Morphological Characteristics of HER2 Over-Expressing and Basal-Like Breast Cancers and the Association between Lymphocytic Tumor Infiltrate and Prognosis
Anita L Bane, Sameer Parpia, Greg Pond, Vikaash Kumar, Gabriella Gohla, Mark N Levine, Timothy Whelan. McMaster University, Hamilton, ON, Canada
Background: Gene expression profiling of human breast cancers has defined 5 molecular subtypes; luminal A/B, HER2 over-expressing, basal-like and claudin-low. Distinguishing morphological features have been described for some molecular subtypes particularly basal-like tumors. The goal of this study was to identify morphological characteristics associated with each of the molecular subtypes of breast cancer and examine their association with prognosis.
Design: 943 T1 and T2, lymph node negative, primary invasive breast cancers treated with breast conserving surgery (BCS) and adjuvant radiation had formalin fixed paraffin embedded (FFPE) tumor blocks available for TMA construction. On the basis of IHC expression of ER, PR, HER2, Ki67, EGFR, CK5/6, Claudins 3,4,7 and E-cadherin the tumors were classified as luminal A, luminal B, HER2 over-expressing, basal-like or claudin-low. A centralized pathology review was additionally performed on one full face section of each tumor by an expert breast pathologist who was unaware of the molecular subtype at the time of review. Kaplan-Meier methods were used to estimate overall survival at 12 years. Chi-square and log-rank tests were used to compare tumor characteristics and overall survival between subtypes.
Results: A molecular subtype was assignable in 872 of 943 tumors (83%), of which 357 (46%) were luminal A, 222 (28%) were luminal B, 32 (4%) were HER2 over-expressing, 110 (14%) were basal-like and 61 (8%) were claudin-low. When compared to luminal A type tumors, HER2 over-expressing and basal-like tumors were more likely to be grade III (43% and 81% vs 3%, p<0.001), have an extensive lymphocytic infiltrate (39% and 47% vs 4%, p<0.001)), to have a central scar (28% and 45% vs 17%, p<0.001) and to have circumscribed tumor margins (38% and 49% vs 9%, p<0.001). HER2 over-expressing and basal-like tumors with an extensive lymphocytic infiltrate had a statistically significant (p=0.011) better overall survival (82.0% at 12 years, 95% confidence interval: 67.6% to 90.5%) than ER negative tumors without such an infiltrate (62.9% at 12 years, 95% confidence interval: 49.9% to 73.4%).
Conclusions: HER2 over-expressing and basal-like breast cancers share a number of morphological characteristics in common and both are distinctly different from luminal A tumors. HER2 over-expressing and basal-like tumors frequently demonstrate an extensive lymphocytic infiltrate which has prognostic significance in these ER negative subtypes.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 29, Tuesday Morning