Intrinsic Subtypes from PAM50 Gene Expression Assay in a Population-Based Breast Cancer Cohort: Differences by Age, Race, and Tumor Characteristics

Abstract

Background Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology (LACE) and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% Luminal A, 20.5% Luminal B, 13.0% HER2-enriched, 9.8% Basal-like, and 3.6% Normal-like. Among low-risk endocrine positive tumors (i.e. estrogen and progesterone receptor positive by immunohistochemistry, Her2 negative, and low histologic grade), only 76.5% were categorized as Luminal A by PAM50. Continuous-scale Luminal A, Luminal B, HER2-enriched, and Normal-like scores from PAM50 were mutually positively correlated; Basal-like score was inversely correlated with other subtypes. The proportion with non-Luminal A subtype decreased with older age at diagnosis, p trend < 0.0001. Compared with non-Hispanic whites, African-American women were more likely to have Basal-like tumors, age-adjusted odds ratio (OR) 4.4 (95% CI 2.3,8.4), whereas Asian and Pacific Islander women had reduced odds of Basal-like subtype, OR 0.5 (95% CI 0.3,0.9). Conclusions Our data indicate that over 50% of breast cancers treated in the community have Luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathological criteria to higher-risk subtypes. Impact Subtyping in a population-based cohort revealed distinct profiles by age and race.

Tumor biology in older breast cancer patients – What is the impact on survival stratified for guideline adherence? A retrospective multi-centre cohort study of 5378 patients

“…Even though the difference is statistically significant the difference in actual numbers are small. Still our results are in line with Sweeny et al and Caan et al [13,14]. Both authors published similar results using the intrinsic classification.…”

OPTIMA prelim: a randomised feasibility study of personalised care in the treatment of women with early breast cancer

“…28,29 Luminal A breast cancer is broadly recognised as having a low proliferation rate (typically grade 1 or 2), being strongly positive for steroid hormone receptor expression and expressing HER2 at normal levels, although some 25% of such cancers have a different molecular subtype. 30 Molecularly classified luminal A breast cancer makes up 50-55% of all breast cancers diagnosed in the developed world. 30 …”

“…30 Molecularly classified luminal A breast cancer makes up 50-55% of all breast cancers diagnosed in the developed world. 30 …”

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