Eliza Del Fiol Manna

Background: Pembrolizumab plus chemotherapy is the standard perioperative treatment for high-risk stage II–III triple-negative breast cancer (TNBC), based on the overall survival benefit in KEYNOTE-522. In Brazil, pembrolizumab is approved but not funded by the public health system (SUS), which covers ~76% of the population. We estimated the population impact of delayed access.Materials and Methods: A nationwide counterfactual model estimated the consequences of a 10-year delay in pembrolizumab availability within SUS. The annual eligible cohort was derived from breast-cancer incidence, private-coverage data, TNBC prevalence, and the stage II–III proportion. Treatment effect used the 5-year KEYNOTE-522 update (OS 86.6% vs 81.7%; HR 0.66). Preventable deaths were computed from the absolute 5-year mortality reduction and life-years lost from restricted mean survival time, under 95%, 75%, and 50% uptake, with deterministic and probabilistic sensitivity analyses.Results: Of 73,610 annual breast-cancer cases, approximately 5,384 women were eligible within SUS. At 95% uptake, a 10-year delay was associated with 251 preventable deaths per annual cohort 2,506 preventable deaths and 5,156 life-years lost overall, corresponding totals were 1,979 deaths (75%) and 1,319 deaths (50%). Results were most sensitive to treatment effect and TNBC prevalence, and probabilistic analyses consistently supported substantial benefit.Conclusion: Delayed incorporation of perioperative pembrolizumab into SUS is expected to cause substantial avoidable deaths and life-years lost among women with high-risk early TNBC. These estimates quantify the clinical cost of delayed access and may inform health-technology-assessment and reimbursement decisions.

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease. However, there are gaps in translating how individual genomic variation affects phenotypic presentation. The expansion of criteria for genetic testing and the increasing utilization of comprehensive genetic panels may enhance the identification of individuals carrying P/LP variants linked to hereditary breast cancer. Individualized risk assessment could facilitate the implementation of personalized risk-reduction strategies for these individuals. Preventive interventions encompass lifestyle modifications, chemoprevention, enhanced surveillance through breast imaging, and risk-reducing surgeries. This review addresses the current literature’s inconsistencies and limitations, particularly regarding risk factors and the intensity of preventive strategies for women with P/LP variants in moderate- and high-penetrance genes. In addition, it synthesizes the latest evidence on risk assessment and primary and secondary prevention in women at high risk of breast cancer.

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease. However, there are gaps in translating how individual genomic variation affects phenotypic presentation. The expansion of criteria for genetic testing and the increasing utilization of comprehensive genetic panels may enhance the identification of individuals carrying P/LP variants linked to hereditary breast cancer. Individualized risk assessment could facilitate the implementation of personalized risk-reduction strategies for these individuals. Preventive interventions encompass lifestyle modifications, chemoprevention, enhanced surveillance through breast imaging, and risk-reducing surgeries. This review addresses the current literature's inconsistencies and limitations, particularly regarding risk factors and the intensity of preventive strategies for women with P/LP variants in moderate- and high-penetrance genes. In addition, it synthesizes the latest evidence on risk assessment and primary and secondary prevention in women at high risk of breast cancer.

Female breast cancer is the most commonly diagnosed malignancy worldwide. Risk assessment helps to identify women at increased risk of breast cancer and allows the adoption of a comprehensive approach to reducing breast cancer incidence through personalized interventions, including lifestyle modification, chemoprevention, intensified surveillance with breast imaging, genetic counseling, and testing. Primary prevention means acting on modifiable risk factors to reduce breast cancer occurrence. Chemoprevention with tamoxifen, raloxifene, anastrozole, and exemestane has already shown benefits in decreasing breast cancer incidence in women at an increased risk for breast cancer. For healthy women carrying BRCA 1 or BRCA 2 pathogenic/likely pathogenic (P/LP) germline variants, the efficacy of chemoprevention is still controversial. Adopting chemoprevention strategies and the choice among agents should depend on the safety profile and risk–benefit ratio. Unfortunately, the uptake of these agents has been low. Lifestyle modifications can reduce breast cancer incidence, and the recommendations for BRCA 1 or BRCA 2 P/LP germline variant carriers are comparable to the general population. This review summarizes the most recent evidence regarding the efficacy of chemoprevention and lifestyle interventions in women with sporadic and hereditary breast cancer.

Purpose. Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive, fibrosing interstitial pneumonia. The recognition of the risk factors for IPF is mandatory for disease prevention. The aim of the present systematic review is to evaluate the association between occupational and environmental exposures and the risk of IPF. Methods. Original observational studies published before July 3rd (2020) were identified through electronic searches of the PubMed, Embase, Cochrane and Web of Science databases. To meet the inclusion criteria, studies had to describe the exposure assessment, and the diagnosis had to be based on clinical history, computed tomography (CT) and/or histology. Results. Eight studies met the inclusion criteria for the systematic review, including a total of 2084 patients. A quantitative meta-analysis could not be performed due to the heterogeneity of the studies. Smoking was associated with an increased risk of IPF, but there was no clear dose-response relationship for smoking years and pack-years consumption. Exposure to birds and occupational exposure to metal and organic dust at work were also associated with the risk of IPF. Conclusions. This systematic review revealed an association between smoking, exposures to birds and cat allergens and occupational exposures to metal, wood and organic dusts and the risk of IPF, although the findings were controversial among the studies. Further investigations should integrate genetic susceptibility analysis, dose-response relationships, and direct measures of exposure, performing adjustments for possible confounders.

The aim of this study was to evaluate the association between immunohistochemical expression of topoisomerase IIα, HER2 and hormone receptors and response to primary anthracycline-based chemotherapy in locally advanced breast cancer. We analyzed 109 medical charts of patients treated with primary anthracycline-based chemotherapy in the Women's Integral Health Care Center from 1996 to 2004. The clinical and pathological response to primary chemotherapy was associated with topoisomerase IIα and HER2 expression and hormone receptor negativity. Statistical analysis was performed using chi-squared, Fisher's exact test and Mann-Whitney test. No statistical association between clinical response and expression of topoisomerase IIa, HER2 and hormone receptor negativity was found. However, there was an association between complete pathological response and hormone receptor negativity (P = 0.0289). The present study suggested that these markers should not be considered predictors of response to primary anthracycline-based chemotherapy, and prospective studies must be designed for this purpose.