First-line treatment for patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer can be either hormone therapy or chemotherapy, depending primarily on whether patients have symptomatic visceral disease. However, other markers, such as the count of circulating tumor cells (CTCs), may have greater prognostic value in the decision of first-line treatment. “Circulating tumor cell count is a major and reproducible prognostic factor in metastatic breast cancer, but the clinical utility of CTC count remains to be demonstrated,” said Dr Francois-Clement Bidard of Paris, France. Dr Bidard was an investigator in the STIC CTC trial, which was a large, randomized, multicenter, phase 3 trial to compare 2 strategies of choosing the first-line type of treatment: decision by clinician versus by CTC levels.
To compare these strategies, the clinical and pathologic characteristics of 530 patients were registered at the start of the study, along with the a priori treatment recommended by clinicians (either hormone therapy or chemotherapy). The CTC count for each patient was also determined using the CellSearch® CTC kit, which is approved for use in the United States. Patients were then randomized to receive either the a priori treatment or treatment based on their CTC: hormone therapy if <5 CTC/7.5 mL and chemotherapy if ≥5 CTC/7.5 mL. In addition to standard statistical tests to analyze the data, multiple correspondence analysis (MCA) was used to identify and describe any underlying structures in the data set.
Based on clinician evaluation, the a priori treatment was hormone therapy for 371 (70%) patients and chemotherapy for 159 (30%) patients. Major adverse prognostic factors were lymphocytopenia (39%), pleuropulmonary metastases (37%), having ≥3 metastatic sites (34%), liver metastases (20%), and having a patient performance status equal to 2 or 3 (7%). The characteristics found to be independently associated with the a priori choice were age (P = 0.01), evaluation center (P <0.001), prior (neo)adjuvant chemotherapy (hazard ratio [HR], 0.47 favoring chemotherapy; P = 0.02), elevated serum glutamic oxaloacetic transaminase (HR, 0.41; P <0.001), liver (HR, 0.45; P = 0.005), and bone-only (HR, 3.16 favoring hormone therapy; P <0.001) metastases, >10-year disease-free interval (HR, 3.45; P = 0.003).
Of the patient set, 205 (39%) had elevated CTC counts (≥5 CTC/7.5 mL). Using MCA, the first 2 axes were CTC and prior chemotherapy for early breast cancer, with the other clinicopathologic factors being distributed accordingly. Of the 263 patients randomized to the CTC-driven decision arm, a priori hormone therapy (186 patients, 71%) was confirmed in 122 patients (68%) and switched to chemotherapy in 58 (32%) patients; a priori chemotherapy (77 patients, 29%) was confirmed in 35 (49%) patients and switched to hormone therapy in 37 (51%) patients. Pending the outcome of continued follow-up of these patients, these data may support the use of CTC counts as a prognostic tool in determining first-line therapy in HR+/HER2– metastatic breast cancer. Demonstrating the clinical utility of CTC counts should “help to personalize the first-line regimen in HR+/HER2– metastatic breast cancer patients,” said Dr Bidard.
Bidard F-C, et al. ESMO 2016. Abstract 226PD.