The prognostic and predictive significance of cytokeratin 5/6 and epidermal growth factor receptor in metastatic triple-negative breast cancer treated with maintenance capecitabine

Abstract

Background: Capecitabine is the most widely used agent for maintenance chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). However, there are no biomarkers for identifying mTNBC patients who could benefit from capecitabine maintenance. Methods: The prognostic roles of cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), and maintenance therapy were evaluated in mTNBC patients. Both CK5/6 and EGFR were detected using immunohistochemistry. Of 115 patients who achieved disease control, 56 received capecitabine maintenance therapy and 59 underwent observation. The progression-free survival (PFS) and overall survival (OS) of the patients were evaluated. Results: The median PFS and OS were longer in the maintenance group than that in the observation group (7.3 versus 5.7 months, P=0.0016; 22.4 versus 17.9 months, P=0.0055). Patients with basal-like TNBC had a poorer survival times than in those with non-basal-like TNBC (P=0.0062). Capecitabine maintenance significantly prolonged the OS of non-basal-like TNBC patients (P=0.0257), while in the basal-like TNBC patients, the difference was not significant (P=0.0541). Multivariate analysis revealed that the prolonged OS was related to age >50 years (P=0.005), presence of visceral metastases (P=0.035), response to initial therapy (P=0.017), maintenance therapy (P=0.033), and CK5/6 and EGFR status (P=0.032). Compared with the observation group, toxicities of all grades were more frequently observed in the maintenance group, including neutropenia, 85.71% vs. 25.87%, P<0.001; thrombocytopenia, 55.36% vs. 11.86%, P<0.001; anemia, 82.14% vs. 52.54%, P= 0.001; nausea 83.47% vs. 11.86%, P<0.001; vomiting 69.64% vs. 8.47%, P<0.001; and hand-foot syndrome (HFS) 32.14% vs. 1.69%, P<0.001. Conclusions: Our study revealed that patients with non-basal-like TNBC had a better clinical outcome than those with basal-like TNBC, and capecitabine maintenance treatment significantly prolonged PFS and OS in patients with TNBC. Patients with non-basal-like TNBC could benefit from maintenance therapy with capecitabine and CK5/6 and EGFR are biomarkers for TNBC prognosis.