Why Doctors Are Reconsidering The Breast Cancer Risk Of Estrogen-Only HRT
If you have ever even thought about hormone therapy, you have probably heard some sort of warning about how it may cause breast cancer. This ideas floated around the scientific space for years, and was hardened in 2002, when early findings from the Women's Health Initiative (WHI) linked hormone therapy to blood clots, stroke, and breast cancer.
These 2002 findings have since been categorically disproved, but the number of women using hormone therapy remains low due to the prevailing incorrect information on the risks of the drugs.
A new clinical perspective published in Obstetrics & Gynecology 1makes the case that the warning was never as simple as the WHI made it seem. They say taking estrogen on its own appears to lower breast cancer risk for women who have had a hysterectomy. Keep reading to see what the science says.
Where the confusion started
In the 2002 research, the WHI tested two different hormone therapy treatments. Over 16,000 women who still had a uterus were given a combination of estrogen and a progestin. Estrogen alone causes the endometrium to thicken, which significantly increases the risk of uterine or endometrial cancer. That's why women with an intact uterus are generally only prescribed combination HRT.
A separate group of nearly 11,000 women had their uteruses removed via hysterectomy were given estrogen by itself, since there is nothing for the progestin to protect without a uterus. Each of those groups were compared with its own placebo group.
After more than 20 years of tracking, women on the combination therapy had a modestly higher rate of breast cancer than their placebo group, along with a higher rate of death from breast cancer (though that second difference was small enough that it could have been chance). Women taking estrogen alone had fewer breast cancer cases than their placebo group: 30 diagnoses per 10,000 women each year, compared with 37 per 10,000. Deaths from breast cancer in that group were also 40% lower than the placebo.
The authors make a point of how unusual this is. The form of estrogen used in the WHI, conjugated equine estrogen, is the only medication that has been shown to reduce deaths from breast cancer. Even trials of drugs specifically studied for cancer prevention have not produced the same results.
What happened when researchers pooled the trials
To check whether the WHI data on estrogen lowering breast cancer risk was a fluke, investigators combined it with nine smaller randomized trials of estrogen-alone therapy2, with 14,282 participants in total.
Among women taking estrogen alone, 3.6% were diagnosed with breast cancer, compared with 4.7% of those on placebo. That's a 23% lower risk, leading the authors to conclude that estrogen use alone significantly reduces breast cancer incidence.
A separate review of the WHI trials in context3, focused specifically on breast cancer diagnosed before age 55, pointed the same direction. Women using estrogen-only therapy had a lower risk than women using no hormone therapy, while those on estrogen plus a progestin had a slightly higher risk (that may have come down to chance).
What it means if you carry a BRCA1 or BRCA2 variant
Researchers followed 676 women with a BRCA1 or BRCA2 variant who still had their breasts and were using hormone therapy, and matched each one to a woman with the same variant who was not taking any hormones.
Over 15 years, 24.3% of the women using estrogen alone were diagnosed with breast cancer, compared with 47.3% of the women using no hormone therapy. Overall, estrogen-only users had a 63% lower risk. Most of them were using estradiol through the skin, in a patch or gel, which was linked to a 54% lower risk. Women using estrogen plus a progestin had roughly the same risk as non-users.
Notably, researchers in this study did not recommend any change to mammogram or MRI screening for carriers using hormone therapy.
What researchers still cannot say
Almost all of the strongest evidence associated with breast cancer risk reduction comes from studies using conjugated equine estrogen, but most American women are currently prescribed a different form of estrogen. Clinicians have largely shifted to estradiol, which is well-tolerated because it is chemically identical to the estrogen your body naturally produces. Trials of estradiol have been too small to produce conclusive results regarding breast cancer risk.
The authors are also careful to note that this research is not an endorsement of gynecologic surgery purely to remove the uterus, just because because estrogen alone is only an option for women without a uterus. They still encourage patients weighing surgery for fibroids, heavy bleeding, or ovarian cysts to consider keeping the uterus, and want to see randomized data on estradiol before that advice changes. What they do argue is that breast cancer risk belongs in that conversation alongside heart disease risk, endometrial cancer risk, and the recovery involved in surgery.
The takeaway
If the risks of cancer have been preventing you from trying hormone therapy, let this research be your sign to dig a little deeper and talk to your doctor about the pros and cons of this drug. HRT has the potential to have a large, positive impact on your health, so the question to ask isn't whether HRT causes cancer, but which type, at what dose, and to whom. Your surgical and family cancer history, along with your current symptoms, will help inform whatever decision you and your doctor make.
And, if the ups and downs of HRT in recent years has shown us anything, it's that the research in this space is still developing, which means this is a conversation worth revisiting with your doctor every couple of years. What makes sense for you and your body in this moment can change over time, and so can the science.