Breast cancers with 10 or more positive lymph nodes at the time of diagnosis are staged as pathological N3a (pN3a) and they have poor prognosis. Recent studies showed five-year disease-free survival (DFS) and overall survival (OS) rates of N3a disease as 43-66 and 58-81 %, respectively. We herein present outcomes of our patients with stage pN3a breast cancer. Among 2,578 patients diagnosed with invasive breast carcinoma at Hacettepe University Hospital between 2002 and 2012, 218 patients (8.4 %) had pN3a disease and were included and analyzed retrospectively in this study. Patients with internal mammary, infraclavicular, and supraclavicular node metastasis or distant metastasis at initial diagnosis were excluded. Demographic features, tumor characteristics, treatment regimens, and patient outcomes in terms of DFS and OS were analyzed. Lymph node ratio was defined as the ratio of positive to total removed lymph nodes. The median age was 49. Most common histological subtype was ductal carcinoma (82.1 %). About 82.6 % of patients had stage T2/T3 cancers and 47.7 % (104) had grade III cancers. Estrogen and progesterone receptors were positive in 133 (61 %) and 121 (55.5 %) patients, respectively. HER2 status was known for 213 patients and was positive in 87 (39.9 %) patients. A total of 27 (12.6 %) patients had triple-negative tumors. Lymphovascular invasion, extracapsular extension, and perineural invasion were present in 106 (48.6 %), 105 (48.2 %), 20 (9.2 %) cases, respectively. A total of 18 patients (8.3 %) received neoadjuvant and 200 patients (91.7 %) received adjuvant chemotherapy, mostly with anthracycline- (95 %) and taxane (60 %)-containing regimens. A total of 210 patients (96.3 %) received radiotherapy. Median follow-up was 39.5 months. A total of 96 patients relapsed on follow-up and 64 patients died. Nineteen of the relapses were locoregional and 77 were distant relapses. The 5-year DFS rate was 46.2 % and the OS rate was 69.8 %. In multivariate Cox regression analysis, grade III disease (HR 1.899, 95 % CI 1.196-3.017, P = 0.007), perineural invasion (HR 2.519, 95 % CI 1.341-4.731, P = 0.004), and lymph node ratio (≥ 0.9 vs. <0.9) (HR 2.290, 95 % CI 1.368-3.835, P = 0.002) were significantly associated with DFS, and grade III disease (HR 2.679, 95 % CI 1.500-4.782, P = 0.001) and lymph node ratio (≥ 0.9 vs. <0.9) (HR 2.182, 95 % CI 1.211-3.932, P = 0.009) were significantly associated with OS. Patients with pN3a disease in our cohort have comparable survival rates with other reports in the literature. Within this high risk group of patients, those with grade III disease, perineural invasion, and lymph node ratio ≥ 0.9 seem to confer poorer prognosis.

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Purpose. To evaluate the proportion of premenopausal women who experience persistent ovarian escape (OE) while receiving ovarian suppression (OS) therapy for estrogen receptor positive (ER+) breast cancer treatment. The study also examines clinical factors that may predispose to higher risk of persistent OE. Methods/Materials. This was a retrospective, "real-world" study to evaluate premenopausal women receiving adjuvant endocrine OS therapy. The primary objective was to measure the percentage of persistent OE within the first 3 months of OS injections (using either leuprolide or goserelin). The secondary objective was to associate baseline clinical data (age, body mass index (BMI), and previous chemotherapy) with the probability of OE. Results. Of the 46 patients included in this analysis, 11 (23.9%) women did not achieve OS within 3months. Three women (6.5%) remained in OE at 12 months. Older age (Odds Ratio 0.86 (0.76-0.98), p=0.024) was associated with lower chance of developing OE. BMI, previous chemotherapy, and drug used (tamoxifen versus aromatase inhibitor) did not correlate with the likelihood of OE in this patient cohort. Conclusion. Among the premenopausal women who did not attain complete ovarian suppression, young age was a significant risk factor for likelihood of OE. Although the clinical relevance of this finding is not yet known, it should prompt further studies to determine whether inadequate OS is associated with higher recurrence risk for ER+ breast cancer patients. The Oncologist 2021;9999:• • Implications for Practice: Because up to a quarter of premenopausal women do not attain adequate ovarian suppression within the first three months of GnRH agonist therapy, bloodwork should be checked to ascertain hormone levels prior to starting aromatase inhibitor therapy, and at regular intervals, for these women.

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