BackgroundSexual concerns are a major unaddressed need among survivors of breast cancer (BC) with significant negative effects on quality of life. We longitudinally analyzed sexual health over time, using patient-reported outcomes.MethodsPatients with stage I-III BC prospectively included from the CANcer TOxicity cohort (CANTO) provided data at diagnosis, then 1, 2, and 4 years afterward. Sexual concerns outcomes included poor body image (score ≤91/100), poor sexual functioning (≤16/100), poor sexual enjoyment (≤66/100), and sexual inactivity (EORTC QLQ-B23). Multivariate generalized estimating equation models assessed associations with sexual concerns after diagnosis, adjusting for age, sociodemographic, tumor, treatment, and clinical characteristics.ResultsNearly 78.1% among 7895 patients reported at least one sexual concern between diagnosis and 4 years’ follow-up. Over time, the proportion of patients reporting sexual concerns either increased or remained constant with diagnosis. Less than half (46%, range 11.4-57) of the patients with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations (range 11.4-57.4). Factors consistently associated with sexual concerns up to 4 years after diagnosis included already reporting the same concern at diagnosis [odds ratio (OR)poor body image 3.48 [95% confidence interval (CI) 3.11-3.89]; ORsexual inactivity 9.94 (95% CI 8.84-11.18), ORpoor sexual function 9.75 (95% CI 8.67-10.95), ORpoor sexual enjoyment 3.96 (95% CI 3.34-4.69)], endocrine therapy use [ORpoor body image 1.15 (95% CI 1.01-1.31); ORsexual inactivity 1.19 (95% CI 1.02-1.39), ORpoor sexual function 1.17 (95% CI 1.01-1.37), ORpoor sexual enjoyment 1.23 (95% CI 1.00-1.53)], and depression [ORpoor body image 2.00 (95% CI 1.72-2.34); ORsexual inactivity 1.66 (95% CI 1.40-1.97), ORpoor sexual function 1.69 (95% CI 1.43-2.00), ORpoor sexual enjoyment 1.94 (95% CI 1.50-2.51)]. Outcome-specific associations were also identified.ConclusionsSexual concerns seem frequent, persistent, and insufficiently addressed. Pretreatment concerns, endocrine therapy, and emotional distress are commonly associated factors. A proactive evaluation of sexual health across the care continuum is needed, to promptly identify patients suitable for multidisciplinary counseling, referral, and supportive interventions.

Background We aimed to generate a model of cancer-related fatigue (CRF) of clinical importance two years after diagnosis of breast cancer building on clinical and behavioral factors and integrating pre-treatment markers of systemic inflammation. Methods Women with stage I-III HR+/HER2- breast cancer were included from the multimodal, prospective CANTO cohort (NCT01993498). The primary outcome was global CRF of clinical importance (EORTC QLQ-C30≥40/100) two years after diagnosis (year-2). Secondary outcomes included physical, emotional, and cognitive CRF (EORTC QLQ-FA12). All pre-treatment candidate variables were assessed at diagnosis, including inflammatory markers (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon gamma, IL-1 receptor antagonist, TNF-α, and C-reactive protein), and were tested in multivariable logistic regression models implementing multiple imputation and validation by 100-fold bootstrap resampling. Results Among 1208 patients, 415 (34.4%) reported global CRF of clinical importance at year-2. High pre-treatment levels of IL-6 (Quartile 4 vs.1) were associated with global CRF at year-2 (adjusted Odds Ratio [aOR]: 2.06 [95% Confidence Interval 1.40-3.03]; p=0.0002; AUC=0.74). Patients with high pre-treatment IL-6 had unhealthier behaviors, including being frequently either overweight or obese (62.4%; mean BMI 28.0 [SD 6.3] Kg/m2) and physically inactive (53.5% did not meet WHO recommendations). Clinical and behavioral associations with CRF at year-2 included pre-treatment CRF (aOR vs no: 3.99 [2.81-5.66]), younger age (per 1-year decrement: 1.02 [1.01-1.03]), current smoking (vs never: 1.81 [1.26-2.58]), and worse insomnia or pain (per 10-unit increment: 1.08 [1.04-1.13], and 1.12 [1.04-1.21], respectively). Secondary analyses indicated additional associations of IL-2 (aOR per log-unit increment:1.32 [CI 1.03-1.70]) and IL-10 (0.73 [0.57-0.93]) with global CRF and of C-reactive protein (1.42 [1.13-1.78]) with cognitive CRF at year-2. Emotional distress was consistently associated with physical, emotional, and cognitive CRF. Conclusions This study proposes a bio-behavioral framework linking pre-treatment systemic inflammation with CRF of clinical importance two years later among a large prospective sample of survivors of breast cancer.

Background: Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (HR+ BC) with unfavorable features have an increased risk of relapse and are currently candidate for additional treatment strategies. We evaluated the real-world clinicopathological characteristics, treatment patterns and survival outcomes of these patients within the CANcer TOxicities study (CANTO, NCT01993498). Patients and methods: This is a retrospective analysis of the prospective data collected within CANTO between 2012 and 2022. Patients with high-risk HR+ BC were defined either by the identification of at least four positive axillary lymph nodes (LNs) or one to three positive axillary LNs with a tumor size >5 cm or histologic grade 3 (cohort 1). The definition 1-3 positive LNs with Ki-67 >20% was also considered (cohort 2). The KaplaneMeier method was used for survival analysis. Results: Patients with high-risk HR+ BC represented 15.0%-19.6% of HR+ BC (cohort 1 and 2, respectively) in the CANTO cohort. Of the 1266 patients in cohort 1, 617 patients (49.0%) had >4 LNs, 327 (26.0%) had tumor >5 cm and 727 (57.6%) had grade III tumors. 79.9% had a favorable Charlson comorbidity score and 88.1% stage II/IIIA. Patients with >10 LNs accounted for 11.8%. (Neo)adjuvant chemotherapy was administered in 94.2%. Endocrine therapy was prescribed in 97.3%, mostly with aromatase inhibitors and discontinued in 34.3%, mainly for adverse events. Patients enrolled at least 6 years before data extraction had a 5-year invasive disease-free survival and 5year distant relapse-free survival of 79.9% [95% confidence interval (CI) 77.2% to 82.4%] and 83.5% (95% CI 80.9% to 85.7%), respectively. Conclusions: This real-world study confirms that patients with HR+ BC and unfavorable clinicopathological features are at risk of relapse early in their adjuvant treatment trajectory, despite (neo)adjuvant chemotherapy. It is imperative to implement innovative treatment approaches for high-risk patients, ideally adding them as early as possible to the adjuvant treatment.

Patients with HR+ BC with unfavourable features have an increases risk of relapse. Our aim was to describe clinico-pathological characteristics, adjuvant treatments and survival outcomes of patients with high-risk HR+ BC, using RW data reported in the Cancer Toxicities (CANTO) prospective observational study (NCT01993498). Baseline features and treatment patterns were collected from CANTO cohort for all women with HR+ BC at high-risk of relapse defined either (1) ≥ 4 positive pathologic axillary lymph nodes (LN) or (2) 1 to 3 positive axillary LN with a tumor size ≥ 5 cm or grade III. HR+ BC not respecting these criteria were classified as non-high risk. Invasive disease free survival (IDFS) and distant metastasis free survival (DMFS) were calculated. Bilateral BC were excluded. Among HR+ BC patients, 1266 (15.0%) were at high-risk of relapse. The median age at diagnosis was 54.3 yrs (range 22-87), 589 (47.2%) were premenopausal, and 79.9% had a favorable Charlson comorbidity score. Germline BRCA1 or BRCA2 mutations were reported in 3.5% and 8.0%, respectively. 617 patients (49.0%) had ≥ 4 positive LN, 327 (26.0%) had tumor size ≥ 5 cm and 727 (57.6%) grade III tumors. 1192 (94.2%) received (neo)adjuvant chemotherapy (1155 with anthracyclines-based regimens) and 97.3% had endocrine therapy (56.1% with aromatase inhibitors). Notably, 33.8% discontinued endocrine therapy (ET) for adverse events. The table reports the survival rates.Table: 132PAfter a median follow up of 6.2 yrsHigh-risk HR+ BCNon-high risk HR+BC5y-IDFS80.9%93.6%10y-IDFS67.6%78.1%5y-DMFS84.4%96.8%10y-DMFS72.2%85.9% Open table in a new tab This RW data showed that patients with high-risk HR+ BC have a considerable risk of relapse and lower event free survival, which highlights the potential benefit of adding new therapies in the adjuvant setting. Rate of treatment discontinuations due to ET-related adverse events underscores the importance of a support system to manage adverse events adequately.

Purpose:Radiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limited further improvement. The aim of our study was to assess the incidence of RILI in current practice and to determine clinical and dosimetric risk factors associated with RILI occurrence. Material and methods:Data from 3 out of the 10 top recruiting centers in CANTO-RT, a subset of the CANTO prospective longitudinal cohort (NCT01993498), were retrospectively analyzed for RILI occurrence. This cohort, which recruited invasive cT0-3 cN0-3 M0 breast cancer patients from 2012 to 2018, prospectively recorded the occurrence of adverse events by questionnaires and medical visits at the end of, and up to 60 months after treatment. RILI adverse events were defined in all patients by the association of clinical symptoms and compatible medical imaging. Results:RILI was found in 38/1565 (2.4%) patients. Grade II RILI represented 15/38 events (39%) and grade III or IV 2/38 events (6%). There were no grade V events. The most frequently used technique for treatment was 3D conformational RT (96%). In univariable analyses, we confirmed the association of RILI occurrence with pulmonary medical history, absence of cardiovascular disease medical history, high pT and pN, chemotherapy use, nodal RT. All dosimetric parameters were highly correlated and had close predictive value. In the multivariable analysis adjusted for chemotherapy use and nodal involvement, pulmonary medical history (OR=3.05, p<0.01) and high V30 Gy (OR=1.06, p=0.04) remained statistically significant risk factors for RILI occurrence. V30 Gy >15% was significantly associated with RILI occurrence in a multivariable analysis (OR=3.07, p=0.03). Conclusion:Our study confirms the pulmonary safety of breast 3D RT in CANTO-RT. Further analyses with modern radiation therapy techniques such as IMRT are needed. Our results argue in favor of a dose constraint to the ipsilateral lung using V30 Gy not exceeding 15%, especially in patients presenting pulmonary medical history. Pulmonary disease records should be taken into account for RT planning.

Long term treatment related toxicity is a major issue for breast cancer patients in the adjuvant setting. Predicting toxicities may allow us to adapt the treatment strategy. We assessed whether the metabolomic profile of patients may predict long-term toxicities. High-resolution untargeted metabolomics was performed at baseline for 857 ER-positive, HER2- breast cancer patients from the CANTO prospective cohort. Four metabolomic profiles per patient were produced: (i) shared and annotated metabolites (n=224), (ii) annotated but not always common metabolites (n=456), (iii) annotated but not always shared metabolites (n=766) and (iv) all metabolites (n=1693, FullMet). Samples were split into a discovery and validation set. We benchmarked algorithms adapted for high dimensional analysis (LASSO, Adaptive LASSO, machine learning, and deep learning) in order to select best models for prediction. 30.0% of patients were >65 years old, 24.4% <50 years old, 20.4% had BMI>30, 12.7% had previous history of neurological disorders, 6.1% had diabetes. 69.6% presented with pT1, 25.7% with pT2 and 3.4% with pT3; 11.1% had lymph node involvement. Among all benchmarked, adaptive LASSO was the most interesting statistical method with limited optimism bias. It also allows the selection of a subset of metabolites of particular interest. The addition of rare metabolites as well as non-annotated metabolites significantly increase the predictive power of models. Metabolic toxicity prediction mainly relied on endogenous metabolites while neurological toxicities were partly predicted using exogenous/environmental metabolites. In the validation set, compared to clinical data alone (AUC 0.50-0.54), addition of metabolomics data shows moderate (AUC = 0.55-0.60) but significant (p<0.05 adjusted for multiple comparison) predictive ability for neurological and metabolic toxicities. Breast cancer patient metabolomic profile at baseline improves toxicity prediction after adjuvant chemotherapy, similar to what is reported for genomic fingerprints. Untargeted metabolomics allows the achievement of higher performance by taking into account environmental exposure, metabolites linked to microbiota as well as rare and uncommon metabolites.

ET is the mainstay treatment (tx) for HR+ eBC but they have persistent side effects that negatively affect QoL, leading to early tx discontinuation and compromising outcomes. We describe the incidence of ET toxicity and its QoL impact in CANTO. CANTO (NCT01993498) is a prospective, longitudinal cohort study enrolling pts with invasive (cT0-cT3, cN0-3, no metastases) BC from 26 French cancer centres. Pts with HR+, HER2– eBC treated with adj ET were followed for the first 3 years (yrs) after eBC diagnosis. Pt demographics, clinical data, adherence, symptoms and QoL were collected. Questionnaires were administered at baseline (BL), 3–6 months (mo; M0) after primary surgery, chemotherapy or radiotherapy completion (whichever came last), and 12 mo, 36 mo and 60 mo after M0. Descriptive analyses were conducted for frequency of symptoms and mean/median QoL questionnaires summary scores. Of the 5564 pts who met the inclusion criteria (median age: 57 yrs), 63% were post-menopausal and 52% had stage I eBC at diagnosis. The table shows QoL and toxicity data. Global and functioning QoL remained high at BL and during tx. BC-specific symptoms persisted during tx. Pain was the most prevalent toxicity in the first 3 yrs; prevalence of muscular and joint pain increased over time. Mean intensity of global, muscular and joint pain all remained high over the course of ET (median intensity: ∼6 [0–10 scale]). ET adherence was 81–93% over time; in the first 3 yrs, 23% switched ET and 7% discontinued adj ET; toxicity was the main reason cited.Table: 346PBLM012 mo36 moMean EORTC QLQ-C3083807980Global health status68686666Physical functioning91858485Role functioning87808283Emotional functioning65727071Cognitive functioning82797778Social functioning91838586Insomnia43414342Fatigue28363534Pain15283029Mean EORTC QLQ-BR23Body image88757779Future perspective49566164Sexual functioning26262624Breast symptoms13262016Systemic therapy side effects11201918Arm symptoms9211917Toxicity, %Global and back pain-717472Muscular and back-323638Joint and back-596870 Open table in a new tab . While global and functional QoL remained high in the first 3 yrs after eBC diagnosis, BC-specific symptoms slightly increased/persisted during ET. This study confirmed long-term toxicity of ET, particularly pain. Better management of symptoms and supportive interventional strategies are needed to further improve QoL in eBC.

Les données de résultats cliniques en vie réelle avec le pembrolizumab en monothérapie chez des patients avec cancer bronchique non à petites cellules (CBNPC) avancé précédemment traités restent limitées. Notre objectif était d’estimer la survie globale (SG) et la survie sans progression en vie réelle (SSPvr) en France avec le pembrolizumab en monothérapie chez des patients avec CBNPC avancé antérieurement traités par chimiothérapie, exprimant PD-L1, après l’autorisation donnée à la suite de l’étude de phase III KEYNOTE-010 (KN010), dans laquelle une SG médiane de 11,8 mois (IC 95 % : 10,4–13,1) et un taux de SG à 12 mois de 48,9 % (IC 95 % : 45,1–52,6) ont été rapportés. À l’aide de la plateforme de données ESME CBP (Epidémio-STRATEGIE médico-économique/Cancer Broncho-Pulmonaire ; NCT03848052), nous avons identifié des patients adultes avec CBNPC confirmé histologiquement, à un avancé (stade IIIB ou IV), dont la tumeur exprime PD-L1 (TPS ≥ 1 %), traités avec au moins une ligne de chimiothérapie et ayant initié pembrolizumab en monothérapie entre le 12 mai 2017 et le 31 décembre 2018. Les patients présentant des mutations tumorales d’EGFR ou d’ALK devaient avoir reçu une thérapie ciblée appropriée avant de recevoir pembrolizumab. Les patients ayant déjà reçu pembrolizumab dans un essai clinique étaient exclus. Cette analyse intermédiaire était prévue dans un plan d’analyse statistique avec une extraction des données au 31 août 2019. La SG et la SSPvr ont été estimées par la méthode de Kaplan–Meier. Trois cent quatre patients ont été inclus avec un suivi médian par patient de 5,9 mois (intervalle : 0–24). Les caractéristiques des patients et les résultats de SG/SSPvr sont présentés dans le Tableau 1. Les résultats cliniques du pembrolizumab dans les CBNPC avancés exprimant PD-L1 et antérieurement traités par chimiothérapie ont été similaires à ceux des essais cliniques, confirmant ainsi l’efficacité du pembrolizumab en vie réelle en France.

Abstract Background As survival rates among breast cancer patients improve there is an increasing need to address breast cancer survivors’ (BCS) issues, professional life being a key aspect. Return to work (RTW) of BCS has been largely studied, but studies on job maintenance and its determinants are scarce. We aim to study job maintenance after RTW and the associated factors among BCS. Methods We used data from the CANTO cohort, a French prospective cohort of BCS. We included 1643 BCS aged <57 at diagnosis (dx) who returned to work two years after dx. We excluded self-employed BCS. Using multinomial logistic models, we assessed the association between activity status one year after they return to work. (i.e. active, sick leave, or unemployed, retired or invalidity) and sociodemographic, clinical, health status and work-related factors. Results Overall, 87% of BCS were active, 10% were on sick leave and 3% were on unemployment, retirement or invalidity one year after they return to work. In the fully adjusted model being on sick leave was associated with stage III at dx (OR: 1.89, 95% CI: 1.11-3.22), being severely fatigued at the moment of returning to work (OR: 1.53, 1.04-2.27), and having workplace accommodations (OR: 1.79, 1.14-2.81). The unemployed, retired, invalidity status was negatively associated with professional life being more than or as important as one’s personal life (OR: 0.51, 0.26-0.98) and being <50 years old (OR: 0.51, 0.27-0.96), and positively associated with having a fixed-term contract (OR: 2.69, 1.39-5.18) and working for a small company (OR: 2.73, 1.24-6.02). Conclusions A non-negligible proportion of BCS are non-active one year after they return to work. While clinical factors are associated with sick leave, work related factors are associated with the unemployed, retired, and invalidity status. RTW should not be regarded as the ultimate goal and future policies should focus on ensuring people are ready to return to work and maintain their jobs. Key messages • A non-negligible proportion of breast cancer survivors are non-active one year after they return to work. • Future policies should ensure job maintenance along with return to work.

Background: Clinical trials allow development of innovative treatments and ameliorate the quality of clinical care in oncology. Data show that only a minority of patients are enrolled in clinical trials. We assessed enrolment in clinical trials and its correlates among women with early breast cancer. Methods: We included 9516 patients with stage I-III breast cancer from the multicenter, prospective CANTO study (NCT01993498), followed-up until year 4 (Y4) post-diagnosis. We assessed factors associated with enrolment using multivariable logistic regression. In exploratory, propensity score matched analyses, we used multiple linear regression to evaluate the relationship of enrolment in clinical trials with the European Organisation for Research and Treatment of Cancer Quality Of Life (QoL) questionnaire (EORTC QLQ-C30) Summary Score and described clinical outcomes (distant disease event, invasive disease event, and death by any cause) according to enrolment. Results: Overall, 1716 patients (18%) were enrolled in a clinical trial until Y4 post-diagnosis of breast cancer. Socioeconomic factors were not associated with enrolment. Centres of intermediate volume were most likely to enrol patients in clinical trials [versus low volume, odds ratio 1.45 (95% confidence interval (CI) 1.08-1.95), P= 0.0124]. Among 2118 propensity score matched patients, enrolment was associated with better QoL at Y4 (adjusted mean difference versus not enrolled 1.37, 95% CI 0.03-2.71, P =0.0458), and clinical outcomes (enrolled versus not enrolled, distant disease event 7.3% versus 10.1%, P = 0.0206; invasive disease event 8.2% versus 10.5%, P =0.0732; death by any cause 2.8% versus 3.7%, P =0.2707). Conclusions: In this large study, one in five patients enrolled on a clinical trial until Y4 after diagnosis of early breast cancer. Geographical and centre-related factors were significantly associated with enrolment in clinical trials. Inclusion in clinical trials seemed associated with improved QoL and clinical outcomes. Access to innovation for early-stage breast cancer patients should be encouraged and facilitated by overcoming organizational and geographical barriers to recruitment.

CRA is common among premenopausal women with early BC and may determine substantial impact on post-CT QOL. We examined factors associated with CRA in a modern cohort of patients receiving current standard (neo)adjuvant CT regimens (anthracycline [A]- and taxane [T]-based) and the relationship between CRA and long-term QOL. We used CANTO, a multicenter, prospective cohort of stage I–III BC (NCT01993498) to include premenopausal women aged ≤50 years at BC diagnosis, treated with CT, and not receiving adjuvant ovarian-function suppression. In the main analysis, our outcome of interest was CRA at year-1 (Y1), year-2 (Y2), and year-4 (Y4) after diagnosis. Multivariable logistic regression models assessed associations between CRA at each time-point and covariates. Among women with follow-up (FU) ≥4 years and menses status available at all time-points, multivariable linear regression models assessed the relationship between persistent CRA (defined as never resumption of menses) and QOL at Y4 (EORTC QLQ-C30/BR23), adjusting for QOL at diagnosis and all covariates. Among 1676 women, mean age at diagnosis was 42.2 years (SD 5.6). 83.1% reported CRA at Y1, 72.8% at Y2 and 66.7% at Y4, with expected variability across age groups and other patient characteristics (Table). Among 745 women with FU ≥ 4 years, 57.7% had persistent CRA, which was associated with worse sexual function (estimate vs resumption at any time -7,0 [95% CI -12,1 to -1,9]) and more long-term CT-related side effects (i.e. dry mouth, dysgeusia, hot flushes, headaches, alopecia; +3,0 [95% CI +0,1 to +6,0]).Table: 1551OFactors associated with CRAY1Y2Y4% CRAOR*% CRAOR*% CRAOR*Age 18-34 35-39 40-44 ≥4553 72 87 95- 2,0 (1,2-3,5) 6,3 (3,6-11,3) 26,5 (12,7-55,2)27 51 78 93- 3,1 (1,6-5,8) 9,6 (5,1-17,9) 39,0 (19,2-79,2)23 44 73 89- 2,0 (0,9-4,3) 7,9 (3,7-16,7) 22,5 (10,0-50,7)BMI 18,5-25 ≥25 <18,584 81 92- 0,6 (0,4-0,9) 5,2 (1,2-23,1)72 74 72- 1,0 (0,7-1,4) 1,3 (0,6-3,0)66 69 55- 1,0 (0,7-1,6) 0,6 (0,2-1,4)CT type AT A T84 64 83- 0,2 (0,1-0,5) 0,4 (0,2-0,8)73 60 76- 0,3 (0,1-0,9) 0,7 (0,3-1,4)67 65 61- 0,8 (0,2-2,5) 0,4 (0,2-0,9)Hormonotherapy No Yes73 87- 2,1 (1,4-3,2)57 77- 2,3 (1,5-3,4)59 69- 1,7 (1,1-2,8)*Adjusted by socioeconomic, comorbidities, n. children, age at menarche, smoke, alcohol; (95% CI) Open table in a new tab *Adjusted by socioeconomic, comorbidities, n. children, age at menarche, smoke, alcohol; (95% CI) Most women reported CRA, including more than half with persistent CRA. Older age, receipt of hormonotherapy, combination of AT and a lower BMI were associated with higher rates of CRA. Persistent CRA was associated with worse sexual function and long-term CT-related side effects.

Genetic mutations on breast cancer (BC) susceptibility genes such as BRCA 1 or 2, are well known risk factors for BC development. 5-10% of BC are associated with a gBRCAm, which can impact tumor characteristics and management of the associated BC. Using the French prospective ongoing CANTO cohort (NCT01993498) we conducted a retrospective analysis focusing on clinical characteristics and patterns of care of eBC by gBRCA status. Data from 9368 women diagnosed with stage I to IIIa BC from 2012 to 2017 were analysed by BRCA status. Demographics, medical and family history, disease characteristics and BC treatment were examined overall and per subgroup populations. In this cohort, 169 (1.8%) patients (pts) had a gBRCAm (92 gBRCA1m and 77 gBRCA2m), 2226 (28%) were gBRCA wild type (wt) and 6573 (70.2%) gBRCA unknown (uk). Women with gBRCAm were younger than gBRCAwt or uk (mean age 43.7 years [95% CI: 42.0–45.4] versus (vs) 53.7 [53.2 - 54.1] vs 58.2 [57.9 - 58.5] respectively) at BC diagnosis. Tumours of pts with gBRCAm were characterized by higher proportion of triple negative (TN) subtype (44% [36.7-52.2] vs 13.3% [12.1 - 14.7] vs 7.9% [7.3 - 8.6]), higher stage II/IIIa (65.1% [57.4-72.2] vs 52.0% [50.0-53.9] vs 49.0% [47.8-50.2], higher histological grade 3 (67.9% [60.2-74.8] vs 32.9% [31.1-34.8] vs 25.5% [24.5-26.6]) when compared to gBRCAwt and uk pts. gBRCAm pts were more likely to undergo radical mastectomy (46.2% [35.0-50.4] vs 24.9% [23.3-26.6] vs 22.5% [21.5-23.6] ) with more axillary dissection (51.5% [43.7-59.2] vs 40.5% [38.4-42.2] vs 34.5% [33.4-35.7]) compared to gBRCAwt and uk pts. gBRCAm pts were also more likely to receive chemotherapy 92.9% [87.9-96.3] vs 56.4% [54.5-58.4] vs 49.4% [48.2-50.6] especially in the neo adjuvant setting (39.1% [31.6-46.8] vs 16.4% [15.0 -17.8] vs 11.5% [10.7-12.3]). In our cohort, 30% of eBC pts had their gBRCAm status tested; of them 7.1% had gBRCAm 1 or 2. Consistent with prior research, women with gBRCAm had a substantial proportion of higher stage TN tumours and were treated with aggressive chemotherapy. Further studies on clinical outcomes of eBC pts with gBRCAm are warranted.

Enrolment in CT affords access to innovation to pts with cancer. Few data extensively characterize factors associated with enrolment and its relationship with patient-reported (PROs) and clinical outcomes in pts with BC. We included 9456 pts with stage I-III BC from the multicenter, prospective CANTO cohort (NCT01993498), followed-up until year-4 (Y4) post-diagnosis (dx). Enrolment in a CT was allowed at any time post-dx. Multivariable logistic regression assessed factors associated with enrolment. Multiple linear regression and Cox proportional hazard models evaluated the relationship of enrolment with quality of life (QOL; EORTC QLQ-C30 summary score) and clinical outcomes (distant disease free [dDFS], invasive [iDFS] and overall survival [OS]; adjusting by age, stage, subtype, comorbidities), respectively. Overall, 1700 pts (18%) were enrolled in a CT, 37% and 32% in a phase III therapeutic and supportive care CT, respectively. Clinical and socio-economic factors were not associated with enrolment. There was some inter-regional variability in enrolment rates (median, 15% [Q1-Q3, 12-24%] across 13 French regions). Small size centers were less likely to enroll pts in CT (Table). Among pts enrolled in a CT vs not, QOL at Y4 post-dx was similar (mean score [SD], 80.6 [13.6] vs 80.7 [13.9]; padjusted=0.68), and hazard ratios were 0.82 for dDFS (95% CI 0.68, 0.99; p=0.04), 0.85 for iDFS (0.71, 1.02; p=0.08), and 0.79 for OS (0.59, 1.06; p=0.12).Table: 134PFactors associated with enrolment in a CT% enrolled (row)Odds Ratio*95% CIpBody Mass Index, kg/m2<25≥25171911.10.9,1.20.56Charlson comorbidity Index0≥1171911.10.9,1.30.32EducationPrimary schoolHigh schoolCollege20191711.11.10.9,1.40.8,1.40.330.68Income (€/month)2000-4000<2000>400019191710.90.90.7,1.10.8,1.10.260.38BC StageIIIIII14222011.61.31.3,1.90.9,1.7<.010.08ProvenanceIle-de-FranceCenter/North FranceSouth France15192011.21.51.0,1.51.2,1.90.01<.01Center sizeSmallMediumLarge15191611.41.21.1,1.90.8,1.60.020.40*by year of dx, age, medical history, psychological factors, BC treatment, proximity to center of care Open table in a new tab *by year of dx, age, medical history, psychological factors, BC treatment, proximity to center of care In this large study of early BC, 1/5 pts enrolled in a CT over 4 years post-dx. Pts were adequately represented irrespective of clinical and socio-demographic features, whereas enrolment seemed mostly impacted by geographical and center-related factors. In this cohort, enrolment was not associated with worse PROs, and there were indications of associations with improved clinical outcomes. Access to innovation for cancer pts should be encouraged and facilitated, including by overcoming organizational barriers to recruitment.

Background: Information on real-world clinical outcomes for pembrolizumab monotherapy among patients with previously treated advanced NSCLC remains limited. Our aim was to estimate overall survival (OS) and real-world progression-free survival (rwPFS) in France for pembrolizumab monotherapy in previously treated, PD-L1-expressing advanced NSCLC patients following approval based on the phase III trial KEYNOTE-010 (KN010), where a 11.8 month median OS (95% CI: 10.4 to 13.1) and a 48.9% 12-month OS rate (95% 45.1, 52.6) were reported. Methods: Using the Epidemiological Strategy Medical Economics Advanced or Metastatic Lung Cancer (ESME-AMLC) Data Platform [NCT03848052], we identified adult patients with histologically confirmed, PD-L1 TPS ≥1%, advanced (stage IIIB or IV) NSCLC treated with at least one prior chemotherapy regimen and who initiated pembrolizumab monotherapy between 12 May 2017 and 31 December 2018. Patients with EGFR/ALK genomic aberration were required to have been treated with an appropriate targeted therapy prior to pembrolizumab. Patients who received pembrolizumab in a clinical trial were excluded. This planned interim analysis was based on a prespecified statistical analysis plan, with data cut-off on August 31, 2019. OS and rwPFS were estimated using the KM method. Results: A total of 304 patients were identified, with a median follow-up of 5.9 months (range: 0, 24). Patient characteristics and OS/rwPFS results are shown below. Table 110POverallECOG 0–1ECOG ≥2N30413163Age, median (range), yr62.5 (37, 92)62 (37, 92)63 (42, 85)Current/former smoker, n (%)276 (90.8)122 (93.1)55 (87.3)Non-squamous histology, n (%)261 (85.9)112 (85.5)54 (85.7)History of brain metastasis, n (%) TPS120 (39.5)49 (37.4)25 (39.7)1–49%147 (51.0)56 (43.8)29 (50.9)≥50%141 (49.0)72 (56.3)28 (49.1)NR1636Median OS, mos. (95% CI) OS rate, % (95% CI)13.7 (9.9, NR)16.2 (10.2, NR)5.4 (2.8, NR)12 mos52.9 (45.9, 59.5)55.5 (44.7, 65.0)38.0 (24.1, 51.7)Median rwPFS, mos. (95% CI) rwPFS rate, % (95% CI)2.8 (2.1, 3.7)3.3 (2.3, 5.7)1.4 (1.4, 2.6)12 mos21.6 (16.3, 27.4)24.3 (16.1, 33.3)12.1 (4.1, 24.8) Open table in a new tab Conclusions: Clinical outcomes among previously treated advanced, PD-L1 expressing NSCLC patients were consistent with clinical trial results thus supporting the effectiveness of pembrolizumab in the real-world setting in France. Clinical trial identification: ESMECSM2019–24. Legal entity responsible for the study: UNICANCER. Funding: MSD. Disclosure: M. Pérol: Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: Roche; Advisory/Consultancy, Advisory Boards/Symposium: Eli Lilly; Advisory/Consultancy, Advisory Boards/Symposium: Novartis; Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: AstraZeneca; Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: Takeda; Advisory/Consultancy, Advisory Boards/Symposium: MSD; Advisory/Consultancy, Advisory Boards/Symposium: Bristol-Myers Squibb; Advisory/Consultancy, Advisory Boards/Symposium/Institutional grants: Boehringer-Ingelheim; Advisory/Consultancy, Advisory Boards/Symposium: Pfizer; Advisory/Consultancy, Symposium: Amgen; Advisory/Consultancy, Symposium/Institutional grants: CHUGAU; Advisory/Consultancy, Symposium: Illumina. T. Filleron: Research grant/Funding (institution): BMS. All other authors have declared no conflicts of interest.

Using the large national CANTO cohort of patients with early breast cancer (BC), we assessed cognitive functioning change after cancer treatments. We included patients with newly diagnosed invasive stage I-III BC enrolled in the pre-defined substudy of CANTO focused on cognitive evaluation (CANTO-Cog) and healthy control women (HC) group-matched for age and education. Episodic and working memory, executive functions, processing speed, attention, cognitive complaints (FACT-COG), cognitive fatigue (FA12), anxiety/depression (HADS) were assessed with neuropsychological tests and self-report questionnaires, before treatment (baseline), 3-6 months (M3-6) and 15-18 months (M15-18) after treatment completion. We used linear mixed models to study the change of objective cognitive functions and cognitive complaints by group while adjusting for age, education, neurological/psychiatric previous history, anxiety and cognitive fatigue. We further tested the effect of adjuvant chemotherapy (CT). We studied 276 localized BC patients who had performed at least one follow-up assessment after baseline (mean age 54±11 years, adjuvant treatments: 94% radiation therapy, 83% hormonotherapy, 62% CT). Patients were compared to 135 matched HC. At all times, patients reported significantly more cognitive fatigue than HC (p=0.002). After adjustments, patients had lower baseline working memory, processing speed and attention scores than HC (all p≤0.001), and the difference remained significant over follow-up. Cognitive complaints were similar between groups at baseline (p=0.23), but increased in patients after treatment (p group x time=0.024). At M3-6, 36% of patients reported clinically significant cognitive complaints vs 13% of HC. In particular, cognitive complaints of patients treated with CT increased after treatment and decreased at M15-18 without return to baseline level (p CT x time<0.001). Cognitive difficulties are an important concern in BC patients, starting at diagnosis. Chemotherapy induces cognitive complaints within 6 months after treatment completion, which decrease over follow- up without return to baseline level.

Perceived discrimination (PD) in the workplace of individuals diagnosed with cancer has been reported in the literature. Our study aimed at understanding the clinical and social factors related to reported PD in the workplace after return to work (RTW) of women diagnosed with early breast cancer (BC). We used data from a French longitudinal cohort (CANTO; NCT01993498) including women diagnosed with stage I-III BC. Our analysis was conducted among 2130 women working and ≥5 years younger than legal retirement age at BC diagnosis (dx) who had returned to work two years afterwards. Logistic regression models were created, with PD in the workplace after RTW (i.e. being downgraded, unwillingly relocated or refused a promotion, or losing responsibilities) self-reported two years after dx as dependent variable and household income per capita (HI) as independent variable. Adjustment for age, working conditions before and after RTW (e.g. working part/full-time, size of the company, changes in working hours after RTW, number of months worked since RTW), clinical and health variables were carried out. To clarify the role of health in the association between HI and PD, stratified analyses by health status one year after dx (measured with QLQC30-GHS below/over 60) were carried out. Overall, 26% of women reported PD in the workplace after RTW, ranging from 20% when HI >3500€ to 29% when HI <1500€. After adjustment for working conditions, the association between HI and PD attenuated (table). After stratification by health status, no association between HI and PD was found among women with poor health status or among women with good health status.Table 235PMultivariable logistic regression of association between HI and PD in the workplace after RTWHousehold Income (€/month)%OR (95% CI)Model 1: Adjusted for age + clinical variables *Model 1 + Adjusted for working conditions>350012.5RefRef3000-350010.11.19 (0.75 to 1.89)1.15 (0.71 to 1.85)2000-300027.31.34 (0.92 to 1.95)1.24 (0.84 to 1.84)1500-200024.41.56 (1.07 to 2.29)1.30 (0.87 to 1.94)<150025.71.53 (1.04 to 2.24)1.40 (0.93 to 2.11)* stage at dx, treatment, Charlson at dx Open table in a new tab * stage at dx, treatment, Charlson at dx After adjusting for working conditions, HI was not associated with reporting discrimination at work.