Regional Nodal Irradiation for Early-Stage Breast Cancer

Summary and Comment |
July 22, 2015

Regional Nodal Irradiation for Early-Stage Breast Cancer

  1. Henry Mark Kuerer, MD, PhD, FACS

Two landmark trials — EORTC 22922/10925 and MA.20 — show an advantage for distant disease-free survival with RNI but no benefit for overall survival, the primary endpoint.

  1. Henry Mark Kuerer, MD, PhD, FACS

The potential survival advantage of regional nodal irradiation (RNI) in high-risk and node-positive early breast cancer is controversial in the modern era of effective adjuvant therapies and a greater understanding of molecular subtypes. Now, investigators have conducted two trials to address this issue.

In the EORTC 22922/10925 study by Poortmans and colleagues, 4004 patients were randomized to whole-breast or chest-wall radiotherapy with RNI (supraclavicular and internal mammary radiotherapy) versus without RNI (controls) from 1996 to 2004. Of these patients, 76% had breast-conserving surgery, 24% had mastectomy, 44% were node-negative, 96% had tumor size <5 cm, 43% had one to three positive nodes, 25% received adjuvant chemotherapy, 30% received adjuvant hormonal therapy, and 30% received both chemotherapy and hormonal adjuvant therapy.

At 10 years, the RNI group had similar rates of overall survival (OS; the primary endpoint) compared with controls (82.3% and 80.7%, respectively) but better rates of disease-free survival (DFS; 72.1% vs. 69.1%; P=0.04) and distant DFS (78.0% vs. 75.0%; P=0.02). The RNI group also had a higher rate of pulmonary fibrosis (4.4% vs. 1.7%; P<0.001).

In MA.20 study by Whelan and colleagues, 1832 patients were randomized to whole-breast radiotherapy with RNI (supraclavicular, internal mammary, and axillary irradiation) versus without RNI (controls) from 2000 to 2007. All patients had breast-conserving surgery, 90% were node-positive, 85% had one to three positive nodes, 99% had tumor size <5 cm, 91% received adjuvant chemotherapy, and 76% received adjuvant endocrine therapy.

At 10 years, the RNI group had similar rates of OS (the primary endpoint) compared with controls (82.8% and 81.8%, respectively) but better rates of DFS (82.0% vs. 77.0%; P=0.01), isolated local-regional DFS (95.2% vs. 92.5%; P=0.009; 63% of regional recurrence included the axillary nodes), distant-DFS (86.3% vs. 82.4%; P=0.03), and OS for estrogen receptor (ER)-negative patients (81.3% vs. 73.9%; P=0.05). The RNI group also had higher rates of grade 2 or higher pneumonitis (1.2% vs. 0.2%; P=0.01) and lymphedema (8.4% vs. 4.5%; P=0.001).

Comment

It is difficult to determine how to integrate these results into clinical practice, as more patients routinely receive taxanes and anti-HER2 directed therapies. The studies were designed prior to an understanding of molecular subtypes and the use of multigene expressions profiling. It is clear that RNI was associated with a 3% to 4% improvement in distant-DFS, but it is unknown if this would have been achieved with improved systemic therapies. The MA.20 study did demonstrate a 7.4% absolute improvement in OS among patients with ER-negative disease that approached significance. This group of patients may deserve consideration, although the results may not apply to ER-negative patients with smaller lesions or complete pathologic response to neoadjuvant therapy, as these subgroups are known to have improved prognosis. Also, it is too early to know the late cardiac effects of RNI, but it did increase pulmonary fibrosis and lymphedema in the short term. Finally, some radiation oncologists have been hesitant to deliver internal mammary radiotherapy, but these results suggest that if a decision is made to deliver RNI, it should be in conjunction with internal mammary nodal fields.

Editor Disclosures at Time of Publication

  • Disclosures for Henry Mark Kuerer, MD, PhD, FACS at time of publication Consultant / Advisory board Lightpoint Medical, Inc. Speaker's bureau Physicians’ Education Resource, LLC Royalties McGraw-Hill Professional; UpToDate, Inc. Grant / Research support National Cancer Institute; Genomic Health, Inc. Editorial boards Annals of Surgical Oncology Leadership positions in professional societies NRG Oncology (Institutional PI and Breast Committee); Society of Surgical Oncology (Chair, Curriculum Ad Hoc Committee, Breast Program Directors)

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