Predictors for the outcomes of patients with estrogen receptor-positive, HER2-negative advanced breast cancer treated using palbociclib plus endocrine therapy
A cyclin-dependent kinase (CDK) 4/6 inhibitor, palbociclib (PAL), combined with endocrine therapy is frequently used for the treatment of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer. However, as predictors for the outcomes remain unclear, we retrospectively investigated them. A total of 36 patients with ER-positive, HER2-negative advanced breast cancer were treated using PAL plus endocrine therapy at our hospital. Treatment outcomes, objective response rates (ORR), progression-free survival (PFS) and post-treatment overall survival (OS) were analyzed. As possible predictive biomarkers, retinoblastoma protein (Rb), phosphorylated Rb (pRb) and different CDKs were immunohistochemically investigated using primary tumor tissues. Non-visceral metastasis, use of fulvestrant (FUL) and the 1st- or 2nd-line treatment were significant predictors for a better ORR (P = 0.0080, P = 0.0080 and P = 0.0080, respectively). No objective response (OR) was observed in patients with progesterone receptor (PR)-negative, CDK6-positive or cytosolic cyclin E1-positive tumors. Non-visceral metastasis and use of FUL were significant predictors for a better PFS (P = 0.0030 and P = 0.0443, respectively). The Cox proportional hazards model revealed that visceral metastasis (hazard ratio [HR], 4.9; P = 0.0019) and PR-negativity (HR, 3.2; P = 0.0411) were independent predictors for a poorer PFS. Non-visceral metastasis, pRb-negativity and CDK6-negativity were significant predictors for a better OS (P = 0.0281, P = 0.0014 and P = 0.0396, respectively). The Cox proportional hazards model revealed that visceral metastasis (HR, 7.2; P = 0.0131) and pRb-positivity (HR, 18.5; P = 0.0060) were independent predictors for a poorer OS. In conclusion, PR-negativity and pRb-positivity in primary tumors may be independent predictors for PFS and OS, respectively. CDK6-positivity and cytosolic cyclin E1-positivity may be predictors for a poorer OS and ORR, respectively. Further investigation is needed to confirm these factors.