August 2024 SOCRA Source Journal - Journal - Page 46
studied extensively and a large
pool of data analysis has found
that premenopausal women
have approximately 20% - 30%
higher risk of breast cancer
(Dolle et al. 2009). Additionally,
previous studies have reported
that the risk of oral contraceptive
(OC) use is concentrated
among younger premenopausal
women (Rosenberg et al. 1996).
These 昀椀ndings are consistent
with the mechanism through
which oral contraceptive use
impacts the risk of breast
cancer in young women by
studying the role of estrogen
in promoting the growth and
vascularization of cancer cells,
in particular, the mechanism
of transcription which affects
estrogen binding to its receptor
in ER+ in mammary and ovarian
cancer cells. However, some
publications have approached
a second mechanism whereby
estrogen promotes the growth
of ER– and ER+ cancer by
enhancing angiogenesis and
stromal cell recruitment (Gupta
et al. 2007). One million cases
of breast cancer are diagnosed
annually around the world and it
is rated that over 170,000 harbor
the TNBC (estrogen receptor/
progesterone receptor/Her2negative) phenotype (Anders
and Carey 2009). According
to data from gene expression
microarrays, most TNBC share
characteristics with Basal Like
(BL) subtype. The Basal Like
molecular subtype exhibits a
unique molecular pro昀椀le and
a set of risk factors including
aggressive and early pattern of
metastasis, limited treatment
options, and poor prognosis.
Most population-based
researchers have found a higher
proportion of TNBC tumours
46
among premenopausal African
American women, pregnancy at
an early age, shorter duration
of breast feeding, and elevated
hip-to-waist ratio might be
particular risk factors. TNBC
clinical diagnostics illustrate the
preferential relapse in visceral
organs which include the central
nervous system. Although initial
response to chemotherapy might
be more profound, relapse
is early and common among
TNBC when compared with
luminal breast cancers. The
armamentarium of “targeted
therapeutics” for triple negative
breast cancer is evolving and
includes strategies to inhibit
angiogenesis, epidermal growth
factor receptors and other
kinases (Anders and Carey 2009)
.
5. Biomarkers and Molecular
Targets of TNBC
Breast cancer of the triple
negative phenotype overlaps
with BL breast cancer;
however, TNBC has signi昀椀cant
clinical implications, such
as an association with poor
survival rates, higher incidence
of recurrence and distant
metastasis. Furthermore,
research has highlighted the
need for a better understanding
of TNBC and it has received
considerable critical attention
for the following reasons.
First, the heterogeneity of this
disease re昀氀ects the activation of
different genetic pathways and
various cellular targets in which
these genetic changes occur.
Second, chemotherapy, which
is associated with high toxicity,
is the main treatment option.
TNBC patients are treated
typically with a combination of
radiation, chemotherapy and
surgery. TNBC patients seem to
achieve higher response rates
SOCRA SOURCE © May 2024
to chemotherapy, but this does
not convert into Overall Survival
(OS) or superior Progression Free
Survival (PFS) (Rodríguez-Pinilla
et al. 2006).
According to gene expression
analysis, TNBC is a subtype
of breast cancer with a
heterogeneous behavior. This
analysis is not only useful to
understand the disease, but to
identify the new molecular target
for its treatment (Lehmann et al.
2011). Some of TNBC biomarkers
as potential therapeutic targets
are shown on page 47 (Table 2)
and the classic diagnostic and
therapeutic strategies for TNBC
are discussed below.
6. The Clinical Therapy
of TNBC
The TNBC patients are classi昀椀ed
into two types: some patients
respond to treatment, while the
majority has a poor outcome at
the clinical level. Additionally,
the nature of this disease is
highly aggressive with poor
viable therapeutic options
and OS. It exhibits a high rate
of incidence among Hispanic
women and African American
women under 40 years of age. In
recent years, there has been an
increasing amount of literature
on neoadjuvant therapeutic
approaches. Clinical studies show
neoadjuvant therapeutics such
as anthracyclines and taxanes are
improving survival rates in TNBC
women with a clinical response
rate on top of 85%, while the
pathologic study of (pCR) has the
rate of response between 30%40% (von Minckwitz et al. 2012).
Clinical triple negative tumours
display a special manner of
relapse with a high risk of
developing distant metastasis