Identification of Luminal Subtypes of Breast Carcinoma Using Surrogate Immunohistochemical Markers and Ascertaining Their Prognostic Relevance

Abstract

Background: Therapeutic decisions in breast carcinoma are being made on the basis of tumor cell proliferation using exorbitant genomic tests. The 2013 St Gallen meeting advocated surrogate definitions for classifying tumors into luminal subtypes on the basis of immunohistochemical (IHC) markers. We studied the classification of estrogen receptor (ER)-positive tumors using these definitions as well as different methods for Ki-67 labeling index (LI) estimation.

Patients and methods: A total of 541 ER⁺ invasive breast carcinoma cases from January 2012 to December 2012 were evaluated for Ki-67 LI by the average and hot spot methods. The IHC results of ER, PR, and human epidermal growth factor receptor 2 (HER2) were noted. HER2 IHC equivocal (2+) samples were subjected to HER2 fluorescence in-situ hybridization testing. Luminal subgroups created on the basis of the 2013 St Gallen meeting guidelines were correlated with clinicopathologic variables and disease-free survival.

Results: The distribution of luminal subtypes was as follows: luminal A-like, 13.3%; luminal B-like (HER2^-), 57.9%; and luminal B-like (HER2⁺), 28.8%. Approximately 6% of cases were recategorized into different subgroups when the average method was used instead of the hot spot method for Ki-67 LI assessment. Younger patients (≤ 50 years), grade 3 tumors, positive axillary nodes, recurrence, and distant metastasis had a positive statistical correlation with luminal B-like (HER2^-) subtype. Patients with luminal B-like (HER2^-) tumors had a shorter disease-free survival compared to patients with luminal A-like tumors.

Conclusion: Ki-67 LI, irrespective of the method of assessment, along with PR, can be efficiently used to divide ER⁺ tumors into prognostic subgroups in Indian patients.

Keywords: Breast cancer; Hormone receptors; Immunohistochemistry; Ki-67 labeling index; St Gallen meeting.