The Basics: A Primer on Hormonal Therapies in Metastatic Breast Cancer

Insight Articles
December 16, 2015
Anna Shaffer, Contributing Writer

After Michele Briggs, 49, of Frederic, Wisconsin, was diagnosed with metastaticinfo-icon breast cancer in January 2015, her doctor recommended hormonal therapyinfo-icon.

“He said I needed to get my body to stop producing estrogeninfo-icon, because the estrogen was feeding the cancer,” she says.

Hormonal therapy is a whole-body (systemicinfo-icon) treatment that is used for cancers that depend on estrogen — a hormoneinfo-icon that occurs naturally in the body — to grow. These types of cancers are hormone-sensitive.

Guidelines recommend hormonal therapy as the first treatment, when possible, for metastatic, hormonesensitive disease.

What Is Hormonal Therapy?

Hormone-sensitive breast cancer cells have proteins called receptors that receive messages from hormones and tell cancer cells to grow. These cancers are called hormone receptorinfo-icon-positive. If estrogen receptors are present, the cancer is called estrogen receptor-positiveinfo-icon. If progesteroneinfo-icon receptors are present, the cancer is progesterone receptor-positiveinfo-icon. Breast cancers may be estrogen- or progesterone-positive, or both.

Hormonal therapies slow or stop hormone receptor-positive breast cancer growth by blocking estrogen’s effects or reducing the body’s estrogen levels. In metastatic breast cancer, the goal of hormonal therapy is to shrink or control the cancer while maintaining your quality of lifeinfo-icon.

“Metastatic breast cancer is increasingly seen as a disease that needs long-term management,” says Generosa Grana, MD, director of the MD Anderson Cancer Center at Cooper in Camden, New Jersey. “The goal is to find the best therapies with the most tolerable side effects to achieve control of the disease and optimize quality of life.”

Hormonal therapy is not the same as hormone replacement therapyinfo-icon (HRT), used to relieve symptoms of menopauseinfo-icon. HRT should not be used in women affected by breast cancer.

Who Gets Hormonal Therapy?

Hormonal therapy will probably be the first treatment your doctor recommends if you have cancer in the bone or lymphinfo-icon nodes or a small amount of disease in the lungs or liver, Dr. Grana says. If you have a lot of disease in your lungs or liver, you will probably get chemotherapyinfo-icon first because hormonal therapies can take longer to have an effect. You may get hormonal therapy at a later time.

Some hormonal therapy is recommended for all women, and some is specific to whether you’ve started menopause.

How Hormonal Therapy Works

Hormonal therapy works by blocking the production of estrogen or by stopping estrogen from interacting with its receptorinfo-icon. Some hormonal therapies are given as a pill, while others are given by injectioninfo-icon or as liquid.

Your doctor will monitor treatment through tests such as physical exams, blood tests or imaginginfo-icon scans. If one treatment stops working or causes too many side effects, your doctor may switch you to another.

Your doctor may also talk to you about joining a study of a new treatment, called a clinical trial. “Participating in a clinical trialinfo-icon may give a patient access to new and exciting medicines while also benefitting other women,” Dr. Grana says.

Your Hormonal Therapy Options

Which hormonal therapy your doctor recommends depends on several factors, including what medicines you’ve taken, possible side effects, menopausal status and health history.


SERMs, or selective estrogen receptorinfo-icon modulators, block estrogen from reaching estrogen receptors. SERMs such as tamoxifeninfo-icon and toremifene (Fareston) may be used until the cancer grows or spreads. Tamoxifen is not recommended in those who have had blood clots.

Gail Conyers, 55, of Elkhorn, Nebraska, was excited when she heard tamoxifen was given as a daily pill. “It allowed me to take vacations,” Gail says. She has mild side effects and is grateful she can “continue to live my life as if I didn’t have breast cancer.”

Ovarian Suppressioninfo-icon

If you are premenopausalinfo-icon, estrogen’s effects may be removed by temporarily shutting down the ovaries with an LHRH (luteinizing hormone-releasing hormone) agonist such as goserelininfo-icon (Zoladex), leuprolide (Leupron) or triptorelin (Trelstar). These medicines are usually paired with other forms of hormonal therapy. Another option is permanent ovarian suppression through surgeryinfo-icon called oophorectomyinfo-icon.

Aromatase Inhibitors

If you are postmenopausalinfo-icon, your doctor may recommend medicines called aromatase inhibitors or AIs as your first hormonal therapy, either alone or combined with other treatment. AIs such as anastrozoleinfo-icon (Arimidex), letrozoleinfo-icon (Femarainfo-icon) and exemestaneinfo-icon (Aromasininfo-icon) are given as a daily pill to stop an enzyme, aromatase, that makes small amounts of estrogen.

AIs may also be used with ovarian suppression in premenopausal or perimenopausalinfo-icon women. After Sara Mihaly, 36, of San Diego, was diagnosed with bone metastasisinfo-icon in November 2014, 11 months after her initial breast cancer diagnosisinfo-icon, her doctor took her off tamoxifen and started treatment with leuprolide and letrozole.

In July 2015 Sara decided to have an oophorectomy.“It ended my fertilityinfo-icon permanently, but I already had three children,” she says. If you are premenopausal and concerned about fertility, talk with your doctor.


ERAs, or estrogen receptor antagonists, may be used if the cancer stops responding to other hormonal therapies. Fulvestrant (Faslodexinfo-icon) stops the action of estrogen on cancer cells and is given as an injection.

Megestrolinfo-icon Acetate

Progestininfo-icon hormonal therapy such as megestrol acetate (Megace), a syntheticinfo-icon form of the hormone progesterone, can be used in metastatic disease, although its use has declined.

New Advances

Two targeted therapies, both pills, have been shown to increase the benefit of hormonal therapy. They have been FDAinfo-icon approved to treat hormone receptor-positive, HER2-negative metastatic breast cancer.

Everolimus (Afinitor) is an mTORinfo-icon inhibitor that stops cancer cells from dividing. It is approved for use with exemestane in postmenopausal women with cancer that grows after treatment with letrozole or anastrozole. Studies have shown this combination can slow cancer growth better than exemestane alone.

Palbociclib (Ibrance), a CDK 4/6 inhibitor, targets enzymes that help cancer cells to grow and divide. It is approved for use with letrozole as a first treatment for postmenopausal women. Studies have shown that palbociclib improves the time from the start of treatment until the cancer grows or spreads. Palbociclib has also been shown to be effective when given with fulvestrantinfo-icon.

Other advances allow hormonal therapy to be combined with trastuzumabinfo-icon (Herceptininfo-icon) and other HER2-positive targeted therapies.

Treatment Challenges

Every person reacts differently to hormonal therapy. You may have difficult side effects, or you may have minor or no problems.

“When I was first put on hormonal therapy, I sat on the phone with the pharmacistinfo-icon and he told me every side effect. I was terrified,” Michele says. “I thought, ‘Do I really want to do this?’”

Bone thinning or pain, hot flashes, night sweats, insomniainfo-icon and fatigueinfo-icon, and changes in sexual desire or comfort can happen. Aromatase inhibitors may also cause achiness. Targeted therapies sometimes paired with hormonal therapies may cause other side effects such as risk of infectioninfo-icon and mouth sores.

You may also feel more anxious or irritable. “I had some emotional issues tied in with treatment-induced menopause. For no reason, I would start thinking about something or hear a song on the radio and start to cry,” Michele says.

Lifestyle and diet changes along with prescriptioninfo-icon and over-the-counterinfo-icon medicines can help ease side effects, Dr. Grana says.

Gail does deep water aerobics twice a week to help manage muscle pain and stiffness. Michele rests when her body tells her to. She takes denosumabinfo-icon (Xgevainfo-icon) with calcium supplements to help keep her bones strong. Duloxetineinfo-icon (Cymbalta), an antidepressantinfo-icon, helps control achiness and moodiness.

To help manage hot flashes, Gail wears sleeveless tops and avoids tight-fitting clothes. Sara takes an herbal medicineinfo-icon recommended by her naturopathic doctor. “It cut my hot flashes in half,” she says. “But I don’t take anything unless I approve it through my oncologistinfo-icon.”

Sara also goes to the gym, lifts weights, and does Zumba four days a week. “Sweating, dancing and having fun makes me feel better. For me, it’s just as critical as my medication,” she says.

“The nice thing about hormonal therapy is we have a variety of choices,” Dr. Grana says. “The key is communicating with your physicianinfo-icon if you have side effects, because there are likely things that can be done to make them more tolerable.”

Paying for Treatment

If you are having difficulty paying for treatment, look for patient assistance programs. Doctors often have social workers on staff who can direct you to resources, so be sure to let your doctor know you are having problems rather than not taking your medicine.

“Sometimes your doctor’s office has to do a bit of work for you,” Sara says. “You have to be your own advocate.”

Getting Answers

If you have questions about hormonal therapy, don’t be afraid to ask your oncologist or oncology nurseinfo-icon. Websites such as LBBC.ORG are also a good source of information, Dr. Grana says.

Getting a second opinion helped Michele feel good about moving forward with her treatment plan. She also recommends keeping a notepad with a list of questions f or your doctor.

“The only stupid question is the one that isn’t asked,” she says. “Writing everything down helps make sure you get the most out of every visit.”

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