Adjuvant Radiotherapy in Pre-Menopausal Women with Breast Cancer

Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, Wilson KS, Knowling MA, Coppin CM, Paradis M, Coldman AJ,
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

Reviewers: John Han-Chih Chang, MD and Ken Blank, MD
Source: N Engl J Med. 1997 Oct 2;337(14):956-62.

Possibly more than any other cancer, the treatment of breast cancer has evolved over the past twenty years. Surgery to remove the entire breast (simple, modified and radical mastectomy) has been largely replaced by breast conserving surgery (lumpectomy and biopsy) followed by radiation. In addition, the efficacy of chemotherapy has been proven in large randomized trials. Chemotherapy is now prescribed for a majority ofbreast cancer patients.

Radiation therapy utilizes high-energy electromagnetic waves to kill cancer cells. Unlike chemotherapy which travels throughout the whole body, radiotherapy only kills cancer cells in spots where the radiation beam isaimed. For this reason, radiation is called a "local" treatment. Surgery,too, is a "local" treatment, removing cancer cells in and around thesurgeon's knife but leaving distant cells intact. The combination of twolocal therapies (surgery and radiotherapy) often help too decrease the riskof the cancer returning in the original spot (local control). One of thecontroversies in breast cancer is whether or not the combination of twolocal therapies will help not only to improve local control but also overallsurvival.

Two large randomized trials, one from Denmark and the other from Canada, published in the October 2, 1997 issue of the New England Journal of Medicine resolve this question. Both trials found that the addition ofradiotherapy following mastectomy improves both local tumor control and survival. The Canadian study found the relative risk of dying from breast cancer 15 years after diagnosis was reduced by nearly one third when radiotherapy was utilized in the treatment.

Both studies examined only women who were at high risk for local and distant recurrence. This group includes women with positive axillary lymph nodes, cancer >5cm or growing into the breast skin or the fascia underlying the breast. Women in both studies underwent mastectomy and chemotherapy and were then randomized to radiation or no further treatment. The trial from Denmarkfound a 9% difference in the overall survival at 10 years favoring the radiotherapy group. The risk of local recurrence in the Danish trial diminished significantly when radiotherapy was added: from 32 to 9%. The Canadian study was smaller but the results were strikingly similar.

Whether or not the results from these trials can be extrapolated to women who receive breast conservation surgery is unknown. Large randomized trials in women who receive breast conservation surgery followed by radiation have consistently shown the addition of radiation to decrease local recurrence without impacting on overall survival. However, the Danish trial found an overall survival difference with the addition radiation to mastectomy only after very long follow-up. This long term follow-up may be needed in the breast conservation trials to demonstrate that radiation helps with overall survival.

The advances in treatment of breast cancer have dramatically improved survival and cosmesis. The advances include earlier detection by screening mammography and the efficacy of chemotherapy. Now, for the first time in a randomized clinical study, radiotherapy has been proven to help survival as well as local control.