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Evolving Concepts in HER2 Evaluation in Breast Cancer
1. EVOLVING CONCEPTS IN HER2 EVALUATION
IN BREAST CANCER: HETEROGENEITY,HER2-
LOW CARCINOMAS AND BEYOND
Dr Kalyan Kusum Mukherjee, MBBS, MD,FCCM,ECMO
Associate Prof and Head of dept of Medical Oncology
Head of the department clinical and translational research
Chittaranjan National Cancer Institute, India
2. ABOUT BREAST CANCER
Conventional Histopathology is the dissesive factor for
treatment in breast cancer (BC).
BC is divided into 4 sub groups: Luminal A, Luminal B,
Her 2 enriched and Triple negative (TNBC)
This has predictive and prognostic importance
11. OUTLINES
Documents the changes that have contributed to a
better evaluation of the HER 2 status in clinical
practice.
Discuss the different scenarios encompasing HER
2 heterogeneity
Complexity of HER 2 equivocal results
HER 2 low BC
HER 2 mutation.
15. HER 2 GUIDELINES
When to test: Primary, recurrent and metastatic cancer, if
tissue sample available
Acceptable methods: IHC, ISH (FISH and CISH)
Other methods: PCR, ELISA, Southern blot, mRNA
assay and DNA microarray.(Used for research only)
Which specimen: Core biopsy or surgical specimen
25. HETROGENEITY (CONTD..)
3 distinct type of HER 2 status described
1. Clastard 2. Mosaic 3. Scattered
HER 2 generic heterogeneity in BC is more common in
equivocal status in IHC, ISC
Most probably HER 2 heterogeneity is a cause of equivocal
HER 2 results.
Increased frequency of chromosome 17 polysomi is seen.
Is associated with worst patient outcome in terms of DFS
and OS.
Less response to anti HER 2 therapy. And this group should
be different therapeutic approach.
38. About 55% of BCs express low levels of HER2 in
the absence of gene amplification
HER2-low are either ER+ or ER– (less frequent)
NSABP B-47 demonstrated that adjuvant
trastuzumab is not effective in these tumours, likely
due to their low or absent addiction to HER2
signalling. Similarly, other agents disrupting the
HER2 pathway have shown modest activity in
HER2-low tumours
39. A paradigm shift in the definition of HER2 status in breast cancer
42. CONT
Through NGS it has come to light that breast carcinoma
can harbor HER 2 activating mutations along with gene
amplification.
HER 2 somatic mutation (Less prevalent) frequently
occur on HER 2 neg. or Her 2 low BC.
Majority of cases, Her 2 mutation affect actions 19-20
coding TK domain and remaining relate to axon 8 extra
cellular domain.
The most common mutation are L755S, V777L and
D79H/Y. These are misscence mutation of the kinase
domain of the protein. PI3KC is the most common co
mutated gene in HER 2 mutation. L755S mutation is
resistance to Lapatinib. Irreversible HER 2 EGFR TKI
Niratinib inhibit the proliferation of cell bearing all
mutations.
43. PREVALENCE, DISTRIBUTION AND SIGNIFICANCE OF
HER 2 SOMATIC MUTATION
HER 2 mutation also causes resistance to anti Her
2 therapeutic compound.
44. CONCLUSION:
Assessment of Her 2 is key to treatment decision
making for BC patients
Heterogeneity of HER 2 may hamper the correct
identification of two responders to anti HER 2
agents.
Transcriptomic analysis may identify HER 2
enriched Carcinoma that is highly sensative to anti
HER 2 therapy
HER 2 mutation are emerging as important
molecular alterations
45. CONTD..
The dichotomous def of Her 2 pos vs Her 2 neg
disease is currently experiencing in wave of
changes by identifying HER 2 low category.
New therapeutic compound in the form of antibody
drug conjugates may be effected
46. ACKNOWLEDGEMENT
Dattatreya Mukherjee, MBBS student and
Undergraduate Medical Researcher of Jinan
University helps in scientific writing
ESMO pro e learning and ASCO e learning
materials