ASCO/CAP HER2 guidelines update -...
41
ASCO/CAP HER2 guidelines update Caterina Marchiò University of Turin Pathology Unit, FPO-IRCCS Candiolo
Transcript of ASCO/CAP HER2 guidelines update -...
ASCO/CAP HER2 guidelines update
Caterina MarchiòUniversity of Turin
Pathology Unit, FPO-IRCCS Candiolo
Outline
• The evolution of HER2 scoring recommendationsby ASCO/CAP
• Changes in the 2018 focused update: criticaldiscussion step by step
• The future of HER2 evaluation in breast cancer
TO AVOID FALSE POSITIVE
TO AVOID FALSE NEGATIVE
TO ANSWER SPECIFIC CLINICAL QUESTIONS
- Review of pre-analytical and analytical steps
- Rising the thresholdsfor positive results(30% cut-off, HER2/CEP17>2.2)
- Sensitivity raher thanspecificity => thresholds lowered
- ISH algorithm => HER2/CEP17 ratio and HER2 copy number
- Integration of 2013 guidelines (i.e. “focusedupdate”)
- Score 2+ definition- “ISH Groups 2, 3, 4”
by Press et al. 2016
2007 2013 2018
Les fils rouges of ASCO/CAP recommendations
5 Clinical questions addressed
Clinical question 1
What is the most appropriate definition for IHC 2+ (IHC equivocal)?
2018 ASCO/CAP recommendations
Score 2+ definition in 2013
=> “Invasive breast cancer showing“circumferential membrane staining that isincomplete and/or weak/moderate and within > 10% of tumor cells or complete and circumferential membrane staining that isintense and within < 10% of tumor cells.”
Score 2+ definition
2018 ASCO/CAP recommendations
Unusual Score 2+ staining patterns
Baso-lateral membrane staining
Unusual Score 2+ staining patterns
Complete intense membrane staining in < 10% of tumor cells
What to do?
• Test all available blocks (including the LND mets if any)
=> if still <10%: report the percentage of HER2 positive cells
Useful information for any retesting in case of relapse or metastatic disease
Impact of intra-tumor heterogeneity:the neoadjuvant setting
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
Impact of intra-tumor heterogeneity:the neoadjuvant setting
pCR rates
Impact of intra-tumor heterogeneity:the neoadjuvant setting
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
CORE BIOPSY
Impact of HER2 heterogeneity on anti-HER2 treatment
Clinical question 2
Must HER2 testing be repeated on a surgicalspecimen if initially negative on core biopsy?
2018 ASCO/CAP recommendations
HER2 repeat following a negative result on core biopsy
➢ Integration of core biopsy and surgical specimen info (importance of accurate clinical info)
➢ Preanalytical phase control
Clinical questions 3, 4, 5
Unusal ISH patterns
2018 ASCO/CAP recommendations
2018 ASCO/CAP recommendations
FISH Groups according to Press M et al, J Clin Oncol 2016
BMC Cancer 2014
HER2CEP17
BMC Cancer 2014
Chr17
HER2CEP17
=> Complex patterns of Chr 17 geneticrearrangement in breast carcinomas
J Pathol 2009
Rare
More frequent
2018 ASCO/CAP recommendations
FISH Groups according to Press M et al, J Clin Oncol 2016
2018 ASCO/CAP recommendations
FISH Groups according to Press M et al, J Clin Oncol 2016
Additional work-up means …
• Perform IHC/ review IHC (also on additional blocks)
– Report acc. to IHC score
• If score 2+ confirmed:
– Count additional cells (additional observer)
Discordant scoring: resultadjudicated per internal
procedures
Concordant scoring
ISH
AMPNOT Amp
HER2 POSITIVEHER2 negative
SCORE 0 SCORE 1+ SCORE 2+ SCORE 3+
EQUIV
B. Bradfield D. J. Slamon
NEJM 2001
In HER2+ patients
San Antonio Breast Cancer Symposium, December 5-9, 2017
Population of “HER2-low” breast cancer patientsScore 1+/2+ not amp (HER2/CEP17 <2 and HER2 copy number < 4)
Molecular subtyping by PAM50
Luminal B in the large majority (76%)HER2 mRNA levels much closer to HER2-negHER2-enriched in 5% of cases
Marchiò C et al, Am J Surg Pathol 2018
N=45
HER2-directed ADC in clinical development
Pernas S & Tolaney S, Therapeutic Advances in Medical Oncology 2019
What’s next?
ISH
AMPNOT Amp
HER2 POSITIVEHER2 negative
SCORE 0 SCORE 1+ SCORE 2+ SCORE 3+
EQUIV
ISH
AMPNOT Amp
HER2 negative
SCORE 0 SCORE 1+ SCORE 2+ SCORE 3+
EQUIV
“HER2 low” HER2 POSITIVE
Acknowledgements
Breast Unit IRCCS CandioloAnna SapinoFilippo MontemurroRiccardo Ponzone
Giuseppe VialePatrizia Dell’Orto
IHCIvana SarottoFISHLaura CasorzoPatologia MolecolareTiziana Venesio
Research LabLaura Annaratone, Enrico Berrino, Erica PeanoChiara Piccinelli
Traguardi di Eccellenza nelle Scienze mediche Esplorando le Omiche
Anne Vincent-Salomon
FrédériquePenault-Llorca
