Differences Are Important: Breast Cancer Therapy in Different Ethnic Groups

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death amongAsianwomen.Hormonal receptor (HR) –positive tumors are the most common type of breast cancer, and treatment of metastatic disease remains palliative. Endocrine therapy is the cornerstone of treatment of patients with HRpositive metastatic breast cancer (MBC). In postmenopausal patients, aromatase inhibitors have become the treatment of choice in first-line therapy with a median progression-free survival (PFS) of approximately 10months.Upon disease progression, second-line treatment options include other classes of aromatase inhibitors (steroidal or nonsteroidal), the estrogen receptor antagonist fulvestrant, and tamoxifen, which have modest efficacy (median PFS, 3 to 6 months). More recently, further understanding of mechanisms of anti-estrogen therapy resistance (eg, cell cycle kinase aberrations) fostered improvement in MBC therapy. Antiestrogen therapies function partly through suppression of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) activity, and reactivation of these kinases has been implicated in endocrine resistance. Indeed, in the first-line setting, palbociclib (a smallmolecule CDK4/6 inhibitor) has shown efficacy in patients with HR-positive, human epidermal growth factor receptor 2 (HER2) –negative, recurrent or de novo MBC in combination with letrozole. The Palbociclib Ongoing Trials in the Management of Breast Cancer (PALOMA) -2 trial is adouble-blindphase III trial inwhich themedian PFS was 24.8 months in the palbociclib plus letrozole group compared with 14.5 months in the placebo plus letrozole group (hazard ratio [HR], 0.58; 95% CI, 0.46 to 0.72; P , .001). In addition, in the Mammary Oncology Assessment of LEE011’s (Ribociclib) Efficacy and Safety (MONALEESA-2) trial, ribociclib (another CDK4/6 inhibitor) also improved the median PFS of patients with HR-positive, HER2-negative, recurrent or de novo MBC who had not received treatment of metastatic disease (HR, 0.56; 95% CI, 0.43 to 0.72; P , .001). In the PALOMA-3 trial, the combination of palbociclib with fulvestrant significantly improved the median PFS in patients with HR-positive, HER2-negative MBC to 9.5 months, compared with 4.6 months among patients treated with fulvestrant and placebo (HR, 0.46; 95% CI, 0.36 to 0.59; P , .001).