Estrogen Only HRT Reduces Breast Cancer Risk

Medically reviewed by Dr. Mindy Goldman MD

It’s been 27 years since the launch of the massive Women’s Health Initiative (WHI) study on the potential risks and benefits of Hormone Therapy.1 While the initial findings were published in the early ‘00s, the study continues to follow some participants. 

In December 2019, the long-term follow-up of the WHI was presented at the San Antonio Breast Cancer Symposium. And the headline is this: Taking postmenopausal estrogen therapy alone is associated with a lower risk of breast cancer. 

Let’s unpack this new finding.

First, some quick background on the original WHI study (for more detail, see our previous article, How Hormone Therapy Got a Bad Rap). This was the “gold standard” randomized controlled trial designed to see whether hormone therapy (HT) protected against heart disease in healthy women after menopause. One arm of the trial looked at the effects of estrogen only (E) and another looked at estrogen + progestin (E+P). Both arms were stopped early when it was found that it neither protected against heart disease. Additionally, the E arm showed increased risk of stroke, and the E+P arm showed increased risk of breast cancer.2

The new finding presented last month pertained to the E arm; so estrogen only. Not the E+P arm, which is the one that originally showed a link to increased breast cancer risk, and still does. 

Now, the initial findings for the E arm back in 2004 did suggest a lower risk of breast cancer, but the numbers were not statistically significant. The big news from the follow-up study is that there is now a significant reduction in risk of breast cancer (23% less) and a significant reduction in breast cancer mortality (44% reduction) compared to placebo.3 Yes, a lower risk of breast cancer for women who took estrogen only versus a placebo! We still don’t have scientific explanations as to why estrogen alone would be associated with lower risks of breast cancer. But these new findings are exciting.

It’s important to remember that the types of hormones used during the WHI study were not the types of hormones that are often used today. In the WHI study, women were taking oral estrogen made from pregnant mare’s urine. These days, knowledgeable doctors prescribe bio-identical estrogen such as Vivelle and Climera patches. This new formulation seems to be more safe when it comes to heart disease and stroke risks.4 And the types of progestins used now are often a micronized progesterone. Some studies suggest that this might have different effects on the breasts.5 But there have been no randomized controlled trials that have studied these new forms of HT. 

But still, the long term data are really interesting and suggest that using estrogen alone might actually protect against getting breast cancer or dying from the disease.

So, what do we do with this information? 

Well, we start asking more questions. For instance:

If a woman has a uterus, taking estrogen alone still increases her risk for uterine cancer. But, what if instead of adding in the progestin to protect her uterus, we regularly monitor her uterus with ultrasounds or biopsies? 

Should more hysterectomies be done so women don’t have to use a progestin? Most medical experts would likely argue against this, as every surgery has risks. And studies show that hysterectomy increases the risk of urinary incontinence,6 which rates pretty low on anyone’s quality-of-life meter. But how do we balance surgical risks and quality of life against risk for breast cancer? Especially when we don’t know for sure whether the same risks and benefits exist for the types of hormones that are prescribed now?

Should we rethink surgical counseling for people who are at very high risk for breast cancer, like those with the BRCA gene mutations? These women have a 70% risk of breast cancer compared to the 12% risk for all women. They’re also at higher risk for ovarian cancer and are typically counseled about risk-reducing surgeries to remove their breasts and ovaries. The latter throws them into surgical menopause. If these women choose not to remove their breasts, should gynecologists counsel them to remove their uterus along with their ovaries so they can take estrogen-only HT? And might that protect against breast cancer in these high risk women? And, how do you balance the surgical and quality of life risks associated with hysterectomy for these high risk women?  

These are all unanswered questions, but interesting things to consider as more long term follow-up is published from WHI. But, one thing has become clear: HT with estrogen alone is much safer than we had thought when it comes to breast cancer risk. And this should provide reassurance to women who have relied on this form of HT to alleviate their menopause symptoms.

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Bibliography:

1. Design of the Women’s Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group.

2. Manson, J. E. et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 310, 1353–1368 (2013).

3. Ragaz, J. et al. Abstract P6-13-04: Estrogen-alone based hormone replacement therapy (HRT) reduces breast cancer (BrCa) incidence and mortality whereas estrogen plus progestin Provera based HRT increases both BrCa incidence and BrCa mortality: A comparative analysis of Women’s Health Initiative trials. Poster Session Abstracts (2019) doi: 10.1158/1538-7445.sabcs18-p6-13-04.

4. Scarabin, P.-Y. Progestogens and venous thromboembolism in menopausal women: an updated oral versus transdermal estrogen meta-analysis. Climacteric 21, 341–345 (2018).

5. Asi, N. et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst. Rev. 5, 121 (2016).

6. Kudish, B. I. et al. Hysterectomy and urinary incontinence in postmenopausal women. Int. Urogynecol. J. 25, 1523–1531 (2014).

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