Locoregional Recurrence Risk in Breast Cancer Patients with Estrogen Receptor Positive Tumors and Residual Nodal Disease following Neoadjuvant Chemotherapy and Mastectomy without Radiation Therapy

Hindawi Publishing Corporation International Journal of Breast Cancer Volume 2015, Article ID 147476, 7 pages http://dx.doi.org/10.1155/2015/147476 Research Article Locoregional Recurrence Risk in Breast Cancer Patients with Estrogen Receptor Positive Tumors and Residual Nodal Disease following Neoadjuvant Chemotherapy and Mastectomy without Radiation Therapy Shravan Kandula,1,2 Jeffrey M. Switchenko,3 Saul Harari,4 Carolina Fasola,5 Donna Mister,1,2 David S. Yu,1,2 Amelia B. Zelnak,2,6 and Mylin A. Torres1,2 1 Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA 3 Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA 4 Department of Pathology, Emory University, Atlanta, GA 30322, USA 5 Department of Radiation Oncology, Stanford Medical Center, Stanford, CA 94305, USA 6 Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA 2 Correspondence should be addressed to Mylin A. Torres; Received 2 April 2015; Accepted 1 July 2015 Academic Editor: Ian S. Fentiman Copyright © 2015 Shravan Kandula et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) and mastectomy, locoregional recurrence (LRR) rates are unclear in women with ER+ tumors treated with adjuvant endocrine therapy without postmastectomy radiation (PMRT). To determine if PMRT is needed in these patients, we compared LRR rates of patients with ER+ tumors (treated with adjuvant endocrine therapy) with women who have non-ER+ tumors. 85 consecutive breast cancer patients (87 breast tumors) treated with NAC and mastectomy without PMRT were reviewed. Patients were divided by residual nodal disease (ypN) status (ypN+ versus ypN0) and then stratified by receptor subtype. Among ypN+ patients (𝑛 = 35), five-year LRR risk in patients with ER+, Her2+, and triple negative tumors was 5%, 33%, and 37%, respectively (𝑝 = 0.02). Among ypN+/ER+ patients, lymphovascular invasion and grade three disease increased the five-year LRR risk to 13% and 11%, respectively. Among ypN0 patients (𝑛 = 52), five-year LRR risk in patients with ER+, Her2+, and triple negative tumors was 7%, 22%, and 6%, respectively (𝑝 = 0.71). In women with ER+ tumors and residual nodal disease, endocrine therapy may be sufficient adjuvant treatment, except in patients with lymphovascular invasion or grade three tumors where PMRT may still be indicated. 1. Introduction Traditionally, postmastectomy radiation (PMRT) decisions have been guided by pathologic findings in breast cancer patients treated with initial surgery. In this setting, data from several studies have led to guidelines which have identified patients most likely to benefit from PMRT: those with primary tumors greater than five centimeters, four or more positive lymph nodes (pN2), or one to three positive lymph nodes (pN1) with high-risk features such as extracapsular extension (ECE) and lymphovascular invasion (LVI) [1–3]. However, these same recommendations do not necessarily apply to patients treated with neoadjuvant chemotherapy (NAC) where the initial extent of disease is unknown and can be modified in as many as 80% of patients [4]. There are no published randomized trials to guide the use of PMRT in women treated with NAC [5]. Retrospective studies have suggested that both advanced initial clinical stage and residual pathologic nodal disease (ypN) are associated with a higher risk of locoregional recurrence (LRR) in women 2 treated with NAC [6–11]. However, there are many instances in which the initial clinical stage is unclear despite physical exam and modern imaging. The inaccuracies of physical exam are best demonstrated by the results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 which found that 40% of clinically node negative (cN0) patients on physical exam were actually pathologically node positive (pN+), while 25% of cN+ patients were actually pN0 [12]. Modern imaging has resulted in only modest improvements in detection of axillary nodal metastases, with broad sensitivity and specificity ranges reported for ultrasound (43.5–86.2% and 40.5–86.6%, resp.) [13–16], magnetic resonance imaging (MRI) (36–78% and 78–100%, resp.) [16–20], and full body fluorodeoxyglucose- (FDG-) positron emission tomography (PET)/computed tomography (CT) (20–100% and 75–100%, resp.) [21]. Therefore, clinical staging may not accurately reflect the extent of disease prior to NAC and may lead to under- or overtreatment with PMRT. Furthermore, other studies have indicated that residual nodal response following NAC plays a larger role in determining LRR risk than initial clinical stage or primary breast tumor response (ypT status) [9, 22]. Patients with complete nodal response to NAC were found to have a very low risk of LRR despite having locally advanced disease initially at presentation [23, 24]. Therefore, ypN status is arguably a more robust and consistent predictor of LRR in the NAC setting. Nevertheless, as there is heterogeneity in the risk of LRR among pN1 patients, there is also potentially a spectrum of LRR risk among ypN1 patients. Few studies have examined the impact of receptor status on LRR risk in ypN+ or ypN0 patients. The LRR risk is unclear in patients with estrogen receptor positive (ER+) tumors and ypN+ disease who are treated with adjuvant endocrine therapy without PMRT. The Early Breast Cancer Trialists Collaborative Group meta-analysis demonstrated that the addition of PMRT significantly improved 15-year breast cancer-specific survival in patients with a greater than 10% LRR risk [25]. The Athena Breast Health Network thus adopted an absolute LRR risk threshold of 10% before recommending PMRT in patients treated with NAC [26]. The aim of our research was to compare LRR risk among breast cancer patients with ER+ tumors (treated with adjuvant endocrine therapy) and those patients with nonER+ tumors following NAC and mastectomy without PMRT. Given the shortcomings of initial clinical staging, we also sought to identify additional objective pathological factors that contribute to a five-year LRR risk of greater than 10%. 2. Materials and Methods 2.1. Patient Population. At our institution, NAC is typically administered in patients with large primary tumor to breast size ratios, locally advanced or initially unresectable breast cancers, and/or triple negative and Her2+ tumors. Following approval from the institutional review board, the medical records of breast cancer patients treated with modern anthracycline and/or taxane-based NAC between 1997 and 2011 were reviewed. 553 breast cancer patients (with noninflammatory, nonmetastatic canc (...truncated)