Outcomes of locally advanced breast cancer patients with ≥10 positive axillary lymph nodes

Abstract

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.

Prognostic Factors in Operated Stage IIIC, Pathological N3a Breast Cancer Patients

“…In the current study, the HER2 positivity rate was 40.4%. This was also consistent with a previous retrospective study in Turkey [10]. The proportion of operable stage IIIC BC was approximately 13% in 2 large randomized adjuvant trastuzumab trials [19,20].…”

“…The lymph node ratio (LNR) was previously defined as the number of positive lymph nodes compaired to the total number of removed lymph nodes [10,11]. In the present study, we used 0.75 as the cut-off point because the largest DFS and OS differences were found when 0.75 was taken as the cut-off point.…”

“…These patients constitute only a small subset of the study population in large-scale prospective BC trials [6]. Retrospective studies usually have nonhomogeneous patient populations [7,8,9,10]. A recent study noted that, unlike early recurrence, the tumor biology may have a more important role than the tumor load (positive lymph nodes) for late recurrence in ER-positive disease [11,12].…”

Risk Factors for Locoregional Recurrence After Postmastectomy Radiotherapy in Breast Cancer Patients with Four or More Positive Axillary Lymph Nodes

“…In addition, Chang et al 20 and Koca et al 21 reported that the 5-year lrr rate was 13%-24% in patients with breast cancer at stage pN3 after pmrt, and the 5-year dfs was only about 46%. Those results are consistent with our finding that patients with pN3 breast cancer had a high risk of lrr after pmrt.…”

Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers

“…Metastatic occurrence often accompanies disease relapse, contributing to an 80% mortality rate, and estimated 450 000 deaths worldwide. 1,5,6 Treatment of breast cancer is complicated by the presence of different molecular subtypes. These subtypes include: luminal A, luminal B, Her2 overexpressing (Her2+), and basal-like breast cancers.…”