[2031] Poor 10 yr breast cancer specific survival and relapse free survival for HER2 positive T1N0 tumors.
Norris B, Chia S, Cheang M, Gilks B, Gown A, Huntsman D, Olivotto I, Nielsen T, Speers C, Gelmon K.. British Columbia Cancer Agency, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada; PhenoPath Laboratories, Seattle, WA; British Columbia Cancer Agency, Victoria, BC, Canada
Background: Although trastuzumab (T) improves OS and DFS in HER2 + early breast cancer the majority of the patients in the adjuvant T studies were node positive. We report 10 yr patient outcomes for HER2 + T1N0 tumors to aid decisions regarding the use of adjuvant systemic therapy (AST) including T.
Methods: We have established a tissue microarray of 4150 primary early stage invasive breast cancers seen in females in British Columbia in 1986-1992 who have >10 yrs follow-up. A training set (n= 2088) was immunostained for ER and HER2 using new rabbit monoclonal antibodies SP1 and SP3, and HER2 tested for amplification (amp) by FISH (Vysis PathVision), as well as estrogen receptor (ER) IHC (SP1) by Phenopath (Gown) Results were stratified by whether or not patients had received AST. 10yr Breast Cancer Specific Survival (BCSS) and Relapse Free Survival (RFS) are reported. All p values are log rank unless stated otherwise.
Results: N = 2088 with 735 T1N0 cases. HER2 by IHC 
neg (0) 904 (45.7%), 1+ 742 (37.5%), 2+ 90 (4.5%), 3+ 243 (12.3%). FISH (scored in 399 samples) HER2 non amp AR <2.0 n= 331 (83%). HER2 amp AR > 2.0 n=68 (17%). For this analysis, HER2 0 
1+ are considered negative, IHC 3+ and FISH amp are positive. p-values for HER2 grouping HER2+ vs. HER2- in BCSS and RFS are significant.
| HER2-ER+ | HER2-ER- | HER2+ER+ | HER2+ER- | |
| Training Set n=2088 | 1192 (64%) | 421 (23%) | 96 (5.2%) | 144 (7.8%) |
| 10 yr BCSS | 79% | 68% | 61% | 52% |
| 10 yr RFS | 69% | 64% | 51% | 45% |
| T1N0 n=647 | 445 | 140 | 20 | 42 |
| 10 yr BCSS | 91% | 89% | 85% | 70% |
| 10 yr RFS | 78% | 81% | 75% | 61% |
The impact of AST for the total cohort and the subgroup T1N0 was assessed. For patients who received no AST comparing HER2 positive vs. negative, BCSS was respectively 60% vs. 86%, p<0.0001 and RFS was 76 % vs. 91%, p=0.0154. HER2 amp was associated with higher grade (GR) (Kendall
s tau-b:0.204, p=0.0102); 69% of HER2 amp tumours were grade 3 versus 39% of non-amp cases.Conclusions: HER2 amplification or overexpression is correlated with a poorer outcome in the entire cohort and T1N0 tumors. This increased risk of recurrence and lower BCSS supports consideration of adjuvant AST including T in women with T1N0 disease. Additional analysis of the cohort by FISH, T<1cm vs. >1cm and hormone receptor status on outcome will be presented. Supported by a research grant from the Canadian Breast Cancer Research Alliance (CBCRA), sanofi-aventis and by Roche Pharmaceuticals.
Friday, December 15, 2006 7:00 AM
Poster Session II: Prognosis and Response Prediction: Prognostic Factors I (7:00 AM-9:00 AM)