The Role Of HRs And BCL2 In Identifying Luminal A-like Subtypes Of Triple-Positive Breast Cancers

Objective:Triple-positive breast cancer(TPBC)is a tumor that simultaneously expresses estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor-2(HER2).Among TPBC tumors,some tumors behave more like luminal A subtypes,while others behave more like non-luminal HER2 + tumors.The luminal A-like subtype represents a special subtype of triple-positive breast cancers with a favorable prognosis but benefits less from HER2-targeted therapy.However,little is known about how to identify luminal A-like TPBCs.Therefore,this study aims to explore a clinically feasible method to identify luminal A-like TPBCs using immunohistochemical(IHC)markers to enable individualized treatment of triple-positive breast cancers.Methods:Our cohort enrolled 190 consecutive patients with early-stage(stage I-III)triple-positive breast cancer diagnosed,treated and followed up in the Second Hospital of Jilin University between 2013 and 2019.According to the expression of hormone receptors and B-cell lymphoma2(BCL2),we classified 190 triple-positive tumors into a luminal A-like subgroup(cohort A)and a non-luminal A-like subgroup(cohort B).Patients whose IHC staining displayed≥50% in both ER and PR scores and B-cell lymphoma 2(BCL2)positivity were classified as cohort A,and the rest were enrolled in cohort B.Pearson chi-square test and Fisher’s exact test were used to analyze the clinicopathologic features of cohort A and cohort B.Median follow-up time of cohort A and cohort B was calculated with the Reverse Kaplan–Meier method.Kaplan–Meier plotter and log-rank test were used to compare the survival difference between cohort A and cohort B and the efficacy of trastuzumab therapy in the two cohorts.Using the Cox proportional hazard model,a multivariate survival analysis was performed for disease-free survival(DFS)of TPBC patients.To explore whether detecting the expression of ER,PR and BCL2 via IHC can help identify a luminal A-like subtype of triple-positive breast cancers,which has a relatively better prognosis but benefits less from trastuzumab therapy.Results:1.The proportion of patients with HER2 gene amplification in cohort A was significantly higher than in cohort B(p=0.001).There was no significant difference in other clinicopathological features between the two cohorts.2.The DFS of cohort A was significantly better than that of cohort B(p=0.031);When neither cohort was treated with trastuzumab,the DFS of cohort A was still better than that of cohort B(p=0.072).3.Cohort A was associated with better disease-free survival.The local recurrence or distant metastasis in cohort B was 3.509 times higher than in cohort A(95%CI 1.046–11.776,p = 0.042).The tumor stage is another important factor affecting the prognosis of TPBC.The local recurrence or distant metastasis in stage Ⅲpatients was 3.426 times higher than in stage Ⅰ-Ⅱ patients(95%CI:1.252-9.571,p=0.017).4.In cohort A,there was no statistically significant difference in DFS between patients treated with trastuzumab and those without trastuzumab(p=0.663).In cohort B,patients treated with trastuzumab had significantly better DFS than those without trastuzumab(p=0.032).However,when both cohorts were treated with trastuzumab,there was no significant difference in DFS between the two cohorts(p=0.667).5.Trastuzumab therapy did not significantly improve disease-free survival in patients with triple-positive breast cancers(HR = 1.780,95%Cl 0.581–5.459,p=0.313).Conclusions:This study found differences in clinical behavior and response to treatment between the luminal A-like subgroup(cohort A)and the non-luminal A-like subgroup(cohort B)in triple-positive breast cancers.The prognosis of cohort A was significantly better than that of cohort B,and cohort A benefited less from trastuzumab therapy.Therefore,identifying luminal A-like TPBC is essential to guide the individualized treatment of TPBC patients,enabling the precise treatment of TPBC patients.In conclusion,detecting the expression of ER,PR and BCL2 via IHC can help identify a luminal A-like subtype of triple-positive breast cancers,which has a relatively better prognosis but benefits less from trastuzumab therapy.