BRC455821_sm_Suppl._Material.pdf (938.17 kB)
Supplementary Material for: Therapeutic Advances and New Directions for Triple-Negative Breast Cancer
dataset
posted on 2017-02-07, 10:01 authored by Andreopoulou E., Kelly C.M., McDaid H.M.Triple-negative breast cancer (TNBC) is a molecularly
diverse grouping with poor prognosis for which chemotherapy
remains the foundation of treatment. The molecular
heterogeneity of the disease rationalizes its diverse
biological behavior and differential response to
treatment. Estimates of up to 20% of patients diagnosed
have germline mutations in DNA-damage repair-pathway
genes, namely BRCA1 and 2, and this can be used
to select patients likely to respond to platinums and/or
inhibitors of poly(ADP-ribose) polymerase (PARP). Similar
strategies can be utilized in other subtypes of TNBC
that have ‘BRCA-like’ tumor biology due to the presence
of mutations in alternate DNA-damage repair genes. The
diverse biological behavior of TNBC and its variable response
to chemotherapy were largely decoded following
genotyping studies that enabled the identification of distinct
molecular subtypes, such that the biological and
genetic heterogeneity of the disease could be understood.
This subsequently enabled the identification of
therapeutic ‘vulnerabilities’ for each subtype that encompass
biological processes including proliferation, DNA
repair, apoptosis, angiogenesis, immune modulation,
and invasion and metastasis. To expedite the development
of therapies for high-risk, early-stage breast cancer,
we have adopted novel trial designs and re-defined
endpoints as surrogates of clinical outcomes. The purpose
of this review is to highlight the current standard
and experimental treatment options for TNBC.