Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment
http://cancerdiscovery.aacrjournals.org/content/9/2/176" rel="nofollow - http://cancerdiscovery.aacrjournals.org/content/9/2/176
Researchers reveal potential for exploring new treatment options for triple-negative breast cancerResearchers from Caris Life Sciences® and
Fox Chase Cancer Center – Temple Health announced the presentation of
two studies revealing the potential for exploring new therapeutic
options for triple-negative breast cancer (TNBC) at the 2015 San Antonio
Breast Cancer Symposium (SABCS). Researchers used Caris Molecular Intelligence®, Caris's panomic, comprehensive tumor profiling
service, to assess biomarker profiles in subsets of patients with TNBC,
an aggressive type of breast cancer in which the cancer cells lack
estrogen receptor (ER), progesterone receptor (PR), and human epidermal
growth factor receptor (HER2). In the studies, multiplatform tumor profiling
confirmed molecular differences between rare and aggressive subsets of
TNBC, which can potentially lead to new treatment options and clinical
trial strategies. "Triple-negative
breast cancer remains challenging because of its aggressive and complex
nature, its high rate of recurrence and propensity to become a
metastatic disease, and the lack of an effective targeted therapy," said
Elias Obeid, MD, MPH, assistant professor in the Departments of
Clinical Genetics and Medical Oncology at Fox Chase. "With the
advancement of comprehensive molecular profiling
technology and our partnership with Caris Life Sciences, our
understanding of the differences in the subtypes of triple negative
breast cancer is unfolding, as well as our understanding of the
molecular drivers of the disease that may serve as potential targets for
new therapies." The
first study compared the biomarker profiles of patients with
quadruple-negative breast cancer (QNBC) – a subgroup of TNBC that lacks
androgen receptor (AR) expression – against those of patients with TNBC
who are AR-positive (AR+), confirming the molecular heterogeneity of
TNBC. In the second study, researchers identified differences in the
molecular profiles of BRCA1/2-mutated and BRCA1/2-non-mutated TNBCs, providing insights into potential targeted treatment strategies for these tumor subtypes. Both
studies utilized Caris Molecular Intelligence's multi-technology
approach, which included protein expression analysis
(immunohistochemistry [IHC]), gene copy number analysis (chromogenic or
fluorescence in situ hybridization [CISH or FISH]), and gene sequencing (SEQ, using Next-Generation or Sanger sequencing). http://www.news-medical.net/news/20151207/Researchers-reveal-potential-for-exploring-new-treatment-options-for-triple-negative-breast-cancer.aspx" rel="nofollow - http://www.news-medical.net/news/20151207/Researchers-reveal-potential-for-exploring-new-treatment-options-for-triple-negative-breast-cancer.aspx
https://robertanagourney.wordpress.com/2015/07/01/chemosensitivity-testing-what-it-is-and-what-it-isnt-2/" rel="nofollow - https://roberta - nagourney.wordpress.com/2015/07/01/chemosensitivity-testing-what-it-is-and-what-it-isnt-2/
From the post, a brief overview
1. Cancer
patients are highly individual in their response to chemotherapies.
This is why each patient must be tested to select the most effective
drug regimen. 2. Today we realize that cancer doesn’t grow too
much it dies too little. This is why older growth-based assays didn’t
work and why cell-death-based assays do. 3. Cancer must be tested
in their native state with the stromal, vascular and inflammatory
elements intact. This is why we use microspheroids isolated directly
from patients and do not grow or subculture our specimens.
4. Predictions of response are not based on arbitrary drug
concentrations but instead reflect the careful calibration of in vitro
findings against patient outcomes – the all-important clinical database.
5. We do not conduct drug resistance assays. We conduct drug
sensitivity assays. These drug sensitivity assays have been shown
statistically significantly to correlate with response, time to
progression and survival. 6. We do not conduct genomic analyses
for there are no genomic platforms available today that are capable of
reproducing the complexity, cross-talk, redundancy or promiscuity of
human tumor biology. 7. Tumors manifest plasticity that requires
iterative studies. Large biopsies and sometimes multiple biopsies must
be done to construct effective treatment programs. 8. With chemotherapy, very often more is not better. 9. New drugs are not always better drugs. 10. And finally, cancer drugs do not know what diseases they were invented for.
Gene Expression Profiling for Diagnosis of Triple-Negative Breast Cancer: A Multicenter, Retrospective Cohort Study
Background: Triple-negative breast
cancer (TNBC) accounts for 12–20% of all breast cancers. Diagnosis of
TNBC is sometimes quite difficult based on morphological assessment and
immunohistochemistry alone, particularly in the metastatic setting with
no prior history of breast cancer.
Methods: Molecular profiling is a
promising diagnostic approach that has the potential to provide an
objective classification of metastatic tumors with unknown primary. In
this study, performance of a novel 90-gene expression signature for
determination of the site of tumor origin was evaluated in 115 TNBC
samples. For each specimen, expression profiles of the 90 tumor-specific
genes were analyzed, and similarity scores were obtained for each of
the 21 tumor types on the test panel. Predicted tumor type was compared
to the reference diagnosis to calculate accuracy. Furthermore, rank
product analysis was performed to identify genes that were
differentially expressed between TNBC and other tumor types.
Results: Analysis of the 90-gene
expression signature resulted in an overall 97.4% (112/115, 95% CI:
0.92–0.99) agreement with the reference diagnosis. Among all specimens,
the signature correctly classified 97.6% of TNBC from the primary site
(41/42) and lymph node metastasis (41/42) and 96.8% of distant
metastatic tumors (30/31). Furthermore, a list of genes, including AZGP1, KRT19, and PIGR,
was identified as differentially expressed between TNBC and other tumor
types, suggesting their potential use as discriminatory markers.
Conclusion: Our results demonstrate
excellent performance of a 90-gene expression signature for
identification of tumor origin in a cohort of both primary and
metastatic TNBC samples. These findings show promise for use of this
novel molecular assay to aid in differential diagnosis of TNBC,
particularly in the metastatic setting. https://www.frontiersin.org/articles/10.3389/fonc.2019.00354/full" rel="nofollow - https://www.frontiersin.org/articles/10.3389/fonc.2019.00354/full
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