Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

The Clinical Utility of lncRNAs and Their Application as Molecular Biomarkers in Breast Cancer.

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, and treatment response. Particularly, the lncRNAs DSCAM-AS1 and GATA3-AS1 serve as examples of this because of their high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates to use as molecular biomarkers in clinical practice. However, lncRNA studies in breast cancer are limited in sample size and are restricted to the determination of their biological function, which represents an obstacle for its inclusion as molecular biomarkers of clinical utility. Nevertheless, due to their expression specificity among diseases, such as cancer, and their stability in body fluids, lncRNAs are promising molecular biomarkers that could improve the reliability, sensitivity, and specificity of molecular techniques used in clinical diagnosis. The development of lncRNA-based diagnostics and lncRNA-based therapeutics will be useful in routine medical practice to improve patient clinical management and quality of life.

Time intervals to care and health service use experiences of uninsured cancer patients treated under public financing in Mexico City.

BACKGROUND: The present study assesses the time intervals from symptom discovery to treatment start and describes the health service use experiences of uninsured patients with cancer of the breast, cervix uteri, testicle, and prostate before their arrival to the cancer hospital. METHODS: This cross-sectional study included 1468 patients who were diagnosed between June 2016 and May 2017 and received treatment for the selected cancers in two of the largest public cancer hospitals in Mexico City, financed through Seguro Popular. Data was collected through a survey administered via face-to-face interviews with patients and a review of their medical files. RESULTS: The median time between detection (symptom discovery or first abnormal screening test) and treatment start was 6.6 months. For all types of cancer, the longest interval was the diagnostic interval -between the first use of healthcare services and the confirmation of cancer. Less than 20% cancer patients were diagnosed in the earliest stages that are associated with the best chances of long-term survival. The participants described a high use of private services for their first consultation, the use of several different types of health services and multiple consultations before arrival to the cancer centers, and 35% perceived being misdiagnosed by the first doctor they consulted. CONCLUSIONS: Most cancer patients treated in the two largest public institutions available for the uninsured faced long delays to get diagnosed and started treatment at advanced stages. Strengthening quality and access for effective early cancer diagnosis and treatment is key to improve patient outcomes in low and middle-income settings.

Physicians' attitudes and perceived barriers to adherence to the national breast cancer clinical practice guidelines in Mexico: a survey study.

BACKGROUND: Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians' adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. METHODS: A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants' characteristics, adherence, attitudes, and barriers. RESULTS: Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0-5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2-3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. CONCLUSIONS: We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines.

The Evolution of Clinically Aggressive Triple-Negative Breast Cancer Shows a Large Mutational Diversity and Early Metastasis to Lymph Nodes.

In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease. We sequenced the whole exome of 16 lesions from four patients who did not respond to therapy, and took several follow-up samples, including samples from tumors before and after treatment, as well as from the lymph nodes and skin metastases. We found substantial intrapatient genetic heterogeneity, with a variable tumor mutational composition. Early truncal events were MCL1 amplifications. Metastatic lesions had deletions in RB1 and PTEN, along with TERT, AKT2, and CCNE1 amplifications. Mutational signatures 06 and 12 were mainly detected in skin metastases and lymph nodes. According to phylogenetic analysis, the lymph node metastases occurred at an early stage of TNBC development. Finally, each patient had three to eight candidate driving mutations for targeted treatments. This study delves into the genomic complexity and the phylogenetic and evolutionary development of aggressive TNBC, supporting early metastatic development, and identifies specific genetic alterations associated with a response to targeted therapies.

Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.

Breast cancer is one of the leading causes of mortality in women worldwide, and neoadjuvant chemotherapy has emerged as an option for the management of locally advanced breast cancer. Extensive efforts have been made to identify new molecular markers to predict the response to neoadjuvant chemotherapy. Transcripts that do not encode proteins, termed long noncoding RNAs (lncRNAs), have been shown to display abnormal expression profiles in different types of cancer, but their role as biomarkers in response to neoadjuvant chemotherapy has not been extensively studied. Herein, lncRNA expression was profiled using RNA sequencing in biopsies from patients who subsequently showed either response or no response to treatment. GATA3-AS1 was overexpressed in the nonresponder group and was the most stable feature when performing selection in multiple random forest models. GATA3-AS1 was experimentally validated by quantitative RT-PCR in an extended group of 68 patients. Expression analysis confirmed that GATA3-AS1 is overexpressed primarily in patients who were nonresponsive to neoadjuvant chemotherapy, with a sensitivity of 92.9% and a specificity of 75.0%. The statistical model was based on luminal B-like patients and adjusted by menopausal status and phenotype (odds ratio, 37.49; 95% CI, 6.74-208.42; P = 0.001); GATA3-AS1 was established as an independent predictor of response. Thus, lncRNA GATA3-AS1 is proposed as a potential predictive biomarker of nonresponse to neoadjuvant chemotherapy.

Prognosis of breast cancer diagnosed during pregnancy and early postpartum according to immunohistochemical subtype: A matched case-control study.

PURPOSE: Pregnancy-associated breast cancer (PABC) poses a clinical challenge and its prognosis remains controversial. During the pregnancy and postpartum periods, the breast undergoes biological events that may uniquely influence disease behavior and treatment response. This study aimed to assess if a PABC diagnosis influences survival compared to non-PABC. METHODS: A single-center record review was performed to identify PABC patients diagnosed from January 2007 through June 2018. Two controls were matched to each PABC case by stage, immunohistochemical (IHC) subtype, age (± 3) and year of diagnosis (± 2). Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was used to assess the impact of PABC on outcomes. RESULTS: 125 PABC patients (pregnant: 62; postpartum: 63) and 250 controls were included. Median follow-up was 67.7 and 73.4 months, respectively. 4-year DFS was 62% in pregnant vs 78% in controls (p = 0.010), and 63% in postpartum vs 83% in controls (p = 0.034). Subanalysis by IHC subtype revealed a significantly inferior DFS in PABC with hormone receptor-positive/HER2-negative (p = 0.032) and HER2-positive disease (p = 0.005) compared to corresponding non-PABC patients. 4-year OS was similar between case groups and controls. Multivariate analysis supported the independent impact of pregnant and postpartum status on DFS (p < 0.05). CONCLUSION: Patients diagnosed during pregnancy and early postpartum are at high risk of recurrence. Further research is warranted to better characterize PABC tumor biology and enable the identification of novel therapeutic interventions to improve treatment outcomes.

Prospective Study of Fertility Preservation in Young Women With Breast Cancer in Mexico.

BACKGROUND: Despite the risk of treatment-related infertility, implementation of fertility-preservation (FP) strategies among young patients with breast cancer is often suboptimal in resource-constrained settings such as Mexico. The "Joven & Fuerte: Program for Young Women With Breast Cancer" strives to enhance patient access to supportive care services, including FP measures through alliances with assisted-reproduction units and procurement of coverage of some of these strategies. This study describes patients from Joven & Fuerte who have preserved fertility, and assesses which characteristics were associated with the likelihood of undergoing FP. METHODS: Women aged ≤40 years with recently diagnosed breast cancer were prospectively accrued. Sociodemographic and clinicopathologic data were collected from patient-reported and provider-recorded information at diagnosis and 1-year follow-up. Descriptive statistics, chi-square test, and simple logistic regression were used to compare patients who preserved fertility with those who did not. RESULTS: In total, 447 patients were included, among which 53 (12%) preserved fertility, representing 38% of the 140 women who desired future biologic children. Oocyte/embryo cryopreservation was the most frequently used method for FP (59%), followed by temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy (26%), and use of both GnRHa and oocyte/embryo cryopreservation (15%). Younger age, higher educational level, being employed, having private healthcare insurance, and having one or no children were associated with a significantly higher likelihood of preserving fertility. CONCLUSIONS: By facilitating referral and seeking funds and special discounts for underserved patients, supportive care programs for young women with breast cancer can play a crucial role on enhancing access to oncofertility services that would otherwise be prohibitive because of their high costs, particularly in resource-constrained settings. For these efforts to be successful and widely applied in the long term, sustained and extended governmental coverage of FP options for this young group is warranted.

Recomendaciones de la Sociedad Mexicana de Oncología para la vacunación contra Covid-19 en personas con cáncer en México.

No disponible.

Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic.

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Different Phenotypes of Locally Advanced Breast Cancer During Neoadjuvant Systemic Treatment.

PURPOSE: Neutrophils are among the key cellular players in the inflammatory milieu produced in patients with breast cancer (BC), and strong evidence exists in terms of the prognostic value of assessing the neutrophil-to-lymphocyte ratio (NLR) in patients with BC. In this study we sought to determine whether the baseline NLR correlates with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) in patients with locally advanced BC in the neoadjuvant chemotherapy (NAC) setting. METHODS: We analyzed the pretreatment NLR from the first blood count of patients treated from 2007 to 2015 in terms of pCR, DFS, and OS in patients with locally advanced BC. Patients received standard medical care based on national guidelines. RESULTS: A total of 1519 patients were included in the study. Median age was 49 years (22-88). The cutoff point for NLR was 2.0. NLR was not associated with pCR or DFS. However, patients with high NLR had worse OS in the presence of triple-negative BC (105.9 months; 95% confidence interval [CI], 100.2-111.5] vs. 98.7 months; 95% CI, 91.1-106.3; P = .029), Her2 overexpression (114.0 months; 95% CI, 110.5-118.0 vs. 100.8 months; 95% CI 95.7-105.9; P = .019), and residual disease after NAC for both phenotypes. Multivariate analysis showed that NLR was independently associated with OS (hazard ratio, 1.4; 95% CI, 1.02-1.95; P = .037). CONCLUSIONS: Pretreatment NLR in patients with locally advanced BC correlates with OS as an independent prognostic factor. This influence depends on phenotype and residual disease. Routine assessment of this parameter could be an easy and affordable tool for defining prognosis.

Patients' satisfaction with a supportive care program for young breast cancer patients in Mexico: Joven & Fuerte supports patients' needs and eases their illness process.

OBJECTIVE: The aim of this study was to evaluate patients' outlook and satisfaction with "Joven & Fuerte: Program for Young Women with Breast Cancer (YWBC) in Mexico" (J&F) and to determine its strengths and areas of improvement to better fulfill patients' information and supportive care needs. METHODS: Patients enrolled in J&F for ≥ 6 months at three cancer referral centers were invited via a messaging application to anonymously complete an online survey exploring their perspectives of the program's information delivery, support services, and research component. Descriptive statistics, chi2 test, Student t, and ANOVA were used for analysis. RESULTS: Of 484 eligible patients, 28% completed the survey. The program overall was useful/very useful according to 97% and aided 82% to better cope with their illness. The timing, clarity, and usefulness of the information provided were each described as good/very good by ≥ 83% for the written format and ≥ 98% for the verbal one. Eighty-four percent of patients were very satisfied (≥ 9/10) with psychological support and genetic assessment. The number of support services used was significantly associated with patients' perception of J&F's usefulness. Regarding fertility issues, 45% recalled being informed about preservation strategies and J&F financially supported 27/39 of interested patients. Fifty-eight percent were unaware of J&F's ongoing research component. CONCLUSIONS: Patients' satisfaction with J&F is very high, reflecting that the program is meeting Mexican YWBC's needs by providing useful information means and support services in a limited-resource setting. Efforts must keep up to guarantee the program's continuity and advocate for its extension to other oncologic centers.

Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapy-induced toxicity in patients with locally advanced breast cancer: a randomized, controlled, double-blinded clinical trial.

INTRODUCTION: Background: antineoplastic treatment for locally advanced breast cancer (LABC) includes neodjuvant chemotherapy (NeoCT). However, side effects occur frequently, affecting the functional capacity and quality of life of patients as a result of the proinflammatory state of this therapy. In this work, omega-3 polyunsaturated fatty acids (PUFA Ω-3) were administered as they have been reported to modulate some molecular pathways such as nuclear factor-kappa B (NF-κB), which is associated with toxicity secondary to the administration of anthracyclines. Objective: to evaluate the effects of PUFA Ω-3 on the toxicity, side effects, body composition, cardiometabolic profile and quality of life in women with LABC after NeoCT. Methods: fifty-three women with LABC were included in a double-blinded, placebo-controlled clinical trial. Patients randomly received 2.4 g/day of PUFA Ω-3 (EPA 1.6 g and DHA 0.8 g) or placebo during NeoCT with adriamycin/cyclophosphamide followed by paclitaxel+/-trastuzumab. Adverse effects related to chemotherapy were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) and the Subjective Global Scale of the Edmonton Symptom Assessment System (ESAS). Body composition and cardiometabolic blood profile were also evaluated. Results: no significant differences were found between groups in the hematological and anthropometric toxicity parameters. Within the Edmonton scale, xerostomia presented a significant improvement (p = 0.032) in patients supplemented with PUFA Ω-3. Conclusion: supplementation with PUFA Ω-3 showed no change in body composition, cardiometabolic profile or toxicity due to NeoCT. It only showed significant improvement in xerostomia.

INTRODUCCIÓN: Introducción: uno de los tratamientos para el cáncer de mama localmente avanzado (CMLA), es la quimioterapia neoadyuvante (QTNeo). Sin embargo, los efectos secundarios afectan el estado funcional y la calidad de vida de los pacientes, especialmente por el estado inflamatorio que originan. En este trabajo se administraron los ácidos grasos poliinsaturados omega 3 (AGPI Ω-3), ya que modulan negativamente algunas vías moleculares como las que inducen la activación del factor nuclear-kappa B (NF-κB), involucrado con los mecanismos de toxicidad secundaria a la administración de antraciclinas. Objetivo: valorar el efecto de los AGPI n-3, sobre la toxicidad de la QTneo, la composición corporal, el perfil cardiometabólico y la calidad de vida en mujeres con CMLA durante la QTNeo. Métodos: se incluyeron cincuenta y tres mujeres con CMLA, en un estudio clínico doble ciego controlado con placebo. Las pacientes recibieron aleatoriamente 2,4 g/día de AGPI Ω-3 (EPA 1,6 g y DHA 0,8 g) o placebo durante la quimioterapia neoadyuvante con adriamicina/ciclofosfamida seguido de paclitaxel +/- trastuzumab. Se evaluaron los eventos adversos relacionados con la quimioterapia mediante los Criterios de terminología común para eventos adversos (CTCAE, versión 4.03) y la escala Global subjetiva del Sistema de Evaluación de los Síntomas de Edmonton (ESAS), la composición corporal y la toxicidad cardiometabólica. Resultados: no hubo diferencias significativas entre los grupos en los parámetros de toxicidad hematológica y antropométricos. La xerostomía de la escala de Edmonton, presento una mejora significativa (p = 0,032) en los pacientes suplementados con AGPI Ω-3. Conclusión: la suplementación con AGPI Ω-3 no mostró cambios en la composición corporal ni en la toxicidad del tratamiento neoadyuvante, solamente se encontró una mejoría significativa en la xerostomía.

Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients.

PURPOSE: The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC). METHODS: We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis. RESULTS: Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02). CONCLUSION: Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.

MicroRNA-143 is Associated With Pathological Complete Response and Regulates Multiple Signaling Proteins in Breast Cancer.

Almost 55% to 80% of patients with breast cancer have an unfavorable pathological complete response to chemotherapy. MicroRNAs are small noncoding RNAs involved in cancer progression; however, their utility as predictors of pathological complete response to neoadjuvant chemotherapy is unclear. Here, we investigated if miR-143 could discriminate between pathological complete response and no-polymerase chain reaction of patients with locally advanced triple negative breast cancer that have received a fluorouracil-cisplatin/paclitaxel-based neoadjuvant treatment. Data showed that miR-143 exhibited a significant low expression ( P < .0006) in patients that achieved pathological complete response in comparison to nonresponder group. Receiver operating characteristic curve analysis suggested that miR-143 could be a good predictor of pathological complete response (area under curve = 0.849, P < .0006). Moreover, Kaplan-Meier analysis indicated that before neoadjuvant therapy low levels of miR-143 were associated to increased disease free survival. To gain insights into cellular functions of miR-143, we firstly showed that miR-143 was severely repressed in breast cancer cell lines and tumors in comparison to normal mammary cells and tissues. Ectopic restoration of miR-143 using RNA mimics inhibited both cell proliferation and migration and sensitized breast cancer cells to cisplatin therapy in vitro. To decipher the signaling networks regulated by miR-143, we used a high-throughput enzyme-linked immunosorbent assay-based phosphorylation antibody array. Phospho-proteomic profiling revealed that miR-143 coordinately reduced the protein levels and phosphorylation status of multiple oncoproteins involved in AKT, WNT/ß-catenin, SAPK/JNK, FAK, and JAK/STAT signaling pathways. Moreover, low miR-143 and high GSK3-ß, RAF1, paxillin, and p21CIP1 expression levels in a large cohort of patients with breast cancer were associated with worst outcome. In summary, miR-143 could be a potential predictor of response to neoadjuvant therapy and it may function as a divergent regulator of diverse signaling networks to suppress cell proliferation and migration in breast cancer.

Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population.

BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

Usefulness of positron emission mammography in the evaluation of response to neoadjuvant chemotherapy in patients with breast cancer.

Our study examines the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of Neoadjuvant chemotherapy (NAC) with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers. One-hundred and eight patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with 18F-FDG-PEM scans before and after of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG). After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ± 0.26 vs. 1.9 ± 0.18; P < 0.001) and LTB exhibited a significant decay after the first course of NAC (15.8 ± 1.36 vs. 5.5 ± 0.49; P < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (P = 0.52). Two PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.

Impact of Delayed Adjuvant Radiotherapy in the Survival of Women with Breast Cancer.

Objective Our objective was to determine whether a delay in adjuvant radiotherapy is related to a decrease in relapse-free survival and disease-specific survival of women with operable breast cancer. Methods Data on 1000 patients diagnosed with breast cancer were recorded. The cohort was divided into five groups according to the timing of radiotherapy: ≤30 days, 31 to 60 days, 61 to 90 days, 91 to 120 days, and >120 days. The relapse-free survival and disease-specific survival were also calculated in relation to the number of patients. Results This study found no statistical difference for delays in adjuvant radiotherapy in patients with early breast cancer, but we noted a statistical decrease in disease-specific survival in patients with locally advanced breast cancer receiving radiotherapy after a delay of at least 60 days. Conclusion Waiting times for radiotherapy should be as short as reasonably achievable, given the specific risk factors in the individual patient.