first, like certain selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors and gabapentin.

“Cutting out alcohol and exercising more both improve symptoms of menopause and independently reduce breast cancer risk, so there’s a lot that women can do to make lifestyle changes that benefit their health,” she said.

With such a variety of options available with risks and benefits, a serious discussion with your doctor is important as menopause symptoms approach.

Dr. Lauren Kelly is an internal medicine resident physician in New York City working with the ABC News Medical Unit.