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Purpose:Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.Patients and Methods:One-hundred and ninety patients with stage I–III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan–Meier method.Results:Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14–0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10–0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.Conclusions:Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

Pathological response to carboplatin plus docetaxel by germline BRCA status

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC.Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated.Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event.Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.

Further description of patient population and exploratory analysis.

PURPOSE COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments. METHODS This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group. RESULTS There were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine. CONCLUSION To our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.

The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the farreaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.

Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine’s expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150–0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.

BACKGROUND Approximately 7% of women diagnosed with breast cancer (BC) are under 40 years old. Chemotherapy may adversely affect ovarian function therefore fertility is an issue to be addressed for these patients. Patients with cancer in Latin America have limited access to fertility preservation. However age at first birth in women from Latin America is lower than in developed country and the needs of fertility preservation may be different from developed countries. The aim of the present study was to describe the reproductive status and clinical pathological features of young women diagnosed with BC in Latin America. METHODS LACOG 0414 is a prospective registry in Latin America which included young patients with < 40 years old with diagnosis of BC and indication of (neo) adjuvant chemotherapy. Demographic data, reproductive status and clinical pathological information were retrieved from patients` medical charts. This study was approved by local ethics committees and regulatory authorities. RESULTS A total of 343 patients (pts) from 19 different sites distributed in 4 Latin American countries were included: Brasil (N=132 pts), Mexico (N=112 pts), Peru (N=83 pts) and Cuba (N=16 pts). The mean age at BC diagnosis was 34.02 (±4.17) years (14% had < 30 years, 41% had 30-35 years and 44% had 36-40 years). From all included patients, 245 (71.42%) already had children at the time of BC diagnosis. From those the median number of children per women was 2 (range 1–6). The probability of having children at the time of diagnosis was significantly higher with increased age, being as high as 80% in those aged between 36 and 40 years old. There was no difference in terms of having a child at BC diagnosis within the 4 countries, by stage at diagnosis or per breast cancer subtypes. In terms of educational level, approximately 8% of patients were Illiterate and only 40% had university degree. Stages at BC diagnosis were the following: 12% stage I, 49% stage II, 35% stage III and 3% stage IV. The distribution of BC subtypes was: luminal 48%, HER2-positive 29% and triple negative 23%. CONCLUSION To our knowledge, this is the first study describing reproductive status of young patients diagnosed with BC in Latin America. Despite the lack of access to fertility preservation programs in the region, we found that a high number of patients had children at diagnosis of BC. Considering the high prevalence of advanced disease and aggressive subtypes the socioeconomic impact of young BC patients in Latin America needs to be addressed. Citation Format: Werutsky G, Villarreal-Garza C, Morante Cruz ZD, Debiasi M, Zaffaroni F, Fonseca A, Castro-Sánchez A, Platas A, Gómez Moreno H, Bretel D, Ortiz RM, Reinert T, Dybal V, Liedke P, Barrios C. Reproductive status and clinical pathological characteristics of young women diagnosed with breast cancer in Latin America: LACOG 0414 study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-24.

Triple-negative breast cancer (TNBC) is a heterogeneous and complex disease characterized by the absence of immunohistochemical expression of estrogen receptor, progesterone receptor and HER2. These breast tumors present an aggressive biology and offer few opportunities to be treated with targeted therapy resulting in bad disease outcomes. The epidemiology of TNBC is intriguing where the understanding of its biology has progressed quickly. One of the peculiarities of this type of cancer is a high prevalence in Afrodescendants and Hispanic patients compared to Caucasian women. In this review we describe some features of TNBC, focusing in the Hispanic population, such as epidemiological, clinicopathological features and molecular features and the correlation between TNBC prevalence and the human development index.

Purpose:Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.Patients and Methods:One-hundred and ninety patients with stage I–III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan–Meier method.Results:Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14–0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10–0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.Conclusions:Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

DDIT4 gene encodes a protein whose main action is to inhibit mTOR under stress conditions whilst several in vitro studies indicate that its expression favors cancer progression. We have previously described that DDIT4 expression is an independent prognostic factor for tripe negative breast cancer resistant to neoadjuvant chemotherapy. We herein report that high DDIT4 expression is related to the outcome (recurrence-free survival, time to progression and overall survival) in several cancer types. We performed in silico analysis in online platforms, in pooled datasets from KM Plotter and meta-analysis of individual datasets from SurvExpress. High levels of DDIT4 were significantly associated with a worse prognosis in acute myeloid leukemia, breast cancer, glioblastoma multiforme, colon, skin and lung cancer. Conversely, a high DDIT4 expression was associated with an improved prognostic in gastric cancer. DDIT4 was not associated with the outcome of ovarian cancers. Analysis with data from the Cell Miner Tool in 60 cancer cell lines indicated that although rapamycin activity was correlated with levels of MTOR, it is not influenced by DDIT4 expression. In summary, DDIT4 might serve as a novel prognostic biomarker in several malignancies. DDIT4 activity could be responsible for resistance to mTOR inhibitors and is a potential candidate for the development of targeted therapy.

Purpose: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. Experimental Design: The study population includes 190 patients with stage I–III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. Results: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. Conclusions: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline–taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649–57. ©2016 AACR.

Introduction: In a previous work we found differences in immune gene sets enrichment in NSCLC between genders, regardless their smoking status, where women had higher expression of gene sets associated with immune processes. Based in this fact, we hypothesize fewer benefits from immune checkpoint inhibitors in women patients compared than men patients. Objectives: Evaluate the benefit (in terms of progression-free survival) of women patients from immune checkpoint inhibitors nivolumab and pembrolizumab in published randomized phase III trials. Methods: We evaluated by meta-analysis four randomized phase III studies, two of prembrolizumab (Herbst et al., 2015 and Reck et al., 2016) and two of nivolumab (Borghaei et al., 2015 and Brahmer et al., 2015). We analyzed TCGA data for lung adenocarcinoma to evaluate differences in the expression of PDCD1, CD274 genes (encoding for PD-1 and PD-L1, respectively). Results: For all studies, it was observed an overall HR=0.79 (CI95%:0.71-0.87;P Conclusion: Although there are not differences between genders in the expression of PDCD1 and CD274 genes , such as is previously described for expression for PD-1 and PDL-1 proteins, in our meta-analysis we shown that women have modest benefit from anti immune checkpoint inhibitors. Blockade of PD1 and PD-L1 is a promising therapy in lung cancer; however, a better stratification of patients should be done. Meta-analysis of four phase III randomized studiesStudyAll patientsMenWomenWeightHazard Ratio IV, Fixed, 95% CIWeightHazard Ratio IV, Fixed, 95% CIWeightIV, Fixed, 95% CIReck et al., 201610.6%0.50 [0.37, 0.68]10.4%0.39 [0.26, 0.581]8.0%0.71[0.40, 1.26Brahmer et al., 201513.7%0.63 [0.48, 0.8217.8%0.63 [0.46, 0.86]11.2%0.75[0.46, 1.22]Borghaei et al., 201530.3%0.91 [0.76, 1.0926.6%0.81 [0.63, 1.04]37.8%1.02[0.78, 1.33]Herbst et al., 201545.40.85 [0.73, 0.98]45.2%0.78 [0.64, 0.95]43.0%1.04[0.81, 1.33]Total (95% Cl)100.0%0.79 [0.71, 0.87]100.0%0.71 [0.62, 0.80100.0%0.97[0.82, 1.14]Heterogeneity: Chi2=14.73,df=3 (P=0.002); I2= 80% Test for overall effect: Z= 4.73 (P Citation Format: Joseph A. Pinto, Luis A. Mas, Carlos S. Vallejos, Jhajaira Araujo, Leny Bravo, Alfredo Aguilar, Zaida Morante, Denisse Bretel, Henry L. Gomez, Christian Rolfo. Decrease of benefit from immune checkpoint inhibitors in women with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2614. doi:10.1158/1538-7445.AM2017-2614

e18113 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It is well known that there are differences in the outcome between genders; however the effects of the sex in the prognosis have not been previously properly defined. Our aim was to evaluate in a meta-analysis, differences in healthcare outcomes between women and men with NSCLC in terms of overall survival (OS) and progression-free survival (PFS). Methods: We searched for references of published studies of hospitalary databases indexed in PubMed/Medline. We retrieved 67 references (from 1989 to 2016), of which eleven references were eligible for data extraction. In total, 11 references were evaluable for OS. Meta-analysis for Hazard Ratios (HR) obtained from univariate and multivariate analysis were analyzed in different groups. The meta-analysis was done in the software Review Manager 5.3. Results: In total, 7 studies had information for OS univariate analysis, 7 studies for OS multivariate analysis, only, one for PFS univariate analysis and one for PFS multivariate analysis. The meta-analysis for OS univariate analysis resulted in a HR = 0.75 (P < 0.00001; 95% CI: 0.71 to 0.79) for women compared to men, although there was a high statistical heterogeneity between cohorts (P < 0.0001). In the meta-analysis for OS multivariate analysis was estimated a HR = 0.75 (P < 0.00001; 95% CI: 0.73 to 0.78), with statistical heterogeneity between cohorts (P = 0.0005). Conclusions: Our study quantified a 25%-risk reduction of death for women with NSCLC compare with male men patients with the same diagnosis.

The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and 'triple-negative' disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints., SCOPUS: ar.j, info:eu-repo/semantics/published

Latin America and the Caribbean have not yet developed strong clinical cancer research programmes. In order to improve this situation two international cancer organisations, the Latin American Society of Clinical Oncology (SLACOM) and the European Society of Medical Oncology (ESMO) worked closely with the Peruvian Cooperative Oncology Group (GECOPERU) and organised a clinical cancer research workshop held in Lima, Peru, in October 2015. Many oncologists from different Latin American countries participated in this gathering. The opportunities for and strengths of clinical oncology research in Latin American and Caribbean countries were identified as the widespread use of the Spanish language, the high cancer burden, growing access to information, improving patient education, access to new drugs for research centres, regional networks and human resources. However, there are still many weaknesses and problems including the long timeline for regulatory approval, lack of economic investment, lack of training and lack of personnel participating in clinical research, lack of cancer registries, insufficient technology and insufficient supplies for the diagnosis and treatment of cancer, few cancer specialists, low general levels of education and the negative attitude of government authorities towards clinical research.