Association of Endocrine Therapy for HR+/ERBB2+ Metastatic Breast Cancer With Survival Outcomes.

Importance: Evidence suggests that patients with human epidermal growth factor receptor 2-positive (ERBB2+ [formerly HER2+]) metastatic breast cancer (MBC) have different clinical characteristics and outcomes according to their hormone receptor (HR) status. The place of endocrine therapy (ET) for patients with HR+/ERBB2+ is still not clearly defined in this setting. Objective: To evaluate the association of HR status and first-line inclusion of ET with outcomes among patients with ERBB2+ MBC. Design, Setting, and Participants: This cohort study was an analysis of clinical data from the French clinical Epidemiological Strategy and Medical Economics (ESME) cohort, including patients with MBC who started treatment between 2008 and 2017. The last date of follow-up was June 18, 2020. Data were analyzed from May 2021 to May 2022. Exposures: Patients were treated with first-line ERBB2-targeted therapy and either chemotherapy (CT) with or without ET or ET alone. For the study of the association of maintenance ET with outcomes, we included patients treated with first-line ERBB2-targeted therapy with CT and with or without maintenance ET. Main Outcomes and Measures: Median overall survival (OS) and median first-line progression-free survival (PFS) were reported using the Kaplan-Meier method. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Multivariable analysis included age at MBC, time to MBC, number of metastatic sites, type of metastases, and Eastern Cooperative Oncology Group performance status. Results: Among 4145 women with ERBB2+ MBC, 2696 patients had HR+ (median [IQR] age, 58.0 [47.0-67.0] years) and 1449 patients had HR- (56.0 [47.0-64.0] years) tumors. The median OS for patients with HR+ vs HR- tumors was 55.9 months (95% CI, 53.7-59.4 months) vs 42.0 months (95% CI, 38.8-45.2 months), confirmed in multivariable analysis (hazard ratio, 1.40; 95% CI, 1.26-1.56; P < .001). The median PFS for patients with HR+ vs HR- tumors was 12.2 months (95% CI, 11.5-12.9 months) vs 9.8 months (95% CI, 9.2-11.0 months; P = .01), and the HR was 1.15 (95% CI, 1.06-1.26; P < .001). In multivariable analysis, no significant difference was found in OS or PFS for 1520 patients treated with ERBB2-targeted therapy with CT and with or without ET vs 203 patients receiving ERBB2-targeted therapy with ET, regardless of type of ERBB2-targeted therapy (trastuzumab or trastuzumab with pertuzumab). This result was confirmed by matching patients using a propensity score. Using the time-dependent ET variable among patients with ERBB2-targeted therapy with CT, those with maintenance ET had significantly better PFS (hazard ratio, 0.70; 95% CI, 0.60-0.82; P < .001) and OS (hazard ratio, 0.47; 95% CI, 0.39-0.57; P < .001). Conclusions and Relevance: These results suggest that ET-containing first-line regimens may be associated with benefits among a subgroup of patients with HR+/ERBB2+ MBC.

Management and outcome of male metastatic breast cancer in the national multicenter observational research program Epidemiological Strategy and Medical Economics (ESME).

BACKGROUND AND AIMS: Because of its low prevalence, metastatic breast cancer (MBC) in males is managed based on clinical experience with women. Using a real-life database, we aim to provide a comprehensive analysis of male MBC characteristics, management and outcome. METHODS: The Epidemiological Strategy and Medical Economics Data Platform collected data for all men and women ⩾18 years with MBC in 18 participating French Comprehensive Cancer Centers from January 2008 to November 2016. Demographic, clinical, and pathological characteristics were retrieved, as was treatment modality. Men were matched 1:1 to women with similar characteristics. RESULTS: Of 16,701 evaluable patients, 149 (0.89%) men were identified. These men were older (median age 69 years) and predominantly had hormone receptor HR+/HER2- disease (78.3%). Median overall survival (OS) was 41.8 months [95% confidence interval (CI: 26.9-49.7)] and similar to women. Median progression-free survival (PFS) with first-line therapy was 9.3 months [95% CI (7.4-11.5)]. In the HR+/HER2- subpopulation, endocrine therapy (ET) alone was the frontline treatment for 43% of patients, including antiestrogens (n = 19), aromatase inhibitors (n = 15) with luteinizing hormone-releasing hormone (LHRH) analogs (n = 3), and various sequential treatments. Median PFS achieved by frontline ET alone was similar in men [9.8 months, 95% CI (6.9-17.4)] and in women [13 months, 95% CI (8.4-30.9)] (p = 0.80). PFS was similar for HR+/HER2- men receiving upfront ET or chemotherapy: 9.8 months [95% CI (6.9-17.4)] versus 9.5 months [95% CI (7.4-11.7)] (p = 0.22), respectively. CONCLUSION: MBC management in men and women leads to similar outcomes, especially in HR+/HER2- patients for whom ET should also be a cornerstone. Unsolved questions remain and successfully recruiting trials for men are still lacking.

[Prognostic assessment and treatment of early breast cancer]. / Évaluation pronostique et traitement du cancer du sein précoce.

Prognostic assessment and treatment of early breast cancer. Breast cancer is the most common cancer occurring in France and worldwide. In 2017 it has been estimated that 59.000 women in France have been diagnosed with breast cancer. Breast cancer prognosis depends on multiple factors: tumor stage (TNM), histology, molecular sub-type and grade. The treatment of early breast cancer usually involves different strategies, such as surgery, chemotherapy, endocrine therapy, targeted therapies and radiotherapy, on the basis of the different sub-types.

Évaluation pronostique et traitement du cancer du sein précoce. Le cancer du sein est le cancer le plus fréquent chez la femme en France métropolitaine et dans le monde, avec environ 59 000 nouveaux cas estimés en France en 2017. Le pronostic du cancer du sein repose sur plusieurs facteurs : le stade (TNM), le type histologique, le sous-type moléculaire et le grade. La prise en charge du cancer du sein précoce se base sur plusieurs stratégies combinées en fonction des différents sous-types : la chirurgie, la chimiothérapie, l'hormonothérapie, les traitements ciblés et la radiothérapie.

Assessment of the efficacy of successive endocrine therapies in hormone receptor-positive and HER2-negative metastatic breast cancer: a real-life multicentre national study.

BACKGROUND: For luminal metastatic breast cancer (MBC), endocrine therapy (ET) is the recommended initial treatment before chemotherapy. Our objective was to evaluate the efficacy of multiple ET lines in a real-life study. METHODS: The Breast Cancer Epidemiological Strategy and Medical Economics (ESME) project analysed data from all patients with systemic treatment for MBC initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. The primary end-point was the successive progression-free survival (PFS) evaluation. RESULTS: The ESME research programme included 9921 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2) negative (HER2-) MBC. Before any chemotherapy, 4195 (43.4%), 1252 (29.8%) and 279 (6.6%) patients received one, two or three ET ± targeted therapy, respectively. The median PFS for first-, second- and third-line ET ± targeted therapy was 11.5 (95% confidence interval [CI], 10.8-12.1), 5.8 (95% CI, 5.3-6.1) and 5.5 (95% CI, 4.6-6.3) months, respectively. In a multivariate analysis, time from diagnosis to metastatic recurrence (P < 0.0001), presence of symptoms at metastatic relapse (P = 0.01), number of metastatic sites (P = 0.0003) and their localisation (P < 0.0001) were prognostic factors for PFS1. Duration of previous PFS was the only prognostic factor for subsequent PFS (10% threshold). Ten percent of the patients showed long-term response to ET, with a total treatment duration before chemotherapy ≥43.6 months. CONCLUSIONS: Median PFS in our HR+/HER2- real-life cohort is similar to median first-line PFS reported in clinical trials, regardless of ET used as second- and third-line treatment. Despite the international consensus on early initiation of ET, the latter is not prescribed in most of the cases. Patients with a low tumour burden may achieve prolonged response on ET.

Prognostic assessment and systemic treatments of invasive local relapses of hormone receptor-positive breast cancer.

The rate of local recurrences, after breast-conserving surgery or mastectomy for hormone receptor-positive (HR+) breast cancer, has dramatically changed in last decades, due to advances in surgical and radiation techniques and a more extensive use of adjuvant systemic treatments. However, the occurrence of local recurrences remains a major predictor for distant metastasis and is responsible for increased cancer-specific death. It has been estimated that 1 in 4 HR+ and HR-ipsilateral breast recurrences leads to widespread metastatic disease, with an annual mortality rate of 10% in the first 5 years. Nevertheless, very few studies have been conducted to evaluate the optimal care of purely HR+ local relapses of breast cancer, after surgical removal. In this review we have highlighted the available knowledge on prognostic assessment and systemic treatment for women experiencing local relapses of HR+ breast cancers, underlying unsolved questions and controversial clinical aspects.

The challenge of rapid diagnosis in oncology: Diagnostic accuracy and cost analysis of a large-scale one-stop breast clinic.

PURPOSE: Rapid diagnosis is a key issue in modern oncology, for which one-stop breast clinics are a model. We aimed to assess the diagnosis accuracy and procedure costs of a large-scale one-stop breast clinic. PATIENTS AND METHODS: A total of 10,602 individuals with suspect breast lesions attended the Gustave Roussy's regional one-stop breast clinic between 2004 and 2012. The multidisciplinary clinic uses multimodal imaging together with ultrasonography-guided fine needle aspiration for masses and ultrasonography-guided and stereotactic biopsies as needed. Diagnostic accuracy was assessed by comparing one-stop diagnosis to the consolidated diagnosis obtained after surgery or biopsy or long-term monitoring. The medical cost per patient of the care pathway was assessed from patient-level data collected prospectively. RESULTS: Sixty-nine percent of the patients had masses, while 31% had micro-calcifications or other non-mass lesions. In 75% of the cases (87% of masses), an exact diagnosis could be given on the same day. In the base-case analysis (i.e. considering only benign and malignant lesions at one-stop and at consolidated diagnoses), the sensitivity of the one-stop clinic was 98.4%, specificity 99.8%, positive and negative predictive values 99.7% and 99.0%. In the sensitivity analysis (reclassification of suspect, atypical and undetermined lesions), diagnostic sensitivity varied from 90.3% to 98.5% and specificity varied from 94.3% to 99.8%. The mean medical cost per patient of one-stop diagnostic procedure was €420. CONCLUSIONS: One-stop breast clinic can provide timely and cost-efficient delivery of highly accurate diagnoses and serve as models of care for multiple settings, including rapid screening-linked diagnosis.