Triple negative breast cancer (TNBC), the most heterogeneous and aggressive breast cancer has always remained a global burden. To understand the molecular pathogenesis, we stratified the seven subgroups of TNBC propounded by Lehmann et al (2011) as:  TNBC with alterations of the DNA damage repair and cell cycle checkpoint pathways (Basal Like 1 & 2 (BL1, BL2)),  with upregulation of cell signalling and cell motility pathways (mesenchymal (M), mesemchymal stem like (MSL)),  with upregulated cell survival pathways (BL2, M, MSL)  With upregulated angiogenesis pathways (BL2, MSL),  With upregulation of pathways associated with T cell signalling,  With upregulated Androgen receptor signalling pathways. Our objective was to prioritize the basic molecular heterogeneity of TNBC in redefining our choice of drugs.
Lehmann’s TNBC subgroups showed deregulation of diverse molecular pathways necessitating targeted therapeutics. We conducted a Meta-Analysis on12 randomized reported trial cases (n = 1170), solely under the following classes of drug regimens:  DNA destabilizers,  PARP inhibitors,  Microtubule stabilizers,  Angiogenesis inhibitors,  Antimetabolite,  T cell targeted therapy; as single or combinational therapies. Radiotherapy recipients were excluded.
Best therapeutic efficacies of DNA destabilizers with angiogenesis inhibitors in combination than monotherapy with either (OR: 5.011-7.286; p value< 0.001) indicated a significant prevalence of basal like TNBCs in populations. Statistical significance with antimetabolites as combination therapy (OR: 2.343; p value: 0.018) and not with microtubule stabilizer (OR: 0.377) were remarkable, indicating probability of less predominance of M or MSL type TNBC in a population. PARP inhibitors or T cell targeted therapies were also found promising (OR: 1.120, 1.040 respectively), warranting their targeted usage for BRCA1 deficient and IM type TNBCs respectively.
For TNBC treatment, personalized medicine and not a generalized treatment strategy should be considered.
Clinical trial identification
Legal entity responsible for the study
Netaji Subhas Chandra Bose Cancer Research Institute
All authors have declared no conflicts of interest.