Patient education: Treatment of early-stage, hormone-responsive breast cancer in postmenopausal females (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 females to be cured.

After surgery, systemic (body-wide) anticancer treatment may be given to eliminate any 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 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 breast cancer: endocrine (hormone) therapy, chemotherapy, and trastuzumab (Herceptin). The first of these, endocrine therapy, is used in females who have what is called "hormone-responsive" cancer, meaning it grows in response to the female hormone estrogen. This article will focus on adjuvant therapy for postmenopausal females with hormone-responsive breast cancer. Adjuvant treatment for premenopausal females with hormone-responsive breast cancer is discussed in a separate monograph. (See "Patient education: Treatment of early-stage, hormone-responsive breast cancer in premenopausal females (Beyond the Basics)".)

Adjuvant treatment for females with hormone-nonresponsive breast cancers, as well as a discussion about the side effects and indications for chemotherapy and anti-human epidermal growth factor receptor 2 (HER2)-directed therapy in females with HER2-positive breast cancer, is presented elsewhere. (See "Patient education: Treatment of early HER2-positive breast cancer (Beyond the Basics)".)

DEFINING HORMONE-RESPONSIVE BREAST CANCER — 

Some breast cancers require the female hormone estrogen to grow, while other breast cancers are able to grow without estrogen. Whether a tumor is hormone responsive is determined by checking if it contains hormone receptors, namely estrogen receptors (ER), progesterone receptors (PR), or both.

If you have a tumor that contains hormone receptors (called 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 endocrine therapy is to prevent breast cancer cells from being stimulated by estrogen. In postmenopausal females with early hormone-responsive breast cancer, the two endocrine treatments most often used are the class of drugs called selective estrogen receptor modulators (SERMs) or another class called aromatase inhibitors (AIs). Among the SERMs, tamoxifen (brand name: Nolvadex) is the most commonly prescribed.

The SERMs were the first agents used as a treatment for breast cancer, and while both SERMs and AIs reduce the risk of recurrence and death due to breast cancer, research indicates that AIs are more effective than tamoxifen and should be preferentially administered. That said, multiple options exist, and you should talk with your doctor about the one that is most appropriate for your situation.

Aromatase inhibitors — AIs are a type of medicine that block estrogen from being produced in postmenopausal females. Examples of these medications include anastrozole (brand name: Arimidex), letrozole (brand name: Femara), and exemestane (brand name: Aromasin).

Studies comparing the effects of tamoxifen with those of AIs as a primary treatment when taken for five years find that AIs are superior. In addition, studies show that for females who have been on tamoxifen for two or three years, there is also a benefit of switching to an AI. Finally, for females who have completed a five-year course of tamoxifen, there are benefits to taking an AI or continuing tamoxifen for up to another five years, as compared with stopping all treatment.

In all cases where an AI is used, treatment with AIs should last for at least five years regardless of whether it is preceded by tamoxifen treatment. There is evidence that continuing AI treatment to complete a total of seven to ten years of endocrine therapy (including treatment with either an AI or tamoxifen) reduces the risk of recurrence as well as new breast cancers, particularly in females at highest risk of recurrence (eg, those with large tumors or evidence of cancer in their lymph nodes), although it has not as yet been shown to affect overall survival rates. Females who have a low risk of recurrence and are concerned about the side effects associated with taking an AI for longer might reasonably opt to stop after five years of treatment (see 'Side effects' below). However, extending treatment is an option for females at lower risk who are tolerating treatment well and want to further reduce their risk of future recurrence. Your doctor can talk to you about your situation and help you weigh the risks and benefits.

Side effects — Side effects of aromatase inhibitors include bone loss and bone fractures, and pain in the muscles and joints. Bone-related side effects are more frequent in females who continue taking an AI beyond the initial five years. Unlike tamoxifen, it does not increase the risk that one could develop cancer of the uterus.

Tamoxifen — Tamoxifen (brand name: Nolvadex) is a SERM and prevents estrogen from binding to the estrogen receptor, thereby preventing estrogen from stimulating the growth of the breast cancer cells. Although it has typically been recommended that females remain on it for five years, studies now show that for females who choose to take tamoxifen rather than an AI, treatment should be for 10 years. However, whether all females require a 10-year course of tamoxifen is unclear, and you should talk with your doctor about whether a longer course of tamoxifen is advised.

Side effects — Tamoxifen may increase the risk of the following, particularly in females 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 education: Deep vein thrombosis (DVT) (Beyond the Basics)")

There has been some suspicion that tamoxifen might also increase a woman’s risk of stroke, but studies have not confirmed this.

For most females, 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 females with risk factors for blood clots or a 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. Since blood clots most commonly occur around the time of surgery, females undergoing surgery should discontinue tamoxifen for a week or two before and after surgery if possible.

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

Adding abemaciclib — This is a type of medication called a cyclin-dependent kinase (CDK) 4/6 inhibitor. It works by blocking the function of specific proteins in the body that cause cancer cells to grow and multiply. For some people with high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, doctors might consider adding abemaciclib to endocrine therapy (an AI or tamoxifen). Your doctor can talk to you about whether you are a candidate for this therapy based on the characteristics of your cancer. The most common side effect of abemaciclib is diarrhea.

CHEMOTHERAPY IN ADDITION TO ENDOCRINE THERAPY — 

Chemotherapy provides benefit for some females with ER-positive early breast cancer, especially females with positive lymph nodes. It is less clear which females with ER-positive and lymph node negative breast cancer need chemotherapy.

Two tools are available to help determine what your chances are of having a recurrence (ie, your prognosis), in which case your doctor may feel chemotherapy is indicated. Ask your doctor or nurse if these tools would be helpful:

●Oncotype DX assay, also known as 21 gene recurrence score assay, can help to estimate your risk of a breast cancer relapse, which can help to predict if there is a benefit of having chemotherapy.

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/research/participate/clinical-trials

●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 doctors that covers what may be components of surveillance after breast cancer treatment is provided in the following table (table 1).

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 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 — 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: Deciding about breast reconstruction after mastectomy (The Basics)
Patient education: Choosing surgical treatment for early-stage breast cancer (The Basics)
Patient education: Ductal carcinoma in situ (DCIS) (The Basics)
Patient education: Mastectomy (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: Breast cancer guide to diagnosis and treatment (Beyond the Basics)
Patient education: Treatment of early HER2-positive breast cancer (Beyond the Basics)
Patient education: Treatment of early-stage, hormone-responsive breast cancer in premenopausal females (Beyond the Basics)
Patient education: Lymphedema after cancer surgery (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 endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer
Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer
Treatment for hormone receptor-positive, HER2-negative advanced breast cancer
Overview of the approach to early breast cancer in older women
HER2 and predicting response to therapy in breast cancer
Hormone receptors in breast cancer: Clinical utility and guideline recommendations to improve test accuracy
Breast-conserving therapy
Mechanisms of action of selective estrogen receptor modulators and down-regulators

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)

●American Cancer Society

●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)

[1-8]