Background
Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated.
Patients and Methods
In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints.
Results
From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19.
Conclusions
Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.
BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44–0.90 for BRCA1; HR = 0.72; 95%CI, 0.47–1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40–1.1 for BRCA1; HR = 0.78; 95%CI, 0.44–1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28–0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11–1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21–0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11–1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.
The development of gene expression signatures since the early 2000′s has offered standardized assays to evaluate the prognosis of early breast cancer. Five signatures are currently commercially available and recommended by several international guidelines to individualize adjuvant chemotherapy decisions in hormone receptors-positive/HER2-negative early breast cancer. However, many questions remain unanswered about their predictive ability, reproducibility and external validity in specific populations. They also represent a new hope to tailor (neo)adjuvant systemic treatment, adjuvant radiation therapy, hormone therapy duration and to identify a subset of patients who might benefit from CDK4/6 inhibitor adjuvant treatment. This review will highlight these particular issues, address the remaining questions and discuss the ongoing and future trials.
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