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.

Ovarian Suppression: Early Menopause and Late Effects.

OPINION STATEMENT: Around 90% of breast tumours are diagnosed in the early stage, with approximately 70% being hormone receptor-positive. The cornerstone of adjuvant therapy for early-stage hormone receptor-positive breast cancer is endocrine therapy, tailored according to disease stage, biological characteristics of the tumour, patient's comorbidities, preferences and age. In premenopausal patients with hormone receptor-positive breast cancer, ovarian function suppression is a key component of the adjuvant endocrine treatment in combination with an aromatase inhibitor or tamoxifen. Moreover, it can be used during chemotherapy as a standard strategy for ovarian function preservation in all breast cancer subtypes. In the metastatic setting, ovarian function suppression should be used in all premenopausal patients with hormone receptor-positive breast cancer to achieve a post-menopausal status. Despite its efficacy, ovarian function suppression may lead to several side effects that can have a major negative impact on patients' quality of life if not properly managed (e.g. hot flashes, depression, cognitive impairment, osteoporosis, sexual dysfunction, weight gain). A deep knowledge of the side effects of ovarian function suppression is necessary for clinicians. A correct counselling in this regard and proactive management should be considered a fundamental part of survivorship care to improve treatment adherence and patients' quality of life.

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.

Diagnostic delays in breast cancer among young women: An emphasis on healthcare providers.

Despite advances in breast cancer care, breast cancer in young women (BCYW) faces unique challenges, diagnostic delays, and limited awareness in many countries. Here, we discuss the challenges and consequences associated with the delayed diagnosis of BCYW. The consequences of delayed diagnosis in young women - which generally varies among developed, developing, or underdeveloped countries - are severe due to a faster breast tumor growth rate than tumors in older women, also contributing to advanced cancer stages and poorer outcomes. Though there are many underlying reasons for diagnostic delays due to age, the article delves explicitly deep into the diagnostic delay of BCYW, focusing on healthcare providers, potential contributing factors, its consequences, and the urgent need to start minimizing such incidences. The article suggests several strategies to address these issues, including increasing awareness, developing educational programs for healthcare providers to identify signs and symptoms in young women, developing clear diagnostic guidelines, and improving screening strategies.

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.

Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Latin America and the Caribbean Code Against Cancer 1st Edition: Medical interventions including hormone replacement therapy and cancer screening.

Prostate, breast, colorectal, cervical, and lung cancers are the leading cause of cancer in Latin America and the Caribbean (LAC) accounting for nearly 50% of cancer cases and cancer deaths in the region. Following the IARC Code Against Cancer methodology, a group of Latin American experts evaluated the evidence on several medical interventions to reduce cancer incidence and mortality considering the cancer burden in the region. A recommendation to limit the use of HRT was issued based on the risk associated to develop breast, endometrial, and ovarian cancer and on growing concerns related to the over-the-counter and without prescription sales, which in turn bias estimations on current use in LAC. In alignment with WHO breast and cervical cancer initiatives, biennial screening by clinical breast examination (performed by trained health professionals) from the age of 40 years and biennial screening by mammography from the age of 50 years to 74, as well as cervical screening by HPV testing (either self-sampling or provider-sampling) every 5-10 years for women aged 30-64 years, were recommended. The steadily increasing rates of colorectal cancer in LAC also led to recommend colorectal screening by occult blood testing every two years or by endoscopic examination of the colorectum every 10 years for both men and women aged 50-74 years. After evaluating the evidence, the experts decided not to issue recommendations for prostate and lung cancer screening; while there was insufficient evidence on prostate cancer mortality reduction by prostate-specific antigen (PSA) testing, there was evidence of mortality reduction by low-dose computed tomography (LDCT) targeting high-risk individuals (mainly heavy and/or long-term smokers) but not individuals with average risk to whom recommendations of this Code are directed. Finally, the group of experts adapted the gathered evidence to develop a competency-based online microlearning program for building cancer prevention capacity of primary care health professionals.

Effect of receiving a customizable brochure on breast cancer patients' knowledge about their diagnosis and treatment: A randomized clinical trial.

BACKGROUND: Patients' lack of knowledge about their own disease may function as a barrier to shared decision-making and well-being. This study aimed to evaluate the impact of written educational materials on breast cancer patients. METHODS: This multicenter, parallel, unblinded, randomized trial included Latin American women aged ≥18 years with a recent breast cancer diagnosis yet to start systemic therapy. Participants underwent randomization in a 1:1 ratio to receive a customizable or standard educational brochure. The primary objective was accurate identification of molecular subtype. Secondary objectives included identification of clinical stage, treatment options, participation in decision-making, perceived quality of information received, and illness uncertainty. Follow-up occurred at 7-21 and 30-51 days post-randomization. CLINICALTRIALS: gov identifier: NCT05798312. RESULTS: One hundred sixty-five breast cancer patients with a median age of 53 years and 61 days from diagnosis were included (customizable: 82; standard: 83). At first available assessment, 52%, 48%, and 30% identified their molecular subtype, disease stage, and guideline-endorsed systemic treatment strategy, respectively. Accurate molecular subtype and stage identification were similar between groups. Per multivariate analysis, customizable brochure recipients were more likely to identify their guideline-recommended treatment modalities (OR: 4.20,p = 0.001). There were no differences between groups in the perceived quality of information received or illness uncertainty. Customizable brochure recipients reported increased participation in decision-making (p = 0.042). CONCLUSIONS: Over one third of recently diagnosed breast cancer patients are incognizant of their disease characteristics and treatment options. This study demonstrates a need to improve patient education and shows that customizable educational materials increase patients' understanding of recommended systemic therapies according to individual breast cancer characteristics.

Exploring the Potential Role of Circulating microRNAs as Biomarkers for Predicting Clinical Response to Neoadjuvant Therapy in Breast Cancer.

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide. Neoadjuvant therapy (NAT) is increasingly being used to reduce tumor burden prior to surgical resection. However, current techniques for assessing tumor response have significant limitations. Additionally, drug resistance is commonly observed, raising a need to identify biomarkers that can predict treatment sensitivity and survival outcomes. Circulating microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been shown to play a significant role in cancer progression as tumor inducers or suppressors. The expression of circulating miRNAs has been found to be significantly altered in breast cancer patients. Moreover, recent studies have suggested that circulating miRNAs can serve as non-invasive biomarkers for predicting response to NAT. Therefore, this review provides a brief overview of recent studies that have demonstrated the potential of circulating miRNAs as biomarkers for predicting the clinical response to NAT in BC patients. The findings of this review will strengthen future research on developing miRNA-based biomarkers and their translation into medical practice, which could significantly improve the clinical management of BC patients undergoing NAT.

A nationwide pilot study on breast cancer screening in Peru.

Introduction: A high prevalence of advanced breast cancer (BC) is a common scenario in Latin America. In Peru, the frequency of BC at Stages III/IV is ≈50% despite implementation of a programme for breast cancer screening (BCS) along the country. We carried out a study to assess the feasibility and develop an instrument to evaluate the knowledge, barriers and perception about BCS in a nationwide pilot study in Peru among candidates for BCS. Methods: We conducted a systematic review of 2,558 reports indexed in PubMed, Scopus, Web of Science, Medline-Ovid and EMBASE, regarding to our study theme. In total, 111 were selected and a 51-items survey was developed (eight items about sociodemographic characteristics). Patients were recruited in public hospitals or private clinics, in rural and urban areas of nine departments of Peru. Results: We surveyed 488 women from: Lima (150), Cajamarca (93), Ica (59), Arequipa (56), Loreto (48), Ancash (38), Junín (15), Puerto Maldonado (15) and Huancavelica (14); 27.9% of them were from rural areas. The mean of age was 53.3 years (standard deviation ± 9.1). Regarding education level, 29.8% had primary, 33.2% secondary and 37.0% higher education. In total, 28.7% of women did not know the term 'mammogram' and 47.1% reported never receiving a BCS (36.9% from urban and 73.5% from rural population). In women that underwent BCS, only 67% knew it is for healthy women. In total, 54.1% of patients had low levels of knowledge about risk factors for BC (i.e. 87.5% of women respond that injuries in the breast produce cancer). Cultural, economic and geographic barriers were significantly associated with having a mammogram where 56.9% of participants considered a cost ≤ 7 USD as appropriate. Mammogram was perceived as too painful for 54.9% of women. In addition, women with a self-perception of low-risk for BC and a fatalistic perception of cancer were less likely to have a BCS. Conclusion: We found that it is feasible to conduct a large-scale study in Peru. The results of this pilot study highlight an urgent need of extensive education and awareness about BCS in Peru.

Current Scenario of Clinical Cancer Research in Latin America and the Caribbean.

In Latin America and the Caribbean (LAC), progress has been made in some national and regional cancer control initiatives, which have proved useful in reducing diagnostic and treatment initiation delays. However, there are still significant gaps, including a lack of oncology clinical trials. In this article, we will introduce the current status of the region's clinical research in cancer, with a special focus on academic cancer research groups and investigator-initiated research (IIR) initiatives. Investigators in LAC have strived to improve cancer research despite drawbacks and difficulties in funding, regulatory timelines, and a skilled workforce. Progress has been observed in the representation of this region in clinical trial development and conduct, as well as in scientific productivity. However, most oncology trials in the region have been sponsored by pharmaceutical companies, highlighting the need for increased funding from governments and private foundations. Improvements in obtaining and/or strengthening the LAC cancer research group's financing will provide opportunities to address cancer therapies and management shortcomings specific to the region. Furthermore, by including this large, ethnic, and genetically diverse population in the world's research agenda, one may bridge the gap in knowledge regarding the applicability of results of clinical trials now mainly conducted in populations from the Northern Hemisphere.

Characterization of triple negative breast cancer gene expression profiles in Mexican patients.

Triple negative breast cancer (TNBC) is an aggressive type of cancer that accounts for ~23% of breast tumors in Mexico. In an attempt to understand in an improved way the behavior of TNBC, throughout the years, gene expression in these tumors has been studied. Lehman et al identified 6 subtypes of gene expression in TNBC with distinct characteristics. In the present study, it was aimed to assess clinical, pathological and prognostic characteristics of TNBC in a Mexican-based cohort. A total of 55 patients diagnosed with TNBC at Mexico's National Institute of Cancer (INCan) were included. Tumor needle biopsy samples were obtained and subjected to microarray analysis. Patients were thus classified into one of the 6 TNBC molecular subtypes. The prognostic, clinical and pathological information of patients was obtained, and differences across molecular subtypes were sought. Out of the 55 included patients, the following subtypes were identified: 9 basal-like-1, 11 basal-like-2 (BSL2), 16 immunomodulatory (IM), 12 mesenchymal, 6 androgen receptor-like and 1 mesenchymal stem-like. Mean follow-up time was 47.1 months. The IM molecular subtype had the best overall survival (OS) (median OS was not reached). BSL2 had the worst OS (15 months). A complete pathologic response to neoadjuvant chemotherapy was obtained more often in the IM subtype (P=0.032). No significant associations were found between any of the clinical or pathological characteristics and the TNBC molecular subtypes. The results obtained from the present study should be considered when seeking to implement a clinical-molecular model for TNBC patient care, particularly in Hispanic-based populations, as they have been frequently underrepresented in clinical studies assessing TNBC molecular subtypes.

Status of breast cancer in Latin American: Results of the breast cancer revealed initiative.

The Breast Cancer Revealed initiative was designed and conducted to know the status of breast cancer at each point of breast cancer care, through i) prevention, ii) detection, iii) diagnosis, iv) treatment, and iv) the capacity of our health systems. The expert panel from 11 Latin American countries identified several strategies and proposed high impact priorities, including implementation of prevention policies, improve primary healthcare capacity for breast cancer screening, have adequate infrastructure to make effective and timely diagnoses, have a multidisciplinary team in the treatment process, access to a variety of treatments for all types of patients, have a coordinated and articulated system from primary care to specialized hospital. In a region with limited resources, prioritization in high-impact strategies for breast cancer control could lead to improved clinical outcomes and quality of life for our patients.

LuciA-15 - a real-world prospective study of PARP inhibitors for the treatment of patients with HER-2 negative metastatic breast cancer with germline and/or somatic mutation of BRCA genes or homologous recombination repair related genes.

Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) improve progression free survival among patients with HER2 negative (HER2-ve) advanced breast cancer (ABC) and a BRCA1 or BRCA2 mutation compared to chemotherapy (CT). The objective of this prospective study was to evaluate the clinical benefit of PARPi treatment in terms of response, outcomes and survival by breast cancer type and treatment in a Latin-American population. Methods: From September 2019 to April 2023, we analyzed the data of patients with HER2-ve ABC with germline and/or somatic mutation of BRCA1 or BRCA2, or in the homologous recombination repair genes, treated with olaparib or talazoparib in daily clinical practice by oncologist from Argentina and México. real-world objective response rate (rwORR), best response rate, real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were analysed with R software and RStudio version 14.0. Results: After a median follow-up of 18.07 months (95% CI 10.53-30.07), 51 patients were treated with PARPi. Mean age at starting treatment was 47.08 years. 62.7% had ER + ve/HER2-ve and 35.3% had triple negative breast cancer (TNBC). 62.7% and 37.3% of patients received talazoparib and olaparib, respectively. BRCA 1 and 2 germline mutations were the most common alterations found in 96% of patients. 37.5% of patients received platinum-based CT in the (neo)adjuvant/metastatic setting. At the time to starting PARPi treatment, 57.5% had visceral metastasis, the median number of metastatic sites was 2 (range 1-4), the median number of lines was 2 (range 0-8), and 23.5% and 31.4% received PARPi in the 1st line and 2nd line, respectively.The rwORR was 47.0%, and the median real-world progression-free survival-1 (rwPFS1) was 7.77 months (95% CI 5.67-14.7). There was a tendency of better rwPFS1 in patients with versus without previous CT in the advance setting, 6.37 months (95% CI 5.03-8.73) and 14.30 months (95% CI 6.47-NR), respectively (p 0.084). The median rwOS was 26.97 months (95% CI 13.50-NR) and higher in the subgroup of patients naïve for CT versus previous exposure to CT in the advance setting, the median rwOS was 32.1 months (95% CI 27.0-NR) versus 13.0 (95% CI10.1-NR), respectively (p 0.022). The medium real-world progression-free survival-2 (next treatment after PARPi failure) was 4.00 months (95% CI 3.43-7.13). Treatment was discontinued due to adverse events in 4.0% of patients. Conclusion: This is the first evidence in a Latin-American population that replicates the data already published in randomised clinical trials and other scanty real-world evidence studies in this field, showing positive results in rwORR and rwPFS, and encouraging data in rwOS. Notably, there was a high proportion of patients with visceral progression even with visceral crisis and need for CT. Interestingly, there were similar rwOS results among subgroups (TNBC versus ER + ve/HER2-ve, talazoparib versus olaparib, etc).

Exposición a material particulado y su relación con el cáncer de mama. Mecanismos fisiopatológicos / Exposure to particulate matter and its association to breast cancer. Pathophysiological mechanisms

Introducción. El cáncer de mama es el tipo de cáncer que genera más muertes en mujeres en el mundo. Aunque se reconoce el aporte de factores genéticos, hormonales y de estilos de vida como sus principales causas, las hipótesis que señalan que la contaminación del ambiente juega un papel importante en su desarrollo, han tomado mucha fuerza en los últimos años. Estas hipótesis surgen debido a que el aumento en la incidencia del cáncer de mama coincide con procesos de industrialización, además de mayor presencia en regiones urbanas y con altos niveles de contaminación. El objetivo de este artículo fue consolidar información sobre los mecanismos fisiopatológicos que puedan explicar la relación entre cáncer de mama y la contaminación por material particulado. Metodología. Se realizó una búsqueda de literatura en PubMed, Google Académico y Epistemonikos para documentos publicados sobre el tema desde enero de 2016 hasta el 3 de agosto de 2022. Resultados. Se encontró que algunos de los mecanismos que podrían explicar dicha relación incluyen: alteraciones endocrinas que favorecen cambios hormonales, induciendo el crecimiento mamario; cambios en las características histológicas del tejido normal, como involución reducida de unidades lobulares ductales terminales; formación de aductos de hidrocarburos aromáticos policíclicos-ácido desoxirribonucleico (HAP-ADN), con mutación específica del gen TP53; activación de la proliferación en la línea celular MCF-7; y, alteraciones en la metilación del ADN. Conclusión. Si bien órganos distales como la mama no son la primera entrada de los contaminantes ambientales al cuerpo, estos sí pueden verse afectados tras la exposición a largo plazo, a través de diferentes mecanismos de disrupción endocrina y daño al ADN principalmente

Breast cancer is the type of cancer that causes the most deaths in women worldwide. Although the contribution of genetic, hormonal and lifestyle factors are recognized as its main causes, the hypotheses that indicate that environmental pollution has an important role in its development have taken on great strength during the last years. These hypotheses are based on the increase in the incidence of breast cancer that coincides with industrialization processes, in addition to its greater presence in urban regions with high levels of pollution. The aim of this study was to consolidate information on the pathophysiological mechanisms that can explain the relationship between breast cancer and air pollution by particulate matter. Methodology. A literature search was carried out in PubMed, Google Scholar and Epistemonikos for documents published on this topic from January 2016 until August 3rd 2022. Results. Some of the mechanisms that could explain this association include endocrine alterations that favor hormonal changes, inducing breast growth; changes in the histological characteristics of normal tissue such as reduced involution of terminal duct lobular units; formation of polycyclic aromatic hydrocarbons-deoxyribonucleic acid (PAH-DNA) adducts, with specific mutation of the TP53 gene; an increase in cell proliferation in the MCF-7 cell line; and alterations in DNA methylation. Conclusion. Although distal organs such as the breast are not the entry site of environmental pollutants into the body, they can be affected after prolonged exposure, mainly through different mechanisms of endocrine disruption and DNA damage

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.

Concordance between Ki-67 index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint.

Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.