Steroid hormones and their receptors play a role in the development and treatment of breast cancer. Endocrine therapy is now a mainstay in the treatment of estrogen receptor-positive breast cancer. In the adjuvant setting, 5 years of endocrine therapy significantly reduce recurrence rate and mortality. Tamoxifen is the molecule of choice for premenopausal women, whereas aromatase inhibitors are currently used for postmenopausal women. Optimal duration and treatment strategies involving adjuvant therapy in early breast cancer are largely discussed, and the benefits of extended adjuvant endocrine therapy beyond 5 years are still controversial. Cases of resistance, de novo or acquired, to endocrine therapy have been described, and emerging therapies are developed to counteract specific mechanisms of resistance.

627 Background: The POSITIVE trial showed that temporary interruption of adjuvant endocrine therapy (ET) after 18–30 months to attempt pregnancy did not increase short-term recurrence risk in young women with hormone receptor–positive (HR+) breast cancer (BC). However, whether this effect varies by baseline recurrence risk and the timing of interruption remains uncertain. Methods: Using the French National Health Data System (SNDS), we emulated two target trials among women aged ≤42 years with early-stage HR+ BC diagnosed between 2011 and 2020. Trial 1 emulated the POSITIVE design, comparing ET interruption at 18–30 months with uninterrupted ET for ≥24 months. Trial 2 compared nine ET-interruption windows (6-month intervals) with uninterrupted ET for ≥24 or ≥60 months. The primary endpoint was the 5-year risk of BC events. Analyses used a clone–censor–weight approach with marginal structural models. Results: In Trial 1 (n = 10,835), ET interruption at 18–30 months was associated with a 5-year BC event risk of 17.2%, compared with 16.0% for uninterrupted ET ≥24 months (risk difference, 1.2 percentage points; 95% CI, −0.7 to 3.1). Risk varied by baseline recurrence risk: interruption had minimal impact in low- or intermediate-risk women (risk difference, −0.6 percentage points; 95% CI, −2.7 to 1.6) but increased risk in high-risk women (risk difference, 5.8 percentage points; 95% CI, 1.8 to 10.0). In Trial 2 (n = 22,916), earlier ET interruption was associated with higher 5-year BC risk, which decreased with longer prior ET duration. Compared with uninterrupted ET ≥24 months, interruption at 6–12 months increased risk by 8.3 percentage points, whereas interruption at 24–30 months increased risk by 2.7 percentage points. Low- or intermediate-risk women showed comparable risk when interruption occurred at 24–30 months, whereas high-risk women required ≥36–42 months of ET to achieve similar safety. Among pregnancy-seeking women, 64% conceived, and 47% resumed ET. Conclusions: The oncologic impact of temporary ET interruption depends on baseline recurrence risk and prior ET duration. Interruption after 24 months appears safe for low- or intermediate-risk women, whereas high-risk patients may benefit from delaying interruption to at least 36 months. These findings support a risk-adapted approach to fertility counseling.

Importance: Data on fertility after breast cancer (BC) relative to the general population are lacking. Objective: To compare the time-to-pregnancy between women with and without prior BC seeking to become pregnant. Design: Prospective exposed-unexposed cohort study. Women were included from March 13, 2018 to June 27, 2019. Data were collected every six months via online questionnaires for up to three years. Setting: Participants were recruited through the French collaborative network for cancer research Seintinelles*. Participants: Exposed women (cases) were women aged 18-43 years with a history of localized BC who had completed treatment, without relapse. Unexposed women (controls) were women of the same age group with no history of BC. Exposure(s): The exposure of interest was a prior history of BC. Main Outcome(s) and Measure(s): The primary endpoint was time-to-pregnancy. The hypothesis tested was formulated before data collection. Secondary endpoints included the use of ART, including the use of cryopreserved material, factors associated with time-to-pregnancy, and pregnancy and neonatal outcomes. Statistical analysis was based on Kaplan-Meier survival analysis and multivariate Cox proportional-hazards models with adjustment for confounding factors by inverse probability of treatment weighting (IPTW). Results: We enrolled 4351 women in this study. Follow-up data were available for 642 women (76 cases, 566 controls) who sought to become pregnant during the study period. Median time-to-pregnancy was 5 months (95% CI: 3 months to 7 months) for cases and 3 months (95% CI: 2 months to 5 months) for adjusted controls, with no significant difference between the groups (p=0.34). Cases were more likely to resort to the use of ART than controls (RR=13.9, 95% CI [2.2- 154.6]), but time-to-pregnancy was similar in cases and controls, with and without ART use. Time-to-pregnancy was influenced by factors such as age, parity, menstrual cycle regularity, BMI, and ART, but not by prior BC. Pregnancy and neonatal outcomes did not differ significantly between cases and controls. Conclusions and Relevance: Time-to-pregnancy, in women seeking to become pregnant, was similar for women with and without a history of BC, raising hopes for women with BC wishing to have children. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Seintinelles scientific board approved the FEERIC project on December 7, 2015, and the Sud Ouest Outre Mer II ethics committee approved the project on October 5, 2017 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

ABSTRACT Background Vinorelbine is commonly used to treat metastatic breast cancer (mBC), while thiotepa is known for its ability to cross the blood–brain barrier. Methods Our retrospective study aimed to compare the efficacy and safety of vinorelbine with or without thiotepa in patients with HER2‐negative mBC. We used propensity score inverse probability of treatment weighting to ensure comparability between groups. Results Vinorelbine‐thiotepa was not significantly associated with improved median progression‐free survival (PFS) (4.9 vs. 3.0 months, p = 0.138) or median overall survival (OS) (11.8 vs. 11.9 months, p = 0.961) compared to vinorelbine. However, in the central nervous system (CNS) metastasis subgroup, vinorelbine‐thiotepa was associated with a longer median PFS (4.9 vs. 2.1 months, p = 0.013) and CNS‐PFS (6.12 vs. 2.20 months, p = 0.007). The combination was also associated with a higher rate of grade ≥ 3 adverse events (54.3% vs. 37.9%, p = 0.021). Conclusion While no overall benefit in PFS or OS was found, vinorelbine‐thiotepa may be associated with improved PFS in mBC patients with CNS metastasis.

Background:Data on fertility after breast cancer (BC) relative to the general population are lacking. This study aimed to compare the time-to-pregnancy between women with and without prior BC seeking to become pregnant. Methods:We conducted a prospective exposed-unexposed cohort study between March 13, 2018 and June 27, 2019, recruiting participants via the collaborative network Seintinelles. Women aged 18-43 years with a history of localized BC without relapse (exposed) were compared to women without BC (unexposed). Follow-up data were collected every six months over three years. The primary endpoint, time-to-pregnancy, was analyzed using Kaplan-Meier survival analysis with inverse probability weighting. Censoring was performed if women stopped trying to conceive for personal reasons, were lost to follow-up before conception, or completed the study without achieving pregnancy or using assisted reproductive technologies (ART). Findings:Among 4351 women enrolled, 642 sought pregnancy during the study period (76 exposed, 566 unexposed). Among them, 50 exposed (65.8%) and 402 weighted unexposed women (weighted percentage 71.0%) became pregnant at least once. Median time-to-pregnancy was 5.0 months, 95% CI [3.0-7.0] for exposed and 3.0 months, 95% CI [2.0-5.0] for unexposed women (difference in median time-to-pregnancy: 2.0 months, 95% CI [-2.5; 5]). Two years after starting to seek pregnancy, 74.9% of weighted unexposed women and 74.1% of exposed women obtained a pregnancy. Overall, 15 exposed women (19.8%) used either ART methods (n = 7, 9.2%) or cryopreserved material (n = 8, 10.5%) and 25 unexposed women (4.4%) used ART.The median time-to-pregnancy was 3.0 months for both exposed and unexposed women (95% CI [2.0; 5.0] and [2.0; 4.0] respectively) (difference in median time-to-pregnancy: -0.0 months [-2.0; 3.0]) in women who sought pregnancy spontaneously, and 14.0 months for exposed (95% CI [6.0-27.0]) and 17.6 months for unexposed women (95% CI [17.6-30.0]) in women seeking pregnancy with ART. Interpretation:In this study from a French collaborative research network, we found no strong evidence of a largely reduced time-to-pregnancy in exposed women seeking to become pregnant compared with unexposed women. Further research on fertility outcomes in the broader population of BC survivors is warranted. Funding:The FEERIC study was funded by Institut National du Cancer (InCA), InCA-SHS, grant no. 2016-124, and is part of the Young Breast Cancer Project, funded by Monoprix.

Introduction: Breast cancer (BC) is the most prevalent cancer among women, and increasing attention is being paid to the side effects of treatments, including the potential impact on fertility. Concerns about pregnancy-induced recurrence have existed for decades, but recent data suggest that pregnancy after BC is safe. Additionally, there is a growing interest in understanding the fertility potential and pregnancy outcomes in BC survivors. However, data on fertility rates post-BC compared to the general population remain sparse. Objectives: The FEERIC study aims to compare the time-to-pregnancy between women with and without previous BC who initiate pregnancy attempts over a three-year follow-up period. Materials and Methods: The FEERIC (FErtility, ContracEption After Breast Cancer) study is a prospective case-control study involving women aged 18-43 years, with localized, relapse-free BC, and completed treatment. Controls were women of the same age group without BC. Data were collected via online questionnaires over three years. Participants were recruited through Seintinelles, a French social network for cancer research. The primary endpoint was time-to-pregnancy, with secondary endpoints including factors associated with time-to-pregnancy, use of ART, and pregnancy outcomes. Statistical analysis involved Kaplan-Meier survival analysis and multivariate Cox Proportional-Hazards models, adjusted for confounding factors using Inverse Probability of Treatment Weighting (IPTW). Results: From December 2018 to June 2019, 4351 women were enrolled, and a total 642 women (76 cases, 566 controls) initiated pregnancy attempts and had follow-up data available. Median time-to-pregnancy was 5 months (IQR: 2.0-7.0) for cases and 3 months (IQR: 2.0-6.0) for controls, with no significant difference between the groups (p=0.34). Most women (61 cases (80.3%) and 541 controls (95.5%)) attempted to conceive through unprotected intercourses only. A total of 7 cases (9.2%) and 25 controls (4.5%) used ART methods. In cases, only 8 women (10.5%) reused cryopreserved materials during their attempts. Most pregnancies occurred spontaneously: among these 50 cases and 402 controls who achieved pregnancy, 42 cases (84.0%) and 382 controls (95.0%) conceived after unprotected intercourses only, while 8 cases (16.0%) and 20 controls (5.0%) conceived after ART methods. After univariable and multivariable analyses, age at pregnancy attempt, previous children at study inclusion, menstrual cycle regularity, BMI, and ART use were independent predictors of time-to-pregnancy, while the case or control status was not. Conclusions: The probability of pregnancy for women attempting conception post-BC treatment is comparable to that of the general population. Future research should explore long-term reproductive health and the psychosocial impacts of fertility post-BC treatment to guide supportive care practices. Citation Format: Anne-Sophie Hamy, Agathe Chabassier, Clara Sebbag, Clémentine Garin, Christine Rousset-Jablonski, Isabelle Ray Coquard, Laura Sablone, Lauren Darrigues, Elise Dumas, Angélique Bobrie, William Jacquot, Marc Espié, Sylvie Giacchetti, Floriane Jochum, Aullène Toussaint, Geneviève Plu-Bureau, Lorraine Maitrot-Mantelet, Anne Gompel, Paul Gougis, Raphaëlle Bas, Christine Decanter, Bernard Asselain, Lili Sohn, Guillemette Jacob, Florence Coussy, Fabien Reyal. Comparison of Time-to-Pregnancy in Young Breast Cancer Survivors versus the general population: a Prospective Case-Control Study (FEERIC) from a collaborative research network [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-04-13.

This perspective underscores the evolution and significance of neoadjuvant therapy in breast cancer, tracing its history and efficacy in improving outcomes. It delves into the correlation between achieving complete response and long-term survival, emphasizing the predictive value of treatment response estimation. Neoadjuvant chemotherapy in HER2-positive early breast cancer, particularly with taxanes and anti-HER2 therapies, emerges as a cornerstone, offering enhanced breast conservation rates and prognostic insights. The focus on individualized care, tailored to treatment response, underscores the need for adaptive strategies. Additionally, the article discusses the ongoing debate surrounding anthracyclines' role and the benefits of dual HER2 blockade. Ultimately, advocating for a personalized approach, guided by treatment response assessment, ensures optimal outcomes in HER2-positive breast cancer management.

Navigating the complex landscape of breast cancer treatment involves distinct strategies for luminal and triple-negative subtypes. While neoadjuvant chemotherapy historically dominates the approach for aggressive triple-negative tumors, recent evidence highlights the transformative impact of immunotherapy, alongside chemotherapy, in reshaping treatment paradigms. In luminal cancers, endocrine therapy, notably aromatase inhibitors, demonstrates promising outcomes in postmenopausal patients with low-grade luminal A tumors. However, integrating targeted therapies like CDK4/6 inhibitors in neoadjuvant setting remains inconclusive. Identifying predictive factors for treatment response, especially in luminal tumors, poses a challenge, emphasizing the necessity for ongoing research. A multidisciplinary approach, tailored to individual patient profiles, is crucial for maximizing efficacy while minimizing toxicity. As we strive to optimize breast cancer management, a comprehensive understanding of the distinct characteristics and treatment implications of luminal and triple-negative subtypes, including the transformative role of immunotherapy, is essential for informed decision-making and personalized care.

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.

Abstract Background: Triple-negative breast cancers (TNBC) exhibit major responses to dose-dense, dose-intense (DD-DI) neoadjuvant chemotherapy (NAC) (1). Although chronomodulated chemotherapy has shown efficacy and reducing toxicity in other cancers, there are no data in breast cancers (2). We report here a series of patients with TNBC treated with DD-DI NAC and analyzed the association between chemotherapy time infusion and pathological complete response rate (pCR) and residual tumor burden (RCB). Patients and Methods: Patients with non-metastatic TNBC treated at breast cancer disease center, St Louis hospital (Paris, France), with neoadjuvant DD-DI cyclophosphamide (1200 mg/m2 d1) – epirubicin (75 mg/m2 d1) q2w (SIM regimen) followed by 12 injections of paclitaxel (80 mg/m2) qw were included. Starting time of each chemotherapy infusion were systematically recorded. Primary endpoint was pCR defined as no residual invasive tumor in breast and in lymph nodes. Patients were dichotomized into “morning” and “afternoon” infusion groups, independently for “SIM” and “paclitaxel” regimens. Two timing cut-offs were defined according to: 1) median time of all infusions 2) cut-off maximizing morning/afternoon differences of RCB. Statistical differences between the two patient groups were assessed for metabolic response at 2 courses at Pet scan (breast delta SUVmax), RCB class (0-1 vs 2-3), pCR, dose reduction rate and 24-months event-free survival (24-months EFS). Results: Between January 2018 and January 2022, 93 patients were included. Median age was 51 (28-74). Majority of SIM administrations occurred between 12:00 and 15:00 and Paclitaxel administrations between 11:20 and 14:30. Median follow-up was 32.4 months. Main characteristics between “morning group” or “afternoon” groups in the SIM or paclitaxel were similar. pCR was obtained in 48.9% of the whole population. Regardless of cut-offs defined, no difference in pCR rate was observed. Similarly, no differences were observed between morning and afternoon groups in terms of either metabolic response, dose reduction rate or 24-months EFS (table 1). Conclusion: Time of DD-DI NAC infusion is not associated with differences in pCR rate nor in RCB, toxicity and EFS in patients with early TNBC. As immunotherapy combined with NAC is a new standard in TNBC, the impact of immunotherapy infusion time combined with NAC is under evaluation. References: 1. Giacchetti S et al. Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen. Br J Cancer. 2014;110(6):1413-9. 2. Printezi MI et al. Toxicity and efficacy of chronomodulated chemotherapy: a systematic review. The Lancet Oncology. mars 2022;23(3) Table 1: Differences between “morning” and “afternoon” groups in SIM and paclitaxel regimen, with two timing infusion cut-offs. “SIM morning” Group “SIM afternoon” Group p-value “SIM morning” Group “SIM afternoon” Group p-value “Paclitaxel morning” Group “Paclitaxel afternoon” Group p-value “Paclitaxel morning” Group “Paclitaxel afternoon” Group p-value Median time infusion RCB differences Median time infusion RCB differences Chosen cut-off time 13:38 12:09 12:55 13:33 Number of patients n=48 n=45 n=22 n=71 n=47 n=46 n=56 n=37 pCR rate (%) 48.9 48.9 p=1.000 45.5 50.0 p=0.899 46.8 51.1 p=0.838 50.0 47.2 p=0.963 RCB class 0-1 vs 2-3 63.8 vs 36.2 62.2 vs 37.8 p=0.822 59.1 vs 40.9 64.3 vs 35.8 p=0.870 61.7 vs 38.3 64.4 vs 35.5 p=0.748 66.1 vs 33.9 58.3 vs 41.7 p=0.531 Metabolic response (%) -54.9 -54.3 p = 0.919 -54.7 -54.6 p = 0.981 -53.9 -55.3 p = 0.809 -52.8 -57.5 p= 0.415 Dose reduction rate (%) 20.8 37.8 p=0.116 27.3 29.6 p=1.000 25.5 32.6 p=0.601 25.0 35.1 p=0.412 24-months EFS (%) 92.9 87.7 p=0.76 97.9 82.6 p=0.34 84.5 92.1 p=0.15 94.2 84.4 p=0.53 Citation Format: Clementine Bouchez, Simona Catozzi, Caroline Cuvier, Laetitia Someil, Cedric De Bazelaire, Catherine Miquel, Nozha Mhamdi, Luis Teixeira, Marc Espie, Emilie Moati, Leonor Droin, Annabelle Ballesta, Sylvie Giacchetti. Effect of neoadjuvant dose-dense dose-intense chemotherapy timing infusion on complete histological response rate among patients with triple negative breast cancer (SIMCLOCK) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-06.

Background: More than half of Breast Cancer (BC) patients take chronically used non-cancer treatments (denoted as comedications) at BC diagnosis. Epidemiological evidence has reported that several non-cancer treatments may modify BC risk, BC recurrence, and overall survival (OS). The ADRENALINE project (Atlas for DRug and brEast caNcer survivAL INtEraction) analyses the impact of the use of each commonly prescribed non-cancer treatment at BC diagnosis on OS using the French social security system data on a comprehensive cohort of French BC patients. Methods: We identified all women diagnosed with an incident BC treated with surgery in France from 2011 to 2017 and affiliated to the general health insurance scheme. Women with concomitant cancer or metastases at diagnosis were discarded from the analyses. Comedication intake was defined as the delivery in pharmacy of at least 3 months of full treatment (e.g. 90 pills) the 6 months preceding BC diagnosis. A Cox proportional hazard model was used to estimate the hazard ratio (HR) for each molecule. The model was adjusted on more than 100 confounding variables: social factors, comorbidities and other comedications by Inverse Probability of Treatment Weighting (IPTW). We assumed that the adjustment was sufficient to control for confounding if the standardized mean difference of each confounder after adjustment did not exceed 0.1. Molecules which did not pass the adjustment quality test were discarded. Results: Overall, 235,368 patients were included in the study. Among 219 selected drugs, 91 passed the adjustment quality test. The full set of results is available on a web application (https://adrenaline.curie.fr). Several drugs or drug classes were associated with an improved survival: statins (e.g. rosuvastatin, HR=0.65, p< 0.001); proton-pump inhibitors (HR=0.93; p=0.002); or beta-blocking agents (atenolol, HR=0.78, p=0.003). Conversely, anti-anemic preparations (folic acid and ferrous sulfate) had a significant deleterious effect (HR = 1.63; p< 0.001). Drugs from the same therapeutic class, could have different effects: within benzodiazepines, bromazepam was protective (HR = 0.91; p = 0.038) while oxazepam was deleterious (HR = 1.37; p < 0.001). Conclusion: ADRENALINE reports the impact on BC survival of 219 widely prescribed drugs. It can be used to identify molecules with a potential protective or deleterious effect relative to BC. Some of them are currently under mechanistical investigation within a drug screening program. This atlas highlights candidates to drug-repurposing trials or pharmacovigilance warnings, and will be extended to cancers of other localizations in a near future. Citation Format: Elise Dumas, Beatriz Grandal, Paul Gougis, Sophie Houzard, Aurélien Latouche, Aullène Toussaint, Samar Alsafadi, Judith Abecassis, Lidia Delrieu, Thierry Dubois, Nadir Sella, Marc Espie, Bernard Asselain, Annabelle Ballesta, Benjamin Marande, Eric Daoud, Enora Laas, Amyn Kassara, Floriane Jochum, Elaine Del Nery, Elodie Anthony, Christine Le Bihan-Benjamin, Philippe-Jean Bousquet, Chloé-Agathe Azencott, Fabien Reyal, Anne-Sophie Hamy. Comedications at Breast Cancer diagnosis impact overall survival: results from the ADRENALINE (Atlas for DRug and brEast caNcer survivAL INtEraction) study (n=235,368) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-06.

Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10％ of cancers.We assume that most cancers are the result of germline mutations of low to mod-erate penetrance,combined with acquired mutations due to external carcinogenic stressors.With their accumulation over time,aging is associated with an increased risk of mul-tiple cancer development in a given individual.For decades,germline genetics have been based on familial linkage studies enabling most high-penetrance genes to be identified.More recently,population-wide studies have led to the identifi-cation of considerable numbers of polymorphisms associated with cancer risk.However,most of them are of unknown functional value,thus limiting their translational application.

INTRODUCTION:The subcutaneous (H-SC) formulation of trastuzumab was demonstrated to be as effective and safe as intravenous (H-IV) and highly preferred by patients in early breast cancer. The present randomized MetaspHER trial (NCT01810393) has been the first study assessing patient's preference in metastatic setting and we report the final analysis with long term follow-up. METHODS:Patients with HER2-positive metastatic breast cancer who completed a first line chemotherapy with trastuzumab and achieved a long terms response lasting more than 3 years were randomized to receive 3 cycles of 600 mg fixed-dose H-SC, followed by 3 cycles of standard H-IV, or the reverse sequence. The primary endpoint was overall preference for H-SC or H-IV at cycle 6 and was previously reported. Secondary endpoints included safety over 1 year of treatment and with 4 additional years follow up. Overall survival (OS) and progression free survival (PFS) were assessed in this final analysis. RESULTS:A total of 113 patients were randomized and treated and the median follow-up duration was 45.4 months (range: 0.8-48.8). After the cross over period all patients excepted 2 pursued the H-SC. During the 18 cycles overall treatment period, at least 1 adverse event (AE), 1 AE of grade ≥3, and 1 serious adverse events (SAE) were respectively reported among 104 patients (92.0%), 23 patients (20.4%), and 16 patients (14.2%), respectively. Also, 10 patients (8.9%) experienced at least 1 cardiac event, including 4 patients (3.5%) with ejection fraction decreased. Beyond cycle 18 no significant additional safety concern emerged. PFS and OS rates at months 42 were 74.8% (64.7%-82.4%) and 94.9% (88.2%-97.9%), respectively. No factor appeared related to the survival outcome excepted the complete response status at baseline. CONCLUSION:The safety was consistent with the known H-IV and H-SC profiles without any safety concern raised over a prolonged exposure to H-SC.

Introduction. - Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. Methods. - Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. Results. - One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P < 0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). Conclusion. - Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision. (C) 2021 Elsevier Masson SAS. All rights reserved.

Background: Patients with triple-negative breast cancers (TNBC) have a poor prognosis unless a pathological complete response (pCR) is achieved after neoadjuvant chemotherapy (NAC). Few studies have analyzed changes in TIL levels following dose-dense dose-intense (dd-di) NAC. Patients and methods: From 2009 to 2018, 117 patients with TNBC received dd-di NAC at our institution. We aimed to identify factors associated with pre- and post-NAC TIL levels, and oncological outcomes relapse-free survival (RFS), and overall survival (OS). Results: Median pre-NAC and post-NAC TIL levels were 15% and 3%, respectively. Change in TIL levels with treatment was significantly correlated with metabolic response (SUV) and pCR. High post-NAC TIL levels were associated with a weak metabolic response after two cycles of NAC, with the presence of residual disease and nodal involvement at NAC completion. In multivariate analyses, high post-NAC TIL levels independently predicted poor RFS and poor OS (HR = 1.4 per 10% increment, 95%CI (1.1; 1.9) p = 0.014 and HR = 1.8 per 10% increment 95%CI (1.3–2.3), p < 0.0001, respectively). Conclusion: Our results suggest that TNBC patients with TIL enrichment after NAC are at higher risk of relapse. These patients are potential candidates for adjuvant treatment, such as immunotherapy, in clinical trials.