Frederique Penault Llorca : PT1a/b breast cancer : Prognostic and predictive factors.

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Frederique Penault Llorca : PT1a/b breast cancer : Prognostic and predictive factors.

  1. 1. PT1a/b breast cancer Prognostic and predictive factors. Frédérique PENAULT LLORCA, France, on behalf of the ODISEE group (Nina RADOSEVIC-ROBIN, Magali LACROIX-TRIKI, Bernard LOUIS, Isabelle ROCHE- COMET, Marie-Sophie SOYBERAND, Florence DALENC, Yazid BELKACEMI)
  2. 2. Outlines 1. Definition 2. Specific specimens handling 3. Tumor characteristics
  3. 3. PT1a/b breast cancer • TNM UICC 2010, OMS 2012 classifications ─ T1mi: micro-invasion ≤1mm • Associated to extended and:or high grade DCIS, distinct entity? ─ T1a: >1mm & ≤5mm ─ T1b: >5mm & ≤10mm • Clinical (T) vs pathological (pT) ─ Gross measurement (before fixation) vs microscopic ─ If multiple: size of the biggest ─ pT evaluation can be hampered by previous biopsies (fragmentation, hematomas …..)
  4. 4. Mandatory items in the path report National (INCa, 2011) et international guidelines1 • Tumor size • Histologic type (OMS 2012) • Elston et Ellis histologic grade • In situ component (%, type, grade) • Multicentricity or multifocality • Surgical margins(mm) • Embolies • Hormonal receptors2: ER et PR • HER2, whatever the size3,4 • Node status • pT/pN stage (TNM UICC 2010) 1 Lester SC et al. Arch Pathol Lab Med 2009 2 Hammond ME et al. JCO 2010 3 Wolff AC et al. JCO 2007 4 Penault-Llorca et al. Ann Pathol 2010 HER2
  5. 5. Tissue handling The inital biopsy might be the only tumor material => the pathologist must spare tissue when possible • Inclusion of biopsies in different cassettes • Whole inclusion of the tumor in surgical specimen • Do not exhaust the blocks • Provide tumor phenotype on the biopsies (ER, PR, HER2, +/- Ki67
  6. 6. Histopathological Characteristics Hanrahan (2007) Kennedy (2007) Gonzalez- Angulo (2009) Cancello (2011) Theriault (2011) Lacroix- Triki (2012) Population T1a,b N0 T1a,b N0 T1a,b N0 T1mi,a,bN0 T1a,b N0 T1a,b N0 N 51246 123212 965 1691 1012 375 Histopath ductal lobular 77% 6% 74-76% 6% 77% 75% 9% 78% 72% 9% Grade I II III 33% 46% 21% 78-82% 17-21% 42% 46% 12% 51% 40% 9% Embolies 5% 4% HR+ 83% 80-86% 83% 89% 76% 93% HER2+ 10% 10% 9% 4% Low Ki67 52% 95%
  7. 7. 0 10 20 30 40 50 60 70 80 90 100 CANALAIRE (CCI) LOBULAIRE (CLI) CCI / CLI TUBULEUX MEDULLAIRE MICROPAPILLAIRE MUCINEUX METAPLASIQUE PAPILLAIRE MIXTE CRIBRIFORME APOCRINE pT1a pT1b 86% 14% Median Tumor size= 8 mm (1 – 10 mm) CCI CLI other 72 % 11 % 17 % * * 53 % of tubular carc Tumor size and histotype in Odissee N = 323 N = 52
  8. 8. Histograde, proliferation, DCIS and invasion CIS - CIS + 50.4 % 40.1 % 9.4 % 82.5 % 11.3 % 6.7 % 36 % 64 % Elston & Ellis grade Mitotic count 10 HPF Associated DCIS LOW GRADE, LOW PROLIF, ~ 1/3 WITH DCIS BAS INTERMED HAUT Embolies 6 % 94 % Absent Present 1 2 3
  9. 9. Hanrahan (2007) Kennedy (2007) Lacroix-Triki (2012) Park (2012) Population T1a,b N0 T1a,b N0 T1a,b N0 T1b,c N0 N 51246 123212 375 1043 Lobular Mixed 6% 6% 3-6% 9% 1% 3-5% 0.6-1% Tubular 4-5% 9% 2-3% Mucinous 3% 2-3% 1% 13-15% Papillary 0.5% 1% Micropapillary 2% 1% Cribriform 0.5% 0.4%
  10. 10. Molecular subtypes Molecular classification using IHC (ER, PR, HER2, Ki67, EGFR, CK5/6, AR) 1, 2, 3 Cancello (2011) Lacroix-Triki (2012) Population T1mi,a,b N0 T1a,b N0 N 1691 375 Luminal A 52% 85% Luminal B 37% 12% HER2+ (RH-) 5% 1% Triple negative / Basal-like 6% 1% Apocrine 1% • Luminal A = HR+, HER2-, Ki67<14%) • Luminal B = HR+ & Ki67≥14% or HER2+ • HER2+ = HR - & HER2+ • Triple negative = HR - HER2- • Basal-like = HR - HER2- CK5/6+ and/or EGFR+ • Apocrine = HR- HER2 AR+ 1 Cheang MC et al. JNCI 2009 2 Nielsen T et al. CCR 2004 3 Farmer P et al. Oncogene 2005
  11. 11. Molecular subtypes in OdisseeMOLECULAI LUMINAL A LUMINAL B HER2 TRIPLE-NEG BASAL-LIKE TRIPLE-NEG NON-BASAL-LIKE APOCRINE 84.7 % 19.7 % 0.9 % 1.2 % 0.3 % 1.2 % N = 324 N = 51 : missing data
  12. 12. HER2+ sub group Cancello et al. BCRT 2011, Gonzalez-Angulo et al. JCO 2009, Sanchez-Munoz et al. Breast J 2010, Theriault et al. Clin Breast Cancer 2011, Banerjee et al. Lancet Oncol 2010, Chia et al. JCO 2008, Curigliano JCO 2009, Joensuu et al. CCR 2003 • HER2 overexpression unfrequent: mean 6% of the cases (range 4-14%) • More frequent inT1mi/T1a • High grade • High proliferation (Ki67>20%) as compared to HER2- • More frequently HR - • With extended or multifocal DCIS • Young age HER2
  13. 13. Take-home messages 1. Same handling as other invasive breast cancer but a specific strategy of tissue sparing should be organized (importance +++ to specify the clinical size in the request form) 2. Know the technical limitations due to the size of the tumor 3. T1a,b N0 Profile: usually : invasive ductal – NOS, low grade, low proliferation, HR+ (intense and diffuse), HER2-, wihout embolies…

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