What to Know About Hormone Replacement Therapy (HRT) and Cancer Risk

If you’re approaching or experiencing menopause, you may have been following the news about the removal of the black box warning from some hormone replacement therapy (HRT) products. The U.S. Food and Drug Administration (FDA) reserves its black box warning for the most serious and immediate safety issues posed by a medication.

So, what does this change to the HRT black box warning mean for you? First, removing the black box warning does not mean previous research is wrong or that HRT, also known as menopausal hormone therapy, is now safe for everyone. Although certain types of HRT products no longer carry a black box warning, they can still pose safety concerns. Details of these concerns appear in the patient information handouts you get from the pharmacy when you fill a prescription.

Why did the FDA decide to remove the HRT black box warning?

The FDA originally put the black box warning in place based on studies from more than 20 years ago that suggested HRT increased the risk for breast cancer and heart disease. Those studies included older women and used forms of hormones that are not as commonly used today. More recent findings from HRT research, as well as availability of newer types of HRT, have led experts and the FDA to update their conclusions and warnings.

Experts now agree that the benefits and risks related to taking HRT depend on each person’s health history. For some people with menopausal symptoms, the benefits of HRT can outweigh the risks.

“In medicine, it’s never one-size-fits-all. Risks and benefits will be different for different people. Just as with other medical recommendations, the standard guideline applies to the average-risk population,” said Julie Gralow, MD, Chief Medical Officer at the American Society of Clinical Oncology (ASCO) and a breast cancer specialist.

Is HRT safe?

HRT can be safe for many people. “If you’re under the age of 60, or it’s been no more than 10 years since menopause began, the risks of taking HRT are much lower than if you start taking it later,” said Dr. Gralow.

When considering risks and benefits, the type of hormones in HRT matter, too. HRT can include one or a combination of two hormones called estrogen and progesterone.

While one serious warning is being removed, a black box warning is still in place for estrogen-only HRT products. They can increase the likelihood of cancer of the lining of the uterus (endometrial cancer). Regardless of cancer status, people who have a uterus should not take an estrogen-only form of HRT. Instead, combination HRT that includes both estrogen and progesterone may be an option because progesterone has a protective effect on the uterus.

Considerations before you start HRT

The decision to use HRT depends mainly on your personal health history and current health status. For example, people who do not have a history of cancer or heart disease may have a low risk of complications from HRT. However, HRT may not be recommended for people with a history of cancer, heart disease, or bone problems. These people may need to take certain types of HRT due to a higher risk of side effects. And HRT recommendations may differ for people with a uterus and for those who have had their uterus removed (hysterectomy).

As you weigh the benefits and risks, consider these factors:

• Which menopause-related symptoms you have
• The severity of your symptoms
• Your heart and bone health
• Your insurance coverage and any possible out-of-pocket costs
• Your cancer history, in particular if you’ve had breast cancer that is hormone receptor-positive (HR+) or are being treated for it, as that may carry particular risks

Why is HRT risky for people with HR+ breast cancer?

Taking HRT when you have HR+ breast cancer is not recommended. Why? Because HRT adds hormones to the body. The hormones in HRT can stop cancer treatments from working the way they should.

In HR+ breast cancer, the cancer cells have proteins on them called hormone receptors. These can be estrogen receptors, progesterone receptors, or both. Cancer cells depend on the hormones to grow. Treatment given to people with HR+ breast cancer often includes different types of treatment, including medicines that block these hormone receptors. This type of cancer treatment is called hormone therapy and is very different from hormone replacement therapy. 

HRT can also be a concern after treatment. If you’ve been treated for HR+ breast cancer, “There is always some small risk that a few cancer cells could have been left behind after treatment. If those cells express a hormone receptor, the hormones in HRT could make them grow,” said Dr. Gralow.

However, having a history of HR+ breast cancer does not mean taking HRT is entirely off the table. Your doctor will look at the type, stage, and grade of your cancer to determine your risk. They will also factor in how long it’s been since you were diagnosed, as well as which cancer and hormonal treatments you’re taking now or have received in the past. In addition, they’ll ask about your menopause symptoms and how disruptive they are to your life. They will also look at the other risks related to HRT, such as heart and bone health, to determine if HRT may be an option for you.

For people with other types of breast cancer, such as hormone receptor-negative (HR-) breast cancer, researchers know less about the risks of HRT. Other cancer types can have hormone receptors as well, including some types of endometrial, ovarian, or cervical cancer. Experts don’t yet know if HRT makes those cancers grow. It’s also not clear if HRT increases your risk of cancer if someone in your family had an HR+ cancer, even if you haven’t had it yourself. You can discuss these concerns with your doctor when considering HRT.

Talk with your doctor

If you’re in perimenopause or have reached menopause and are interested in HRT, be sure to discuss it with your doctor. This is especially important if you’ve had cancer or are in treatment for cancer.

Talk to your doctor about your health history, including:

• If you or any family members have had cancer in the past, what type of cancer it was, and if it was HR+
• Your personal risk of cancer or cancer recurrence
• If you’ve had your uterus removed
• Your personal risk of other health issues, such as weakened bones, stroke, or blood clots, that might happen with various HRT options

Also discuss your experience with menopause, including:

• When you had your last period
• Which symptoms you have, how long you’ve had them, and how severe they are
• Any treatments or therapies you may have tried for your symptoms 

By working closely with your health care team, you can find the right path forward. The goal is to make sure you have the tools, treatment, and support you need to feel as healthy and comfortable as possible.

Dr. Gralow is the Chief Medical Officer at ASCO.