Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

Abstract

Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

“…83 A recent study showed that the survival of patients with ER þ /PR þ / HER2 þ tumors was superior to those with ER þ /PR À /HER2 þ tumors across all stages, confirming that loss of PR is an unfavorable event. 106 These results highlighted the clinical importance of separating ER þ /PR þ /HER2 þ tumors from ER þ / PR À /HER2 þ tumors. Based on currently available data, the most commonly used IHC surrogates for luminal HER2 subtype are ER and/or PR þ /HER2 þ , which may be further divided into ER þ /PR þ /HER2 þ and ER þ /PR À /HER2 þ subtypes.…”

Expression of Breast Cancer Subtypes Based on the Most Important Biomarkers: Comparison of Clinicopathological Factors and Survival

“…Moreover, the risk of mortality for the triple negative subgroup was at the maximum level in all stages. Inversely, the risk of luminal B/HER2+ was minimum in all stages (33). Overall, there has been increasing attention to new molecular classifications of BC, based on the genetic map (3,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43), which can improve the prognostic power with low cost and high accessibility.…”

“…Also, determination of gene expression is useful in making decisions about BC treatment (16,(20)(21)(22). In previous studies on DNA microarray in BC patients, biomolecular subtypes were assessed separately with different clinical outcomes (23).…”

Prognostic Factors of Recurrence (Early and Late) and Death in Breast Cancer Patients in Iranian Women

“…Many studies on hormone receptors have shown that negative estrogen and progesterone receptors increase response to weakly treatment, among breast cancer patients (27,28).…”