Stage III Breast Cancer

Overview

Stage III breast cancer is characterized by one of the following:

1. A primary cancer that measures less than 5 cm (2 inches) in size and causes axillary (underarm) lymph nodes to be attached to each other or other structures
2. A primary cancer that is greater than 5 cm (2 inches) in size and involves axillary lymph nodes
3. A primary cancer that is attached to the chest wall or skin

Breast cancer that has spread to the lymph nodes is commonly referred to as node-positive disease.

Effective treatment of Stage III breast cancer requires both local and systemic therapy. Local therapy consists of surgery and/or radiation and is directed at destroying any cancer cells in or near the breast. Systemic therapy is directed at destroying cancer cells throughout the body, and may include chemotherapy, hormonal therapy, or targeted therapy. Systemic therapy may be administered before surgery, which is called neoadjuvant therapy.

The following is a general overview of treatment for Stage III breast cancer. Multi-modality treatment, which utilizes two or more treatment techniques, is increasingly recognized as an important approach for improving a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Web site is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their cancer physician.

Local Therapy: Surgery and Radiation 

Systemic Therapy

• Chemotherapy 
• Targeted Therapy 
• Hormonal Therapy

Local Therapy: Surgery and Radiation

Surgery and radiation are considered local therapies because they can treat the cancer in the breast and prevent cancer recurrence in the affected breast and surrounding area, but cannot treat cancer that has already spread to other locations in the body.

Surgery: Surgery for Stage III breast cancers may consist of mastectomy or lumpectomy. A mastectomy involves removal of the entire breast, whereas a lumpectomy involves removal of the cancer and a portion of surrounding tissue. Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to have a lumpectomy are also treated with radiation therapy. This combination of 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 lumpectomy alone.[1] [2]

Some patients who are not initially candidates for breast-conserving therapy may become eligible after treatment with chemotherapy. Systemic treatment before surgery is called neoadjuvant therapy. Neoadjuvant chemotherapy is a recommended treatment for many women with Stage III breast cancer.

For more detailed information, go to Surgery for Breast Cancer.

Radiation therapy: Regardless of type of surgery (mastectomy or lumpectomy), the addition of radiation therapy appears to reduce the risk of recurrence among women with Stage III breast cancer.[3] Radiation therapy can also play a role in the treatment of women who have cancer that remains inoperable even after neoadjuvant chemotherapy.

For more detailed information, go to Radiation Therapy for Breast Cancer. 

Systemic Therapy: Chemotherapy, Targeted Therapy, and Hormonal Therapy

Systemic therapy is treatment directed at destroying cancer cells throughout the body. Some patients with Stage III breast cancer already have small amounts of cancer that have spread outside the breast that the surgery or radiation does not treat. These cancer cells cannot be detected with any of the currently available tests and are referred to as micrometastases. The presence of micrometastases causes breast cancer recurrence following local treatment with surgery and/or radiation therapy alone. An effective systemic treatment is needed to eliminate micrometastases in order to improve a patient’s duration of survival and potential for cure.

Examples of systemic therapies that are commonly used in the treatment of Stage III breast cancer include:

Chemotherapy 

Targeted Therapy 

Hormonal Therapy

Furthermore, some patients who are not initially candidates for surgery may become eligible for this treatment after undergoing chemotherapy. Systemic treatment before surgery is called neoadjuvant therapy. Neoadjuvant chemotherapy is a recommended systemic therapy for many women with Stage III breast cancer.

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs and can be administered through a vein or delivered orally in the form of a pill.

Neoadjuvant chemotherapy: Neoadjuvant therapy is treatment administered before surgery. The purpose of neoadjuvant therapy is to immediately treat and shrink the cancer in order to increase the likelihood that it may be completely removed with surgery. A committee of physicians, called The Consensus Conference Committee, has published treatment guidelines stating that neoadjuvant chemotherapy is “the treatment of choice” for patients with Stage III breast cancer and is “worthy of consideration” in patients with Stage IIA and IIB breast cancer.[4] 

Chemotherapy options: There are many different chemotherapy drugs and combinations of drugs (regimens). The regimen consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) was the first standard combination used to treat individuals with early-stage breast cancer and has been in use for many years. CMF chemotherapy is typically administered for six cycles over a period of approximately four to six months.[5] 

Research shows that the inclusion of the chemotherapy drug doxorubicin in adjuvant chemotherapy increases the number of women that can expect to survive without evidence of cancer compared to combination chemotherapy without doxorubicin.[6] CAF (cyclophosphamide, doxorubicin, and fluorouracil) and AC (doxorubicin and cyclophosphamide) are also considered standard chemotherapy regimens for the treatment of early-stage breast cancer. However, these regimens are typically associated with more side effects than CMF .

Taxanes: The taxanes are a class of chemotherapy drug that have been shown to improve cancer-free survival in women with Stage II-III breast cancer.[7] The taxanes are typically combined with AC chemotherapy.

Dose-dense chemotherapy: AC, TAC, CMF and other chemotherapy regimens are typically administered every 3 weeks. Dose-dense chemotherapy refers to chemotherapy treatment that is administered more frequently. Dose-dense treatment is given every 2 weeks rather than at the conventional 3-week interval in order to increase the total amount of chemotherapy used to treat the cancer.

Researchers have reported that patients with node-positive breast cancer treated with dose-dense chemotherapy live longer without cancer recurrence than patients treated with conventional chemotherapy. The 2,005 patients involved in one study received chemotherapy treatment with doxorubicin, paclitaxel, and cyclophosphamide either every three weeks (conventional treatment) or every two weeks (dose-dense). At four years, 82% of patients treated with dose-dense therapy were disease-free, compared to 75% of those treated with conventional chemotherapy.[8] 

Targeted Therapy

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.

Herceptin® (trastuzumab): Herceptin is a targeted therapy that binds to a protein known as HER2. Twenty to thirty percent of breast cancers overexpress (make too much of) HER2, and could potentially respond to treatment with Herceptin. Results from an important clinical trial indicate that adding Herceptin to chemotherapy improves survival for patients with advanced HER2-positive breast cancer.[9] Herceptin has also been shown to improve survival among women with early-stage HER2-positive breast cancer that is node-positive or high-risk node-negative.[10] 

Hormonal Therapy

Estrogen causes some cancers to grow. The breasts, uterus and other female organs are composed of cells that contain estrogen receptors. When cells that have estrogen receptors become cancerous, exposure to estrogen increases the cancer’s growth. Cancer cells that have estrogen receptors are referred to as estrogen receptor-positive (ER-positive) cancers. 

The growth of ER-positive breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. This is the goal of hormonal therapy for breast cancer. Hormonal therapy drugs include tamoxifen as well as a newer of drugs known as aromatase inhibitors. Aromastase inhibitors include Femara® (letrozole), Arimidex® (anastrazole), and Aromasin® (exemestane). In premenopausal women, surgical removal of the ovaries or suppression of ovarian activity may also be used to reduce estrogen exposure.

 For more information, go to Hormonal Therapy for Breast Cancer.

References

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