A number of important questions about the role of radiation therapy in primary breast cancer are being evaluated in current clinical trials. One of the few local therapy questions addressed by the 2000 NIH Consensus Conference was postmastectomy radiation therapy in women with one to three positive nodes. A major Intergroup trial now addressing this question is particularly salient because of several recently reported randomized studies suggesting a survival benefit to treatment in this population. Many researchers believe that the benefits of radiation therapy — like adjuvant systemic therapy — exist in a continuum, with the greatest absolute benefit occurring in patients with the greatest risk for recurrence.

POSTMASTECTOMY RADIATION THERAPY

Recent trials have shown a survival benefit following radiotherapy in all node-positive women, but the degree of benefit is unclear in patients with one to three positive nodes. Part of the dilemma is based upon the discrepancy in the rates of locoregional failure without radiotherapy in those trials in comparison to failure rates reported in American series... Based upon these results, the statement produced from the consensus conference convened by the American Society for Therapeutic Radiology and Oncology to address the controversies regarding patient selection for postmastectomy radiotherapy stated that while there was a consensus that patients with four or more positive lymph nodes should receive radiation therapy, the data were less clear for patients with one to three positive nodes.

—Lori Pierce, MD
2000 NIH Consensus Conference. Abstract

There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy will benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary tumor… At this time, the role of postmastectomy radiotherapy for women with one to three positive lymph nodes remains uncertain and is being examined in a randomized clinical trial.

—2000 NIH Consensus Statement. Full-Text

INDIVIDUALIZING POSTMASTECTOMY RADIATION THERAPY

This is a very interesting question that challenges the concept we’ve had for so many years that breast cancer is a systemic disease. While one can quibble with aspects of the Danish and British Columbia trials, it is important that the subset that seemed to benefit the most in terms of survival — women with small tumors with a limited number of positive nodes — is consistent with everything else we believe about aggressive local-regional therapy. The ongoing Intergroup trial is very important. This study is using modern radiotherapy techniques. One would hope that the incidence of late cardiac morbidity is going to be very low. In the nonprotocol setting, we evaluate these one to three node-positive cases individually. We discuss radiation therapy in patients with large nodal metastases, extracapsulary extension and large primary tumors, particularly with lots of lymphatic invasion in the breast. We also discuss this option in a woman who is very anxious to minimize her risk of failure and wants to opt for treatments that may give very little benefit. Node-positive disease is a continuum. I suspect that this will also be true of the benefits of postmastectomy radiation therapy.

DANISH BREAST CANCER COOPERATIVE GROUP (DBCG) 82B RANDOMIZED TRIAL: POSTOPERATIVE RADIOTHERAPY IN HIGH-RISK PREMENOPAUSAL BREAST CANCER PATIENTS GIVEN ADJUVANT CHEMOTHERAPY CLOSED PROTOCOL 10 YEAR RESULTS   Overgaard M et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 1997;337:949-955. Abstract     DANISH BREAST CANCER COOPERATIVE GROUP RANDOMIZED DBCG 82C TRIAL: POSTOPERATIVE RADIOTHERAPY IN HIGH-RISK POSTMENOPAUSAL BREAST CANCER PATIENTS GIVEN ADJUVANT TAMOXIFEN CLOSED PROTOCOL 10 YEAR RESULTS   Overgaard M et al. Postoperative radiotherapy in high-risk post-menopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353:1641-1648. Abstract     BRITISH COLUMBIA RANDOMIZED TRIAL: ADJUVANT RADIOTHERAPY AND CHEMOTHERAPY IN NODE-POSITIVE PREMENOPAUSAL WOMEN WITH BREAST CANCER CLOSED PROTOCOL 17 YEAR RESULTS   Ragaz J et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Me d 1997;337:956-962. Abstract Ragaz J et al. Postmastectomy radiation (RT) outcome in node (N) positive breast cancer patients among N 1-3 versus N4+ subset: Impact of extracapsular spread (ES). Update of the British Columbia randomized trial. Proc ASCO 1999; Abstract 274.   POSTMASTECTOMY LOCAL RECURRENCE (LR) WITH OR WITHOUT DISTANT METS (DM) IN 4 ECOG TRIALS (MEDIAN OF 12.1 YEARS OF FOLLOW-UP)   Recht A et al. Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: Experience of the Eastern Cooperative Oncology Group. J Clin Oncol 1999;17:1689-1700. Abstract   SWOG-S9927: PHASE III RANDOMIZED STUDY OF POSTMASTECTOMY RADIOTHERAPY IN WOMEN WITH STAGE II BREAST CANCER WITH ONE TO THREE POSITIVE NODES OPEN PROTOCOL     Would you recommend posmastectomy radiation therapy for the following patients? S U R G E O N S

Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and surgery in early breast cancer: An overview of the randomized trials. N Engl J Med 1995;333:1444-55. Abstract

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomized trials. Lancet 2000;355:1757-70. Abstract

Bartelink H et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 2001;345:1378-87. Abstract

Pierce LJ. Treatment guidelines and techniques in delivery of postmastectomy radiotherapy in management of operable breast cancer. J Natl Cancer Inst Monogr 2001;30:117-24. Abstract

Recht A et al. Postmastectomy radiotherapy: Clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001;19:1539-69. Abstract

Whelan TJ et al. Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol 2000;18:1220- 9. Abstract

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