Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer

B Fowble, A Hanlon, G Freedman, N Nicolaou, J Hoffman, E Sigurdson, M Boraas, M Torosian, L Goldstein
International Journal of Radiation Oncology, Biology, Physics 2000 July 1, 47 (4): 883-94

PURPOSE: To compare outcome for ipsilateral breast tumor recurrence (IBTR), or regional node recurrence, initial and subsequent distant metastases, and overall and cause-specific survival in women treated with conservative surgery and radiation based on whether or not radiation was targeted to the internal mammary nodes (IMN).

METHODS AND MATERIALS: From 1979-1994, 1383 women with Stage I-II breast cancer underwent wide excision, axillary node dissection with >/=10 nodes removed, and radiation. Median follow-up was 6 years; median age was 55 years. A total of 114 women had radiation targeted to the IMN with deep tangents and 1269 did not. Women who received IMN treatment were more often axillary node-positive (40% vs. 25%, p = 0. 002), had central or inner quadrant tumors (61% vs. 40%, p = 0.001), and had T2 tumors (47% vs. 31%, p = 0.001). All axillary node-positive women received adjuvant chemotherapy and/or tamoxifen. For axillary node-negative women, 13% of the IMN treatment group received adjuvant systemic therapy compared to 37% of the no treatment group (p = 0.001). Radiation was directed to the breast only in 97% of the axillary node-negative women who had IMN treatment and 99% of the no IMN treatment group. For axillary node-positive women, 98% of the IMN-treated group had radiation to the breast and supraclavicular nodes +/- a posterior axillary field compared to 77% of the no IMN treatment group (p = 0.001). There were no significant differences between the two groups for median age, menopausal status, histology, final surgical margin, estrogen and progesterone receptor status, or the number of positive nodes.

RESULTS: There were no significant differences in the 5- and 10-year cumulative incidence of an IBTR, regional node recurrence, initial or total distant metastases for the two groups. Similarly 5- and 10-year actuarial overall and cause-specific survival were not significantly different. However, subset analysis revealed a statistically significant increase in initial (29% vs. 15% at 10 yr, p = 0.002) and total (30% vs. 17% at 10 yr, p = 0.01) distant metastases and a significant decrease in cause-specific survival (76% vs. 89% at 10 yr, p = 0.02) for postmenopausal women who received IMN treatment. These findings could not be attributed to differences in the use of systemic therapy or the number of positive nodes. Axillary node-positive patients did not experience a significant decrease in initial (36% vs. 22% at 10 yr, p = 0.21) or total distant metastases (37% vs. 28% at 10 yr, p = 0.62) or a significant improvement in cause-specific survival (72% vs. 76% at 10 yr, p = 0.76) with IMN treatment regardless of whether the tumor was lateral or medial/central in location. IMN treatment was not associated with an increase in non-breast cancer deaths during this period of observation.

CONCLUSIONS: This retrospective series was unable to identify a significant benefit for IMN irradiation in terms of distant metastases or cause-specific survival for the entire patient population, and in particular, for patients with positive axillary nodes and medially located lesions. The results of the proposed or ongoing prospective randomized trials will further address this controversial issue.

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