Less Is Sometimes More

We have long considered completion axillary node dissection for patients with evidence of nodal metastases – and radiation following breast conserving surgery – as truths that are necessary and critical components of treatment planning for early-stage breast cancer. These treatments are not without impact, however, both in short- and long-term toxicity, as well as cost. As we begin to understand the biology that drives breast cancer growth, it has also become clear that not all treatments considered to be "standard" have a positive benefit-to-risk ratio.

A number of recently presented trials challenge the status quo, and teach us that less may indeed be sometimes better. For women who have evidence of cancer in one to two sentinel lymph nodes, and who have had breast-conserving surgery (therefore requiring radiation that includes the low axilla), the recent update to the National Comprehensive Cancer Network (NCCN) guidelines reflects these data demonstrating lack of additional benefit and increased toxicity from completion axillary dissection.

By Dr. Hope S. Rugo

These new guidelines spare women from an increased risk of lymphedema and neuropathy, as well as delayed recovery and procedure-related pain. However, it is important to keep in mind that the inclusion criteria for these trials required breast-conserving surgery, therefore ensuring that radiation would be recommended postoperatively. For patients with more extensive disease in the axillary nodes, a full dissection is still considered the standard of care.

What should be recommended for women who have had a mastectomy and therefore do not require radiation? This is a more difficult question, as the risk of locoregional recurrence for women with a positive sentinel node who forgo radiation is unknown. For an individual patient, local radiation could be considered in the setting of minimal or limited node involvement to avoid more extensive surgery, although data for this approach are lacking.

For older patients with slow-growing, hormone-responsive, early-stage breast cancer, the risk of local recurrence is low, and the overall risk of recurrence is protracted, extending out to at least 15 years. When surgical margins are clearly negative for tumor, the question for these women is whether or not postoperative radiation is worth the time, expense, and toxicity for the expected benefit. Previous randomized data support omitting radiation for low-risk disease in women over the age of 70 who are also receiving adjuvant hormone therapy.

The data presented by Dr. Fei-Fei Liu and colleagues at the annual meeting of the American Association of Cancer Research (AACR) is the next step in identifying the biology of tumors for which radiation provides little benefit. In this series, women taking tamoxifen and whose tumors were hormone receptor–positive, did not express HER2/neu, and had low rates of proliferation as measured by Ki67, were found to have similar recurrence rates in a randomized prospective trial regardless of the use of adjuvant radiation.

This was particularly true for women over the age of 60, although there were only 103 patients in this analysis. Additional data are needed in a larger cohort with external validation of markers before this approach is incorporated into treatment guidelines. However, it is clear that a subset of women with a subset of breast cancers is unlikely to derive significant benefit from adjuvant radiation therapy for early-stage, low-proliferative, hormone receptor–positive breast cancer.

We are making progress, not only in identifying new therapies, but in learning how to more appropriately use the therapies we already have. Less is indeed sometimes better.

Dr. Rugo, associate editor of The Oncology Report, is Director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.