Breast cancer pathology

Transcription

1 Breast cancer pathology Giancarlo Pruneri, M.D. National Cancer Institute (INT) Milan University of Milan, School of Medicine

2 Currently accepted prognostic/predictive parameters Patient Age characteristics (Race) Disease Tumor size characteristics Tumor type Axillary status Tumor grade Peritumoral vascular invasion Biomarkers Receptor status HER2/neu expression Ki-67 labeling index

3 Spot the difference! The lung cancer experience FFPE material of primary tumor/metastasis NGS with the Hot spot cancer panel FISH for ALK and ROS IHC for PD1 Recurrence after target treatment Re-biopsy Liquid biopsy EGFR KRAS BRAF STK11 ALK PTEN Others NGS /Hot spot T790M not well covered High coverage Easy EGFR RT PCR CE IVD test

4 Biology of the tumor -> CHT/ET sensitivity Prognosis

5 Biology of the tumor A world behind ER and HER2 Sørlie, PNAS, 2001

6 IHC: the universal surrogate (with pros and cons) Sørlie, PNAS, 2001 Montagna, Clin Breast Cancer, 2013

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8 Chemoendocrine therapy in ER+/HER2- disease Relative Indications for chemotherapy: any of Factors not useful in decision* Relative Indications for endocrine therapy alone Grade 3 Grade 2 Grade 1 High proliferation** (Ki-67 >30%) Lower ER and PgR level Intermediate proliferation (Ki-67 16%-30%) Low proliferation (Ki-67 15%) Higher ER and PgR level N 4+ N 1-3 Node negative Peritumoral vascular invasion (PVI) No PVI pt size > 5cm pt size 2 5 cm pt size <= 2cm Patient preference to use all available treatments * If most are present, could constitute a relative indication for chemotherapy ** As assessed by conventional or genetic assays Patient preference to avoid side effects

9 IHC cons: are we trustable? 20% discordance rate for ER and PgR Ki-67: how to count? 15% discordance rate for Her-2

10 San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012 Lessons learned from Phase 1 (continued) Although staining method added some variability, the major source of Ki67 differences (besides patient biology) was scoring method. Estimation vs. Counting Choice of areas to count Invasive Cancer vs. other cells Threshold of brown considered positive 10 This presentation is the intellectual property of the author/presenter. Contact them at torsten@mail.ubc.ca for permission to reprint and/or distribute.

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12 Gene expression is an accurate biomarker in predicting pcr after T/T+L in CALGB40601 Carey, JCO, 2016

13 Prognosticators in breast cancer A crowded market Schmidt, Breast Care, 2014

14 Which one? Kwa, Nat Rev Clin Oncol, 2017

15 Oncotype Dx

16 Bringing it all back home: IHC 4 equals Genomic Health Recurrence Score Cuzick, JCO, 2012

17 Distant disease free survival according to newly defined intrinsic molecular subtypes Maisonneuve, Breast Cancer Res, 2014

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19 N+ patients: not only Mammaprint 2,558 ER+/HER2- pts 5-yrs AI/TAM only Low ROR 10-yrs DR 4.3% independent of N status (N0-N+ up to 3) Lænkholm, JCO, 2018

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21 Which one? No one winner Consider your needings Adding new info -> IHC Fully equipped labs/mdts -> distributed assays Small labs -> externalization Prognosis/biology -> adjuvant/neoadjuvant

22 Coming of age: multigene prognostic tests integrate traditional assays Luminal B tumors (as defined by IHC) -> Ki-67 N0-N1a Two risk categories Distributed assays working in FFPE Reimbursed by health systems Intratumor heterogeneity (spatial and longitudinal) Informative of early AND late relapse Informative in cdk4/6 inhibitors treated pts?

23 Activating ESR1 mutations lead to hormone therapy resistance Toy, Nat Genet, 2013 Robinson, Nat Genet, 2013

24 Magnani, Nat Gen, 2017

25 A clinically meaningful exercise TBD in MTD pt1a pn0(sn) G1 ER/PgR >95% HER2 Neg Ki-67 5% pt1c pn1a(sn) G2 ER 90% PgR 0% HER2 Neg Ki-67 45% All in between?

26 Michelangelo Buonarroti ( ) Cappella Paolina, Palazzo Apostolico Città del Vaticano Innovation or tradition? Conversione di San Paolo Michelangelo Merisi da Caravaggio (1601) Cappella Cerasi Basilica di S. Maria del Popolo, Roma