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Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this study, the authors utilized a nationwide database of breast cancer patients to estimate the association between frequently used drugs taken prior to diagnosis and breast cancer prognosis. And they identified 16 drugs associated with breast cancer outcomes.

Background Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone. Methods This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis. Discussion The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts. Trials registration ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study

ObjectiveAdvanced or recurrent endometrial carcinoma (EC) represents a significant clinical challenge. This study aimed to evaluate patient (age and comorbidities) and disease (histological subtypes and stages) characteristics, treatment patterns and survival outcomes in a real-world French healthcare setting.Methods and analysisIn this national, multi-centre, retrospective observational cohort study, 200 patients with advanced or recurrent EC receiving first- or second-line chemotherapy during the year 2019 were analysed. Data collected included baseline characteristics, treatment regimens, real-world progression-free survival (rwPFS) and overall survival (OS).Results127 and 73 were included in the first and second lines, respectively. Endometrioid carcinoma was the most represented histological subtype (62.0%). Patients in the first line, of whom 31.5% had FIGO (Fédération Internationale de Gynécologie Obstétrique) IVB disease, mainly received a combination of carboplatin and paclitaxel (78.0%), while 131 patients receiving second-line therapy were mainly administered anthracycline (54.2%). Median rwPFS and OS were, respectively, 8.5 and 13.2 months for patients receiving first-line therapy and 4.0 and 9.4 months for patients receiving second-line therapy. In Cox analyses, a diagnosis of carcinosarcoma, the presence of liver metastases and stage IVB disease were associated with worse survival outcomes for patients recieving first-line chemotherapy. Non-platinum chemotherapy and liver metastases were associated with poorer survival in patients receiving second-line chemotherapy.ConclusionsThis study highlights the landscape of metastatic EC treatment in a real-world French setting before the availability of PD1 inhibitors, emphasising the discrepancy between clinical trial data and real-world outcomes. It underscores the necessity for further real-world studies to complement clinical trials for a comprehensive understanding of metastatic EC management.

The impact of adjuvant chemotherapy on breast cancer prognosis has been demonstrated in randomized trials, but its impact is unknown in real-world populations. The aim of this study was to evaluate the effect of adjuvant chemotherapy on the survival of breast cancer patients in an unselected population. This prospective cohort study included 32,502 women treated at the Institut Curie between 1981 and 2008 for a first invasive breast cancer without metastasis. The patients were matched based on their propensity score to receive adjuvant chemotherapy. The matching generated a subsample of 9,180 patients with an overlapping propensity score. In the group without chemotherapy, the overall survival (OS) rates at 5 and 10 years of follow-up were 87.6% (95% CI [86.7-88.6]) and 75.0% (95% CI [73.6-76.5]), respectively, versus 92.1% (95% CI [91.3-92.9]) and 81.9% (95% CI [80.6-83.2]), respectively, in the chemotherapy group. Distant disease-free survival (DDFS) was significantly improved in the five first years (absolute benefit of 3.5%). In a multivariate analysis, adjuvant chemotherapy was associated with better OS (HR = 0.75, 95% CI [0.69-0.83], p<0.0001) and DDFS (HR = 0.82, 95% CI [0.75-0.90], p<0.0001). Adjuvant chemotherapy significantly improves OS and DDFS rates in an unselected population, in accordance with previous results reported by randomized trials.

Predictive biomarkers for tumor response to neoadjuvant chemotherapy are needed in breast cancer. This study investigates the predictive value of 280 genes encoding proteins that regulate microtubule assembly and function. By analyzing 3 independent multicenter randomized cohorts of breast cancer patients, we identified 17 genes that are differentially regulated in tumors achieving pathological complete response (pCR) to neoadjuvant chemotherapy. We focused on the MTUS1 gene, whose major product, ATIP3, is a microtubule-associated protein down-regulated in aggressive breast tumors. We show here that low levels of ATIP3 are associated with an increased pCR rate, pointing to ATIP3 as a predictive biomarker of breast tumor chemosensitivity. Using preclinical models of patient-derived xenografts and 3-dimensional models of breast cancer cell lines, we show that low ATIP3 levels sensitize tumors to the effects of taxanes but not DNA-damaging agents. ATIP3 silencing improves the proapoptotic effects of paclitaxel and induces mitotic abnormalities, including centrosome amplification and multipolar spindle formation, which results in chromosome missegregation leading to aneuploidy. As shown by time-lapse video microscopy, ATIP3 depletion exacerbates cytokinesis failure and mitotic death induced by low doses of paclitaxel. Our results favor a mechanism by which the combination of ATIP3 deficiency and paclitaxel treatment induces excessive aneuploidy, which in turn results in elevated cell death. Together, these studies highlight ATIP3 as an important regulator of mitotic integrity and a useful predictive biomarker for a population of chemoresistant breast cancer patients.

Mammalian cells possess two isoforms of the histone H3–H4 chaperone anti‐silencing function 1 (Asf1), Asf1a and Asf1b. However to date, whether they have individual physiological roles has remained elusive. Here, we aim to elucidate the functional importance of Asf1 isoforms concerning both basic and applied aspects. First, we reveal a specific proliferation‐dependent expression of human Asf1b unparalleled by Asf1a. Strikingly, in cultured cells, both mRNA and protein corresponding to Asf1b decrease upon cell cycle exit. Depletion of Asf1b severely compromises proliferation, leads to aberrant nuclear structures and a distinct transcriptional signature. Second, a major physiological implication is found in the applied context of tissue samples derived from early stage breast tumours in which we examined Asf1a/b levels. We reveal that overexpression of Asf1b mRNA correlate with clinical data and disease outcome. Together, our results highlight a distribution of tasks between the distinct Asf1 isoforms, which emphasizes a specialized function of Asf1b required for proliferation capacity. We discuss the implications of these results for breast cancer diagnosis and prognosis. Anti‐silencing function 1 (Asf1) is a H3–H4 chaperone involved in both replication‐coupled and replication‐independent nucleosome assembly pathways. Here in mammalian cells Asf1b is the physiologically important isoform for cell proliferation and overexpression of Asf1b correlates with prognosis and metastasis status of breast cancer.

The organization of health care for breast cancer (BC) constitutes a public health challenge to ensure quality of care, while also controlling expenditure. Few studies have assessed the global care pathway of early BC patients, including a description of direct medical costs and their determinants. The aims of this multicenter prospective study were to describe care pathways of BC patients in a geographic territory and to calculate the global direct costs of early stage BC during the first year following diagnosis. OPTISOINS01 was a multicenter, prospective, observational study including early BC patients from diagnosis to one-year follow-up. Direct medical costs (in-hospital and out-of-hospital costs, supportive care costs) and direct non-medical costs (transportation and sick leave costs) were calculated by using a cost-of-illness analysis based on a bottom-up approach. Resources consumed were recorded in situ for each patient, using a prospective direct observation method. Data from 604 patients were analyzed. Median direct medical costs of 1 year of management after diagnosis in operable BC patients were €12,250. Factors independently associated with higher direct medical costs were: diagnosis on the basis of clinical signs, invasive cancer, lymph node involvement and conventional hospitalization for surgery. Median sick leave costs were €8,841 per patient and per year. Chemotherapy was an independent determinant of sick leave costs (€3,687/patient/year without chemotherapy versus €10,706 with chemotherapy). Forty percent (n = 242) of patients declared additional personal expenditure of €614/patient/year. No drivers of these costs were identified. Initial stage of disease and the treatments administered were the main drivers of direct medical costs. Direct non-medical costs essentially consisted of sick leave costs, accounting for one-half of direct medical costs for working patients. Out-of-pocket expenditure had a limited impact on the household.

IntroductionReturn to work (RTW) after breast cancer (BC) is still a new field of research. The factors determining shorter sick leave duration of patients with BC have not been clearly identified. The aim of this study was to describe work during BC treatment and to identify factors associated with sick leave duration.Materials and methodsAn observational, prospective, multicentre study was conducted among women with operable BC. A logbook was given to all working patients to record sociodemographic and work-related data over a 1-year period.ResultsWork-related data after BC were available for 178 patients (60%). The median age at diagnosis was 50 years (27–77), 87.9% of patients had an invasive form of BC and 25.3% a lymph node involvement. 25.9% had a radical surgery and 24.2% had an axillary dissection. Radiotherapy was performed in 90.9% of patients and chemotherapy in 48.1%. Sick leave was prescribed for 165 patients (92.7%) for a median of 155 days. On univariate analysis, invasive BC (p=0.025), lymph node involvement (p=0.005), radical surgery (p=0.025), axillary dissection (p=0.004), chemotherapy (p<0.001), personal income <€1900/month (p=0.03) and not having received the patient information booklet on RTW (p=0.047) were found to be associated with a longer duration of sick leave. On multivariate analysis, chemotherapy was found to be associated with longer sick leave (OR: 3.5; 95% CI 1.6 to 7.9; p=0.002). The cost of sick leave to French National Health Insurance was fourfold higher in the case of chemotherapy (p<0.001).ConclusionAdvanced disease and chemotherapy are major factors that influence sick leave duration during the management of BC.Trial registration number NCT02813317.

Background Breast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC. Methods NeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link. Discussion In this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions. Trial registration Clinicaltrials.gov identifier: NCT05011721 . Registration date: 18/08/2021.

Background The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial ( J Clin Oncol 2006;24:5664-5671). Methods The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). Results There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p  <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR ( p  = 0.79). Conclusions After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Trial registration Not applicable.