Prognostic Value of Modified IHC4 Score in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

Abstract

Background: This study aimed to investigate whether an immunohistochemical prognostic model (IHC4 score) can predict the prognosis and the chemotherapy benefit in patients with estrogen receptor-positive (ER+)/human epidermal growth receptor 2-negative (HER2-) metastatic breast cancer (MBC).

Materials and methods: We developed a method to calculate the modified IHC4 (mIHC4) scores based on routine pathological reports and compared them with the original IHC4 scores that were much more difficult to calculate. Univariate and multivariate analyses were used to study the prognostic factors of progression-free survival (PFS) and overall survival (OS). The predictive value of mIHC4 score was also investigated.

Results: The Sun Yat-sen Memorial Hospital data set included 315 patients with newly diagnosed ER+ MBC with a median follow-up of 25.6 months. Univariate and multivariate analysis showed that higher mIHC4 scores in metastatic lesions, but not the ones in primary tumors, were significantly associated with worse PFS and OS. The prognostic value of mIHC4 scores for PFS was validated using an independent Chinese Society of Clinical Oncology- Breast Cancer (CSCO-BC) data set. More importantly, subpopulation treatment effect pattern plot analysis showed that first-line endocrine therapy achieved better PFS and OS than chemotherapy in low-risk patients with ER+/HER2- MBC, whereas first-line chemotherapy was associated with improved PFS and OS compared with endocrine therapy in high-risk ones. The predictive value of mIHC4 score for PFS in selecting first-line endocrine therapy versus chemotherapy was also confirmed in the CSCO-BC data set.

Conclusion: mIHC4 scores in metastatic lesions are prognostic for the PFS and OS in patients with ER+ MBC. Low or high mIHC4 score may indicate the survival benefit in choosing first-line endocrine therapy or chemotherapy in patients with ER+/HER2- MBC, respectively.

Implications for practice: The modified IHC4 (mIHC4) score is easy to implement and able to predict patients with advanced and/or metastatic breast cancer. In addition, with the help of the mIHC4 score, physicians might be able to recommend chemotherapy or endocrine therapy as the first-line treatment for patients with high and low risk as predicted by the mIHC4 score.

Keywords: Chemotherapy; Endocrine therapy; IHC4; Metastatic breast cancer.

Figure 1

Assessment of the agreement between original IHC4 score and mIHC4 score, and the agreement of mIHC4 score between primary and metastatic lesions. Scattering plots show the agreement between the original IHC4 value and the mIHC4 value in the primary tumors (A) and metastatic tumors (B). (C): Scattering plot shows the change of mIHC4 scores between the primary tumors and metastatic lesions. Abbreviation: mIHC4, modified IHC4.

Figure 2

Kaplan‐Meier analysis of survival in patients with different modified IHC4 (mIHC4) scores. (A, B): PFS of patients in different risk subgroups defined by primary (A) or metastatic (B) mIHC4 scores. (C, D): OS of patients in different risk subgroups defined by primary (C) or metastatic (D) mIHC4 scores. *p value for moderate‐risk versus low‐risk subgroups; **p value for high‐risk versus low‐risk subgroups. Abbreviations: OS, overall survival; PFS, progression‐free survival.

Figure 3

Survival analysis of patients in different risk groups defined by mIHC4 scores. Kaplan‐Meier analysis of survival in patients with different primary (A) and metastatic (B) mIHC4 scores in the CSCO‐BC data set. Abbreviations: CSCO‐BC, Chinese Society of Clinical Oncology‐Breast Cancer (CSCO‐BC); mIHC4, modified IHC4; PFS, progression‐free survival.

Figure 4

Assessment of the therapeutic benefit of chemotherapy in patients with varied mIHC4 scores or NOLUS scores. STEPP analysis of the treatment effects (endocrine therapy vs. chemotherapy) on PFS (A, C, D, F) and OS (B, E), across a continuous values of metastatic mIHC4 scores (A–C), and NOLUS score (D–F). The log hazard ratio and its 95% confidence interval are shown in the plots. There is a significant trend that in patients with lower metastatic mIHC4 score, endocrine therapy is better, whereas in patients with higher metastatic mIHC4 score, chemotherapy is better. Abbreviations: mIHC4, modified IHC4; NOLUS, nonluminal disease score; OS, overall survival; PFS, progression‐free survival; STEPP, subpopulation treatment effect pattern plot; SYSMH, Sun Yat‐sen Memorial Hospital.