Hormone Therapy for Breast Cancer

In In The News by Barbara Jacoby

By: Elaine K. Howley

From: usnews.com

This article is based on reporting that features expert sources including Margaret Chen, MD, FACS; Hannah M. Linden, MD

There are a variety of ways cancer cells can grow, and for some kinds of breast cancer, hormones feed these wayward cells. Combating the effects of hormones on cancer cells can help slow or stop the disease’s progression.

All cells have receptors, or proteins, on their surface. These are areas where certain chemicals can bind with the cell to affect how that cell grows or functions. In some women, breast cancer cells have receptors that attach to estrogen and progesterone, two hormones that all women have in their bodies in abundance. Once attached, those hormones can fuel cancer cells to grow.

Hormones Connected With Breast Cancer

The vast majority of breast cancers are fed by hormones. The two main hormones that can play a role in breast cancer are:

  • Estrogen.
  • Progesterone.


Estrogen is the primary female sex hormone that controls the female reproductive system. It’s responsible for the development of the breasts and is critical to the development and regulation of the menstrual cycle. Not just a sex hormone, estrogen is also important in bone health, keeps cholesterol in check and plays a variety of roles in other tissues, including the brain and skin.

Estrogen is produced primarily in the ovaries. The adrenal glands and fat tissue also contribute some estrogen. While estrogen is often thought of as a female sex organ, men have some too, though at lower levels.

A woman’s estrogen levels fluctuate throughout the month as she progresses through her menstrual cycle. Once a woman reaches menopause, her estrogen levels decline because the ovaries are no longer producing as much estrogen.


Progesterone is another hormone that’s involved with the female reproductive system. It’s produced by “a temporary endocrine gland that the female body produces after ovulation during the second half of the menstrual cycle,” the Hormone Health Network reports. Progesterone causes the lining of the uterus to become thicker in the event an egg is fertilized and needs a place to attach to begin growing into a fetus. This is why it’s sometimes referred to as the pregnancy hormone.

Progesterone levels also rise and fall across the monthly menstrual cycle. Men also have progesterone, which is produced in the adrenal glands and testes and is a building block of testosterone.

Disrupting Hormones to Treat Breast Cancer

Of the several different types of breast cancer that can occur, hormonally-driven cancers are the most common. Breastcancer.org reports that “most breast cancers are hormone-receptor-positive,” meaning the cancer cells have hormone receptors on them. All told, about 80% of breast cancers are sensitive to estrogen. Of those, about 65% are also progesterone-receptor-positive, as the cells can be positive for more than one type of receptor.

“Breast cancers are different between every person,” says Dr. Margaret Chen, chief of breast surgery with ProHEALTH Care in New York. “The vast majority of breast cancers are hormone-receptor-positive, which means they grow by the effects of hormones on the breast tumor cells.” Although these cancers tend to be more prevalent, the good news is that there are several ways that these cancers can be treated. “Nowadays, we have a lot of therapies that are very effective” in treating hormone-receptor-positive breast cancers, Chen says.

Dr. Hannah M. Linden, a breast cancer specialist at the Fred Hutchinson Cancer Research Center who also treats patients at the Seattle Cancer Care Alliance, says this is why “the standard of care is to determine whether or not there’s any hormone receptors” on the cells before treatment of the cancer commences. The optimal treatment will be decided based on the types of receptors discovered. “People who don’t have hormone receptors on their tumors don’t benefit from medicines that target those receptors,” Linden explains.

Colloquially, these treatments are often referred to as hormone therapies, but Linden says they’re more accurately described as endocrine therapies. “When we say ‘hormone therapies,’ that implies that you’re adding hormones,” she says, which is the opposite of what these treatments do. Instead, treatments that target hormone receptors on breast cancer cells are designed to block the effects of these hormones on the cancer cells.

Other medications and interventions, such as removing the ovaries, seek to lower the levels of estrogen and/or progesterone in the body. Taken together, these hormone-blocking and hormone-lowering treatments are also sometimes called anti-estrogen therapies and may be used alone or in combination with each other depending on the specific case.

Anti-Estrogen Therapies

Common anti-estrogen therapies fall into three main categories:

  • Selective estrogen receptor modulators, or SERMs.
  • Aromatase inhibitors.
  • Estrogen receptor downregulators.

Selective Estrogen Receptor Modulators

SERMs are among the most widely used medications to treat breast cancer. They work by blocking estrogen from attaching to receptors on the cells. These medications are often used in an adjuvant setting, meaning that they’ll be prescribed after surgery or chemotherapy to prevent the cancer from recurring. These medications may also sometimes be used prior to surgery to help shrink a tumor before it’s removed.

SERMs “block the effects of estrogen on the cancer cells by binding to the estrogen receptors” on the cell, Chen says. SERMs have been around since the 1970s and include three medications:

  • Tamoxifen. Tamoxifen is usually administered as a pill and used to prevent a cancer from coming back. It can be used in both pre- and postmenopausal women and is often prescribed as a daily treatment for very long periods of time – typically five to 10 years. Chen describes tamoxifen as “our workhorse” because it’s so widely used for treatment of breast cancer.
  • Raloxifene (Evista). Raloxifene is a newer SERM that’s used to reduce the risk of recurrence of invasive breast cancer in postmenopausal women.
  • Toremifene (Fareston). Toremifene is also usually administered as a daily pill and is used for metastatic cancer in postmenopausal women.

Though SERMs are very effective and have been shown to improve survival, they can have some serious side effects, including:

  • Menopausal symptoms, such as mood swings, hot flashes and night sweats.
  • Fatigue.
  • Abnormal vaginal bleeding or discharge.
  • Edema in the legs.
  • Chest pain and shortness of breath.
  • Blood clots.
  • Endometrial cancer.

Aromatase Inhibitors

Aromatase inhibitors are another type of anti-estrogen therapy. They work by actually lowering the level of estrogen in your body. “Aromatase inhibitors interfere with an enzyme that helps you make estrogen,” Linden says, which reduces the levels of estrogen available in the body to feed tumor growth. These medications are delivered as a daily pill and, like SERMs, may be administered over a very long period of time, up to 10 years.

Studies have shown that aromatase inhibitors, which are a newer type of endocrine therapy, are the best option for postmenopausal women with hormone-receptor-positive breast cancer. “For postmenopausal women, we would treat with an AI unless they have a contraindication, such as severe osteoporosis,” Chen says. “We find that it actually works better and has fewer side effects” than tamoxifen, particularly the menopausal symptoms. That said, it can cause joint pain and osteoporosis, or a loss of bone density, so your doctor will want to monitor your bones carefully while you’re on any of these medications.

However, aromatase inhibitors “cannot be used unless your body is in natural menopause or in menopause induced by medications or removal of the ovaries,” the Mayo Clinic reports. For women who are “premenopausal and have a high-risk tumor, you can opt for ovarian suppression drugs and use an aromatase inhibitor,” Linden says. Ovarian suppression drugs prevent the ovaries from functioning as they normally would to reduce the amount of hormones they manufacture.

Currently, there are three aromatase inhibitor drugs available:

  • Anastrozole (Arimidex).
  • Exemestane (Aromasin).
  • Letrozole (Femara).

These medications all work the same way to reduce the production of estrogen in the body, but they have slightly different effects. Your doctor may prefer one over another, or you may start with one but move to a different one if side effects become problematic.

Estrogen Receptor Downregulators

Like selective estrogen receptor modulators, this medication blocks hormones from attaching to the cancer cells, which may slow their growth and even kill them. Fulvestrant (Faslodex) is the only estrogen receptor downregulator currently on the market. The medication is usually administered as a monthly shot and is used to treat postmenopausal women with advanced-stage breast cancer. Side effects may include vomiting, nausea, dizziness, muscle and joint pain and other more serious problems such as numbness or tingling in the extremities, vaginal bleeding, mood changes and chest pain.

Targeted Therapies

Another type of treatment focuses in even more precisely on certain parts of cells to stop their growth. “There’s lots of exciting things happening right now in terms of targeted therapies” for hormone-receptor-positive breast cancer treatment, Chen says.

One type are CDK4/6 inhibitors. These inhibitors block cyclin-dependent kinases, which are cellular proteins that cause the cells to divide. A cell that can’t divide can’t grow or reproduce – thus blocking these proteins can slow the progression of tumors. They can have some side effects, including nausea, mouth sores, hair loss, headaches and cause low blood cell counts. Lung inflammation is a rare but serious side effect.

These medications are usually delivered as a once or twice daily pill and are sometimes used alongside other therapies to augment their anti-estrogen effects. Targeted therapies are used to slow the progression of disease in women who have metastatic cancer or disease that’s stopped responding to other types of treatment.

CDK4/6 inhibitors include:

  • Abemaciclib (Verzenio).
  • Palbociclib (Ibrance).
  • Ribociclib (Kisqali).

Another targeted therapy called everolimus (Afinitor) is a daily pill that can be used to treat advanced hormone-receptor-positive breast cancer in some postmenopausal women. It’s often used with the aromatase inhibitor exemestane. This medication blocks mTOR, a cellular protein that facilitates cell growth and division and can stop tumors from forming new blood vessels.

Infections, diarrhea, nausea, shortness of breath and cough can be side effects. Your doctor will also likely check your blood work regularly to make sure your cholesterol and triglyceride levels and blood sugars aren’t adversely affected.

Therapies That Suppress Ovarian Function

LHRH agents are a type of hormonal therapy that suppresses ovarian function. Essentially, these medications induce chemical menopause in premenopausal women, thus lowering estrogen levels in the body. These are given as a once monthly injection. Once the injections stop, the ovaries typically recover their function. LHRH medications are used to treat hormone-receptor-positive breast cancers in premenopausal women, and are also sometimes used to help preserve fertility in women going through breast cancer treatment. LHRH medications include:

  • Goserelin (Zoladex).
  • Leuprolide (Lupron).
  • Triptorelin (Trelstar).

Chen says LHRH agents aren’t appropriate for everyone, but may be useful for “people at high risk of recurrence” or those “whose disease is very aggressive.” LHRH medications may be given in conjunction with tamoxifen or an AI to help them be more effective. LHRH agents cause menopause, so menopausal symptoms are common side effects.


For some women who have not yet been through menopause, surgery may be recommended. An oophorectomy – removal of the ovaries – or a hysterectomy – removal of the uterus – can reduce the body’s estrogen levels, effectively putting the individual into menopause. But being in “early menopause has problems too,” Chen says, so it’s a decision that should be carefully considered. Heart disease and bone loss are two of the top concerns associated with early menopause, and are related to the lack of estrogen, which helps keep the heart and bones healthier.

Long-Term Options

Linden says one of the main drawbacks of anti-estrogen therapies for breast cancer is the lengthy periods of time over which they tend to be prescribed. “Adherence and whether patients take them” is a big obstacle. “If you don’t take it, it doesn’t help you.”

The reason why these medications tend to be prescribed for such long periods is because studies have shown they keep recurrence at bay. “This has been studied a lot,” Linden says, and the evidence shows that overall, five years is better than three, but for some people, depending on the size and other characteristics of the tumor, “10 years is better than five.”

While the chances that most types of cancer are going to recur drops significantly after five years, statistically speaking, “the tragic news is that you’re almost never out of the woods,” Linden explains. There’s simply always a small chance that your cancer can recur, even as long as 25 years or more later. Depending on how likely your cancer is to recur, your doctor may determine that your risk is high and prescribe a medication like tamoxifen for many years to help reduce that risk. Balancing that risk with ongoing treatment is an individual calculation that you should discuss with your doctor.

For some women, taking a pill every day for the next 10 years is no problem, but for others it can be onerous. “Some people just don’t want to be a patient anymore,” Linden says, and the daily reminder of taking a pill can be problematic. For others, the side effects, such as joint pain, stiffness and menopausal symptoms, can be a lot to cope with and they stop taking the medications. “That’s the biggest reasons people stop taking them,” Linden says.

If you’re having issues with your medication, regardless of the reason, speak with your doctor about your options and alternatives. “Sometimes switching brands will get people over that. Or you may be able to work through the stiffness with exercise,” Linden says. Acupuncture has also been shown to be helpful in reducing side effects of these medications. There are other medications that may help address other side effects, so speak up.

“If you’re having symptoms, we’ll work with you on it,” Linden says. “Don’t give up the benefit just because you’re feeling crummy. None of us are going to push someone through feeling miserable to stay on a drug for five years. That’s not a good idea, but we have ways to make adjustments,” to make you much more comfortable.

Lastly, if you’ve recently been diagnosed with a hormone-receptor-positive breast cancer, Chen wants you to know that “they’re very treatable. We have a lot of options and the science is getting better. We’ll be able to tailor treatments better as time goes on,” but right now, there are quite a few tools in the oncologist’s toolbox that can improve your outcomes. “Survival is getting better. Women are living longer because of these treatments, and things are going to continue getting better as time goes by,” she says.