[324] Proliferative Activity and HER-2 FISH Results on Hormone Receptor/HER2 Positive (Luminal Type-B) Breast Cancer

S White, G Ibrahim, SG Karak, L Mnayer, A Ricci, Jr. Hartford Hospital, Hartford, CT

Background: An unusual subset of breast carcinoma is characterized by dual activation of hormone receptor (ER and/or PR) and growth factor receptor (HER2) pathways. By gene expression analysis these have been termed luminal type-B tumors. As a group they appear intermediate between luminal type-A (ER and/or PR positive and HER2 negative) and HER-2 type (ER/PR negative and HER2 positive) breast cancer. Our goal was to explore the proliferative rates of luminal type-B carcinomas (in comparison to luminal type-A and HER2 type tumors) and to confirm the HER2 positive status with FISH analysis.
Design: In a companion study we identified fifteen ER/PR/HER2 triple positive breast cancers, representing all such cases diagnosed at Hartford Hospital from 2002-2007. To these we added 6 further cases that were ER(+), PR(-) and HER2(+) drawn from the same period. Slides and pathology reports were available and reviewed for all cases including confirmation of the immunohistochemical (IHC) ancillary studies. All 21 cases were referred for MIB-1 IHC and HER-2 FISH analyses. Proliferative indices were then compared to reference file cases of luminal type-A and HER2(+) tumors.
Results: The 21 study cases demonstrated proliferative indices ranging from 10-60% (mean = 35.5). This was intermediate between those of 26 reference cases each of luminal type-A and HER(+) breast cancers, i.e. 2-25% (mean = 15.6) and 19-90% (mean = 56.5), respectively. FISH analysis confirmed HER2 amplification in 21/21 (100%) of cases (HER2/CEP17 ratio 2.3 30.5; mean = 18.1).
Conclusions: Hormone receptor/HER2 positive (luminal type-B) carcinomas occupy an intermediate position between luminal type-A and HER2(+) tumors, not only by IHC receptor analyses but also with regard to proliferative indices. HER2 positivity of such tumors is real including classic copper pennies by IHC and amplification by FISH. While it cannot be concluded that this represents a transitional phase between an ER(+)/HER2(-) and ER(-)/HER2(+) phenotype, it remains possible that secondary growth factor receptor activation could, in some cases, be responsible for development of hormone unresponsiveness via crosstalk between downstream moieties of respective hormone and growth factor receptor cascades.
Category: Breast

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 56, Tuesday Morning