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Background: Cancer patients (CPs) are considered more vulnerable and as a high mortality group regarding COVID-19. In this analysis, we aimed to describe asymptomatic COVID (+) CPs and associated factors. Methods: We conducted a prospective study in CPs and health care workers (HCWs) in 4 French cancer centers (PAPESCO [ PAtients et PErsonnels de Santé des Centres de Lutte Contre le Cancer pendant l'épidémie de COvid-19 ] study). This analysis used data recorded between June 17, 2020 and November 30, 2020 in CPs (first 2 waves, no variants). At inclusion and quarterly, CPs reported the presence of predefined COVID-19 symptoms and had a blood rapid diagnostic test; a reverse transcription polymerase chain reaction (RT-PCR) was done in case of suspected infection. Results: A total 878 CPs were included; COVID-19 prevalence was similar in both CPs (8%) and HCWs (9.5%); of the 70 CPs (8%) who were COVID (+), 29 (41.4%) were and remained asymptomatic; 241/808 of the COVID (−) (29.8%) were symptomatic. 18 COVID (+) were hospitalized (2% of CPs), 1 in intensive care unit (ICU) and 1 died (0.1% of CPs and 2.4% of symptomatic COVID [+] CPs). Only the inclusion center was associated with clinical presentation (in Nancy, Angers, Nantes, and Clermont-Ferrand: 65.4%, 35%, 28.6%, and 10% CPs were asymptomatic, respectively). Conclusions: Seroprevalence of COVID-19 in CPs was similar to that observed in HCWs; mortality related to COVID-19 among CPs was 0.1%. More than 40% of COVID (+) CPs were asymptomatic and one third of COVID (−) CPs had symptoms. Only geographic origin was associated with the presence or absence of symptoms. Social distancing and protective measures must be applied in CPs at home and when hospitalized. [ABSTRACT FROM AUTHOR]

Recently many therapeutic classes have emerged in advanced hormone receptor-positive breast cancer, which is the leading cause of cancer death in women. In absence of visceral crisis, treatment relies on endocrine therapy combined with cyclin dependent kinase 4 and 6 inhibitor. Many mechanisms lead to resistance to endocrine therapy, including the activation of intracellular signaling pathways critical for cell survival. Approximately 70% of breast tumors harbor an alteration in the phosphoinositide 3 kinase (PI3K)/Akt pathway, leading to its hyper activation. This pathway is involved in the regulation of growth, proliferation and cell survival as well as in angiogenesis and is consequently a major target in the oncogenesis. An aberrant PIK3CA mutation is a common phenomenon in breast cancer and found in approximately 40% of patients with advanced hormone receptor-positive breast cancer. For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes). [ABSTRACT FROM AUTHOR]

Feline mammary carcinomas are highly malignant tumors usually associated with poor outcome. Nevertheless, survival times can differ significantly according to various prognostic factors. The Elston and Ellis (EE) histologic grading system, originally developed for human breast cancer, is commonly used to grade feline mammary carcinomas, although it is not really adapted for this species, hence the need of a more relevant grading system. Although few veterinary studies attempted to validate previously published results in an independent cohort, the aim of our study was to evaluate the prognostic value of different histologic grading systems in feline invasive mammary carcinomas, including the EE grading system applicable to human breast cancers and the modified and newly designed histologic grading systems recently proposed by Mills et al. Survey data and histologic features of 342 feline invasive mammary carcinomas were analyzed with respect to overall and cancer-specific survival. The histological grading system with best prognostic value was the mitotic-modified Elston and Ellis (MMEE) grading system: grade III carcinomas (P =.04, hazard ratio [HR] = 1.46, 95% CI, 1.01–2.11), grade II (P =.03, HR = 1.39, 95% CI, 1.03–1.88), and grade I carcinomas (HR = 1.00, reference), with decreasing hazard ratios significantly were associated with a worse overall survival, independently from the pathologic tumor size (pT ≥ 20 mm: P =.002, HR = 1.45, 95% CI, 1.15–1.83) and positive nodal stage (P =.001, HR = 1.51, 95% CI, 1.18–1.94). This retrospective study validates Mills et al's proposal to adapt the thresholds for mitotic counts to better assess the histological grade of the highly proliferative mammary carcinomas encountered in the cat. [ABSTRACT FROM AUTHOR]

Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy. A better characterization of this process is needed to overcome this resistance and to develop new tailored therapies. Mechanisms of resistance to hormone therapy result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway. The strategy of combined hormone therapy with targeted agents has shown an improvement of progression-free survival (PFS) in several phase II or III trials, including three different classes of drugs: mTOR inhibitors, PI3K and CDK4/6 inhibitors. A recent phase III trial has shown that fulvestrant combined with a CDK 4/6 inhibitor doubles PFS in aromatase inhibitor-pretreated postmenopausal ER+ breast cancer. Other combinations are ongoing to disrupt the interaction between PI3K/AKT/mTOR and cyclin D/CDK4/6/Rb pathways. Despite these successful strategies, reliable and reproducible biomarkers are needed. Tumor genomics are dynamic over time, and blood-based biomarkers such as circulating tumor DNA represent a major hope to elucidate the adaptive mechanisms of endocrine resistance. The optimal combinations and biomarkers to guide this strategy need to be determined. [ABSTRACT FROM AUTHOR]

Background: Fluoropyrimidines (FPs) carry around 20% risk of G3-5 toxicity and 0.2-1% risk of death, due to dihydropyrimidine dehydrogenase (DPD) deficiency. Several screening approaches exist for predicting toxicity, however there is ongoing debate over which method is best. This study compares 4 screening approaches. Method: 472 patients treated for colorectal, head-and-neck, breast, or pancreatic cancers, who had not been tested pre-treatment for FP toxicity risk, were screened using: DPYD genotyping (G); phenotyping via plasma Uracil (U); phenotyping via plasma-dihydrouracil/uracil ratio (UH2/U); and a Multi-Parametric Method (MPM) using genotype, phenotype, and epigenetic data. Performance was compared, particularly the inability to detect at-risk patients (false negatives). Results: False negative rates for detecting G5 toxicity risk were 51.2%, 19.5%, 9.8% and 2.4%, for G, U, UH2/U and MPM, respectively. False negative rates for detecting G4-5 toxicity risk were 59.8%, 36.1%, 21.3% and 4.7%, respectively. MPM demonstrated significantly (p < 0.001) better prediction performance. Conclusion: MPM is the most effective method for limiting G4-5 toxicity. Its systematic implementation is cost-effective and significantly improves the risk-benefit ratio of FP-treatment. The use of MPM, rather than G or U testing, would avoid nearly 8,000 FP-related deaths per year globally (500 in France), and spare hundreds of thousands from G4 toxicity. [ABSTRACT FROM AUTHOR]