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Section 3
Radiation therapy for primary breast cancer

OVERVIEW

A number of important research questions on 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 in this population.

The research question of whether improved local disease control affects long-term survival is provocative, but consistent with data from the International Breast Cancer Overview that demonstrated fewer breast cancer deaths in women receiving local radiation therapy. This effect was confounded by an increased mortality from cardiovascular complications, which was attributed to prior, imprecise radiation therapy techniques. 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.

RADIATION THERAPY OVERVIEW

When you obtain better local control with radiotherapy or with surgery that reduces the risk of local recurrence, you do get some decrease in the long-term mortality from breast cancer. An absolute reduction of about 20 percent in local recurrence seems to go with an absolute reduction of around about five percent in long-term mortality from breast cancer 10 or 15 years later.

So, although the meta-analysis of the older radiotherapy trials suggested no net benefit, when you look separately at the breast deaths and the nonbreast deaths, it actually shows that better local control does matter in terms of long-term breast cancer survival.

-Richard Peto, FRS

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. The recent report by Recht and colleagues of the patterns of failure found in studies conducted by the Eastern Cooperative Oncology Group notes that the risk of locoregional failure was 13 percent at 10 years in patients with one to three positive nodes. Although this is comparable to the 16 percent actuarial rate seen in the British Columbia trial at 10 years, it is strikingly different from the Danish studies, where the crude rates of locoregional recurrence were approximately 30 percent.

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

CONTINUUM OF RADIOTHERAPY BENEFITS

Some of the controversy in the one to three node subset is quite akin to what happened in adjuvant chemotherapy early on in its development. We used to think that patients with large numbers of nodes benefited, but patients with small numbers of nodes didn't. Then we recognized that patients with small numbers of nodes benefited, but we thought patients with no nodes didn't. Now we recognize that even patients with no nodes in certain subsets can benefit. This principle applies across the spectrum of disease that systemic chemotherapy reduces risk of failure; however, the absolute benefit is harder and harder to see as the absolute risk of failure gets smaller. I think the same must be true in postmastectomy chest wall radiation. It almost certainly has to help patients with one to three positive nodes. The question is, "What is their absolute risk of failure and is the benefit of the reduction conferred by postmastectomy chest wall radiation worth taking?" With the uncertainty surrounding the one to three node-positive group, we have proposed a trial for both pre- and postmenopausal patients to assess this. This trial - sponsored through SWOG - is now open and will be run through the Intergroup. There is a huge subgroup of women out there who fit into this category, and we hope that clinicians will enroll their patients in this study.

-Allen Lichter, MD
Presentation at 2000 Lynn Sage Breast Cancer Symposium

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

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