Background: Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS) and amalgamating all cancer sites. So far, no detailed separate data are available for early BC. Objectives: To describe the creation of the French Early Breast Cancer Cohort (FRESH). Methods: All French women aged 18 years or over, with early-stage BC newly diagnosed between 1 January 2011 and 31 December 2017, treated by surgery, and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, and endocrine therapy), and diagnostic procedures (biopsy, cytology, and imaging) were extracted from hospital discharge reports, outpatient care notes, or pharmacy drug delivery data. The BC subtype was inferred from the treatments received. Results: We included 235,368 patients with early BC in the cohort (median age: 60 years). The BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2⁺ (10.3%), or unidentifiable (n = 44,388, 18.9% of the cohort). Most patients underwent radiotherapy (n = 200,685, 85.3%) and endocrine therapy (n = 165,655, 70.4%), and 38.3% (n = 90,252) received chemotherapy. Treatments and care pathways are described. Conclusions: The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.

Background: Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS). This cohort amalgamates all cancer sites, with no detailed separate data for early BC. Objectives: We describe the French Early Breast Cancer Cohort (FRESH). Methods: All French women aged 18 years or over, with early-stage BC newly diagnosed between January 1, 2011 and December 31, 2017, treated by surgery and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, endocrine therapy), and diagnostic procedures (biopsy, cytology, imaging) were extracted from hospital discharge reports, outpatient care notes or pharmacy drug delivery data. BC subtype was inferred from the treatments received. Results: We included 235,368 patients with early BC in the cohort (median age: 60 years). BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2 ⁺ (10.3%), or unidentifiable ( n =44,388, 18.9% of the cohort). Most patients underwent radiotherapy ( n =200,685, 85.3%) and endocrine therapy ( n =165,655, 70.4%), and 38.3% ( n =90,252) received chemotherapy. Treatments and care pathways are described. Conclusion: The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.

Introduction: Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly BRCA pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to BRCA status. Material and methods: Out of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline BRCA pathogenic variant. We evaluated pre-NAC and post-NAC immune infiltration (TILs). Response to chemotherapy was assessed by pCR rates. Association of clinical and pathological factors with TILs, pCR and survival was assessed by univariate and multivariate analyses. Results: Among 1199 BC patients: 46 were BRCA -deficient and 221 BRCA- proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in BRCA- deficient BC ( p= 0.001), and this association remained statistically significant only in the luminal BC subtype ( p= 0.006). The interaction test between BC subtype and BRCA status was nearly significant ( P _interaction =0.056). Pre and post-NAC TILs were not significantly different between BRCA- deficient and BRCA- proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in BRCA- deficient BC. Survival analysis were not different between BRCA- carriers and non-carriers. Conclusion: BRCA mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC. BRCA -carriers with luminal BCs may represent a subset of patients deriving higher benefit from NAC. Second line therapies, including immunotherapy after NAC, could be of interest in non-responders to NAC. Translational relevance: High lymphocytic infiltration (TILs) seem to reflect favorable host antitumor immune responses. In breast cancer, the variation of TILs before and after neoadjuvant chemotherapy (NAC) according to BRCA status has been poorly described. Little data is available on their value after treatment. We investigated TIL levels before and after NAC and response to treatment in 267 paired biopsy and surgical specimens. In our study, luminal BCs were associated with pathologic complete response (pCR) and higher TIL levels after chemotherapy completion in patients with BRCA pathogenic mutations. Our data supports that (i) NAC should be reconsidered in luminal BCs with BRCA pathogenic mutation, (ii) TILs could be a biomarker for response to immune checkpoint blockade in luminal BCs with BRCA pathogenic variant who did not achieve a pCR and (iii) exploiting the antitumor immune response in luminal BCs could be an area of active research.

Introduction: The Residual Cancer Burden (RCB) quantifies residual disease after neoadjuvant chemotherapy (NAC). Its predictive value has not been validated on large cohorts with long-term follow up. The objective of this work is to independently evaluate the prognostic value of the RCB index depending on BC subtypes (Luminal, HER2 -positive and triple negative (TNBCs)). Methods: We retrospectively evaluated the RCB index on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between RCB index and relapse-free survival (RFS), overall survival (OS) among the global population, after stratification by BC subtypes. Results: 717 patients were included (luminal BC (n = 222, 31%), TNBC (n = 319, 44.5%), HER2 -positive (n = 176, 24.5%)). After a median follow-up of 99.9 months, RCB index was significantly associated with RFS. The RCB-0 patients displayed similar prognosis when compared to the RCB-I group, while patients from the RCB-II and RCB-III classes were at increased risk of relapse (RCB-II versus RCB-0: HR=3.25 CI [2.1-5.1] p <0.001; RCB-III versus RCB-0: HR=5.6 CI [3.5-8.9] p <0.001). The prognostic impact of RCB index was significant for TNBC and HER2 -positive cancers; but not for luminal cancers ( P _interaction = 0.07). The prognosis of RCB-III patients was poor (8-years RFS: 52.7%, 95% CI [44.8 – 62.0]) particularly in the TNBC subgroup, where the median RFS was 12.7 months. Conclusion: RCB index is a reliable prognostic score. RCB accurately identifies patients at a high risk of recurrence (RCB-III) with TNBC or HER2 -positive BC who must be offered second-line adjuvant therapies.

INTRODUCTION: Tobacco use is associated with an increase in breast cancer (BC) mortality. Pathologic complete response rate to neoadjuvant chemotherapy (NAC) is influenced by tumor-infiltrating lymphocytes (TILs) levels and is associated with a better long-term survival outcome. Whether tobacco modifies either tumoral microenvironment such as TIL levels, either pCR rates remains unclear. The aim of our study is to evaluate the impact of smoking status on TIL levels, response to NAC and prognosis for BC patients. METHODS: We retrospectively evaluated pre and post NAC stromal and intra tumoral TIL levels and pCR rates on a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012 at Institut Curie. Smoking status (current, ever, never smokers) was collected in clinical records. We analyzed the association between smoking status, TIL levels, pCR rates and survival outcomes among the whole population, and after stratification by BC subtype. RESULTS: A total of 956 BC patients with available smoking status information were included in our analysis [current smokers, n=179 (18.7%); ever smokers, n=154 (16.1%) and never smokers, n = 623 (65.2%)]. Median pre-NAC TIL levels, pCR rates, or median post-NAC TIL levels were not significantly different according to smoking status, neither in the whole population, nor after stratification by BC subtype. With a median follow-up of 101.4 months, relapse free survival (RFS) and overall survival (OS) were not significantly different by smoking status. CONCLUSION: In this study, we did not find any significant effect of tobacco use on pre and post NAC TILs nor response to NAC and. Though our data seem reassuring, BC treatment should still be considered as a window of opportunity to offer BC patients accurate smoking cessation interventions.