Clinical decision making in postmastectomy radiotherapy in node negative breast cancer.

Ecancermedicalscience. 2018; 12: 874. Published online 2018 Sep 26. doi: 10.3332/ecancer.2018.874 PMCID: PMC6214678 PMID: 30483354 Clinical decision making in postmastectomy radiotherapy in node negative breast cancer Rodrigo Barrientos,1 Suraj Samtani,3 Michael Frelinghuysen,2 Camilo Sotomayor,2 Juan Guillermo Gormaz,3 and Mauricio Burotto4 Rodrigo Barrientos 1Department of Radiation Oncology, Instituto de Radiomedicina IRAM, Santiago, Chile Find articles by Rodrigo Barrientos Suraj Samtani 3Department of Medical Oncology, Clinica Alemana Santiago, Vitacura, Chile Find articles by Suraj Samtani Michael Frelinghuysen 2Radiation Oncology Unit, Hospital Clinico Regional de Concepción, Concepción, Chile Find articles by Michael Frelinghuysen Camilo Sotomayor 2Radiation Oncology Unit, Hospital Clinico Regional de Concepción, Concepción, Chile Find articles by Camilo Sotomayor Juan Guillermo Gormaz 3Department of Medical Oncology, Clinica Alemana Santiago, Vitacura, Chile Find articles by Juan Guillermo Gormaz Mauricio Burotto 4Centro de Investigación Clínica Bradfordhill, Santiago, Chile Find articles by Mauricio Burotto Author information Article notes Copyright and License information Disclaimer 1Department of Radiation Oncology, Instituto de Radiomedicina IRAM, Santiago, Chile 2Radiation Oncology Unit, Hospital Clinico Regional de Concepción, Concepción, Chile 3Department of Medical Oncology, Clinica Alemana Santiago, Vitacura, Chile 4Centro de Investigación Clínica Bradfordhill, Santiago, Chile Correspondence to: Mauricio Burotto. moc.liamg@ottoruboiciruam Received 2018 Apr 25 Copyright © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract For decades, postmastectomy radiotherapy (PMRT) has been recommended for node positive [N(+)] breast cancer patients; nevertheless, the beneficial effect of PMRT for treatment of node negative [N(−)] disease remains under discussion. Nowadays, the biology of breast cancer and the risk factors (RFs) for locoregional failure (LRF) must be included in the decision on whether or not to carry out PMRT. For these reasons, the present review aims to evaluate the rationale use of PMRT in N(−) patients and discuss which subgroups may further benefit from the treatment in present times where the decision must be personalised, according to the RFs of locoregional recurrence (LRR). To perform the analysis, we ponder that LRR of over 10% should be considered unacceptable due to the fact that LRRs generate great morbidity in patients. For this purpose, we consider that routine RT in these patients is not recommended, although there are subgroups of patients with high LRR, in which PMRT could be beneficial. Keywords: postmastectomy radiotherapy, node negative breast cancer, breast cancer radiotherapy Introduction Currently, breast cancer is the second most prevalent cancer in women, after nonmelanoma skin malignant diseases. In fact, it is estimated that 30% of new cancer cases and 25% of deaths caused by cancer in women are due to breast cancer in 2018 [1], with a cumulative incidence and mortality of 126.01/100,000 and 27.91/100,000, respectively [2, 3]. For decades, postmastectomy radiotherapy (PMRT) has been recommended for node positive [N(+)] breast cancer patients. Of note, between 1997 and 2005, three randomised controlled trials reignited the debate about the role of PMRT, especially in the specific clinical setting of N(+) disease patients [4–6]; however, the beneficial effects of PMRT for treatment of node negative [N(−)] disease remains under discussion [7]. The present review has the purpose of evaluating the indications of PMRT in N(−) patients and discusses which subgroups may further benefit from treatment in this setting. To analyse this issue, we ponder that locoregional recurrence (LRR) of over 10% should be considered unacceptable, based on node negative breast conservative randomised trials that showed LRR rates of 6.2%–6.7% [8, 9]. Role of postmastectomy radiotherapy A recent meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) [7] investigated 22 trials that included 8,135 breast cancer patients who were treated with total mastectomy (TM), randomised to receive either further RT or observation. At 20 years of follow-up, N(+) disease patients who received PMRT showed a reduction in risk of LRR from 26% to 8.1%, with a reduction in absolute risk of breast cancer mortality of 8.1% (RR 0.84; 95% CI 0.76–0.94), whereas PMRT in N(−) disease patients increased overall mortality (RR 1.23; 95% CI 1.02–1.49, 2p = 0.03), despite the fact that current numbers show that mortality in N0 patients is low. Locoregional relapse should always be considered for the analysis of PMRT effectiveness because radiation therapy exerts its main benefit decreasing its occurrence. In the context of mastectomised patients, LRR is associated with a diminished quality of life, higher risk of mortality and lack of satisfactory results after performing either surgical or radiation rescue therapy. To clarify the magnitude of this problem, once an LRR has been diagnosed, patients have decreased survival rates (ranging from 46% to 63%) [10–12] and higher risk of distant failure (DF) [13]. In fact, Locoregional control plays an important role in both overall survival (OS) and distant disease [10, 11, 13, 14]. The time of diagnosis is especially relevant considering that adjuvant chemotherapy (QT) has shown poor results and no OS benefit after isolated LRR [15–18]. For all these reasons, and the fact that rational use of irradiation according to normal tissue tolerance doses is rarely associated with acute skin moist desquamation and late adverse effects (such as rib fracture, radiation pneumonitis, ischaemic heart disease and second malignancies) [19–22], we think that certain subgroups of N0 patients would benefit from receiving PMRT. Why PMRT may benefit different subgroups of N(−) patients? Breast cancer is a heterogeneous disease with several molecular subtypes. Perou et al classified breast cancer into four distinct molecular subtypes based on a genetic profile: Luminal A, Luminal B, Her2 enriched and basal-like [23, 24], each of them with variable prognosis and different survival rates. In fact, Triple Negative Breast Cancer (TNBC) (a surrogate of basal-like disease) is associated with an increased risk of LRR [25, 26] and breast cancer specific survival (BCSS) [27]. This continues to be a topic under active investigation, but a proper analysis of the data can help in taking a proper decision regarding whether a patient could benefit from PMRT. As a matter of fact, RT see (...truncated)