August 2024 SOCRA Source Journal - Journal - Page 48
Sacituzumab govitecan is well
tolerated and induced early and
durable responses in pretreated
patients with metastatic TNBC
(Bardia et al. 2017).
rate now is less than 1% whereas
HER2 negativity is de昀椀ned
according to the IHC expression
of score 0-1 or lack of gene
ampli昀椀cation (Wolff et al. 2013).
Biomarker research has found
that isolating the glycoproteins
on the 昀椀rst layer of epithelial
cancer cells can improve delivery
of elevated concentrations
of these molecules. This is
because numerous of these
targets are not need cancer
drivers or speci昀椀c to breast
cancer (Garrido-Castro et
al. 2019). Moreover, the
Palbociclib ongoing trials in the
management of BC studies in
estrogen receptor (ER)+, HER2–
negative Metastatic Breast
Cancer (MBC) demonstrated
a signi昀椀cant progressionfree survival advantage for
palbociclib/CDK4/6 inhibiter in
combination with letrozole or
fulvestrant in the 昀椀rst- or secondline setting compared to these
therapies alone. These studies
revealed preliminary ef昀椀cacy
signals for androgen receptor AR
blockade in MBC, triple negative
patients and predominately
in AR+ and treated ER+ MBC
patients with Palbociclib early in
their metastatic treatment course
(Ribnikar et al. 2019).
Currently, endocrine therapy
is used for ERα expression
patients with of 1% and more
in all stages of breast cancer
(Iwamoto et al. 2012). The IHC
of triple negative tumours shows
that they are invasive of ductal
carcinomas characterized of
central necrosis, high histologic
grade, poor differentiation,
high lymphatic in昀椀ltration,
and high rates of proliferation
processes. Additionally, the triple
negative tumour phenotype
also includes high grade the
histologic breast cancer subtypes
including adenoid cystic apocrine
carcinoma, histocytoid, medullary
and metaplastic carcinoma (Bae
et al. 2011).
7. The Histologic
Characterization of TNBC
The immunohistochemical
diagnosis of TNBC is a type
of breast cancer that does
not express ER, PR and HER2.
However, the American College
of Pathology, the American
Society of Clinical Oncology
and the St. Galen guidelines
have changed the cutoff rate
used to de昀椀ne the estrogen and
progesterone receptor negativity.
The accepted receptor cut off
48
8. TNBC Treatment Strategies
As a result of the heterogeneity
of TNBC, there is an ongoing
effort to develop new targeted
therapies for the different
subtypes. First, DNA- damaging
chemotherapy and DNA repair
targeting is discussed. The DNA
repair system is essential to
maintain the genome material.
BRCA1 and BRCA2 are tumour
suppressor genes involved in
homologous recombinationmediated repair of double
stranded breaks. BRCA1 and
BRCA2 genes mutation leads
to impaired DNA repair function
by homologous recombination
and results in genomic instability
(Hoeijmakers 2001).
Advanced knowledge of the
repair mechanism of DNA has
enabled the development of
new therapeutic approaches
SOCRA SOURCE © May 2024
in TNBC therapies, exploiting
the higher sensitivity of these
tumours to increase the rate
at which the DNA agents are
damaging, for example, platinum
salts and poly ADP-Ribose
Polymerase (PARP) inhibitors.
However, using platinum
compounds in the neoadjuvant
have shown con昀氀icting results,
such as Carboplatiinum to
Paclitaxel, and Liposomal
doxorubicin (Sirohi et al. 2008).
Some TNBC research explains
that the combination of a
platinum agent with PARP
inhibitors might increase the
effectiveness by increasing
double-strand breaks to the point
where even a competent repair
system is overwhelmed (Comen
and Robson 2010). PARP Inhibitor
plays an essential role in the DNA
repair system, by homologues
recombination-mediated repair
of double stranded breaks and
the enzyme activity lacking leads
to persistent DNA lesions that
induce apoptosis (O’shaughnessy
et al. 2011).
Inhibitors of PARP have been
developed as a new treatment
for tumours with a speci昀椀c
de昀椀ciency with the DNA
repair mechanism such as
triple negative breast cancer,
BRCA1and BRCA2 mutations,
(e.g. Olaparib oral active PARP
inhibiter). Several studies have
documented that adjuvant
endocrine therapies that stop
the action of estrogen on breast
tissue can block tumour growths
thereby becoming essential
treatment strategies, which
reduce the risk of recurrence
and death in women with
estrogen receptor ER-positive
disease (Group 2015). This is
not available as an option for