HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer.

PURPOSE: Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC. METHODS: Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0. RESULTS: In total, 855 HER2-negative patients were identified. The median follow-up was 59 months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0. CONCLUSION: Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.

Contagem de leucócitos e morbimortalidade no infarto do miocárdio / Leukocyte count and morbimortality in myocardial infarction

Objetivo: Avaliar a associação entre maiores níveis da contagem total de leucócitos periféricos e relação neutrófilos/linfócitos obtidos na admissão hospitalar, bem como a morbimortalidade em pacientes diagnosticados com infarto do miocárdio. Métodos: Avaliamos 276 pacientes com infarto agudo do miocárdio, entre janeiro de 2014 e novembro de 2015. Os dados clínicos e laboratoriais foram obtidos e relacionados a: internação, complicações intra-hospitalares, readmissões e mortalidade em 30 dias pós-internação. Resultados: A idade média foi 61 anos e 66,7% eram homens. Pacientes com complicações, comparados ao grupo sem complicações, eram mais velhos (60,85 vs. 62,54; p=0,053), tinham níveis de leucócitos (10,23 vs. 11,78; p=0,001) e neutrófilos (7,17 vs. 8,38; p=0,020) aumentados, doença multiarterial (38,2% vs. 74,5%; p<0.001) e supradesnivelamento de ST (49,3 vs. 65,1; p=0,039). Dois grupos foram constituídos pela mediana (10,56) dos leucócitos e demonstraram-se incidências mais elevadas de choque cardiogênico (p<0,001) e mortes (p=0,031) no grupo com maior leucocitose. Houve associação significativa entre leucócitos >10,56 e valores superiores de CK-MB (p=0,001) e troponina (p=0,039). Conclusão: Houve associação entre aumento dos níveis de leucócitos e maior incidência de complicações intra-hospitalares, incluindo morte, até 1 mês após alta hospitalar em pacientes com infarto agudo do miocárdio. A contagem de leucócitos mostrou relação mais evidente do que a relação neutrófilos/linfócitos e sua fácil acessibilidade colocá-o como ferramenta útil para determinação do prognóstico em pacientes com infarto do miocárdio.(AU)

Objective: To evaluate the association of higher levels of total peripheral leukocytes count and neutrophil/lymphocyte ratio at admission, as well as morbidity and mortality in patients diagnosed with myocardium infarction. Methods: We evaluated 276 patients with Acute Myocardial Infarction through January 2014 to November 2015. Clinical and laboratory data were obtained and related to hospital stay, inhospital complications, 30 day readmissions and mortality. Results: The average age was 61 years, 66.7% were male. Patients with complications, compared to the group with no complications, are older (60.85 vs 62.54, p=0.053), had increased levels of leucocytes (10.23 vs 11.78, p=0.001) and neutrophils (7.17 vs 8.38, p=0.020) count, multivessel disease (38.2% vs 74.5%, p<0.001) and ST elevation (49.3 vs 65.1, p=0.039). Two groups were formed by leucocyte median, and a higher incidence of cardiogenic shock (p<0.001) and deaths (p=0.031) was shown in the group with higher leuco cytosis. There was significant association between leucocytes >10.56 and higher CKMB (p=0.001) and troponin (p=0.039) values. Conclusion: Our study confirms an association between increased levels of leucocytes count and higher incidence of inhospital complications, including death, up to one month after hospital discharge in patients with acute myocardial infarction. Leucocytes count showed a more evident relation than neutrophil/lymphocyte ratio, and its easy accessibility poses it as a very useful tool to determine prognosis in patients with myocardial infarction.(AU)