Efficacy of Circulating Tumor Cell Count-Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: The STIC CTC Randomized Clinical Trial.

IMPORTANCE: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS). OBJECTIVE: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment. INTERVENTIONS: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator. DESIGN, SETTING, AND PARTICIPANTS: In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019. MAIN OUTCOME AND MEASURES: The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio. RESULTS: Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years [64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm]; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor-positive, ERBB2-negative metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01710605.

Treatment patterns, clinical outcomes and health care costs associated with HER2-positive breast cancer with central nervous system metastases: a French multicentre observational study.

BACKGROUND: The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. METHODS: This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. RESULTS: 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. CONCLUSION: A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies.

Perception of care and experience of examination in women at risk of breast cancer undergoing intensive surveillance by standard imaging with or without MRI.

OBJECTIVE: Intensive surveillance in women at breast cancer risk is currently investigated in a French prospective, non-randomized, multicenter study, in which standard imaging--mammography±ultrasound ('Mx') and standard imaging combined with magnetic resonance imaging ('MRI') are compared with regard to perception of care and examination experience. METHODS: 1561 women were invited to complete the STAI-State Anxiety Inventory and breast cancer risk perception items at baseline (T0), and MGQ (MammoGraphy Questionnaire) and MRI discomfort items within 2 days after examinations (T1). RESULTS: Baseline compliance was high (>91%). Women from the 'MRI' group were significantly younger and displayed higher education level and risk perception. MRI discomfort related to the duration, immobility, prone position or noise was experienced by more than 20% of women. In multivariate analyses, 'MRI' was associated with more favorable examination psychological experience (p≤.001), especially in women younger than 50; baseline STAI-State anxiety was associated with lower MGQ scores (p≤.001) and higher MRI discomfort (p≤.001). CONCLUSION: In spite of the discomfort experienced with MRI, perception of care and experience with this surveillance procedure was more positive than with standard imaging. PRACTICE IMPLICATIONS: Information and support may assuage some of the adverse effects of an uncomfortable examination technique.

Anxiety and specific distress in women at intermediate and high risk of breast cancer before and after surveillance by magnetic resonance imaging and mammography versus standard mammography.

BACKGROUND: Intensive surveillance in women at intermediate and high breast cancer risk is currently investigated in a French prospective, non-randomized, multicentre study. Two surveillance modalities, standard imaging-mammography ± ultrasound ('Mx')-or standard imaging with magnetic resonance imaging ('MRI'), provided according to the level of breast cancer risk, are compared on psychological distress. METHODS: A total of 1561 women were invited to complete the State-Trait Anxiety Inventory (STAI), Impact of Event Scale (IES) Intrusion and Avoidance subscales and breast cancer-risk perception items at T0 (before examination) and T2 (1 to 3 months later) and the STAI-State anxiety at T1 (just after examination). Multiple regression analyses were performed. RESULTS: Baseline compliance was high (>91%). Between surveillance modalities, women differed significantly for age, education level, breast cancer-risk objective estimates and subjective perception. Mean STAI-State anxiety scores reflected low to moderate distress in both surveillance modalities. At baseline, MRI was associated with lower STAI-State anxiety (p ≤ 0.001) and Avoidance scores (p = 0.02), but at T1 and T2, no difference between surveillance modalities was observed on psychological outcomes. Abnormal surveillance result was associated with a higher STAI-State anxiety (p ≤ 0.01) and IES-Intrusion (p ≤ 0.01) scores; a personal history of breast cancer and higher risk perception was associated with higher psychological distress at T1 and T2. CONCLUSION: Standard breast imaging including MRI does not seem to convey more harmful psychological effects than standard imaging alone. Higher psychological distress observed in the case of history of breast cancer or higher breast cancer-risk perception evidences women with needs for specific support and information.