Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

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The report evaluates the effect of coronavirus disease (COVID-19) pandemic on breast cancer treatment and management at a single-surgeon cancer care unit in one of the hotspots of COVID-19 in India. In response to the pandemic, the adjustments were made in the clinical practice to accommodate social distancing. Patient consultations were done over phone call or in-clinic visit with prior appointment to reduce the risk of exposure to COVID-19. Total number of patients that were treated at the clinic and the essential surgeries performed during the pandemic phases are summarized in the report. The methodology adopted here for care and management of the cancer patients can serve as a guiding principle for cancer care units in the country.

Purpose: Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC). The high TNBC prevalence (>25%) in India remains a challenge in clinical management. Association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. These studies are however predominantly representative of western population. Therefore, we investigated germline profiles of multi-institutional cohort of TNBC patients in India Methods: Using a multi-gene NGS (next-generation sequencing) panel of 26 ACMG recommended genes associated with inherited cancers. Results: In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. Additionally, 8 pathogenic mutations were identified in non-BRCA cancer pre-disposing genes associated with the HR pathway. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. Comparison of allele-frequency with the global databases like TCGA (The Cancer Genome Atlas), gnomAD and Genome Asia 100K indicated that the novel mutations were unique. Furthermore, we identified 48 variants of uncertain significance (VUS) (24.9%). Conclusions: Our study confirms the major proportion of mutations in BRCA1/2 genes in TNBCs in India. Interestingly, a higher proportion of VUS were found in the non-BRCA genes compared to BRCA1/2 emphasizing the need for functional studies of the non-BRCA genes. Additionally, large scale studies are also warranted to elucidate the landscape of germline mutations relevant to the Indian population and their probable clinical implications.

Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (>25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of breast cancer patients in India using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. Of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. We have also assessed the association of clinicopathological parameters such as tumor grade, stage, recurrence to the germline mutational status. Our analysis shows significant association of germline mutational status with family history thus underlin the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: Chaitanyanand Koppiker, Ashwini Bapat, Siddharth Gahlaut, Naveen Luke, Jisha John, Rupa Mishra, Aishwarya Konnur, Namrata Namewar, Ruhi Reddy, Shaheen Shaikh, Rituja Banale, Smeeta Nare, Laleh Busheri, Asha Reddy, Ashraf Mannan, Sabarinathan Radhakrishnan, Selvi Radhakrishna, Santosh Dixit. Germline mutational profiling of TNBCs in an Indian cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB561.

Purpose Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC). The high TNBC prevalence (> 25%) in India remains a challenge in clinical management. Association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. These studies are however predominantly representative of western population. Therefore, we investigated germline profiles of multi-institutional cohort of TNBC patients in India Methods Using a multi-gene NGS (next-generation sequencing) panel of 26 ACMG recommended genes associated with inherited cancers. Results In our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations of which BRCA1 (71.93%) and BRCA2 (14.03%) were most commonly mutated. Additionally, 8 pathogenic mutations were identified in non-BRCA genes associated with the HR pathway. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. Comparison of allele-frequency with the global databases like TCGA (The Cancer Genome Atlas), gnomAD and Genome Asia 100K indicated that the novel mutations were unique. Furthermore, we identified 48 variants of uncertain significance (VUS) (24.9%). Conclusions Our study confirms the major proportion of mutations in BRCA1/2 genes in TNBCs in India. Interestingly, a higher proportion of VUS were found in the non-BRCA genes compared to BRCA1/2 emphasizing the need for functional studies of the non-BRCA genes. Additionally, large scale studies are also warranted to elucidate the landscape of germline mutations relevant to the Indian population and their probable clinical implications.

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.

Objectives: Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods: A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results: Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion: Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC. Citation Format: Madhura Kulkarni, Pooja M. Vaid, Anirudha Puntambekar Puntambekar, Rituja A. Banale, Ruhi Reddy, Rohini Unde, Namrata Namewar, Devaki Kelkar, L.S. Shashidhara, C.B. Koppiker. Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO008.