Quantitative Gene Expression by RT-PCR in the Special Histologic Subtypes of Estrogen Receptor Positive Invasive Breast Cancer
FL Baehner, D Watson, J Anderson, C Millward, I Chen, S Shak. University of California, San Francisco, San Francisco, CA; GHI, Redwood City, CA
Background: ER+ breast ca is characterized by histologic subtypes. The special histologic subtypes are prognostically significant (Rosen, 2009). We report the histologic subtypes of ER+ breast ca and associated patterns of gene expression as measured by the 21 gene assay.
Design: 100K tumors from 7/05 thru 5/09 were included. Tumors were classified by histologic subtype using WHO criteria (IARC 2003). Quantitative expression of 16 cancer related genes was measured from 0 to 15 (relative to reference genes one unit increment associated with a ∼2-fold change in expression). Recurrence Score (RS) was calculated (Paik, NEJM 2004). Descriptive statistics for the RS and individual genes [ER, PR, HER2, invasion gene expression (IGE) and proliferation gene group (PGG)] among subtypes were obtained.
Results: 94.3% were ductal, lobular, or mixed. Using ductal as comparator, papillary ca had the highest ER and PR with low IGE and lowest RS. Medullary-like had the lowest ER, negative PR, higher PGG and highest RS. On average RS was lower for the classic lobular, mixed ductal/lobular, solid/alveolar lobular, tubular, cribriform, mucinous and papillary subtypes. Special histologic subtypes (tubular, cribriform, mucinous) had higher PR, lower IGE, lower PGG and higher ER (except for tubular carcinoma). Tubular cancers rarely had high RS (1.2% in high risk group), due to lower PGG and IGE.
Conclusions: Histologic subtypes have differential expression profiles. The special subtypes have higher ER, PR and lower PG and invasion IGE but outlier cases are not infrequent within this large observational cohort. The variation in gene expression by histologic subtype will be presented in detail.
|Subtype||% of cases||RS (mean)||ER (mean)||PR (mean)||HER2 (mean)||Proliferation Grp (mean)||Invasion grp (mean)|