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.

Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis.

BACKGROUND: Brain metastasis (BM) is a rare event in ovarian cancer patients. The current prognostic scores that have been used for other tumors do not account for specific characteristics of ovarian cancer, such as platinum sensitivity. METHODS: This retrospective cohort study examined patients with ovarian carcinoma and BM who were treated at a single institution from January 2007 to December 2017. Clinical data on the diagnosis of BM and follow-up were collected. Cox regression was used to evaluate prognostic factors for overall survival (OS). RESULTS: Of 560 patients, 26 presented with BM. Eight patients were treated with surgery, 15 with whole-brain radiotherapy (RT), and 5 with stereotactic RT, and 4 patients received systemic treatment at the diagnosis of BM. The median OS was 10.8 months. The following factors were associated with OS: platinum-sensitive recurrence (HR 0.34, 95% CI 0.12-0.99; p = 0.049), higher number of previous treatment lines (HR 1.57, 95% CI 1.12-2.19; p = 0.008), ECOG performance status (HR 2.52, 95% CI 1.24-5.09; p = 0.010), and longer interval from initial diagnosis to BM (p = 0.025). Notably, the number of brain metastasis, the largest tumor size, and progression outside of the CNS were not related to survival. Platinum sensitivity was not associated with any of the classic prognostic factors in brain metastasis patients such as number or size of brain metastasis or disease progression outside the CNS strengthening the hypothesis of the importance of platinum sensitivity to the prognosis of ovarian cancer patients with BM. CONCLUSIONS: The factors related to the biological behavior of the ovarian cancer such as platinum sensitivity at the time of BM diagnosis, fewer number of previous treatment lines and interval from initial diagnosis were associated with survival in ovarian cancer patients with BM, while factors that are usually related to survival in BM in other cancers were not associated with survival in this cohort of ovarian cancer patients. The small number of patients did not allow us to exclude the prognostic role of these former factors that were not associated with survival in the present cohort.

Distinct systemic immune networks define severe vs. mild COVID-19 in hematologic and solid cancer patients.

Introduction: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain. Methods: Here we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients. Results: Individuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection. Conclusion: Our findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study.

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.

[Associated factors of lymphedema in breast cancer patients]. / Fatores associados ao linfedema em pacientes com câncer de mama.

PURPOSE: to determine the prevalence of lymphedema and its associated factors in breast cancer patients. METHODS: Two hundred and fifty women that had undergone more than six months of breast cancer treatment and were being treated at an oncology reference hospital in Juiz de Fora, Minas Gerais, Brazil. They were interviewed and submitted to physical evaluation. Data from the patients' medical records regarding the treatment of breast cancer, the extent of axillary intervention and the tumor were analyzed. Lymphedema was diagnosed when the difference between both upper limbs was 2 cm or more by perimetry. The groups of women with and without lymphedema were compared regarding the possible risk factors, and central tendency, dispersion, and prevalence were measured, with a significance level of 95%. RESULTS: One hundred and twelve women (44.8%) presented lymphedema. A significant difference was found between the groups of women with and without lymphedema regarding the median numbers of removed lymph nodes (p=0.02); presentation of superficial lymphatic thrombosis in the arm ipsilateral to the surgery (p<0.01); local application of radiotherapy, use of chemotherapy (p<0.01 for both); removal of the cuticles of the ipsilateral hand with pliers, and weightlifting after the treatment (p<0.01 and p=0.05, respectively). CONCLUSIONS: the association between lymphedema and the mentioned factors requires an interdisciplinary approach to this condition. It is of paramount importance that health teams and patients become aware of the prevention and treatment of lymphedema, a condition often undervalued.

Fatores associados ao linfedema em pacientes com câncer de mama / Associated factors of lymphedema in breast cancer patients

OBJETIVO: determinar a prevalência e os fatores associados ao linfedema em pacientes com câncer de mama. MÉTODOS: este estudo de corte transversal incluiu 250 mulheres com mais de seis meses de tratamento para o câncer de mama, que compareceram ao Ambulatório de Mastologia e Oncologia para consulta de seguimento em um Centro de Referência em Oncologia, em Juiz de Fora, Minas Gerais. Elas foram entrevistadas e submetidas à avaliação física. Foram colhidos dados de prontuário relacionados ao tratamento da neoplasia, à intervenção axilar e ao tumor. Diagnosticou-se linfedema quando a diferença entre os membros superiores foi maior ou igual a 2 cm pela perimetria. Os grupos de mulheres com e sem linfedema foram comparados em relação aos possíveis fatores de risco, e as medidas de tendência central, dispersão e prevalência foram obtidas admitindo o nível de significância de 95 por cento. RESULTADOS: Cento e doze mulheres (44,8 por cento) apresentaram linfedema. Foi encontrada diferença significativa entre os grupos de mulheres com e sem linfedema em relação à mediana de linfonodos retirados (p=0,02); apresentação de trombose linfática superficial no braço homolateral à cirurgia (p<0,01); quimioterapia e local de aplicação da radioterapia (p<0,01 para ambos); retirada de cutícula da mão com alicate e carregamento de peso após o tratamento (p<0,01 e p=0,05, respectivamente). CONCLUSÕES: a associação entre o linfedema e os fatores citados requer a abordagem interdisciplinar dessa morbidade. Faz-se necessária a conscientização das equipes de saúde e das pacientes quanto à prevenção e formas de tratamento para essa complicação, muitas vezes, subvalorizada.

PURPOSE: to determine the prevalence of lymphedema and its associated factors in breast cancer patients. METHODS: Two hundred and fifty women that had undergone more than six months of breast cancer treatment and were being treated at an oncology reference hospital in Juiz de Fora, Minas Gerais, Brazil. They were interviewed and submitted to physical evaluation. Data from the patients' medical records regarding the treatment of breast cancer, the extent of axillary intervention and the tumor were analyzed. Lymphedema was diagnosed when the difference between both upper limbs was 2 cm or more by perimetry. The groups of women with and without lymphedema were compared regarding the possible risk factors, and central tendency, dispersion, and prevalence were measured, with a significance level of 95 percent. RESULTS: One hundred and twelve women (44.8 percent) presented lymphedema. A significant difference was found between the groups of women with and without lymphedema regarding the median numbers of removed lymph nodes (p=0.02); presentation of superficial lymphatic thrombosis in the arm ipsilateral to the surgery (p<0.01); local application of radiotherapy, use of chemotherapy (p<0.01 for both); removal of the cuticles of the ipsilateral hand with pliers, and weightlifting after the treatment (p<0.01 and p=0.05, respectively). CONCLUSIONS: the association between lymphedema and the mentioned factors requires an interdisciplinary approach to this condition. It is of paramount importance that health teams and patients become aware of the prevention and treatment of lymphedema, a condition often undervalued.

Parasitoses intestinais: uma revisão sobre seus aspectos sociais, epidemiológicos, clínicos e terapêuticos / Intestinal parasitic diseases: a review of social, epidemiologic, clinical and therapeutic aspects

No presente estudo, as enteroparasitoses mais prevalentes no Brasil foram avaliadas segundo determinantes sociais,aspectos epidemiológicos, clínicos e terapêuticos. Através de breve revisão de literatura e com base nos resultadosde estudos de prevalência, são sintetizados achados que corroboram a associação de sua alta prevalência à pobrezae ao subdesenvolvimento. Foi dedicada especial atenção adoenças tais como a esquistossomose, a giardíase, a ancilostomíase,a amebíase, a estrongiloidíase, a ascaridíase e ateníase. Também estão sumarizadas referências às principaisdrogas antiparasitárias, modo de ação, efeitos adversose avaliação da eficácia de cada tratamento. Destaca-se aimportante atualização dos profissionais da atenção primária nesse assunto e o reconhecimento de que esforços são necessários para maximizar os benefícios adquiridos com o tratamento medicamentoso e manter a qualidadeda saúde da população através da melhoria das condiçõesde saneamento e educação em saúde.

In the present study, the most prevalent enteroparasitosisin Brazil were assessed according to social, epidemiologic,clinical and therapeutic aspects. Through a brief review of the literature, and based on the results of several prevalence studies, high prevalence rates associated with povertyin under developed nations were found and stressed inthe article. Diseases such as schistosomiasis, giardiasis,ancylostomiasis, strongyloidiasis, ascaridiasis and taeniasiswere given more emphasis. There are also references to themain antiparasitc drugs and to their mechanism of action,adverse effects, and efficacy. Primary health care professional smust keep abreast of this subject, and be able toacknowledge that efforts are necessary in order to maximize the benefits of drug treatment and maintain the quality of health of the population, through the improvement of sanitary conditions and health education.