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. Outlines
1. Definition
2. Specific specimens handling
3. Tumor characteristics

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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…