(ChemotherapyAdvisor) – A new proposed immunohistochemical (IHC)-based definition of luminal A tumors in patients with breast cancer is hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative/Ki-67 <14% and progesterone receptor (PR) >20%, a study reported in the Journal of Clinical Oncology online December 10.
Currently, two gene expression-based assays can be used to identify intrinsic molecular subtypes of breast cancer and provide risk of relapse and recurrence scores, respectively.
“However, standardized gene expression-based tests are not readily available in most of the world as a result of cost, assay turnaround times, and other logistic issues,” noted Aleix Prat, MD, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and colleagues. “Thus, surrogate definitions of the intrinsic subtypes and/or risk of relapse groups developed using routine pathology and clinical parameters could be of great practical value.”
Previously, the authors’ IHC-based surrogate definition of luminal A and luminal B/HER2-negative subtypes based on quantitative expression of the proliferation-related marker Ki-67 within HR-positive/HER2-negative disease was adopted by the 2011 St. Gallen Expert Consensus Panel Recommendation Guidelines for the systemic treatment of early breast cancer. These guidelines “recommend adjuvant endocrine therapy alone for patients with IHC-luminal A tumors and the addition of chemotherapy for patients with IHC-luminal B/HER2-negative tumors,” Dr. Prat noted.
This study further refines that definition by using quantitative PR expression. The investigators collected gene expression and pathologic features from primary tumors across five independent cohorts.
Among luminal A and B subtypes, clinicopathologic comparisons consistently identified higher rates of PR positivity, HER2 negativity, and histologic grade 1 in luminal A tumors. Luminal A tumors also significantly higher quantitative PR gene and protein expression.
Survival differences within IHC-defined luminal A tumors were predicted using an empiric cutoff of >20% of PR-positive tumor cells, and demonstrated a difference independent of endocrine therapy administration, they found.
However, when intrinsic IHC-based subtypes were used that included the >20% PR-positive tumor cells, no additional prognostic value within HR-positive/HER2-negative disease was observed with the use of the IHC4 score.