We have previously discussed the great disputes and upheavals that occurred among breast cancer surgeons when it was argued that lesser forms of surgery could be safely utilized for women with localized breast cancer. This ultimately led to a randomized trial, published in 1985 by Bernie Fisher and the National Surgical Adjuvant Breast Project, in which women with tumors that were 4 cm or less in size were randomized to three arms: mastectomy, breast conserving surgery (a form of lumpectomy), and breast-conserving surgery combined with whole breast radiation therapy. This milestone study demonstrated that BCS had equivalent survival outcomes with mastectomy. Insofar as radiation therapy was concerned, the addition of RT did not change the survival outcome but did reduce the occurrence of local recurrence in the affected breast.
Let us ponder this for a moment. Survival and mortality for solid tumors, including breast cancer, is generally a result of the risk of systemic metastasis—do the cancer cells spread to distant organs like the liver, lung, bone? We have developed various tools to reduce this risk with the utilization of adjuvant therapy. In the case of breast cancer, this therapy can consist of chemotherapy or hormonal therapy, both of which are systemic and thus can eliminate circulating tumor cells that are theoretically microscopic and have remained after resection of the primary tumor. The use of such systemic therapy has been clearly shown to reduce the risk of recurrence and metastasis and thereby reduce breast cancer-related mortality.
What can radiation therapy contribute in this regard? Radiotherapy is a localized form of treatment and thus theoretically does not affect the systemic spread of metastatic cells. Thus, it is not surprising that it has no significant impact on mortality. What RT is very good at is the prevention of recurrence locally. Thus, while there is a high risk that the tumor will recur in the same breast following lumpectomy, RT would dramatically reduce that risk. This would not necessarily impact mortality but would reduce the risk of a local problem that could necessitate the subsequent need for a mastectomy.
Interestingly, a meta-analysis was published in 2011 by the Early Breast Cancer Trialists Collaborative Group which combined data from a number of studies on over 10,000 women in 17 clinical trials. At 10 years of follow-up, there was a 35% local recurrence rate in the breast for the non-irradiated breast versus a 19% recurrence rate in the women who received RT, for a reduction of local recurrence of about 50%. Interestingly, this study also showed a reduction in mortality at 15 years as well for the radiated versus non-irradiated group (21% versus 25%). It should be appreciated that radiotherapy was also associated with some adverse effects, such as cardiac toxicity and increased risk of second malignancies of the lung, esophagus and other organs.
It does turn out that the impact of adjuvant radiation therapy following breast-conserving surgery for small breast tumors (less than 3 cm) is not so powerful in the older population. Studies in those over 60 or 65 years of age have shown less benefit. This was recently highlighted in a randomized trial published in the New England Journal of Medicine that was conducted in Edinburgh. It included women 65 years of age or older with tumors up to 3 cm in size who were node-negative. To be eligible, the women had to be hormone-receptor positive and treated with adjuvant hormonal therapy.
A total of 1,326 women were randomized to either whole breast irradiation or no radiation. Follow-up was for nine years. The incidence of local breast cancer recurrence was 9.5% in the no-RT group as compared to 0.9% in the RT group, a 10-fold reduction in the local recurrence risk. In contrast, the incidence of distant metastasis was nearly equivalent in the two groups (1.6% in the no-RT group versus 3.0% in the RT group). Furthermore, overall survival at 10 years was also nearly identical in the two groups (80.8% for the no-RT group versus 80.7% for the RT group). In essence, while adjuvant radiotherapy reduced the occurrence of local recurrence, it had no effect on survival or distant metastasis.
What these studies suggest is that, at least for older populations, post-surgery whole-breast RT can be safely bypassed in women receiving adjuvant hormonal therapy.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
