Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

PURPOSE: Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. METHODS: Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. RESULTS: Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). CONCLUSION: Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Obstetric and neonatal outcomes following taxane use during pregnancy: a systematic review.

BACKGROUND: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited. METHODS: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken. RESULTS: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia. CONCLUSIONS: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety.

Taxanes for the treatment of breast cancer during pregnancy: an international cohort study.

INTRODUCTION: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. METHODS: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. RESULTS: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). CONCLUSION: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated.

Differences in medical education before, during, and in the post-peak period of the COVID-19 pandemic-exploring senior medical students' attitudes.

BACKGROUND: The burden that COVID-19 has brought to the economy, healthcare systems, and education is unmatched. Public health and social measures were implemented to halt transmission. Thus, social gathering and in-person learning, core aspects of medical education, were interrupted. Studies have documented the detrimental impact students graduating during the pandemic have had on their confidence and skills. However, data comparing pre-pandemic, pandemic, and post-peak students still lack. This study aimed to identify senior medical students' attitudes regarding their education and compare them according to the three previously described periods. METHODS: In this cross-sectional study, the survey employed was designed based on a previous questionnaire and applied to senior medical students before graduating between January 2018 and June 2022. Answers were collected using a three-point Likert scale and Yes/No questions. Associations between variables were examined using Chi-squared, Fisher's Exact tests, and ANOVA, employing logistic regression to calculate odds ratio (OR) when appropriate. RESULTS: A total of 679 responses were analyzed. Most students (59%) were women. Up to 383, 241, and 55 senior medical students answered the survey before, during, and in the post-peak period of the COVID-19 pandemic, respectively. There was a staggering decrease in the percentage of students in the post-peak compared to the pre-pandemic period that considered certain factors such as being taught about the doctor-patient relationship (62% vs 75%), practicing teamwork (33% vs 54%), preclinical & clinical subjects (44% vs 63%), and being taught to conduct research (22% vs 32%) as "very useful" to their professional traineeship. There was a significant difference between pre-pandemic, pandemic, and post-peak students when asked if the study curriculum accomplished the goal of training a professional with integrity (89% vs 66% vs 64%, p < 0.001), respectively. In a multivariate analysis graduating during the pandemic (OR 3.92; 95% CI, 2.58-5.94) and in the post-peak period (OR 4.24; 95% CI, 2.23-8.07) were independent factors for the appreciation that the study curriculum did not meet its objective. CONCLUSIONS: The pandemic has hindered medical education. Students' appreciation of their instruction has deteriorated. Urgent interventions that halt the negative impact on training, ensure readiness for future problems and improve schooling worldwide are needed.

Activities Performed by ASCO-Sponsored Oncology Student Interest Groups in Latin America: Assessing Members' Preferences and Leaders' Challenges.

PURPOSE: In response to the worldwide shortage of oncologists, ASCO established Oncology Student Interest Groups (OSIGs) to increase oncology exposure at medical schools. However, there is limited guidance on the activities they should undergo. The main purposes of this study were (1) to assess the preferences and perceptions of OSIG members about their group events and (2) to describe the difficulties faced by leaders to carry out OSIGs' tasks. METHODS: In this multicenter, cross-sectional study, group members and leaders from five active Latin American OSIGs were invited to answer anonymous web-based surveys exploring members' attitudes toward group activities and leaders' challenges when carrying them out. Data collection was conducted from March to June 2021. RESULTS: Responses from 142 medical students and four OSIGs leaders were analyzed. In total, 83% of student members considered that lectures with an oncology-related expert was very useful for increasing their overall interest in oncology. For increasing interest in cancer research, 87% deemed that participating in oncology research projects was very useful. Shadowing oncology professionals was very useful for at least 70% of members to increase their oncology knowledge and their interest in following an oncology-related career. Moreover, leaders' main challenges were having a high academic load, little response from members, lack of interesting ideas and protected time for OSIGs' events, and limited support from their school. CONCLUSION: OSIGs' leaders, medical schools, and international oncology organizations should work together to design activities that increase medical students' exposure to oncology-related professionals and encourage their participation in international oncological events. These schools and organizations should actively support OSIG leaders when facing difficulties to prevent members' disengagement and groups' discontinuation.

Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with cancer are considered a priority group for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination given their high risk of contracting severe Coronavirus Disease 2019 (COVID-19). However, limited data exist regarding the efficacy of immunisation in this population. In this study, we assess the immunologic response after COVID-19 vaccination of cancer versus non-cancer population. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from 01st March 2020 through 12th August 12 2021. Primary end-points were anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) seroconversion rates, T-cell response, and documented SARS-CoV-2 infection after COVID-19 immunisation. Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models. RESULTS: This systematic review and meta-analysis included 35 original studies. Overall, 51% (95% confidence interval [CI], 41-62) and 73% (95% CI, 64-81) of patients with cancer developed anti-S IgG above the threshold level after partial and complete immunisation, respectively. Patients with haematologic malignancies had a significantly lower seroconversion rate than those with solid tumours after complete immunisation (65% vs 94%; P < 0.0001). Compared with non-cancer controls, oncological patients were less likely to attain seroconversion after incomplete (risk ratio [RR] 0.45 [95% CI 0.35-0.58]) and complete (RR 0.69 [95% CI 0.56-0.84]) COVID-19 immunisation schemes. Patients with cancer had a higher likelihood of having a documented SARS-CoV-2 infection after partial (RR 3.21; 95% CI 0.35-29.04) and complete (RR 2.04; 95% CI 0.38-11.10) immunisation. CONCLUSIONS: Patients with cancer have an impaired immune response to COVID-19 vaccination compared with controls. Strategies that endorse the completion of vaccination schemes are warranted. Future studies should aim to evaluate different approaches that enhance oncological patients' immune response.

Successful Concomitant Pulmonary Thromboendarterectomy and Heart Transplant.

Heart transplantation remains the gold standard of therapy for patients with end-stage heart failure. Submassive pulmonary embolism in a patient with heart failure is generally considered a contraindication to immediate heart transplantation, given the risk of right heart failure posttransplant. Generally patients must wait for extended periods of time to recover from pulmonary embolism therapies before being listed for transplant. We report a case of successful concomitant pulmonary thromboendarterectomy and heart transplantation.