Stage III

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.

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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 biological 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 website 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

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: Doctors currently recommend that all patients with stage III breast cancer undergo surgical removal of the primary breast cancer. 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 compared to lumpectomy alone.[1],[2] Furthermore, breast-conserving therapy and mastectomy have been shown to produce identical long-term survival.[3]

Some patients who are not initially candidates for breast-conserving therapy may become eligible for breast-conserving therapy after undergoing chemotherapy. Systemic treatment before surgery is called neoadjuvant therapy. Neoadjuvant chemotherapy is a recommended treatment for some women with stage III breast cancer. For more information, go to neoadjuvant chemotherapy.

Surgery for early stage breast cancer may also involve the evaluation of axillary (underarm) lymph nodes to determine the stage of disease and whether cancer has spread outside the breast. For over 30 years, the standard of practice for breast cancer staging has included the removal of approximately 10-25 axillary lymph nodes to help determine whether the cancer has spread. This procedure, called an axillary lymph node dissection, can be associated with chronic side effects, including pain, limited shoulder motion, numbness, and swelling.

A new approach for evaluating whether cancer has spread to the lymph nodes is a sentinel lymph node biopsy . The advantage to this procedure is that it involves the removal of a single lymph node, called the sentinel node, which is the first lymph node to collect excess fluid surrounding the cancer. Prior to surgery, blue dye is injected near the cancer. The dye drains from the area containing the cancer into the nearby lymph nodes, through the sentinel node. The node containing the dye is removed during surgery and evaluated under a microscope to determine whether cancer has spread. Sentinel lymph node biopsy is becoming the standard approach for determining whether cancer has spread to the axillary lymph nodes.[4]

Research now indicates that sentinel node biopsy appears to be just as effective as an axillary lymph node dissection in determining cancer spread to lymph nodes and results in fewer side effects in patients with stage II-III breast cancer.[5]

Ask the Doctor: How can I Ensure I am Getting the Care I need to Avoid Recurrence?

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

Radiation therapy: It is recommended that patients with stage III breast cancers treated with lumpectomy (breast-conserving surgery) receive additional treatment with radiation therapy. The addition of radiation therapy decreases the risk of local cancer recurrence and improves survival.

Three studies have shown that the addition of radiation therapy to mastectomy and chemotherapy reduces cancer recurrences and increases survival among women with stage II-III breast cancer. In a clinical study involving 1,708 women with stage II-III breast cancer, researchers from Denmark reported a reduction in local regional recurrence, an increase in survival, and an increased probability of surviving 10 years or more with radiation therapy (see Table 1). [6]

Table 1 Addition of radiation therapy to chemotherapy improves survival in the treatment of early stage breast cancer

Chemotherapy plus radiation therapy Chemotherapy alone
Local-regional recurrence 9% 32%
Survival at 10 years 54% 45%
Probability of surviving 10 years or more 48% 34%

Canadian researchers reported that, among 319 women with node-positive breast cancer that were randomized to receive chemotherapy plus radiation or chemotherapy alone, 29% fewer patients died and cancer recurrences were reduced by 33% with the addition of radiation therapy.[7]

Finally, researchers from M.D. Anderson have reported that radiation therapy following a mastectomy in patients with node-positive breast cancer appears to drastically reduce the rate of local-regional recurrences. These findings were based on evaluation of the results from 5 clinical trials involving approximately 1,500 women. The outcomes of 469 women who received radiation therapy following a mastectomy were compared to the outcomes of 1,031 women who did not receive additional radiation therapy following a mastectomy. All patients were treated with Adriamycin® (doxorubicin)-based chemotherapy. Women with increasing lymph node involvement or cancer cells near the edge of the surgically removed tissue appear to benefit most from post-mastectomy radiation.[8]

Radiation therapy has also been shown to benefit postmenopausal women with stage II-III breast cancer that receive hormonal therapy. The 1,375 women involved in this study were randomly assigned to receive hormonal therapy for one year alone (689) or hormonal therapy with postoperative radiotherapy to the chest wall and regional lymph nodes (686). Results showed a significant reduction in local regional recurrence and improvement in disease-free survival and survival of 10 years or more for patients who received radiation therapy (see Table 2).[9]

Table 2 Addition of radiation to hormonal therapy improves survival in the treatment of early stage breast cancer

Hormonal therapy plus radiation Hormonal therapy alone
Local-regional cancer recurrence 8% 35%
Disease-free survival 30% 24%
10-year survival 45% 36%

Systemic Therapy: Chemotherapy, Targeted Therapy, and Hormonal Therapy
Chemotherapy
Targeted Therapy
Hormonal Therapy
Strategies to Improve Treatment

References


[1] Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.N Engl J Med. 2002;347:1233-1241.

[2] Lichter AS, Lippman ME, Jr Danforth DN, et al. Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute. Journal of Clinical Oncology, Classic Papers and Current Comments. 1996;1:2-10.

[3] Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347;1227-1232.
[4] Edge SB, Niland JC, Bookman MA, et al. Emergence of sentinel node biopsy in breast cancer as standard-of care in academic comprehensive cancer centers. Journal of the National Cancer Institute. 2003;95:1514-1521.

[5] Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546-553.

[6] Overgaard M, Hansen PS, Overgaard J, et al. Postoperative Radiothearpy in High-Risk Premenopausal Women with Breast Cancer who Receive Adjuvant Chemotherapy. N Engl J Med. 1997;337(14):949-955.
[7] Ragaz J, Stewart MJ, Nhu L, et al. Adjuvant Radiotherapy and Chemotherapy in Node-Positive Premenopausal Women with Breast Cancer. N Engl J Med. 1997;337(14):956-962.
[8] Woodward W, Katz A, Buchholz T, et al. Patterns and predictors of locoregional recurrence in 469 patients treated with post-mastectomy radiation. International Journal of Radiation Oncology, Biology and Physics. 2002;54:91-92. Proceedings from the American Society of Therapeutic Radiation Oncology. Abstract #158.
[9] Overgaard M, Jensen M-B, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353:1641-1648.