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On January 13th and 14th 2022, the Center for Translational Cancer Research organized the virtual third Indian Cancer Genome Atlas (ICGA) Conference 2022 "Biobanking to Omics - Collecting the Global Experience." This conference was planned as the steppingstone to help ICGA understand the road ahead and the probable roadblocks in its preparatory phase as ICGA begins to streamline the tumor tissue biobanking and multi-omics efforts in the Indian subcontinent. The first day of the conference was dedicated to updates on the current status of ICGA, the future prospect, and the global understanding of multi-omics efforts. The key highlights included two keynote speeches by Dr Wui Jin Koh, Senior Vice President and Chief Medical Office, National Comprehensive Cancer Network, and by Dr Christina Curtis, Associate Professor, Stanford University School of Medicine. The first day ended with an intriguing panel discussion on "ICGA updates and Future Steps." The second day focused on biobanking practices across the globe and several aspects of biobank setup such as infrastructure, maintenance, quality control, patient consent, and lessons learned from established biobanking setups. The talk by Rosita Kammler, Head, Translational Research Coordination, International Breast Cancer Study Group, Switzerland, and Ruhul Amin, Director, Bangladesh Medical Research Council were the key highlights. The second day also ended with an engaging panel discussion on "Tumor tissue biobanking - national and international perspectives." Overall, the conference was well received and had good attendance from national and international students, researchers, and faculty from academia as well as industry.
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Bancos de Muestras Biológicas , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , BangladeshRESUMEN
Introduction: The essential goal of neoadjuvant chemotherapy (NACT) is to downstage the primary tumor making it amenable for breast conservation surgery (BCS). However, since the safety of this surgery is paramount, post-NACT breast conservation rates remain low. As per the recommendation of the 2018 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of long-term post-NACT follow-up, we have devised a protocol for imaging, localization, rad-path analysis, and documentation of radiotherapy techniques to ensure the safety of post-NACT breast conservation. Methods: This is a retrospective cohort of 180 breast cancer patients who received NACT and were operated on by a single surgical oncologist from 2015 to 2020. After selection based on published guidelines, patients were treated with neoadjuvant systemic (chemo or hormone) therapy. In cases where primary tumors responded and reduced to 1-2 cm in size mid-NACT, the residual tumors were localized by clips under ultrasound guidance and calcification was wire localized. All patients were treated using appropriate surgical and oncoplastic techniques where indicated. Negative margins were ensured by intra-operative rad-path analysis. Adjuvant chemotherapy and radiotherapy were given as per protocol. Results: In 81 cases that required mastectomy at presentation, we were able to achieve a 72.8% post-NACT BCS rate with the help of oncoplasty. Overall, 142 of 180 (80%) patients were treated with breast conserving surgery of which 80% (121 of 142) were oncoplasty. Margins were assessed on intra-operative frozen and re-excised in the same setting. No positive margins were reported in final histopath of 142 breast conservation procedures. Post-operative complication rates after breast conservation in the first year were at 17% (24 of 142 including two major complications). Patient reported outcomes were satisfactory with increased satisfaction for breast conservation compared with immediate breast reconstruction. Discussion: Employing oncoplastic breast surgery (OBS) techniques following stringent protocols for accurate localization of the residual tumor, intra-operative rad-path analysis, and adjuvant treatments, we show successful breast conservation in 72.8% of our mastectomy-qualified patients after downstaging by NACT. We also report satisfactory outcomes for post-NACT surgery, patient-reported satisfaction, and survival.
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OBJECTIVES: Evaluation of tumor-infiltrating lymphocytes (TILs) distribution in an Indian cohort of breast cancer patients for its prognostic significance. METHODS: A retrospective cohort of breast cancer patients from a single onco-surgeon's breast cancer clinic with a uniform treatment strategy was evaluated for TILs. Tumor sections were H&E stained and scored for the spatial distribution and percent stromal TILs infiltration by a certified pathologist. The scores were analysed for association with treatment response and survival outcomes across molecular subtypes. RESULTS: Total 229 breast cancer tumors were evaluated. Within spatial distribution categories, intra-tumoral TILs were observed to be associated with complete pathological response and lower recurrence frequency for the entire cohort. Subtype-wise analysis of stromal TILs (sTILs) re-enforced significantly higher infiltration in TNBC compared to HER2-positive and ER-positive tumors. A favourable association of higher stromal infiltration was observed with treatment response and disease outcomes, specifically in TNBC. CONCLUSION: Intra-tumoral TILs showed a higher proportion with favourable association with better patient outcomes in an Indian cohort, unlike western cohorts where both stromal and intra-tumoral TILs show similar association with prognosis. With further validation, TILs can be developed as a cost-effective surrogate marker for treatment response, especially in a low-resource setting such as India.
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Linfocitos Infiltrantes de Tumor , Neoplasias de la Mama Triple Negativas , Humanos , Linfocitos Infiltrantes de Tumor/patología , Neoplasias de la Mama Triple Negativas/patología , Estudios Retrospectivos , PronósticoRESUMEN
Genetic approaches in Drosophila have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer in vivo Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: the Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation in vivo We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways. We also find a number of novel connections to Yki and EGFR driven tissue growth, mostly unique to one of the two. Thus, resources provided here would be useful to all researchers who study negative regulators of growth during development and cancer in the context of activated EGFR and/or Yki and positive regulators of growth in the context of activated EGFR. Resources reported here are available freely for anyone to use.