Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer

Abstract

BACKGROUND The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracicwall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median followup of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).

Why do we need irradiation of internal mammary lymph nodes in patients with breast cancer: Analysis of lymph flow and radiotherapy studies

“…According to data published by Poortmans et al, 3 In prospective randomized trial MA20 only 88 of 916 patients with irradiated IMLN had negative axillary LN. 6 In this trial benefits after IMLN irradiation in 10 year overall, disease-free and distant metastatic-free survival accounted to 1.0%, 5.0% and 3.9%, respectively.…”

“…Later study by Postma et al 12 Localization of primary tumour significantly correlated with probability of lymph flow to IMLN. In order to calculate the probability of lymph flow from primary lesions, localized [3][4][5][6][7][8] As in descriptions of some studies we did not find figures that characterized patient distribution according to localization of primary lesion in the breast, we used average rate extracted from two large population based trials. 8,14 In accordance with these studies, we assumed that, on average, 32% of women with BC had internal/central and remaining 68% -external localization of primary tumour.…”

“…Obtained results indicated that in these patients with BC irradiation of IMLN can substantially (1-3%) reduce frequency of local and distant recurrences with borderline improvement in 5-10 year disease-free survival. [3][4][5][6][7][8] Small but reproducible improvement in overall survival that was mentioned in most studies pointed out that in some patients with BC irradiation of IMLN can evidently improve treatment efficacy. At the same time, it is clear that routinely used clinical factors (tumour localization, regional lymph node status) are not very powerful in discriminating those women who would benefit from IMLN irradiation and those who would not.…”

Personalized radiotherapy for invasive breast cancer in 2017

“…Based on the PMRT data, two recent randomized trials (MA20, EORTC), and a Danish cohort study [18][19][20], the indication for RNI was expanded following BCS [21][22][23]. Depending on the number of positive nodes (>3, 1-3, 0 but high risk), the strength of the recommendation to include the supraclavicular/medial axillary region decreases in AGO (++, +, +/-) and in S3 (have to/should/can).…”

A tailored approach to regional nodal irradiation

“…A tailored approach adding regional nodal irradiation only to patients with involvement of the internal mammary nodes is improving prognosis while minimizing morbidity.The results of the EORTC trial on Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer were recently reported in NEJM (July 23 issue) [1]. Patients with centrally or medially located primary tumors irrespective of axillary involvement or externally located tumors with axillary involvement were randomized in a 1:1 fashion to the addition of regional nodal irradiation to the standard breast or chest wall radiation.…”