Triple negative breast cancers
(TNBCs) lack Estrogen receptor, Progesterone receptor and Epidermal growth
factor receptor 2 (HER2) and accounts for approximately 10-20% of breast cancers. They
are common in women under 40 and black women and are characterized by poor
prognosis. The current treatment remains surgery, chemotherapy, and
radiotherapy, but is associated with high relapse risk. This necessitates
the need for novel therapeutic approaches 1.
A large proportion (50-75%) of
TNBCs express Epidermal Growth Factor Receptor (EGFR). However, clinical trials
with EGFR targeting studies have not been promising. A recent study by Foidart
et al2, uncovers an interesting loop involving three genes - EGFR, membrane-type-4 matrix metalloproteinase (MT4-MMP), and retinoblastoma protein
(RB) in TNBCs which could be therapeutically exploited in the management of the
disease. Their studies which were conducted in in human breast tumour specimens,
xenografts, and patient derived TNBCs (PDX-TNBC)
xenografts reveal that approximately half of all TNBC and PDX-TNBC
express the three genes. More than 70% of TNBC samples and PDX-TNBC co-express EGFR
and MT4-MMP, and approximately 60% express RB.
Experiments on TNB cells coexpressing
EGFR and MT4-MMP show that single erlotinib and palbociclib treatments radically
reduce proliferation when compared with control cells. In the xenografts, those
coexpressing MT4-MMP, EGFR, and RB show sensitivity to erlotinib and
palbociclib individually, and display an additive effect when administered
together. This phenomenon is not seen in
xenografts that lack Rb.
This study crucially demonstrates
the efficacy of erlotinib–palbociclib combination in MT4-MMP/EGFR/RB tumors
that represent 50% of TNBC patients, and shows that a subgroup of patients who
could be successfully treated with EGFR and CDK4/6 inhibitors can be identified
by profiling the tumours for the three biomarkers which allows for effective
patient selection and targeted therapy.
References:
2.http://clincancerres.aacrjournals.org/content/25/6/1838