The Estrogen and Breast Cancer Connection

BCRF explores the research discoveries that uncovered this link and provided treatment strategies

Estrogen is a hormone your body makes to regulate sexual and reproductive function. It is a crucial female hormone, contributing to breast development, regulation of the menstrual cycle, and preparing the body for pregnancy and giving birth. It also helps keep your bones strong, your heart healthy, and your moods stable.

Since estrogen plays such an important role in women and there’s a 1 in 8 chance that a woman in the United States will develop breast cancer, investigators have asked, does estrogen increase the risk of breast cancer? For patients and their healthcare teams, this is an important question. Through research, we now know more than ever before about the link between estrogen and breast cancer. However, scientists continue to investigate strategies to better understand the role this hormone plays in the development and treatment of estrogen-fueled breast cancer.

The connection between estrogen and breast cancer

Both men and women have estrogen, but women have much more of it. And how much estrogen they are exposed to over the course of their lifetime can affect their risk of developing breast or other cancers.

The story of estrogen and breast cancer begins in the cells of the breast. Healthy breast cells contain proteins called hormone receptors. The binding of estrogen to its receptor helps direct normal cell functioning. Breast cancer cells can also contain estrogen receptors, and when estrogen attaches to these receptors, it can fuel the growth of cancer.

A British surgeon named George Beatson first noticed the link between hormones and breast cancer in the late 19th century, when he discovered that removing the ovaries of three young female patients with metastatic breast cancer led to their tumors shrinking. But it would take years of step-by-step exploration for the reason to become clear, and the ovarian hormone was definitively identified as estrogen in the 1920s. The next major discovery occurred in the late 1950s when the biochemist Elwood Jensen found that breast cells contained proteins that bind to estrogen. He called these proteins “estrogen receptors” and would go on to invent a test that detected estrogen receptors in breast cancer cells.

Over the next few decades, synthetic estrogen to treat menopausal symptoms would go on to become one of the most prescribed drugs for women in the United States. However, in 2002, the Women’s Health Initiative study — a large, long-term government-sponsored study that investigated the effects of menopausal hormone therapy, dietary modification, and calcium/vitamin D supplementation on health outcomes in postmenopausal women (largely in women over 60) — reported that combined estrogen-progestin therapy was associated with an increased risk of breast cancer, coronary heart disease, stroke, and blood clots. This complicated the use of menopausal hormone therapy, which subsequently fell dramatically. In 2004, results of clinical trials testing estrogen alone (for women who had a hysterectomy) showed no increase in breast cancer risk. And later analyses suggested a reduced risk of breast cancer with estrogen alone. The complexity of these findings nevertheless provided high-quality evidence for real, serious risks with some types of hormone therapy and reshaped the way these medications would be prescribed and discussed with patients.

Does estrogen increase breast cancer risk?

Estrogen does contribute to an increased risk of breast cancer in women. It is one of several factors that can elevate a person’s risk. Others include genetics, family history, and diet/lifestyle.

Early menstruation (before age 11) and late menopause (after age 55) are associated with an increased risk of breast cancer, as both of these events mean a longer exposure to estrogen over time. Postmenopausal women also seem to be at a higher risk of developing cancer, possibly due to the fact that after menopause the body stops producing estrogen cyclically and instead produces it consistently in smaller amounts, in fat cells, and partly due to the enzyme aromatase. The prolonged exposure to estrogen may lead to increased risk of breast cancer in postmenopausal women. However, it is important to note that premenopausal women are not without risk; the incidence of breast cancer in younger women is on the rise.

Some women may have lower lifetime estrogen exposure. For instance, pregnancy — which interrupts estrogen signaling and changes breast tissue — does lower lifetime exposure and has been shown as protective for postmenopausal breast cancer. While lower lifetime exposure can reduce the risk of estrogen-dependent breast cancer, this does not mean these women are broadly protected from breast cancer. Research on estrogen is primarily useful for treatment and prevention strategies, not risk prediction.

Hormone replacement therapy (HRT) and breast cancer risk

Menopausal hormone therapy or hormone replacement therapy (HRT) for treating menopausal symptoms has also been associated with an increased risk of breast cancer. HRT, which consists of either a combination of estrogen and progesterone or estrogen alone, is prescribed to replace the estrogen the ovaries produce less of as you enter menopause and is used to help reduce hot flashes, mood swings, and other menopausal symptoms. It’s also been shown to protect against osteoporosis, the loss of bone density that occurs with the menopausal decrease in estrogen.

After the WHI study caused alarm, many women stopped taking HRT and many doctors stopped prescribing it. But in the two decades since the release of those findings, WHI researchers and others have found that the overall risk of developing cancer with HRT is more complex: Women aged 50 to 59 have a lower risk than women 60 and older, and the risk of breast cancer increases the longer you are on combination HRT.

Adding to the complexity of HRT use is a person’s family history of breast cancer. Women over 50 without a history of breast cancer who are taking combination HRT for five or more years have a slightly increased risk of breast cancer. And in women with no history of breast cancer, estrogen-only HRT—which is prescribed mainly to women who have had hysterectomies—does not increase the risk and may even lower it. Research suggests that the progesterone in HRT, which is included to protect against endometrial cancer, may be the real contributor to the elevated risk, but the jury is still out.

The consensus now is that combination HRT can be appropriate for healthy women with bothersome menopausal symptoms, particularly if they start before age 60 or within ten years of menopause and it’s used at the lowest effective dose for the shortest time necessary. The guidance against HRT in women with a history of breast cancer due to a possible risk of recurrence is currently being reevaluated by researchers. In consideration of the accumulated data, the FDA removed black box warnings from combination HRT medications in November of 2025, citing the risk profile as more nuanced.  

Estrogen and estrogen pathways as treatment targets

Most cancers—around 75-80 percent—are ER-positive, meaning the breast cancer cells have estrogen receptors. Knowing the hormonal status of the cancer is key to choosing the right treatment.

ER-positive cancers are treated with hormone therapy (also known as endocrine therapy), which are medications that block or decrease the estrogen driving the cancer’s growth. They’re often used in conjunction with surgery. The medications can be given before surgery, but are usually prescribed after in order to help keep the cancer from returning. On average, a person will be on hormone therapy for about five years. Read more about hormone therapy here.

Because hormone therapies either block estrogen from binding to its receptor or reduce the amount of estrogen in the body, the side effects can be similar to those experienced before and during menopause and may include hot flashes, bone issues, or changes in sexual desire, memory, mood, energy levels, and quality of sleep. However, these side effects can be managed, and hormone therapy is a very effective treatment for ER-positive breast cancer. It’s well-established that it can significantly reduce the risk of these cancers developing or recurring as well as reduce the risk of dying.

Managing estrogen receptor (ER)-positive breast cancer

Sometimes ER-positive breast cancers stop responding to endocrine treatment. Scientists are trying to determine how genetic mutations, changes at the molecular level, or other factors may be contributing to this resistance. Understanding the root causes of resistance may open the door for other treatments if endocrine therapy fails. 

For example, BCRF researchers discovered that cell cycle proteins CDK4 and CDK6 play a role in the growth of some ER-positive cancers, causing these cancers to grow very quickly if they become overactive. CDK4/6 proteins are therefore a viable target if endocrine therapy stops working. Drugs called CDK4/6 inhibitors were developed as a result. In combination with hormone therapy, they are a mainstay of treatment for metastatic ER-positive breast cancer to prevent the proteins’ growth-promoting function and to stop or slow tumor growth. Now, researchers are working to identify genes that might be responsible for resistance to these drugs.

Research showed that the estrogen receptor may develop ESR1 mutations as treatment progresses, and this was associated with resistance to endocrine therapy. As a result, drugs were developed that are effective in breast cancers regardless of ESR1 mutations.  

Why your support matters in driving breast cancer research breakthroughs

The relationship between estrogen and breast cancer risk is an evolving story, and BCRF is committed to investing in research that will provide more answers and lay the groundwork for improvements in treatments. Since its inception, BCRF researchers have been at the forefront of developing and studying treatments for hormone-related breast cancer. Current research is taking a deeper dive into other contributing factors to the estrogen and breast cancer risk link, examining how estrogen from body fat may fuel breast cancer and trying to find alternatives to HRT for women who are postmenopausal or have a history of breast cancer.

And while the relationship between estrogen and breast cancer may still be under investigation, experts know that earlier diagnosis of breast cancer—whether it’s hormonally driven or not—results in better outcomes for patients, and that regular screenings can help increase the chances of survival.

Donate today and support groundbreaking research on estrogen and breast cancer.