BCT with RT May Be Superior to Mastectomy in Node-Positive Patients

ABSTRACT & COMMENTARY

Synopsis: Breast-conserving therapy (BCT) has only slowly been accepted by many U.S. surgeons largely based on a persistent belief that more radical surgery is more effective therapy. For the subset of patients with positive lymph nodes (which accounts for 30% of all patients), this meta-analysis demonstrates that the use of BCT with radiation therapy appears to lower the risk of recurrence by more than 30% over mastectomy.

Source: Morris AD, et al Cancer J Sci Am 1997;3:6-12.

About 135,000 women will present with clinical early stage breast cancer in the United States in 1997. Despite the fact that several very large studies have demonstrated that breast convserving therapy (BCT) and modified radical mastectomy produce equivalent 10-year survival rates1 and that BCT has been endorsed as a treatment option by a consensus panel of the National Institutes of Health,2 the pattern of care is changing very slowly. In some parts of the country, only a minority of women are undergoing BCT for their early stage breast cancer. The case for BCT continues to get stronger.

Morris and colleagues performed a meta-analysis of all seven prospective randomized trials examining BCT plus radiation therapy vs. modified radical mastectomy. For four of these studies, the authors used published data; for three studies, the original published data were updated at the time of analysis. The pooled odds ratio comparing 10-year survival for BCT vs. mastectomy was 0.91, meaning that patients receiving BCT had a 9% lower risk of dying within 10 years of diagnosis. For the subset of patients with positive axillary lymph nodes, BCT plus radiation therapy led to a 31% reduction in risk of death at 10 years compared to mastectomy (P = 0.03). In two studies, patients with node positive disease also received radiation therapy after mastectomy. In these two studies, there were no significant differences between BCT and mastectomy in survival. The use of radiation therapy (RT) equalized the results. Thus, BCT plus RT is superior to mastectomy alone in the management of node positive early stage breast cancer; however, addition of RT to mastectomy again makes BCT and mastectomy equally effective treatment approaches.

COMMENTARY

Of women with clinical early stage breast cancer who undergo axillary lymph node sampling, about 30% will be shown to have lymph node involvement. These women will receive adjuvant chemotherapy regardless of the primary treatment. In light of this standard systemic therapy approach, it is somewhat surprising to find, in a meta-analysis of studies comparing BCT plus RT to modified radical mastectomy, that the addition of locoregional RT to BCT appears to add to the benefit from systemic adjuvant therapy.

The value of added RT has been addressed in a small number of randomized studies. The Danish Breast Cancer Study Group treated node-positive postmastectomy patients with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) combination chemotherapy and randomized them to receive or not receive regional nodal RT.3 In this study, disease-free survival was improved by the addition of RT, and premenopausal patients had an improved overall survival. In addition, a study from Ragaz and colleagues4 from British Columbia randomized node-positive women post-mastectomy who received adjuvant chemotherapy to receive additional RT or no additional therapy. Disease-free survival was improved for the entire group receiving RT; overall survival was enhanced by the addition of RT in the subset of patients with four or more positive nodes. Thus, one could make a case for the addition of RT to the management of node-positive patients whether their primary therapy was BCT or mastectomy.

Such a recommendation makes me nervous. None of the studies has sufficient follow-up at this time to rule out an adverse survival impact from radiation-induced second tumors. Furthermore, there are tricky technical issues to delivering RT to an axilla that has surgical scarring. Arm edema is an unpleasant treatment side effect. It is also important to minimize lung and heart damage.

However, the data seem to indicate that local/regional RT adds to the survival enhancement mediated by adjuvant chemotherapy. The treatment of first choice is BCT plus RT for all early stage patients. If the patient is honestly informed of the options and chooses to have modified radical mastectomy and has positive lymph nodes, local/regional RT should be added to the treatment regimen, it is hoped in conjunction with adjuvant chemotherapy and/or tamoxifen.

References

1. Early Breast Cancer Trialists’ Collaborative Group. N Engl J Med 1995;333:1444-1455.

2. National Institutes of Health Consensus Development Panel. J Natl Cancer Inst Monograph 1992;11:1-5.

3. Overgaard M, et al. Int J Radiat Oncol Biol Phys 1990;19:1121-1124.

4. Ragaz J, et al. Proc Am Soc Clin Oncol 1996;15:121.