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Archives of General Internal Medicine | Volume 2
&
April 04-05, 2018 | Miami, USA
International Conference on
Internal Medicine & Practice and Primary Care
International Meeting on
Breast Pathology & Cancer Diagnosis
K H Ramesh
Albert Einstein College of Medicine, USA
Treatment implications of genetic heterogeneity detected by FISH testing of
invasive ductal breast cancer
S
tandard screening of breast tumors involves morphologic,
immunohistochemistry (IHC) and fluorescence in situ
hybridization (FISH) analyses to assess pathogenicity and to
identify possible treatment strategies. Among breast cancer
types, invasive ductal carcinoma (IDC), in particular, exhibits
amplification of the HER2 gene that can be detected by FISH as
defined by the current American Society of Clinical Oncology/
College of American Pathologists (ASCO/CAP, 2013) scoring
guidelines. One criterion for amplification of the HER2 gene;
basedon the ratioof HER2 gene signals to centromere 17 signals
ismeasured from20 cells by FISH. A second criterion is based on
having an average of more than 6 copies of HER2 signals per cell
out of 20 cells screened by FISH. If either of these criteriameets,
then individualized therapy with adjuvant chemotherapy and
the HER2-targeted drug Trastuzumab (Herceptin®) is indicated,
which remarkably improves prognosis by decreasing local
recurrence and metastasis. If HER2 is not amplified in the IDC
of breast, then further testing is performed and alternative
treatments are considered, which may have less favourable
prognoses. Our research details cases of genetic heterogeneity
(GH), which is when IDC of breast contains between 5%-50%
of cells that are positive for HER2 amplification by FISH, yet fall
shortinmeetingtheamplifiedstatuscriteriacurrentlymandated
by ASCO/CAP, resulting in the tumor being designated as non-
amplified for the HER2 gene. Of the 998 specimens tested by
FISH for HER2 amplification, 594 (60%) were non-amplified, 284
(28%) were amplified; 120 of the 998 (12%) had GH, of which
77 of 120 (64%) were non-amplified and 43 of 120 (36%) met
the criteria for amplification. Based on these data, an update
to the ASCO/CAP guideline criteria for positive amplification to
include HER2 GH+ would extend to an additional 8% (77/998)
of patients is the beneficial HER2-targeted therapy that is
regulated by ASCO and FDA.
Speaker Biography
K H Ramesh is an alumnus of Bangalore University & Kidwai Memorial Institute of
Oncology; obtained his Doctoral Degree in Human Cancer Cytogenetics under the
guidance of Professors M Krishna Bhargava (MD) and B N Chowdaiah (PhD). He moved
to the US in 1986 and completed his Clinical Cytogenetics training under the guidance
of world renowned Geneticist Avery Sandberg, MD at Roswell Park Cancer Institute,
Buffalo, NY. At present, he is the Director of Cancer CytoGenomics and Associate
Professor of Pathology at Montefiore Medical Center & Albert Einstein College of
Medicine, Bronx, NY. He is also Adjunct Associate Professor at The University of Texas
MD Anderson Cancer Center. He is a Board Certified Clinical Cytogeneticist and a
Diplomate of the American Board of Medical Genetics & Genomics, and Fellow of the
American College of Medical Genetics & Genomics. His expertise is in genetic testing of
leukemia, lymphoma, myeloma and soft and solid tumors. His interests include global
education, football and music.
e:
KRAMESH@montefiore.org