Patient education: Treatment of early-stage, hormone-responsive breast cancer in premenopausal women (Beyond the Basics)

INTRODUCTION — Breast cancer is the most common female cancer in the United States. Finding and treating breast cancer in the early stages allows many women to be cured.

Typically, early-stage breast cancer is treated with both local therapy, which includes surgery and in some cases radiation therapy, and systemic (body-wide) therapy. Systemic therapy can be given either after surgery, which is called "adjuvant" therapy, or before surgery, which is called "preoperative" or "neoadjuvant" therapy.

●The goal of adjuvant systemic therapy is to eliminate or prevent the growth of any cancer cells that may have escaped the breast and that could spread to other organs (metastasize).

●One of the goals of neoadjuvant therapy is to make it more likely that surgery will be able to remove all the cancer, potentially with improved cosmetic outcomes. Giving treatment before surgery can also inform your doctor about whether or not more systemic treatment is needed after surgery, depending on how your cancer responded to treatment.

Regardless of whether it is given before or after surgery, systemic therapy is a very important component of breast cancer treatment, as it significantly decreases the chance that the cancer will return (recur), and it also improves a person's chance of survival.

There are three options for systemic adjuvant or neoadjuvant therapy of early breast cancer: endocrine therapy, chemotherapy, and anti-HER2-targeted therapy. The choice between these treatments depends upon specific characteristics of the cancer, ie, whether it is "hormone-responsive" and whether it makes a protein called human epidermal growth factor receptor 2 (HER2). This is discussed in more detail below.

This article will focus on systemic therapy for premenopausal women with hormone-responsive breast cancer (that is, women who have not yet gone through menopause). Adjuvant treatment for postmenopausal women with hormone-responsive breast cancer is discussed separately. (See "Patient education: Treatment of early-stage, hormone-responsive breast cancer in postmenopausal women (Beyond the Basics)".)

CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.

In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.

DEFINING HORMONE-RESPONSIVE BREAST CANCER — About 50 to 70 percent of breast cancers require the female hormone estrogen (estradiol) to grow, while other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce hormone receptors, which can be estrogen receptors (ER), progesterone receptors (PR), or both. These cancers are known as "hormone responsive."

You will usually find out if your cancer is hormone responsive when you are initially diagnosed. If your breast cancer is hormone responsive, you are more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen. These treatments are referred to as endocrine or hormone therapies.

ENDOCRINE THERAPY OPTIONS — The goal of adjuvant endocrine therapy is to prevent breast cancer cells from receiving stimulation from estrogen, and therefore stop their growth. This treatment is typically given for at least five years, and in some instances 10 years.

The options for endocrine therapy in premenopausal women include:

●The drug tamoxifen.

●A drug or surgery that prevents the ovaries from making estrogen. This is given in combination with either tamoxifen or another class of oral drugs called aromatase inhibitors (AIs). (See 'Ovarian suppression' below and 'Aromatase inhibitors' below.)

Tamoxifen — Tamoxifen (brand name: Soltamox) prevents estrogen from stimulating growth of the breast cancer cells.

Tamoxifen has been recommended for five years, and the benefits last for at least 10 years after the drug is stopped. However, more recent studies show that in some instances taking tamoxifen for more than five years does add further benefit, although the risk of side effects such as uterine cancer increases with longer treatment. (See 'Side effects' below.)

Side effects — Tamoxifen may increase the risk of the following:

●Cancer of the uterus

●Blood clots within deep veins (deep vein thrombosis), usually in the legs, which can travel to the lungs (pulmonary embolism) (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)")

●Birth defects (if a person gets pregnant while taking the drug)

●Cataracts (a condition in which the lens of the eye becomes cloudy, causing vision problems)

Whether tamoxifen increases the risk of stroke, particularly in women under the age of 55, is controversial.

For most women, the benefits of tamoxifen in preventing a recurrence of breast cancer far outweigh the risks of uterine cancer, blood clots, or other long-term effects. However, the risks may be higher for women with risk factors for blood clots or stroke (eg, prior history of blood clots in the leg or lung).

Tamoxifen may cause other side effects, particularly hot flashes and vaginal discharge. Because it is not safe for use during pregnancy, if you are taking tamoxifen and could potentially get pregnant, you should use a nonhormonal form of birth control while you are taking the drug and for about three months after stopping. Your health care provider can talk to you about your birth control options. (See "Patient education: Birth control; which method is right for me? (Beyond the Basics)".)

Ovarian suppression — Ovarian suppression refers to any treatment that causes the ovaries to stop making estrogen. The ovaries can be suppressed in one of several ways:

●Surgical removal of the ovaries (called oophorectomy) or, less commonly, radiation treatment of the ovaries, both of which permanently stop the ovaries from making hormones.

●Drugs called gonadotropin-releasing hormone (GnRH) agonists stop the ovaries from making estrogen temporarily. The most commonly used drug in this class is goserelin (brand name: Zoladex), which is given as a monthly injection. The treatment is usually given for five years.

Ovarian suppression is not given on its own, but is given together with either tamoxifen or an AI. Ovarian suppression with tamoxifen or an AI is often recommended for women with a breast cancer that may place them at a higher than average risk of recurrence (including those who are 35 years or younger or who have received chemotherapy). Based on the characteristics of your tumor and your age, your health care provider may recommend this therapy. Of note, all forms of ovarian suppression cause a rapid onset of menopause symptoms (hot flashes, night sweats, mood swings, vaginal dryness, and weight gain), which can be quite bothersome. Treatment for many of these symptoms is available. (See "Patient education: Non-estrogen treatments for menopausal symptoms (Beyond the Basics)".)

Aromatase inhibitors — A class of drugs that is used for endocrine therapy in postmenopausal women (that is, those who have already been through menopause) is the AIs (including anastrozole, letrozole, or exemestane). In general, AIs are not given alone to premenopausal women.

However, they can be used in combination with ovarian suppression. Additionally, women who are premenopausal before treatment may become menopausal later; an AI may then be considered. You should discuss the indications, risks, and benefits of this option with your doctor.

Side effects — The most common side effects of AIs include:

●Joint pain

●Loss of bone density (osteoporosis)

●Vaginal dryness

ENDOCRINE THERAPY, CHEMOTHERAPY, OR BOTH? — Endocrine therapy is recommended for women with estrogen receptor (ER)-positive breast cancer. If the tumor is also human epidermal growth factor receptor 2 (HER2) positive, chemotherapy and HER2-directed therapy are also options. (See "Patient education: Treatment of early HER2-positive breast cancer (Beyond the Basics)".)

For women with ER-positive, HER2-negative breast cancer, chemotherapy may also be recommended. Based on available evidence, chemotherapy is typically recommended for women with node-positive, ER-positive, HER2-negative breast cancer.

Two tests are available that can help identify those women with ER-positive, HER2-neqative, node-negative early breast cancer who stand to benefit the most from chemotherapy. Your health care provider may order one of these tests to help determine whether you should get chemotherapy:

●The 21-gene recurrence score assay (also called Oncotype DX)

●The 70-gene signature (also called MammaPrint)

PEOPLE WITH A BRCA MUTATION — Mutations in two genes, known as breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2), are associated with an increased risk of hereditary breast (as well as ovarian) cancer. (See "Patient education: Genetic testing for hereditary breast, ovarian, prostate, and pancreatic cancer (Beyond the Basics)".)

People who have a BRCA mutation and have already received chemotherapy may benefit from a medication called a poly(ADP)-ribose polymerase (PARP) inhibitor. This is usually only suggested for people whose disease is considered high risk based on the characteristics of their disease.

FERTILITY PLANNING — If you are planning to get chemotherapy and/or endocrine therapy, and you think you might want to get pregnant in the future, your provider can talk to you about your options. For example, you may choose to freeze your eggs prior to therapy.

LIFESTYLE FACTORS — It is recommended that women with a history of early-stage breast cancer get plenty of physical activity (at least 150 minutes/week), eat a nutritious diet, maintain a healthy weight (body mass index 20 to 25), and limit alcohol consumption.

CLINICAL TRIALS — Progress in treating breast cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials or read about clinical trials at:

●www.cancer.gov/clinicaltrials/

●http://clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/pre-act).

FOLLOW-UP AFTER TREATMENT — A summary of the American Society of Clinical Oncology's recommendations for surveillance after breast cancer treatment is provided in the following table (table 1).

SUMMARY — There are many options for the adjuvant therapy of breast cancer. Expert guidelines can help to guide decisions. However, because individual factors strongly influence the choice of therapy, you should discuss the options for adjuvant or neoadjuvant therapy with your doctor to determine which therapy is best for you.

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Breast cancer (The Basics)
Patient education: Breast reconstruction after mastectomy for cancer (The Basics)
Patient education: Choosing surgical treatment for early-stage breast cancer (The Basics)
Patient education: Ductal carcinoma in situ (DCIS) (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Treatment of early-stage, hormone-responsive breast cancer in postmenopausal women (Beyond the Basics)
Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)
Patient education: Non-estrogen treatments for menopausal symptoms (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Adjuvant systemic therapy for HER2-positive breast cancer
Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer
Overview of breast reconstruction
Diagnostic evaluation of suspected breast cancer
Hormone receptors in breast cancer: Clinical utility and guideline recommendations to improve test accuracy
Breast-conserving therapy
Overview of side effects of chemotherapy for early-stage breast cancer
Tumor, node, metastasis (TNM) staging classification for breast cancer

The following organizations also provide reliable health information.

●National Cancer Institute

      1-800-4-CANCER

      (www.cancer.gov)

●The American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

●American Cancer Society

      1-800-ACS-2345

     (www.cancer.org)

●National Library of Medicine

     (www.nlm.nih.gov/medlineplus)

●Adjuvant! Online

     (http://www.newadjuvant.com/default2.aspx)

●Susan G. Komen Breast Cancer Foundation

     (www.komen.org)