As more women turn to hormones to relieve menopausal symptoms like hot flashes and night sweats, some physicians and scientists say not enough attention is being paid to the small increase in breast cancer risk associated with certain systemic therapies.
The link between breast cancer and hormone therapy has been the subject of heated debate for decades. In 2002, panic ensued after a large study, called the Women’s Health Initiative, found that older women taking a combination hormone pill were developing breast cancer at higher rates. (There was no risk with estrogen-only treatment, used only after a hysterectomy.) Prescriptions for combination hormone therapy plummeted to 5.3 million in 2003, down from 18.8 million in 2001.
But in recent years, the pendulum has swung in the other direction. Federal health officials removed the drugs’ so-called black box warning emphasizing the risks, though they retained language saying the combination drug had been linked to breast cancer and to cardiovascular disease. And in recent months, major medical societies have strongly endorsed these medications for treating menopausal symptoms, which a recent survey found affect nearly half of women aged 40 to 60.
Doctors now recommend starting use within 10 years of menopause and before turning 60 in order to protect women from the heart disease risks. Women today can also use newer hormone formulations that doctors believe are associated with less risk for breast cancer than the older drugs. But there is still a dearth of good data about long-term safety with regards to breast cancer, a message some experts worry is not being conveyed.
“We need to keep cancer in the conversation,” said Garnet Anderson, a scientist at the Fred Hutch Cancer Center who is a principal investigator of the W.H.I. “I’m not saying it should overshadow treating women who have severe menopausal symptoms, but it’s part of the risk-to-benefit balance that has to be weighed on an individual basis. I think it’s being underplayed.”
Dr. Lisa Larkin, founder of Ms. Medicine, a concierge medicine organization that focuses on women in midlife, said many women dealing with menopause symptoms still don’t get the hormone treatment they need. Even though use has doubled over the past five years, fewer than 4 percent of women use hormones. But, Dr. Larkin said, she’s also concerned about patients who have seen all sorts of claims about hormone therapy’s benefits on social media, but have heard nothing about their risks.
Some of these women have a history of breast cancer or are at elevated risk of the disease, and doctors generally say they should avoid the drugs. (The new guidelines from medical societies recommend assessing a woman’s breast cancer and cardiovascular risks before initiating treatment and repeating the assessment every year.)
“The messaging has gone too far,” Dr. Larkin said. “We harmed women for so long by not providing hormones to the right patients, but now we may harm women by giving the wrong patients hormones.”
The W.H.I. found a small increase in the risk of invasive breast cancer among women taking a pill that combined estrogen and progestin, compared to women who took a placebo. There were about four cases of breast cancer per 1,000 women each year among women on the combination hormone therapy, compared to three cases each year per 1,000 women not taking hormones, said Dr. JoAnn Manson, one of the study’s lead investigators. That’s a 26 percent increase in risk.
The cancers found in the combined hormone therapy group were also slightly larger than those in the placebo group. They were also discovered later: 25 percent were found at an advanced stage, compared to 16 percent among the women on placebo, one analysis found. That may be partly because some women taking the combination drug experienced an increase in breast density after one year of treatment. Dense breast tissue is a risk factor for breast cancer and also makes tumors harder to see on a mammogram.
Researchers have continued to follow the women, and further analyses in 2003 and in 2020 confirmed the findings. A statistically significant but modestly increased breast cancer risk in those on combined therapy relative to women taking a placebo was seen in every age group.
The treatment was not associated with an increased risk of death from breast cancer.
Dr. Stephanie Faubion, medical director of The Menopause Society, said it’s important to put the breast cancer risk seen in the W.H.I. study in perspective. “These are tiny numbers in terms of how many women are affected,” she said.
She added, “It’s the same increased risk as overweight or obesity, the same increased risk as one to two glasses of wine a night and roughly the same increased risk as being inactive.” In comparison, a genetic variant like BRCA1 can increase the risk of breast cancer fourfold or more.
However, some cancer doctors argue that, unlike many other factors that drive the cancer, such as the age at which a woman started menstruating, hormone use is among those that women can modify.
“We don’t have the perfect answer, but a lot of people are taking hormone therapy for reasons that are myths, like it keeps your hair young, it keeps your skin young,” said Dr. Larry Norton, a breast cancer specialist at Memorial Sloan Kettering Cancer Center. “It doesn’t really do that.”
Dr. Norton noted that breast cancer rates in the United States dropped after millions of women abruptly quit using hormones in 2002, a decline that was sustained for two decades. (It’s difficult to prove a causal relationship between the declines in hormone use and in breast cancers, though some studies have ruled out other causes, like changes in mammography frequency.)
Studies suggest that the increase in risk starts after about three years of treatment, and declines after a woman stops taking combined hormones.
How long a woman takes the hormones appears to matter. Evidence from observational studies, which is not as strong as data from a randomized trial, suggests that breast cancer risk goes up the longer a woman is on the treatment, Dr. Manson said.
For this reason, some medical guidance has in the past recommended using the lowest-dose products for as short a time as possible. But women who start hormone therapy to treat symptoms like hot flashes and night sweats may experience a recurrence of these symptoms when they discontinue the treatment, making quitting difficult, studies show. And some women experience troublesome symptoms attributed to menopause until late in life.
Doctors said they would like to see more robust research into hormone options commonly used today. These include a patch that contains a type of estrogen called estradiol, used alongside a form of progesterone different from the synthetic progestin used in the W.H.I. (Estrogen delivered through a patch appears less likely than oral estrogen to promote blood clots, another risk identified in the W.H.I.)
Even though new drug formulations are studied for safety and effectiveness in small, short-term clinical trials before they come to market, studies generally don’t follow large numbers of women long-term. This means they can miss less common side effects caused by many years of use.
A systematic review of studies found that combination therapy with the new type of progesterone did not increase breast cancer risk during the first five years of treatment. But the authors also noted that the evidence was limited, and they cautioned that the risk could increase with longer use.
“The breast cancer risk may not be the same” with newer formulations, Dr. Faubion said. “But honestly, we don’t know,” she added.
Until they do know more, women deserve treatment for symptoms that disrupt their lives, Dr. Manson said. She added that it was important to remember that “there is no medication, even Tylenol, that is free of any increased risk.”
The post As Hormone Use Increases, Some Doctors Warn Slight Cancer Risk Is Being Overlooked appeared first on New York Times.
