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.

Following surgery, systemic (bodywide) anticancer treatment is often recommended to eliminate any microscopic tumor cells that might remain in the body. This type of therapy is called adjuvant therapy, and it is a very important component of breast cancer treatment. Adjuvant systemic therapy significantly decreases the chance that the cancer will return (or recur), and it also improves a woman's chance of surviving her cancer.

There are three options for systemic adjuvant therapy of early breast cancer: endocrine therapy, chemotherapy, and trastuzumab (Herceptin®). The choice between these treatments depends upon whether the breast cancer is hormone-responsive and whether it makes a protein called HER2.

This article will focus on adjuvant therapy for premenopausal women with hormone-responsive breast cancer. Adjuvant treatment for postmenopausal women with hormone-responsive breast cancer is discussed separately. (See "Patient information: Early stage breast cancer treatment in postmenopausal women".)

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".

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. The options for endocrine therapy in premenopausal women include the following:

• The drug tamoxifen
• A drug or surgery that prevents the ovaries from making estrogen (see 'Ovarian suppression' below)

Tamoxifen — Tamoxifen (Nolvadex®) prevents estrogen from stimulating growth of the breast cancer cells.

Tamoxifen is usually recommended for five years. Taking tamoxifen for more than five years does not add further benefit, and the risk of side effects such as uterine cancer increases with longer treatment.

Side effects — Tamoxifen may increase the risk of the following, particularly in women over age 50 years:

• Cancer of the uterus (endometrial cancer and sarcoma)
• Blood clots within deep veins (deep vein thrombosis), usually in the legs, which can travel to the lungs (pulmonary embolism) (see "Patient information: Deep vein thrombosis (DVT)")
• Stroke

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, history of smoking), and for those who take tamoxifen for longer than five years.

Tamoxifen may cause other side effects, particularly hot flashes and vaginal discharge.

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 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 (Zoladex®), which is given as a monthly injection. The treatment is usually given for five years.
• Many women who are given chemotherapy become menopausal (ie, their ovaries no longer function), particularly women over age 40.

All forms of ovarian suppression cause a rapid onset of menopause symptoms (hot flashes, night sweats, mood swings, vaginal dryness), which can be severe. Treatment for these symptoms is available. (See "Patient information: Postmenopausal hormone therapy alternatives".)

Aromatase inhibitors — A class of drugs that is used for endocrine therapy in POSTmenopausal women is the aromatase inhibitors (including anastrozole, letrozole or exemestane). In general, aromatase inhibitors are not given to PREmenopausal women.

But women who are premenopausal before treatment may become menopausal; an aromatase inhibitor may then be considered. You should discuss the risks and benefits of this option with your doctor.

Is there a "best" form of endocrine therapy? — Despite years of study, it is not clear which is the best form of adjuvant endocrine therapy in premenopausal women with hormone-responsive breast cancer. Several major ongoing research trials are addressing many of the most pressing clinical questions. You are encouraged to enroll in these trials if you can [1].

ENDOCRINE THERAPY OR CHEMOTHERAPY OR BOTH?

Endocrine therapy is recommended for women with ER-positive breast cancer. However, it is not clear if additional treatment (chemotherapy) is also needed.

• Most doctors agree that endocrine therapy alone is adequate for premenopausal women with low-risk tumors (ie, those that are node-negative, ER/PR-positive, small (less than 1 cm) and lacking unfavorable microscopic features) [2,3].
• It is not clear if endocrine therapy alone is enough for women with higher risk ER-positive breast cancers (ie, those with involved lymph nodes, tumor size larger than 1 cm, or unfavorable microscopic features). Chemotherapy probably provides benefit for some women with ER-positive early breast cancer.

Two tests are available that can help to determine if chemotherapy would be helpful.

• A test called the 21-gene recurrence score assay (also called Oncotype DX™) may be useful to select those women with ER-positive, node-negative early breast cancer who stand to benefit the most from chemotherapy.
• A web-based assessment program (Adjuvant! Online, www.adjuvantonline.com) is available that can assist in estimating the relative risks and benefits of chemotherapy (as well as endocrine therapy).

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/clinical_trials/learning/

       http://clinicaltrials.gov/

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 therapy with your doctor to determine which therapy is best for you.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed every four months on our web site (www.uptodate.com/patients).

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information

Patient information: Early stage breast cancer treatment in postmenopausal women
Patient information: Deep vein thrombosis (DVT)
Patient information: Postmenopausal hormone therapy alternatives

Professional level information

Adjuvant chemotherapy and trastuzumab for HER2-positive early breast cancer
Adjuvant endocrine therapy for premenopausal women with early stage breast cancer
Adjuvant systemic therapy for older women with early stage breast cancer
An overview of breast cancer and treatment for early stage disease
Breast reconstruction in women with breast cancer
Clinical decisions in systemic adjuvant therapy for early breast cancer
Diagnostic evaluation of women with suspected breast cancer
Hormone receptors in breast cancer: Measurement and clinical implications
Mastectomy and breast conserving therapy for invasive breast cancer
Side effects of adjuvant 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.nci.nih.gov)

• The American Society of Clinical Oncology

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

• National Comprehensive Cancer Network

      (www.nccn.com)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus)

• Adjuvant! Online

      (www.adjuvantonline.com/)

• Susan G. Komen Breast Cancer Foundation

      (www.komen.org)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Breast Cancer Forum

      (http://breastcancer.about.com/forum)

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