BackgroundCyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the impact of NLR on survival in mBC patients treated with first line CdK4/6i.MethodsAll mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. The biomarker threshold was defined using ROC curves. We analyzed progression free survival (PFS), overall survival (OS), 12-month PFS and response rate according to NLR in univariable and multivariable analysis.ResultsA total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 33 months [range: 2.9–57]. Median age was 65 years [29-86], 40% patients had good performance status (ECOG-PS 0). Most patients (71%) were included at the metastatic relapse stage and 29% had only bone metastases. Median PFS and median OS were 27 and 51 months, respectively. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.50, CI95% = [0.32–0.79]) and worse OS (HR=0.45, [CI95%: 0.23–0.87]). In multivariable analysis, NLR and ECOG PS were independently factors associated with PFS (p=0.016 and p=0.001, respectively).ConclusionHigh NLR was associated with worse PFS and OS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could help optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

Background HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification). Methods We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed. Results We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15–0.84] and HR = 0.24 [0.07–0.81], respectively). NLR was not associated with worse DFS or OS. Conclusion In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.

A 71-year-old man presented with 6 kg weight loss since 4 months and asthenia. He also had mild cough for a few weeks, sudden stabbing thoracic pain recurring at rest without radiation, and no dyspnea.The patient had a history of chronic weaned alcoholism, active smoking, hypertension on triple therapy, and professional exposure to paint. The last transthoracic echocardiography (TTE) performed 6 months before his admission showed an isolated septal hypertrophy at 13 mm without supplementary cardiac abnormalities. At admission, hemoglobin was 138 g/L, platelet and leukocyte counts were 369 × 10 9 /L and 10.1 × 10 9 /L, respectively, C-reactive protein was 51 mg/L, lactate dehydrogenase (LDH) was 8.57 µkat/L, and troponin I was 86.6 µg/L. Neither clinical nor electrocardiogram additional abnormalities were identified. TTE exhibited a significant necrotic intracardiac mass. Computed tomography (CT) highlighted an 80 × 80 mm infiltrating heart mass centered on the right atrioventricular septum with extension to the tricuspid ring (Figure 1, left image), a mediastino-hilar lymphadenopathy, a 15 mm right posterobasal pulmonary nodule, and a thin layer of right pleural effusion. A biopsy of the mediastinal lesion by endoscopic ultrasound revealed large B cells, strongly positive for CD20 antigen as well as CD19, CD5 (low intensity), CD10, CD38, CD79b, and FMC7 marker proteins with a Ki-67 of 70%. Although biopsy was not large, the pathological diagnosis suggested a diffuse large B-cell lymphoma. During hospitalization, a repeated CT showed increased necrotic areas in mediastinal mass, layer of right pericardial effusion, right posterobasal pulmonary nodule, bilateral pleural effusions with passive atelectasis precluding another biopsy, and hepatosplenomegaly. After occurrence of second-degree atrioventricular This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.