Treatment of Stage II Breast Cancer

This content has been reviewed and approved by

William J. Gradishar, MD FACP
Director, Breast Medical Oncology, Professor of Medicine
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine
 

If you have stage II breast cancer, you have a cancer that is between 2 and 5 centimeters and may have spread to the lymph nodes. Treatment guidelines vary depending on the specifics of the tumor, but always includes surgery—usually a lumpectomy—and removal of lymph nodes as necessary. Radiation, chemotherapy, antiestrogen treatment, and targeted treatments--such as Herceptin® (trastuzumab)—may also be recommended depending on the specifics of the tumor, the your age, and other factors.

Effective treatment of stage II breast cancer requires both local treatment and systemic treatment. Local treatment consists of surgery and/or radiation therapy. It is directed at destroying any cancer cells in or near your breast. Systemic treatment is directed at destroying cancer cells throughout your body. It may include chemotherapy, targeted therapy, or antihormonal therapy. These therapies are often given after surgery. Then they are called adjuvant therapies.

Local Treatment: Surgery and Radiation

Surgery and radiation are considered local treatment. They can treat the cancer in your breast and prevent cancer from recurring (coming back) in that breast and the surrounding area. But they cannot treat cancer that has already spread to other parts of your body.

Surgery - Surgery for stage II breast cancers may consist of a mastectomy or lumpectomy. A mastectomy involves removal of your entire breast. A lumpectomy involves removal of the cancer and some surrounding tissue. A lumpectomy alone is associated with a higher rate of cancer recurrence than a mastectomy.

So if you have a lumpectomy, you will also be given radiation therapy directed at the breast. This combination of a lumpectomy and radiation therapy is called breast-conserving therapy. Clinical studies have shown that breast-conserving therapy is associated with a lower risk of local cancer recurrence than a lumpectomy alone.

Mastectomy and breast-conserving therapy are the current standard of care for the local treatment of stage II breast cancer. Both are considered acceptable options.

Surgery for early-stage breast cancer may also involve checking the lymph nodes in your armpit (axilla) to see if the cancer has spread outside your breast. This helps health care providers tell the stage of your cancer. It is important for determining if you need additional treatments beyond local therapies, such as chemotherapy. There are two ways to check these lymph nodes:

  • Axillary lymph node dissection - For more than 30 years, the standard of practice for telling the stage of breast cancer has included the removal of about 10 to 25 axillary lymph nodes to help tell if the cancer has spread. This procedure is called an axillary lymph node dissection. But a problem with this procedure is that it can have long-lasting side effects. They include pain, limited motion of your shoulder, numbness, and swelling of your arm.
  • Sentinel lymph node biopsy - A new way of telling if cancer has spread to your lymph nodes is a sentinel lymph node biopsy. This procedure involves removing only a single lymph node—called the sentinel lymph node. This is the first lymph node to collect drainage from the area surrounding the cancer. Before surgery, blue dye or radioactive tracer is injected near the cancer.

The dye or radioactive tracer drains from the area containing the cancer into the nearby lymph nodes and is detected most prominently in the sentinel node. The first node containing the dye or tracer is removed during surgery and checked under a microscope to see if it has cancer in it. Sentinel lymph node biopsy is becoming the standard approach for determining whether cancer has spread to the axillary lymph nodes.

Systemic Treatment: Chemotherapy, Targeted Therapy, and Antihormonal Therapy

Systemic treatment aims to destroy cancer cells throughout your body. Despite surgery and radiation, some women with stage II breast cancer already have cancer cells that have spread outside their breast. These are called micrometastases. They cannot be detected with any of the currently available tests. These micrometastases cause breast cancer to recur after surgery and/or radiation therapy. An effective treatment is needed to get rid of micrometastases.

The three main kinds of systemic treatment are discussed below.

Chemotherapy

Chemotherapy involves the use of drugs to kill cancer cells. It is a standard adjuvant therapy for early-stage breast cancer. Chemotherapy may consist of single drugs or combinations of drugs—called regimens. It can be given through your vein or taken by mouth in the form of a pill.

Historically, systemic therapy has been given after surgery. In that case, it is referred to as adjuvant chemotherapy. Clinical trials have shown that adjuvant chemotherapy improves a woman's chance of survival and decreases the risk of cancer recurrence compared with local therapy alone in the treatment of stage III breast cancer.

Chemotherapy options - There are many different chemotherapy drugs and regimens. The CMF regimen (cyclophosphamide, methotrexate, and fluorouracil) was the first standard combination used to treat early-stage breast cancer. It has been used for many years. CMF chemotherapy is typically given for six cycles over a period of about 4 to 6 months.

Research shows that the inclusion of a class of chemotherapy drugs—called anthracyclines (Ellence® [epirubicin] or Adriamycin® [doxorubicin])—in adjuvant chemotherapy may improve outcomes for women compared with combination chemotherapy without anthracyclines. CAF (cyclophosphamide, doxorubicin, and fluorouracil), FAC, FEC, and AC (doxorubicin and cyclophosphamide) are also considered standard chemotherapy regimens for early-stage breast cancer. More recently there has been much interest in identifying who benefits from anthracycline-based therapy. Some data suggest that only a small group of women garner benefit. There are data to suggest the benefit of non-anthracycline based therapy such as TC (docetaxel and cyclophosphamide) in some women with early stage breast cancer.

Taxanes - The taxanes are a group of chemotherapy drugs that include Taxotere® (docetaxel) and Taxol® (paclitaxel). These drugs improve cancer-free survival in women with stage II or stage III breast cancer. The taxanes docetaxel and paclitaxel appear to be similarly effective in the treatment of node-positive breast cancer or high-risk, node-negative breast cancer. Taxanes are typically combined with anthracycline-based chemotherapy. More recently the docetaxel/cyclophosphamide regimen (TC) has been thought to be at least as effective as AC without the risk of cardiac toxicity.

Dose-dense chemotherapy - AC, TAC, CMF, and other chemotherapy regimens are typically given every 3 weeks. Dose-dense chemotherapy refers to chemotherapy that is given more frequently--every 2 weeks. This approach is used to reduce the interval between cycles of chemotherapy. To do this safely, you may receive growth factor shots to ensure your blood counts don't drop too low and to enable them to recover quickly from the effects of the chemotherapy.

Targeted Therapy

Targeted therapy is designed to treat only cancer cells and minimize the damage to healthy cells. Conventional cancer treatments, such as chemotherapy and radiation therapy, kill both healthy cells and cancer cells. This causes side effects that are sometimes severe and unpleasant.

Treatments that target specific aspects of cancer cells may offer the advantages of reduced side effects and improved outcomes. Advances in science and technology have led to the development of several different types of targeted therapies. Monoclonal antibodies are a type of targeted therapy being studied in the treatment of breast cancer.

Some breast cancers have too much of a protein called HER2 on their surface. These are called HER2-positive breast cancers. The HER2 protein binds only with other proteins in your blood—called growth factors. This binding leads to the uncontrolled growth of the cancer cells. About one in four women with advanced breast cancer have HER2-positive breast cancer.

Trastuzumab is a monoclonal antibody that binds to the HER2 protein. Results from an important clinical trial indicate that adding trastuzumab to chemotherapy improves survival for women with advanced HER2-positive breast cancer. Trastuzumab is the first monoclonal antibody to be approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer. Trastuzumab has also been shown to have a major impact in the treatment of HER2+ early-stage breast cancer.

Antihormonal Therapy

Antihormonal therapy can slow the growth of some breast cancer cells by reducing their exposure to estrogen. Estrogen is a female hormone made by your ovaries and other tissue in your body. It serves many critical functions in your body. These include developing your female sex organs in puberty, preparing your breasts and uterus for pregnancy in adulthood, and maintaining your cardiovascular and bone health. Without estrogen, your body cannot sustain pregnancy and is susceptible to heart disease and osteoporosis (thinning of your bones).

Estrogen can also make some cancers grow. Your breasts, uterus, and other female organs are made of cells that are stimulated to grow when exposed to estrogen. These cells have areas on their surface called estrogen receptors. Estrogen in your blood binds to these receptors and stimulates the cells to grow. Cancers that have estrogen receptors are called estrogen receptor-positive (ER-positive) cancers. Although growth of ER-positive breast cancer cells can be prevented or slowed by reducing their exposure to estrogen, antihormonal therapy can also have side effects, such as thinner bones.

Antihormonal therapy appears to benefit all women with early-stage breast cancer. Two main types of antihormonal therapies have been studied in the treatment of early-stage breast cancer:

  • Tamoxifen
  • Aromatase inhibitors

There is evidence that postmenopausal women who have been treated with tamoxifen for 2 years to 5 years may attain additional benefit from switching to an aromatase inhibitor.

Tamoxifen for Early-Stage Breast Cancer

The results of several clinical studies indicate that antihormonal therapy with tamoxifen, either alone or in combination with chemotherapy, can reduce the rate of cancer recurrence and improve the duration of survival in women with ER-positive breast cancer. Tamoxifen should be taken for 5 years. However, many doctors are now suggesting use of an aromatase inhibitor instead of tamoxifen upfront, or a switch to an AI after 2-3 years of Tamoxifen. Tamoxifen does not appear to be beneficial for women with ER-negative breast cancer. 

Aromatase Inhibitors for Early-Stage Breast Cancer

Antiaromatase drugs provide a greater reduction in the risk of cancer recurrence and appear to have fewer side effects than tamoxifen in postmenopausal women. Aromatase inhibitors that are approved for the treatment of early-stage breast cancer include anastrozole, exemestane, and letrozole.

The three antiaromatase drugs have been or are being evaluated in major studies in women in which women were initially treated with tamoxifen. The general outcome from these studies found that using the antiaromatase drugs in postmenopausal women provided a survival advantage after 2 to 3 years of tamoxifen or after 5 years of antiaromatase therapy compared with 5 years of tamoxifen. However, there is still no clear agreement on which approach is "best." Research is ongoing to determine which option provides the best outcome.

Specifically, anastrozole was shown to provide benefit after tamoxifen in the treatment of early-stage breast cancer. Switching from tamoxifen to anastrozole also reduced the risk of a cancer recurrence. One study evaluated 400 postmenopausal women with ER-positive breast cancer who had already been treated with tamoxifen for at least 2 years. Women either kept taking tamoxifen for up to 5 years or switched to anastrozole for a comparable amount of time. There were 60 percent fewer cancer recurrences in the women who switched to anastrozole than in the women who took tamoxifen.

Letrozole was shown to reduce the risk of death and cancer recurrence when used after 5 years of tamoxifen. More than 5,000 postmenopausal women who had completed 5 years of treatment with tamoxifen participated in a clinical trial evaluating letrozole. About half received letrozole. The other half received a placebo (an inactive substitute).

Women treated with letrozole had an 18 percent reduced risk of death and a 40 percent reduced risk of cancer recurrence compared with those who received the placebo. Women with cancer that had spread to the lymph nodes (node-positive cancer) had an even greater benefit from letrozole, with a 39 percent reduced risk of death compared with a placebo.

About 5 percent of women treated with letrozole had a reduced quality of life compared with those treated with a placebo. This included decreased physical function (6 percent), increased pain (5 percent), and decreased vitality (5 percent).

But a large proportion of women considered the side effects to be worth the reduced risk of a cancer recurrence. This trial was stopped early because the benefits of letrozole treatment were so significant. Even if letrozole was not started for years after completion of tamoxifen, there was further risk reduction derived from taking letrozole. Several clinical trials have also shown the benefit of switching to an aromatase inhibitor (exemestane, anastrozole) after 2 to 3 years of tamoxifen therapy compared to tamoxifen alone.

How Long Should I Take Hormonal Therapy?

Tamoxifen has been the standard drug for antihormonal therapy. It is typically taken for 5 years. Research is ongoing to determine if you can benefit from taking antihormonal therapy for very prolonged periods of time (that is, 10 to 15 years).

This content was last reviewed August 15, 2010 by Dr. Reshma L. Mahtani.
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