Abstract P5-06-08: Molecular features of Pregnancy Associated Breast Cancer from a tertiary care cancer centre in India

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Abstract Background: Pregnancy-associated breast cancer (PABC) encompassing breast cancer diagnosed during pregnancy or one-year post-partum is a rare and challenging entity wherein oncologists need to safeguard maternal oncological and foetal outcomes simultaneously. Little is known about genomic signatures which is worth exploring to throw light on aetiopathogeneses, prognosticators and might reveal potential targets with therapeutic relevance. Aim: The study aimed to identify the molecular signatures to identify potential pathways implicated in pathogenesis and therapeutically relevant targets and independent prognosticators for PABC. Methods: Patients with histologically confirmed breast cancer who were pregnant or diagnosed within one year of last pregnancy were included in study during the year 2013-2020 at our tertiary care cancer centre. Bio-specimens (tumour, tumour-adjacent normal, whole blood or plasma) were collected from the patients and the samples were subjected to DNA and RNA extraction and library preparations and then were sequenced at 200 X for tumour and 100 X for blood/tumour adjacent normal on an Illumina Platform and after through check for the quality control were analysed. Results: There was a total of 104 patients enrolled in the registry from the year 2013-2020.Of these, 55 patients contributed at least one bio-specimen (tumour, tumour-adjacent normal, whole blood or plasma) to this study. Among those,7/55 samples were paired (Tumour and blood), with 9 were only plasma. Of the remaining 48 patients, 7 had paired (tumour and normal) samples, 38 had tumours alone and 3 had germlines alone (2 whole blood, one tumour adjacent normal). All the samples were subjected to DNA and RNA extraction.40/48 patients had at least one analyte (DNA or RNA) available. DNA from 29/38 tumour alone, and 6/7 with paired samples and 2/3 patients with germline alone were subjected to successful library preparation and sequencing at 200 X for tumour and 100 X for blood/tumour adjacent normal on an Illumina Platform. DNA Library prep for 1 patient tumour was unsuccessful due to low DNA quantity; however, that for the total RNA succeeded. RNA from 8 patient tumour samples that passed quality control (RIN>5.0) were also subjected to a total RNA library prep specific for fragmented RNA, followed by sequencing on an Illumina Platform to generate at least 50 million PE reads (100 million total reads). There was an overlap of 7 patients with both WES and RNA-Seq data for tumour samples. Eight out of 38 patients were HER2 positive, with four being ER and/or PR positive and four being ER and/or PR negative. Eleven out of 38 patients were ER and/or PR positive and HER2 negative. Fifteen out of 38 patients were triple negative for ER, PR, and HER2 expression. Four patients were HER2 equivocal; among them, three were ER and PR positive, and one was ER and PR negative. The median age of patients was 30 years (22-45). 32 patients were postpartum at diagnosis while 6 were antepartum at diagnosis. Six patients were node-negative, while 32 were node-positive at diagnosis. Twelve patients presented with de novo metastatic disease at diagnosis, and 19 patients experienced metastatic progression post-diagnosis. The median coverage for WES of Tumour samples was 182X and that for germline samples was 96X. Mutations were identified in PI3KCA (17%), TP53 (4%), and 2% in both. 6 patients harboured germline BRCA mutations. Additional mutations were identified in epigenetic modifiers. Pathways involved in PI3K signalling, mTOR signalling, ECM matrix related signalling and cell cycle related processes were de-regulated. Conclusion: The molecular profiling report for pregnancy-associated breast cancer patients presented here constitutes an invaluable, ultra-rare dataset. This will help in identifying factors associated with etiopathological and prognostic significance as well as relevant potential therapeutic targets for novel targeted therapeutics. This may contribute towards finding novel avenues which may enhance treatment armamentrium in this extremely challenging situation -an unmet need! Citation Format: Jyoti Bajpai, Rohan Chaubal, Rajiv Sarin, Venkatesh Kapu, Khushi Patel, Ankita Singh, Jaya Chitra, Shwetali Pandey, Mrudula Madhav, Aishwarya Raja, Anushree Kadam, Khusboo Gandhi, Altaf Siddiqui, Yogesh Khembhavi, Sushmita Rath, Rajendra Badwe, Sudeep Gupta. Molecular features of Pregnancy Associated Breast Cancer from a tertiary care cancer centre in India [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-06-08.

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