Estrogen and Breast Cancer: Yes – NO! – Maybe?

There are few controversies in medicine that have been as long-lasting and confusing as hormone replacement therapy (HRT). The Food and Drug Administration approved Premarin (conjugated estrogens) early in the 1940s. The name, Pre-Mar-In, is purported to derive from the use of pregnant mare’s urine in the preparation of this drug. During the 1990s, Premarin was the #1 most prescribed drug in the US. Most women who complained of hot flashes and other menopausal symptoms received a prescription for Premarin. Questions about a connection between estrogen and breast cancer have lingered for decades. New research seemingly puts that worry to rest (Lancet Oncology, July, 2025).

Why Has the Estrogen and Breast Cancer Controversy Lasted for Decades?

Part of the problem with HRT (hormone replacement therapy) is that the idea of “hormone replacement” is almost by definition confusing. Some people maintain that doctors should not meddle with mother nature. If we were intended to maintain peak hormone levels throughout life, we would do so. Most primates develop reduced levels of both estrogen and testosterone as they age.

Others insist that restoring hormones to peak levels is beneficial. They believe that sex hormones will improve overall health and increase life span. Women are told that boosting estrogen will help build stronger bones and slow cognitive decline. Men are encouraged to take testosterone to restore libido and keep muscles strong.

Estrogen and Endometrial Cancer?

One of the early problems with taking “pure” estrogen is an increased risk of endometrial cancer. That’s because “unopposed” estrogen hormone therapy can cause “proliferation” of the cells lining the uterus (endometrial cells). That can, in turn, lead to an increased risk for endometrial cancer.

Cases of endometrial cancer started rising in the US in the 1960s and 1970s. The National Cancer Institute updated this overview on April, 10, 2025:

“Hormone therapy (HT) with estrogen: Unopposed estrogen

“Based on solid evidence, unopposed estrogen is associated with an increased risk of endometrial cancer. This excess risk can be eliminated by adding continuous progestin to estrogen therapy, but this combination is associated with an increased risk of breast cancer.”

The Big Boomerang!

Please hit your internal pause button. The last sentence from the National Cancer Institute reveals the gigantic paradox facing women. Estrogen hormone replacement therapy by itself increases the risk for endometrial cancer of the uterus. That includes “natural” human-type estrogen.

We frequently hear from women who state that the estrogens in Premarin are not natural to women. They insist that as long as women use “bioidentical” estrogen from plant sources such as 17β-estradiol, they have nothing to worry about.

That may be true for estrogen and breast cancer (more about that shortly). But when it comes to endometrial cells lining the uterus, estrogen is estrogen. Whether it is synthetic, comes from pregnant mares or plants, unopposed estrogen in any form can stimulate the endometrium and increase the risk for endometrial cancer (StatPearls, April 30, 2024).

Estrogen and Breast Cancer…Don’t Worry!

The estrogen and breast cancer debate has raged for decades. In May 2012, an article in The Lancet Oncology suggested that estrogen by itself (without progestin or medroxyprogesterone) does not increase the risk for breast cancer and might even lower it.

The conclusions of this research:

“In conclusion, in this trial oestrogen-alone use for 5·9 years was associated with decreased invasive breast cancer incidence and breast cancer mortality over a median 11·8 years of follow-up in postmenopausal women with prior hysterectomy.”

The key author (Garnet Anderson) was quoted as saying:

“Women who have had a hysterectomy may be reassured that taking estrogen by itself, short term, to relieve menopausal symptoms will not increase their risk of breast cancer.”

Estrogen and Breast Cancer…Do Worry!

Not long after the early publication of the Lancet Oncology paper, a contradictory study was presented to the American Association for Cancer Research (AACR) on April 1, 2012. The research involved roughly 60,000 nurses who participated in The Nurses Health Study. Data were analyzed from 1980 through 2008. Women who took both estrogen and progesterone (Prempro for example) had an 88 percent higher risk of breast cancer after 10 years on the treatment.

Those who took estrogen alone for at least a decade had a 22 percent increased risk of developing breast cancer. Those women who were exposed to just estrogen for more than 15 years had a 43 percent greater chance of being diagnosed with breast cancer.

The lead author, Dr. Wendy Chen, was quoted as saying:

“There’s a continued increase in risk with longer durations of use and there does not appear to be a plateau.”

For reasons unknown, the research never appears to have been published. At least we could not find it. There is, however, a link to the abstract that was presented at the AACR Annual Meeting.

With such conflicting research and dueling headlines (one month women read that “Estrogen Pills Reduce Breast Cancer Risk” and the next they saw that “Long-Term Estrogen Therapy Does Up Breast Cancer Risk”), it is hardly any wonder women were totally confused.

What Women Say About Estrogen and Breast Cancer:

Some women, like this one, strongly favor the drug:

“I had a complete hysterectomy in 1974 due to endometriosis, a very painful disease involving my uterus and ovaries. I took Premarin but did not take progestin since I had no uterus. I have heard that progestin is what may increase the risk of cancer for women taking estrogen.

“Nothing terrible has happened to me all these years on Premarin. At 79, I’m healthy and play tennis and golf regularly.”

Another woman had a serious side effect, but still opts for Premarin:

“After I had a hysterectomy, I was put on a high dose of Premarin for menopausal symptoms. I stayed on it for 30 years. Two years ago, I was diagnosed with early breast cancer. I had a lumpectomy and 7 weeks of radiation. The cancer has not returned.

“Would I do it again? You bet! Surgery and radiation are a small price to pay for 30 years of health and happiness.”

Here is a more recent message about estrogen and breast cancer:

Q. People worry about the problems of hormone replacement therapy (HRT). I know one case doesn’t prove anything, but I took Premarin for 26 years with no negative effects.

The doctor prescribed Premarin after a hysterectomy not to deal with hot flashes or night sweats, since I had none. Instead, it was meant to avoid osteoporosis. My doctors say that it worked. Some have said that with the fears about giving hormones these days, there has been an increase in osteoporosis.

I have seen no negative effects whatsoever from being on Premarin all that time. I have not developed breast cancer, even though having a sister with breast cancer put me at higher-than-average risk. I feel I was fortunate to have had my surgery and to have been on Premarin before they decided long-term HRT was too risky.

A. We appreciate you sharing your story. A recent study supports your experience. The investigators reviewed records from more than 450,000 women under 55 years of age. Those receiving estrogen alone after a hysterectomy were less likely to develop breast cancer (Lancet Oncology, July 2025). On the other hand, women who took both estrogen and progestin had a higher risk of young-onset breast cancer.

Another study (JAMA Network Open, June 23, 2025) also found that estrogen plus progestin was associated with an increase in breast cancer.

Making Sense Out of Confusion When It Comes to Estrogen and Breast Cancer:

First, we must separate estrogen by itself from estrogen plus progesterone. That critical issue often gets overlooked.

1. By itself, estrogen, in any form, increases the risk for endometrial cancer. This is called “unopposed” estrogen therapy. But estrogen, by itself, does not appear to increase the risk for breast cancer. And if you believe the article described above in Lancet Oncology, it may actually lower the risk for breast cancer.
2. To prevent endometrial cancer, doctors add progesterone. This second hormone reduces the risk of endometrial cancer. But, when you add progesterone to estrogen, there appears to be an increased risk of breast cancer (JAMA Network Open, June 23, 2025). This was also the conclusion of the Women’s Health Initiative, especially if women experienced breast tenderness (Breast Cancer Research and Treatment, Feb. 2012).

If you were reading carefully, you will have noticed that the three stories above from women who received estrogen alone all had hysterectomies. They did not risk endometrial cancer by taking “unopposed” estrogen. There were no endometrial cells to worry about.

What About Women Who’ve Not Had a Hysterectomy?

For women with an intact uterus, however, we cannot say that estrogen in any form would be safe without progesterone. And if progesterone is added to estrogen, we worry about the risk of breast cancer.

We know that many women believe that if they take bioidentical estrogen and progesterone, there is nothing to worry about. But large, long-term clinical trials of this combination have, to our knowledge, not been conducted. No drug company would undertake such research. There’s no payoff. We fear that the NIH will not support such research either. Until such studies are carried out, we will worry about the risk of breast cancer in women taking both estrogen and progesterone, even if they are “natural.”

Learn More:

For more information about treating menopausal symptoms and hot flashes without estrogen or progesterone, or a combination of the two, we suggest our Guide to Menopause or The People’s Pharmacy Quick & Hand Home Remedies from National Geographic. You can find both in our People’s Pharmacy Store under Guides or Books.

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