Classic Lobular Carcinoma Characterized by Differential Patterns of Gene Expression

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(ChemotherapyAdvisor) – An 8-year update of the patterns of quantitative gene expression among 286,726 cases of estrogen receptor (ER)-positive breast cancer, as measured by the Oncotype DX™ 21-gene assay, found ductal not otherwise specified (NOS) carcinomas accounted for the majority of cases, 81.8%, Joseph M. Anderson, MD, of Genomic Health, Inc., Redwood City, CA, reported during the 2013 Breast Cancer Symposium held in San Francisco.

Following ductal NOS carcinomas, classic lobular carcinomas accounted for 7.3% of cases, solid and alveolar lobular, 0.4%, and pleomorphic lobular, 0.4%. Classic lobular carcinoma and the lobular carcinoma variants were characterized by differential patterns of gene expression, he noted. For all types, a continuous range of recurrence score was observed.

In this study, Dr. Anderson and colleagues analyzed all tumors from June 1, 2004, to May 31, 2012, using World Health Organization criteria to classify them as classic lobular, solid and alveolar, and pleomorphic lobular carcinomas. Classic lobular carcinoma is characterized by a distinctive morphology, loss of E-cadherin commonly due to mutation, or deletion of CDH1 on chromosome 16q, and a variable clinical course, he noted. Pleomorphic, solid, and alveolar variants, with distinct morphologies and potential differences in outcome, have been described in a previous study.

Quantitative expression of 16 cancer-related genes was measured on a scale from 2 to 15 (relative to reference genes); a 1-unit increment was associated with an approximate two-fold change in expression. Descriptive statistics for the recurrence score and individual genes (ER, progesterone receptor [PR], invasion gene group, and proliferation gene group) among the subtypes were obtained.

“Outlier cases are not infrequent within each of the special subtypes in this large observational cohort,” Dr. Anderson noted. Ductal NOS carcinoma had the greatest percentage of high-risk recurrence score followed by solid and alveolar lobular carcinoma, pleomorphic lobular carcinoma, and classic lobular carcinoma.

Ductal NOS carcinoma also had the highest mean recurrence score, while pleomorphic lobular and classic lobular had the lowest. The highest mean ER expression was found in solid and alveolar lobular carcinoma and lowest in classic lobular and pleomorphic lobular carcinoma. “These results may reflect a submission bias and are not population based,” he pointed out.

The proportion with ER-positive/PR-negative phenotype differed among the subtypes. A higher incidence was observed in solid and alveolar lobular (24%) and pleomorphic lobular carcinomas (19.4%) compared with ductal NOS (14.1%) and classic lobular carcinomas (15.2%).

Solid and alveolar lobular carcinomas had the highest proliferation gene group expression, whereas classic lobular carcinoma had the lowest. Ductal NOS carcinoma had the highest invasion gene group and classic lobular carcinoma, the lowest.

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