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O
ver the last 2 decades there has been great advancement in the field of breast cancer molec-
ular classification and prognostication, and in the understanding of the pathogenesis of
this heterogeneous disease. Applications of high throughput molecular techniques coupled
with state-of-the art bioinformatics approaches have generated vast amounts of data and opened
avenues to refine breast cancer classification and identify novel therapeutic targets with a subse-
quent move towards personalised therapy. Here are our 10 hot topics to watch.
1
. Application of molecular techniques
Rakha and Green
1
provide an update on the appli-
cation of molecular techniques with regard to
breast cancer diagnosis, prognosis and outcome
prediction. They briefly highlight current contri-
butions of this emerging technology towards our
understanding of breast cancer, in addition to the
essential role of immunohistochemistry and other
molecular techniques in the diagnosis and differ-
ential diagnosis of breast lesions.
2
. Molecular profiling
Ross and Gay
2
present a review on the molecular
profiling of advanced breast cancer and the role of
comprehensive genomic sequencing technology.
They discuss massive parallel sequencing and next
generation sequencing (NGS) technology and its
potential applications in breast cancer research
and management, in particular identification of
targetable, clinically relevant genomic alterations.
3
. Stromal-epithelial interactions
McCuaig and colleagues
3
discuss the biological
and clinical significance of stromal-epithelial
interactions in breast cancer. In this review
recent advances in our understanding of how
cancer epithelial cells interact with their
microenvironment and how this knowledge can
be exploited clinically are presented.
4
. DNA damage
Three main pathways play a major role in DNA
repair in breast cancer. This article highlights how
basic science can be translated into clinical bene-
fit. For example, there is evidence to indicate the
efficacy of targeting DNA damage repair mole-
cules in BRCA-mutated breast cancer using PARP
inhibitors.
In contrast, the response to such therapy is lim-
ited in sporadic cases, despite the presence of
evidence of DNA repair defect suggesting differ-
ent mechanisms other than BRCA gene mutation.
The different mechanisms of DNA repair in breast
cancer and the concept of synthetic lethality,
BRCAness and the therapeutic potential of some
proteins involved in DNA repair are highlighted
in the article by Ali et al.
4
5
. Ki67 use
There is a continuous effort to identify new prog-
nostic and predictive markers; however, there is
also a need to refine, validate and further assess
the clinical utility of existing variables. Although
the prognostic value of Ki67 in breast cancer is
well demonstrated and some authors have pro-
vided evidence for its predictive value, at least in
certain situations, its application in routine prac-
tice remains less than what was initially expected.
The issue of reproducibility of Ki67 staining and
scoring, and the use of several cut-off points have
resulted in a delay in its application in routine
practice and some current international guidelines
have recommended not to use Ki67 to guide treat-
ment decisions. This topic and other issues related
to Ki67 use in breast cancer are covered in the
article by Penault-Llorca and Radosevic-Robin.
5
6
. Tumour infiltrating lymphocytes
A topic which has gained a lot of attention fol-
lowing a series of publications demonstrating its
prognostic value and the emerging role of immuno-
therapy is tumour infiltrating lymphocytes (TILs).
Luen et al
6
provide a comprehensive review on
TILs and the emerging role of immunotherapy
in breast cancer. Although breast cancer has not
previously been considered a highly immunogenic
cancer, retrospective analysis of clinical trial sam-
ples has demonstrated the potential role of host
immunosurveillance in influencing the biology of
at least certain subtypes of breast cancer; namely
triple negative and HER2-positive classes. Evi-
dence indicates that TILs are associated with
improved pathological complete response and
patient outcome. In their article they cover the
existing methodologies of assessment of TILs in
breast cancer and efforts to standardise TILs eval-
uation, and discuss clinical relevance of TILs and
ways to improve efficacy of immunotherapeutic
approaches in breast cancer.
Leading pathologists,
Jane E.
Dahlstrom*, Emad A.Rakha
#
,
Sunil R. Lakhani†, Stuart J.
Schnitt‡
and colleagues share
their current ‘hot topics’ in the
field of breast diagnostic and
molecular pathology and the
research to watch.
* ACT Pathology, The Canberra
Hospital and ANU Medical
School, Canberra, Australia;
#
Department of Cellular
Pathology, University of
Nottingham and Nottingham
University Hospitals NHS
Trust, City Hospital Campus,
Nottingham, United Kingdom;
†
Breast Pathology Group, The
University of Queensland
Centre for Clinical Research,
Discipline of Molecular & Cellular
Pathology, The University of
Queensland School of Medicine
and Pathology Queensland,
Brisbane, Australia;
‡
Department
of Pathology, Beth Israel
Deaconess Medical Center
and Harvard Medical School,
Boston, MA, United States.
10
top advances in diagnostic
and molecular pathology
in breast cancer
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