August 2024 SOCRA Source Journal - Journal - Page 45
breast cancers (BLBC) have
been recorded to express ER
and 14% of BLBC express HER–2
demonstrating that nevertheless
of classi昀椀cation technique, not
all BLBC are TNBC. There were
some studies suggesting that
the molecular markers of TNBC,
such as VEGF, EGFR, Src and
mTOR, have been important
for the design of clinical trials
investigating targeted treatments
(Lehmann et al. 2011). However,
16% - 44% of TNBC test negative
for all these markers. Thus, it
is dif昀椀cult to develop targeted
treatment strategies that would be
universally applicable to all TNBC.
The rapidly growing area of
literature on TNBC indicates that
there are six stable subtypes
(Uscanga-Perales et al. 2016)
displaying unique Gene
Expression (GE) signatures
and ontologies, including 2
basal-like subtypes BL1 and
BL2. These have DNA damage
response genes and a higher
expression of cell cycle related
genes, representative cell lines
preferentially responding to
cisplatin. Second, Mesenchymal
(M) and a Mesenchymal StemLike (MSL) subtypes were
enhanced in GE for epithelial
mesenchymal transition.
Growth factor pathways and cell
models responded to PI3K/m
TOR inhibitors and Dasatinib
(abl/src) inhibitor. Third, an
immunomodulatory (IM) and a
luminal androgen receptor (LAR)
subtype, which includes patients
with decreased relapse-free
survival and was characterized by
AR signaling (Table 1) (UscangaPerales et al. 2016)
Such TNBC patients have a
poor outlook, independent of
lymph-node status (Foulkes
TABLE 1
Molecular Subtypes and Characterizes of TNBC
TNBC Subtypes
Characterizes of Triple
Negative Tumour
Basal Like -1 (BLI)
Cellular proliferation and
response to cellular damage
Basal Like -2 (BL2)
Growth factor signalling with
myoepithelial markers
Immunomodulatory Class
Signalling mediated by
immune synapsis
Mesenchymal Class
MET and differentiation
Mesenchymal Stem Cell
MET, differentiation and stem
cell potential, angiogenesis
and growth factor signalling.
Luminal Androgen Receptor
Hormone signaling mediated
by androgen receptor
et al. 2004). An implication of
this is the possibility that TNBC
shares survival biology features
with basal-like breast cancer
and is associated with poor
clinical outcome and high rates
of recurrence following chemotherapy. The negative prognosis
of TNBC is in a large part due to
the excessive risk of developing
visceral metastases (Dent et al.
2007, Hwang et al. 2007).
4. Risk Factors of TNBC
TNBC is associated with increased
risk for visceral metastasis and
lower risk for bone recurrences.
In-vitro and in-vivo research,
and epidemiological data have
revealed that the reproductive
hormones estrogen and
progesterone play an essential
role in breast cancer etiology
(Persson 2000). Risk factors such
as postmenopausal obesity, use
of exogenous hormones and age
at 昀椀rst menarche increase the
risk of developing breast cancer
by increasing systemic exposure
to hormones, which leads
directly to connect the higher
circulating levels of estradiol to
postmenopausal breast cancer.
Additionally, the breast cancer
progress can be affected by
hormone related exposure
(as one of the risk factors),
including, hormone synthesis,
metabolism, and protein
expression. Oral contraceptive
exogenous hormone use was
strongly associated with ER–
rather than ER+ tumours (Althuis
et al. 2004). Socioeconomic
characteristics of population and
family history of breast cancer,
older age, earlier menarche age,
induced abortion, nulliparity, and
lack of breastfeeding all affect
the risk of developing breast
cancer. These factors have been
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