Deciding When Post-Mastectomy Radiation Therapy Is Warranted

Lawrence J. Solin, MD

Radiation therapy is frequently recommended for patients who have undergone mastectomy for breast cancer. For appropriate patients, postmastectomy radiation therapy is associated with improved locoregional control (an absolute decrease in recurrence of 20% to 27%) and better survival (an absolute gain in overall survival of 8% to 9%).^1-3

Current Guidelines

Clinical Trial Evidence

Although recent advances have greatly minimized many of its side effects, radiation therapy still can be associated with serious complications, with cardiac complications among the most common concerns. Thus, it is appropriate to review which patients are most likely to benefit from radiation therapy and which, if any, can avoid it. In a session at the 30th Annual Miami Breast Cancer Conference, Lawrence J. Solin, MD, chair of Radiation Oncology at Albert Einstein Medical Center in Philadelphia, discussed whether all patients with 1 to 3 positive lymph nodes who have undergone mastectomy need postoperative radiation therapy. Guidelines from the American Society of Clinical Oncology,⁴ the National Comprehensive Cancer Network,⁵ and the American College of Radiology⁶ all agree that post-mastectomy radiation therapy is indicated for patients with four or more positive lymph nodes. However, these patients account for only a minority of node-positive mastectomy patients, with most patients having small (T1-2) tumors and 1 to 3 positive nodes, Solin noted. Unfortunately, all three of the above guidelines report that insufficient evidence exists to make any evidence- based post-mastectomy recommendations for patients with 1 to 3 positive nodes.^4-6 Two of the three guidelines do suggest, however, that physicians at least consider chest wall and regional nodal irradiation for these patients.^5,6 The only randomized trial to attempt to address the issue of post-mastectomy radiation therapy in patients with 1 to 3 positive nodes, SWOG 9927, failed to meet its accrual target and was therefore unable to provide answers regarding this controversial issue. This leaves only subset data from other randomized trials and meta-analyses from which to draw conclusions about the usefulness of post-mastectomy radiation therapy in this patient population. Subset analyses from two large, randomized clinical trials that examined a total of 735 patients with 1 to 3 positive nodes both demonstrated an overall survival advantage for patients receiving post-mastectomy radiation therapy, producing a 7% to 9% absolute improvement in long-term survival (15-20 years).^7,8

Individualized Treatment Recommendations

Perhaps even more compelling are results from a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) of women from 20 randomized trials designed to evaluate post-mastectomy radiation therapy.⁹ Again examining the subset of patients who had 1 to 3 positive nodes, the EBCTCG reported that radiation therapy was associated with an absolute reduction in locoregional recurrence of 16.1% at 5 years and an absolute improvement in breast cancer survival of 8.1% at 15 years. It was also of interest to note that investigators reported no evidence of a differential treatment effect among patients grouped by number of positive lymph nodes (ie, 1, 2, or 3). When EBCTCG investigators restricted the data to be more consistent with contemporary treatment regimens and surgical techniques, benefits in locoregional recurrence and breast cancer survival were maintained, albeit at more modest levels (10.1% at 5 years and 3.3% at 15 years, respectively). An ongoing EBCTCG meta-analysis may yield additional clinically relevant information. In the absence of direct randomized clinical trial data examining post-mastectomy radiation therapy in patients with 1 to 3 positive lymph nodes, physicians are left to use their clinical judgment in deciding whether or not to recommend radiation therapy to such patients in their practices.

Solin reported that this population of patients is a heterogeneous mix, with a wide range of prognostic characteristics. Thus, he individualizes his treatment recommendations for these patients, maintaining that tumor size and number of positive lymph nodes are probably the most important considerations, because the larger the tumor and the greater the number of positive lymph nodes, the more obvious the benefit of post-mastectomy radiation therapy. However, particularly in patients with more favorable disease characteristics (eg, smaller tumors and a single positive lymph node), he considers other patient and disease characteristics, including patient age, lymphovascular invasion, extracapsular extension, resection margins, and even the type of adjuvant chemotherapy received. His approach highlights the fact that informed treatment recommendations for this patient population require a multifactorial decision process.

References

1. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337(14):949-955.
2. Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c Trial. Lancet. 1999;353(9165):1641-1648.
3. Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337(14):956-962.
4. Recht A, Edge SB, Solin LJ, et al. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19(5):1539-1569.
5. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer V.3.2012. National Comprehensive Cancer Center Network website. www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed February 6, 2013.
6. Taylor ME, Haffty BG, Rabinovitch R, et al. ACR appropriateness criteria on postmastectomy radiotherapy expert panel on radiation oncology-breast. Int J Radiat Oncol Biol Phys. 2009;73(4):997-1002.
7. Overgaard M, Nielsen HM, Overgaard J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol. 2007;82(3):247-253.
8. Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005;97(2):116-126.
9. Darby S, on behalf of the Early Breast Cancer Trialists’ Collaborative Group. Overview of the randomised trials of radiotherapy in early breast cancer (Abstract). Presented at the 32nd Annual San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, TX.