Investigating Tumor Infiltrating Lymphocytes (TILs) in Triple-Negative Breast Cancer (TNBC) with respect to BRCA mutation status

Abstract

BRCA1 also known as breast cancer susceptbility gene 1, this gene is known for its functon as a tumor suppressor (Hall et al., 1990), the mutaton in this gene has been associated with both sporadic and familial breast and ovarian cancers (Futreal et al., 1994; Godwin et al., 1994), BRCA2 (Breast cancer susceptbility gene2) is also associated with the predispositon of breast and ovarian cancer (Wooster et al., 1995a). Both of these genes play a cru role in the double strand break (DSB) repair of DNA by homologous recombinaton (HR) (Moynahan et al., 2001a; Wang et al., 2007). Through various studies it was seen that the risk of developing breast cancer by the age of 70 is upto 40% to 86% for the BRCA1/2 mutaton carriers (Antoniou et al., 2003; Begg et al., 2008; Brohet et al., 2014; S. Chen et al., 2006a). Breast cancer presents with diferent molecular subtypes according to the expression of hormone receptors –Estrogen receptor (ER), Progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) (Vaz-Luis et al., 2013; ZHANG et al., 2014). Triple negatve breast cancer (TNBC) is characterized as the subtype with negatve expression of the ER, PR and HER2 receptors (Foulkes et al., 2010). It was shown that 19.5% of the TNBC patents had BRCA mutatons (H. Chen et al., 2018; Gonzalez-Angulo et al., 2011). Whereas 53% -75% of BRCA1 mutaton carriers showed triple-negatve phenotype (Atchley et al., 2008). Through various studies it was shown that TNBC is the most immunogenic subtype of breast cancer mainly due to high tumor mutatonal burden and higher tumor infltratng lymphocytes as compared to the other subtypes of (Karn et al.,2017; Valenza et al., 2023). It was shown that the BRCA1/2 mutaton status in cancer is also associated with the increased infltraton of lymphocytes (de Boo et al., 2020). The efect of BRCA1/2 mutaton on the tumorinfltratng lymphocytes for diferent subtypes of breast cancer had been studied extensively for the western cohort (Grandal, Evrevin, Laas, Jardin, Rozete, Laot, Dumas, Coussy, Pierga, Brain, Saule, Stoppa-Lyonnet,Frank, Sénéchal, Lae, Croze, et al., 2020; Solinas, Carbognin, et al., 2017; Telli et al., 2020). In the Indian populaton, the prevalence of TNBC is 27% - 31% (Kulkarni et al., 2020; Sandhu et al., 2016), which is much higher than the prevalence of TNBC in western populaton 12% (Foulkes et al., 2010). Even though the prevalence of TNBC is high in India there isn’t much investgaton done for the Indian cohort of TNBC patents with BRCA1/2 mutaton(Gogia, S G, Pramanik, et al., 2023). Thus, in this study we will investgate the associaton of the BRCA mutaton status with the tumor infltratng lymphocytes in the tumor microenvironment of the TNBC patents.