Review Article
Triple Negative Breast Cancer: What Surgeons Should Know
Omeed Moaven and Kirby I. Bland*
Department of Surgery, University of Alabama at Birmingham, USA
*Corresponding author: Kirby I. Bland, Department of Surgery, University of Alabama at Birmingham, 1720 2nd Ave. South, FOT 1162, USA
Published: 30 Dec, 2016
Cite this article as: Moaven O, Bland KI. Triple Negative
Breast Cancer: What Surgeons Should
Know. Clin Surg. 2016; 1: 1283.
Abstract
Breast cancer has been classified into different subgroups with discrete tumor behavior, prognosis and therapeutic approaches. Triple negative breast cancer (TNBC) is characterized by lack of expression
of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER-
2). TNBC represents a heterogeneous group of tumors with more aggressive biologic behavior and
poorer prognosis. Lack of receptor expression, which excludes hormonal therapy and trastuzumab
as treatment options, is a therapeutic challenge. In this manuscript, we have reviewed our current
knowledge about the epidemiology and contributing risk factors of TNBC, heterogeneity in the
molecular landscape, clinical course of TNBC, and current evidence on available therapeutic options
and developing novel modalities such as targeted therapy. Molecular heterogeneity is an important
contributing factor that could explain the discrepancies in the literature, in terms of various clinical
aspects of TNBC. Genetic features should be considered and studied alongside in the prospective
trials, to better understand and clinically address the heterogeneous nature of this disease.
Keywords: Breast cancer; Triple negative breast cancer; BRCA
Introduction
Breast cancer is a heterogeneous disease at molecular level with diverse clinical manifestations.
Malignant behavior of the tumors and therapeutic strategies are different based on tumors’
hormonal activity, determined by expression of estrogen receptor (ER) and progesterone receptor
(PR), as well as expression of Human Epidermal Growth Receptor 2 (HER2). Microarray analysis
of breast cancers has classified them in 5 different subgroups with different therapeutic options
and prognosis, based on their gene expression profiling [1-3]. These transcriptional subtypes
include: 1) luminal A (ER and/or PR +, HER2 -); 2) Luminal B (ER and/or PR +, HER2 +); 3) HER2
over expression (ER and PR -, HER +), 4) Basal like [ER and PR -, HER2 +/-, cytokeratin and/or
epidermal growth factor receptor (EGFR) +] and finally, 5) normal breast-like (tumors that do not
fit into any of the other categories). Two different cell types of mammary glands, luminal and basal
(myoepithelioid), represent the cellular basis of this molecular classification.
Triple negative breast cancer (TNBC), which is defined by lack of expression of ER, PR and
HER2, represents the most aggressive subtype with higher rate of local recurrence and poorer
clinical outcome [4,5]. There is a significant overlap between TNBC and the basal like transcriptional
subtype but the 2 entities are not exactly identical. While about 73% of TNBCs are basal like tumors,
the rest lack the basal like specific markers [6]. Furthermore, a small proportion of non-TNBCs
produce basal like markers [7]. Lack of therapeutic target for hormonal therapy and trastuzumab is
the clinical a challenge in TNBC, which limits the available effective medical therapy. In this review,
we discuss the epidemiology of TNBC, molecular heterogeneity and their clinical implications,
diagnosis, clinical course and available therapeutic modalities.
Epidemiology, Trends and Risk Factors
TNBC comprises 10-20% of all diagnosed breast cancers. There is a consensus, in various widely
cited epidemiologic studies, that TBNCs are more frequently seen in younger females below 40
years, nonhispanic patients with African ethnic background and those with low socioeconomic
status. However, the data regarding the risk factors of reproductive and menstrual history is more
consistent in hormone receptor positive breast cancers and more controversial in TNBC.
Results from Carey et al. [8], confirm that prevalence of basal-like breast cancer was significantly
higher in premenopausal African-American (AA) females compared to postmenopausal AA
females, and non-AA and the survival was poorer regardless of their age [8]. Bauer et al. in another
population-based study published from the California Cancer
Registry, reported that patients with TNBC more likely tended
to be nonhispanic AA and below the age of 40. Survival was lower
in patients with TNBC regardless of tumor stage [9]. The larger
retrospective populations-based study in 2010, from the California
Cancer Registry by Amirikia and Associates [10] included 375,761
invasive breast cancers, supported the previous findings that
nonhispanic AA are at higher risk to develop TNBC. Higher incidence
of TNBC was observed in younger patients particularly below age 50.
Several smaller population-based studies have shown similar results,
providing strong evidence for racial disparities in developing TNBC
with a trend towards younger patients [11-13].
A multitude of population-based studies have tried to identify the
etiology of TNBC. While many of these studies have revealed that
the risk factors of developing TNBC are different from other types
of breast cancer, further studies are required to better understand
the underlying factors responsible for TNBC development. The
current data regarding the role of menstrual and reproductive
history, breast-feeding and oral contraception, is controversial.
Despite the clear inverse relationship between parity and hormonally
active breast cancers, most of the studies have failed to confirm any
correlation between parity and TNBC. However, Phipps et al. [14]
in a large population based study including 155,723 females showed
that nulliparity decreases the risk of TNBC and increased parity
is associated with increased risk of TNBC. Similar findings were
reported in 2 smaller case-controlled studies [15,16].
Older age at first pregnancy has been shown to be associated
with increased risk of breast cancers with expression of hormonal
receptors while the majority of the studies on TNBC, except two of
them, [17 and 18] did not identify any association between age at first
pregnancy and risk of TNBC. Lactation has been shown to have a
protective effect against TNBC in multiple studies [14,16,17,19] and
lack of breast-feeding is associated with an increased risk of TNBC
[20]. Millekan et al. [16] noted a combination of increased parity and
lack of lactation was also associated with further increase in risk of
TNBC. There is no strong evidence supporting the role of menstrual
history in development of TNBC. Multiple studies have demonstrated
that age of menopause is not associated with TNBC [14,21,22]. While
few studies have reported an association between TNBC and younger
age of menarch, [16,21,23] the rest of the studies have not supported
this finding.
The data regarding TNBC and oral contraceptive (OCP) or
hormonal therapy is also controversial. Ma et al. [24] demonstrated
that women who started using OCP before the age of 18 had a 2.9-fold
increase in TNBC and Dolle et al. [14] showed OCP consumption
more than one year was associated with 2.5-fold increase in TNBC
risk. Other studies, however, did not find any association between
OCP and TNBC. Current hormonal therapy and not past use, is also
reported to be associated with TNBC [19].
Yang et al. [21] pooled the data of 35,568 patients with breast
cancer (1997 TNBC) from 34 studies participating in the Breast
Cancer Association Consortium and studied various risk factors in
different breast cancer subtypes. They noted that lower age at the first
full-term birth, and BMI among younger women < 50 years (not older)
were only associated with ER or PR positive tumors and not TNBC.
age of menarch did not significantly increase the risk of TNBC. They
demonstrated that nulliparity had the lowest prevalence in TNBC
among different subtypes. Only increase parity was associated with
slight increase in TNBC risk [25]. These findings were consistent with
a meta-analysis published earlier and failed to show any association
between the above risk factors and TNBC [26].
Overall, there is significant heterogeneity in TNBC and its
associated risk factors and our knowledge about epidemiology and
etiology of TNBC is limited. Further large prospective populationbased
studies with adequate diversity are required to provide a better
insight regarding the underlying factors that can increase the risk
for developing the most aggressive basaloid breast cancer subtype.
These data are crucial to design effective prevention strategies with
meaningful clinical outcomes.
Cellular and Molecular Biology: Heterogeneity at all Levels
Immunohistochemical classification
By definition, TNBC is diagnosed by lack of expression of
ER, PR and HER2. It is critical to accurately classify TNBC, since
therapeutic options are different for this group of breast cancers.
Immunohistochemistry (IHC) is the standard method for assessment
of receptor expression and where the results for IHC are equivocal (for
HER2) fluorescent in situ hybridization (FISH) assay will be utilized.
There is a wide diversity in preanalytical preparation, assay methods
and interpretations of IHC. Guidelines from American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP)
recommends considering IHC for ER and PR to be interpreted as
negative if positive staining for tumor cell is observed in less than 1%
of the sample [27]. There is more variability in assessment of HER2
expression. In 2013, ASCO/CAP released new guidelines to unify
the detection methods and increase the chances of detecting HER2
amplification [28]. HER2 positive in IHC is defined by 3+ staining i.e.
>10% tumor cells. IHC staining of 0 or 1 is considered as negative and
2 + is categorized as equivocal. If IHC is equivocal, further assessment
with FISH (single probe or dual probe) should be considered. If FISH
results are still equivocal, the HER2 status will not be interpreted
as negative and patient will be considered eligible for trastuzumab.
In addition to lack of ER, PR and HER2, TNBC tumors are usually
positive for EGFR and myoepithelial (basal-cell) cytokeratin 5, 6 and
17 in IHC staining.
Histologic subtypes
TNBCs usually represent as high-grade invasive tumors with high
mitotic count and a central necrosis pattern [29]. Various histological
subtypes including ductal, metaplastic, medullary and adenoid
cystic have been reported for TNBC [30]. Majority of these tumors,
categorized as ductal, generally lack distinctive, uniform histological
features. The rest of TNBCs are rare entities. Metaplastic tumors
represent a heterogeneous subtype with epithelial and mesenchymal
components [31]. Medullary phenotype is distinguished by high
lymphocytic infiltration and has better outcomes, despite its highgrade
histology [32,33]. Adenoid cystic carcinoma represents another
rare histologic subtype with an observed indolent course and good
clinical outcomes [34].
Molecular heterogeneity
Medical therapy is limited in TNBC given lack of HER2 and
hormonal receptor expressions. Thus, it is critical to unravel the
molecular landscape of TNBC and identify deranged druggable
molecular targets and signaling pathways. Gene expression profiling
(GEP) of TNBCs has revealed heterogeneity in mutational phenotype
and aberrancy in signaling pathways. In a meta-analysis of various
GEP studies, Lehmann et al. [35] have analyzed 21 breast cancer
data sets and classified TNBC into 6 molecular subtypes: basallike
(BL1 and BL2), immunomodulatory (IM), mesenchymal (M),
mesenchymal stem-like (MSL) and luminal androgen receptor(LAR).
BL1 is characterized by over expression of cell cycle pathways, loss
of cell-cycle checkpoints and elevated DNA damage response genes.
These features make them susceptible to antimitotic agents (taxanes)
and DNA-damaging agents (Cisplatin) and they have shown the
highest pathologic complete response (52%) [36]. The hallmark of BL2
subtype is aberrant expression of growth factor signaling pathways
and growth factor receptors, with features of myoepithelial origin.
In contrast to BL1, this subtype rarely achieves pathologic complete
response. Unique characteristic of IM is central role for immune
cell signaling at different levels including cell surface antigen and
antigen presentation, cytokines and complement cascade. There is a
significant overlap between medullary breast cancer and IM subtype.
M and MSL subtypes share similar over expression patterns in cell
motility and cell differentiation pathways, various growth factor
signaling pathways and epithelial-mesenchymal transition markers.
What distinguishes MSL, as a separate entity, is amplification of
genes associated with angiogenesis and differential expression
of some specific growth factor pathways, but lower levels of cell
proliferation. Expression profile of M and MSL subtypes are similar
to the metaplastic breast cancer. LAR subtype displays enrichment
of hormone-regulating pathways such as androgen receptor signaling
and steroid synthesis. This subtype is less chemosensitive with only
10% pathologic complete response [36].
BRCA and TNBC
BRCA1 and BRCA2 genes are tumor suppressors that are essential
for DNA repair, apoptosis and maintaining genome stability. BRCA
protein contributes to DNA double-strand breaks by homologous
recombination [37]. Individuals who carry germline mutation
in BRCA1 or BRCA2 have a 60-70% lifetime risk for developing
breast cancer [38]. TNBC has been shown to have higher frequency
of BRCA1 mutation. Among the breast cancer patients who have
BRCA1 mutation, 60-80% are TNBC [39,40]. On the other hand,
about 10% of TNBC patients have mutation in BRCA, predominantly
BRCA1 and to a lesser extent BRCA2 [41-43]. BRCA mutation in
TNBC is affected by age, and ethnic background. TNBC patients
with BRCA mutations are younger compared to those without BRCA
mutation [43]. It is also shown to be more frequent in Caucasian
females compared to African Americans [44]. TNBC patients with
BRCA1 mutation have significantly higher rates of family history of
breast cancer and those with BRCA2 mutations are associated with
family history of ovarian cancer, while TNBC patients without BRCA
mutations were not associated with a higher familial history of either
cancer [43]. National Comprehensive Cancer Network (NCCN)
guidelines recommend genetic risk assessment for TNBC patients
with BRCA mutation who are not older than 60 years.
Clinical Features
Diagnostic imaging
Efficacy of mammography as a diagnostic tool is lower for TNBC
compared to other subtypes of cancer and is considered suboptimal
[45]. Breast density is higher in younger patients who have higher
likelihood of developing TNBC. Moreover, typical features such as
calcification are less frequently seen in mammography of TNBC
patients. Ultrasound (US) is a more sensitive diagnostic tool for
TNBC, although benign radiologic features of TNBC in 20-40% can
interfere with appropriate diagnosis. Magnetic resonance Imaging
(MRI) has been shown to be superior to US and mammography
in detection of TNBC [46]. [(18)F]2-fluoro-2-deoxy-D-glucose
positron emission tomography ((18)F-FDG-PET) has demonstrated
to be a non-sensitive tool for the routine initial diagnosis, but it is
more sensitive in detection nodal and distant metastasis in TNBC
compared to ER positive tumors [47].
Clinical course
TNBC is frequently diagnosed as an interval cancer i.e. between
two routine mammograms, which indicates the rapid growth of
tumor in this subtype. These tumors have more aggressive biologic
behavior with larger tumor size, higher pathologic grade and more
locally advanced, although they have lower rate of lymph node
involvement. In contrast to other breast tumor types, tumor size and
nodal metastasis are not strongly correlated in TNBC [5]. Metastatic
pattern in TNBC is distinct with higher rate of lung and brain
involvement while metastasis to bone and liver is not as frequent [48].
TNBC patients with distant metastasis experience a rapid progression
to death. There is no obvious association between local and distant
metastasis, and despite other tumors, local metastasis cannot predict
distant metastasis.
Recurrence trends are also unique in TNBC. In general, recurrence
occurs faster and after five years the risk declines. While recurrence
in more than half of the ER + cancers happen between 5 to 10 years
after diagnosis, the majority of TNBC recurrence is observed in the
first 1-4 years and rapidly declines thereafter. In a similar fashion, the
majority of tumor related deaths are observed in the first five years
and mortality declines afterward [5].
Therapeutic Modalities
Surgery
Surgical options including total mastectomy and breastconserving
therapy (BCT), i.e. partial mastectomy followed by
radiotherapy, are essentially similar in TNBC compared to other
subtypes. Receptor status has not been widely assessed in the major
prospective randomized trials that have studied surgical outcomes.
Our knowledge about surgical intervention and its outcomes is
confined to the data from retrospective or nonrandomized prospective
studies, with considerable conflicting findings.
Several groups have studied the need for re-excision after
lumpectomy in different subtypes of breast cancer. While Garvey et
al. [49] (N=2520) showed no difference in presence of residual disease
with re-excision between various breast subtypes, Sioshansi et al. [50]
in a smaller study (N=369 with 12.5%TNBC) showed a 20% higher
chance of residual tumor in re-excision, in TNBC. Multivariate
analysis demonstrated an increased risk of residual invasive cancer
in TNBC. Pilewskie et al. [51] have studied the effect of margin
width after BCT on local recurrence in TNBC patients and showed
that negative margin >2 mm was not associated with lower local
recurrence.
A multitude of studies have evaluated treatment outcomes
in various breast cancer subtypes. Ten studies have compared
locoregional recurrence after BCT in TNBC vs. other subtypes. In a
randomized trial (N=498 with 68 TNBC), Millar et al. [52] showed
that TNBC could be predictive of local recurrence. Four other
retrospective studies demonstrated increased local recurrence in
TNBC [53-56]. While the remainder, failed to show any significant
difference [57-61]. In a meta-analysis of the five cohorts among these
studies, Pan et al. [62] demonstrated that local control after BCT is
similar in TNBC vs. non-TNBC. Other studies have compared the
locoregional recurrence of both surgical options (BCT and total
mastectomies) between TNBC and receptor positive tumors and
while some reports demonstrated increased local recurrence in
TNBC, [63-65] others did not show any significant difference [65-
67]. Lowery et al. [68] have reported a meta-analysis of 15 studies
including both BCT (n=7,174) and mastectomy (n=5,418) and their
analysis revealed that local recurrence is increased in TNBC after both
surgical interventions. In contrast, a retrospective study including 768
TNBC patients showed that mastectomy without radiation therapy in
patients with no node metastasis had a higher rate of local recurrence
compared to patients who underwent BCT [69]. Overall, despite the
fact that metastasis and survival is poorer in TNBC, the data regarding
local control and recurrence after surgery is controversial. Although
the trend is toward increased local recurrence in TNBC, it is not well
established if the type of surgical intervention has any impact on local
recurrence and if the tumor subtype should impact the decision for
the type of surgery offered to the patient. The answer, based on the
current literature is no, but future prospective randomized trials
should address this important issue.
Radiation therapy
The paucity of large randomized prospective trials focusing on
impact of radiation therapy in TNBC has been the reason for lack
of consensus guidelines specific to TNBC. Radiation therapy can
be delivered in two different approaches: as part of BCT or post
mastectomy radiation therapy (PMRT). Despite some conflicting
findings, studies have generally indicated advantages of radiation
therapy in management of TNBC. As showed above, radiation as
part of BCT is demonstrated to decrease the locoregional recurrence
in TNBC when compared to mastectomy without radiation [69]. A
meta-analysis of 22 randomized trials on all types of breast has shown
PMRT reduces both local and distant recurrence in patients with
1-3 positive axillary nodes. In line with these findings, a report from
Danish Breast Cancer Cooperative Group Trial showed an increased
risk of distant metastasis in patients who did not receive PMRT [70].
In contrast, other reports showed the increase in distant recurrence is
not significant without PMRT [71]. In a meta-analysis of 12 studies in
patients with TNBC including 2 randomized clinical trials, O’Rorke
et al. [72] demonstrated that adjuvant radiation therapy, regardless of
the surgical approach (both BCT and PMRT), significantly decreases
the risk for locoregional recurrence. While they failed to show any
overall survival benefits, subgroup analysis revealed improved survival
in younger patients with more advanced TNBC (younger than 40 yrs,
T3-4, N2-3). These findings should be cautiously interpreted, as this
study was underpowered in these specific subgroups. There is a clear
necessity for future randomized trials to accurately identify which
TNBC patients would benefit from radiation therapy [72].
Chemotherapy
Lack of drug-specific targets with absence of hormonal and HER2
receptor, to this date, is the major obstacle in medical management of
TNBC. Nonetheless, TNBC has a better response to chemotherapy
when compared to other subtypes, despite its aggressiveness and
higher likelihood of recurrence, which is referred to as “triple negative
paradox” [73]. There is no single preferred chemotherapy agent for
TNBC but it has been demonstrated that dose intensification has
higher therapeutic efficacy [74,75]. Neoadjuvant chemotherapy
is administered with two different strategies: down staging an
inoperable breast cancer to an operable tumor, and also down staging
to make the tumor amenable to BCT. Anthracyclines and Taxanes
are the preferred agents shown to be effective neoadjuvant regimens
in TNBC [76]. Complete pathologic response has been reported in
about 30% of TNBCs and is associated with excellent prognosis [77].
In contrast, tumors that are less sensitive to chemotherapy have worse
clinical outcome [73]. In a prospective randomized trial, Golshan et
al. [78] demonstrated that neoadjuvant chemotherapy, converted
42% of BCT-ineligible tumors, amenable to BCT, which was a 14%
absolute increases in the eligibility for BCT. NCCN guidelines
recommend adjuvant therapy for TNBCs with node involvement
or tumors larger than 1 cm. It is also recommended that adjuvant
chemotherapy be considered for tumors with 0.6-1 cm, although data
is limited for patients older than 70 years. The preferred regimen is
dose-dense doxorubicin/ cyclophosphamide followed by paclitaxel.
Defective DNA repair is a feature in a subgroup of TNBC, namely
BRCA1 positive tumors. This characteristic has put platinum-based
agents forward as attractive chemotherapy agents for neoadjuvant and
adjuvant therapy in TNBC. In cells with DNA repair defect, platinum
based agents can cause apoptosis by breaking DNA crosslink strands.
Although preclinical data and subsequently a small prospective
data supported this concept, [79] RCTs have shown controversial
results. While CALGB 40603 trial has shown a significantly improved
pathologic complete response with addition of carboplatin to the
above regimen [78], a meta-analysis failed to prove any meaningful
impact, of adding platinum based agents to the chemoregimen, on
patients’ survival [80]. Thus, current data does not strongly support a
generalized application of platinum based agents in TNBC.
Targeted therapy
Molecular heterogeneity of TNBC and lack of specific medical
therapy, such as hormonal therapy, as well as resistance to conventional
regimens make targeted therapy and personalized medicine an area of
interest in TNBC translational and clinical research. Only about 30%
of the patients have pathologic complete response to the conventional
chemotherapy. Non-responders, who are the majority comprising
about 70% of the patients, are the ones who would benefit from
novel therapies and are patients in whom targeted therapy has better
outcomes. Various molecular pathways have been studied to identify
targetable aberrations that can be potentially translated to an effective
therapeutic tool. Poly (ADP-ribose) polymerase (PARP) inhibitors
in patients with BRCA mutation with subsequent homologous
recombination can cause double-strand break in replicating cells;
with defective DNA repair, this will lead to selective tumor cell
cytotoxicity. Several ongoing trials are currently studying various
PARP inhibitors, yet no conclusive clinical benefit has reported to
introduce them as part of practice guidelines.
Anti androgen therapy has been studied in LAR subtype and
potential efficacy in patients positive for androgen hormones have
been reported [81]. The PI3K/AKT/mTOR pathway controls various
cellular functions including metabolism, proliferation and motility.
Aberrant activation of this pathway has been shown in about 60%
of TNBCs [82]. PI3K inhibitors are being tested in clinical trials
and a phase I trial has reported improved progression free survival
in metastatic TNBC with addition of PI3K/AKT/mTOR inhibitors
to conventional chemotherapy [83]. Overall, more than 100 clinical
trials are actively studying various targeted therapies including
the abovementioned targets in addition to a multitude of other
targets. Some of the widely studied targets include but not limited
to receptor tyrosine kinase (RTK) such as EGFR and vascular
endothelial growth factor receptor (VEGFR), mitogen-activated
protein kinase/extracellular signal-regulated kinase (MAPK/ERK),
Heat shock proteins (HSP), antiangiogenics and also Immunecheckpoint
inhibitors including anti-programmed cell death 1 (PD-
1), anti-programmed cell death 1 ligand 1 (PD-L1) and anti-cytotoxic
T-lymphocyte protein 4 (CTLA-4) monoclonal antibodies.
Conclusions and Future Directions
TNBC represents a heterogeneous subgroup of breast cancer with
aggressive tumor behavior and poor clinical outcomes. Molecular
profiling has helped to better classify the heterogeneity of these
tumors, but our knowledge is yet limited about clinicopathological
features of these tumors. Large prospective studies with special focus
on environmental-biological-molecular interactions are required to
better delineate underlying causes of triple negative breast tumors.
These data are crucial to accurately define at-risk population and
design preventive strategies. We know younger females and those
with African ethnic background are at higher risk of developing TNBC
but other risk factors, which contribute to tumorigenesis in hormone
receptor and/or HER2 positive tumors, such as reproductive,
menstrual and OCP consumption history, are not considered to be as
significant contributing factors, homogenously across all the TNBCs.
This might imply the heterogenic molecular nature of this
disease with a variety of risk factors differentially contributing to
various subclasses, an area which still would warrant extensive
epidemiological studies.
Despite the unique and heterogeneous nature of this subgroup,
we still do not have a specific and targeted therapeutic plan confined
to the features of TNBC. Currently, we are applying similar rules
for our therapeutic approach to TNBC, as other subgroups. Future
studies are required to define when and which surgical approach
would have better outcomes, and whether, molecular profiles could
serve as markers that can direct our therapeutic decision-making.
Lack of hormonal/HER2 receptors excludes conventional targets
for directed therapy in TNBC and although these tumors are more
sensitive to achieve pathologic complete response with conventional
chemoregimens, the majority of these tumors is not good responders
and eventually would have worse outcomes. It is unclear why a
subgroup of patients has excellent medical response while the rest have
poor clinical outcomes; expanding our knowledge of non-responders
will help to better define the nature of therapeutic obstacles in curing
TNBC. Finding druggable targets and testing these targeted therapies,
either alone or in conjunction with conventional therapies is subject of
a broad spectrum of translational research and clinical trials. Despite
all the advancements in the area of breast cancer, our knowledge in
regards to TNBC is still limited. Designing therapeutic plans specific
to TNBC is the focus of a substantial number of current studies with
the goal to improve the outcomes of this aggressive breast neoplasm.
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