Abstract P3-10-01: Quantitative Gene Expression Analysis in a Large Cohort of Estrogen-Receptor Positive Breast Cancers: Characterization of the Tumor Profiles in Younger Patients (≥40 yrs) and in Older Patients (≥70 yrs)

Abstract

Abstract Background: Previous studies have identified differences in the presentation, biology, and behavior of breast cancer as a function of patient age. To directly study breast cancer tumor profiles as a function of patient age, we examined the Oncotype DX Recurrence Score (RS) and the expression of ER, PR, and proliferation-related genes in a large cohort of invasive breast cancers. Material and Methods: All tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through March 2010 were included. Standard RS testing was performed. Quantitative expression for ER, PR, HER2, and the five proliferation genes, CCNB1, Ki-67, MYBL2, STK15, and Survivin, was measured by quantitative RT-PCR on a scale from 2 to 15 (relative to reference genes), where a one unit increment is associated with an approximate 2-fold increase in expression. The proliferation index (PI), a component of the RS, was calculated as the average of the expression of the five proliferation genes. ER negative tumors (ER<6.5) were excluded. Means and medians were calculated; with this very large sample size, all comparisons between groups were statistically significant (P<0.05). Results: Among the 145,236 breast cancers, 5,794 (4.0%) were ≥40 yrs, 117,740 (81.1%) were 41 — 69 yrs, and 21,702 (14.9%) were ≥70 yrs. A wide range of RS (0 to >80) was observed in all age groups. The mean RS, median RS, and proportion of patients in each of the standard RS groups are shown in the Table. The average RS is slightly higher in the younger age group and lower in the older age group. Similarly, the proportion of high RS tumors is higher in the younger age group and lower in the older age group. However, many young patients are in the low RS group and many older patients are in the high RS group. Small differences in the mean expression of quantitative ER, quantitative PR, and the Proliferation Index were observed. Younger patients had lower mean ER, higher mean PR and higher proliferation. Discussion: Among estrogen receptor positive breast cancers, the average RS is slightly higher in younger patients and is slightly lower in older patients. However, it is notable that a wide range of RS was observed in all age groups; many young patients are in the low RS group and many older patients are in the high RS group. These results demonstrate the importance of standardized quantitative measurement of gene expression on a continuous scale, and suggest that, for ER positive breast cancer, age per se does not predict individual tumor biology. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-01.