Clinical Outcomes And Prognostic Factors In Locally Advanced Breast Cancer Patients With Estrogen Receptor-Positive, Her2-Negative Subtype Treated With Neoadjuvant Chemotherapy And Surgery Followed By Postmastectomy Radiation Therapy

The aim of this study was to determine clinical outcomes and identify reliable prognostic factors in patients with locally advanced breast cancer who had estrogen receptor (ER) positive and HER2 negative subtype treated with neoadjuvant chemotherapy (NAC) followed by mastectomy and PMRT in the modern treatment era. We retrospectively evaluated the relationship between clinicopathological factors and clinical outcomes in 216 patients with ER positive and HER2 negative, stage II or III breast cancer who underwent NAC followed by radical mastectomy and PMRT between March 2005 and December 2013. Locoregional recurrence free survival rate (LRFS), distant metastasis free survival rate (DMFS), and overall survival rate (OS) were calculated as clinical outcomes. All patients received a radical modified mastectomy. Patients were typically treated with anthracycline and taxane-based chemotherapy before surgery. The indications for PMRT were a diagnosis of ≥4 positive axillary lymph nodes by clinical evaluation including ultrasonography before treatment, diagnosis of a positive ipsilateral supraclavicular lymph node, or internal mammary region and a T4 or positive surgical margin of the chest wall. PMRT was performed with up to 50 Gy with photon beams using the partially wide tangential technique to the CW and anterior supraclavicular region. If the surgical margin was positive, an electron boost of 10 Gy to16 Gy was added for the involved area of the CW. Between 2005 and 2007, the IMN (intercostal space 1-3) was prophylactically irradiated if a patient had ≥10 positive lymph nodes or if ≥4 positive lymph nodes and the tumor were located on the inner part of the breast. Between 2007 and 2013, we included the IMNs in the clinical target volumes for all patients. The median follow-up duration was 81 months (range, 12–156 months). Fourteen patients experienced locoregional recurrence, 83 patients experienced distant failure, and 59 patients died of cancer. For all patients, the 5-year LRFS, DMFS, and OS were 94.1%, 69.4 %, and 85.1 %, respectively. Pathological CR rate was 1.4 %. On multivariate analysis, nuclear grade (NG), fat infiltration and nodal ratio (NR; number of positive axillary node/removed node) were significant prognostic factors of DMFS and OS. The patients with low NG (NG1/2) had significantly better 5-year OS than patients with high NG (NG3) (89.3 % vs. 65.0 %, p = 0.001), and patients with low NR (NR<30) had significantly better 5-year OS than patients with high NR (NR≧30) (93.6 % vs. 76.1 %, p=0.0003). The 5-year OS was significantly better in patients with low fat infiltration than those with high fat infiltration (95.6 % vs. 80.2 %, p=0.02). pCR and ypN0 were not significantly related to clinical outcomes. We identified several prognostic factors; in particular, NG, NR, and fat infiltration were significantly related to OS.