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BACKGROUND: With an increased lifespan, survivorship has become a crucial component of breast cancer (BC) care. Among survivorship concerns, adequate contraception counseling is needed in premenopausal patients (pts) not seeking to become pregnant. However, very limited evidence exists on attitudes and factors influencing contraception use over time in premenopausal women with early BC. METHODS: CANTO is a multicenter, prospective cohort study of 12,012 pts with stage I-III BC (NCT01993498). This analysis included women aged ≤50 years with known premenopausal status at BC diagnosis. Contraception use and type were longitudinally evaluated at diagnosis, year-1 (T1) and 2 (T2) after diagnosis. Multivariable logistic regression models assessed associations between clinical, socio-economic, treatment, toxicity (CTCAE) and pts-reported outcome (PROs, EORTC QLQ-C30/BR23) variables, with contraception use after diagnosis. RESULTS: Among 2,900 pts included, mean age at diagnosis was 43.1 (SD 5.6) years, 96.0% of pts already had children at BC diagnosis, 70.8% and 80.0% received chemotherapy and endocrine therapy (ET), respectively. Among patients treated with ET, 80.2% received tamoxifen alone and 19.8% other therapies (either tamoxifen or an aromatase inhibitor or a combination) plus ovarian function suppression (OFS). Following diagnosis, 45.0% of pts at T1 and 65.7% at T2 reported consulting a gynecologist. At diagnosis, 54.2% of pts reported contraception use, with the majority (62.6%) using hormonal methods. Prevalence of contraception use significantly decreased at T1 and T2 (38.9% and 41.2%, respectively; ptrend Citation Format: Matteo Lambertini, Claudia Massarotti, Julie Havas, Barbara Pistilli, Anne-Laure Martin, Alexandra Jacquet, Charles Coutant, Florence Coussy, Asma Dhaini Merimeche, Florence Lerebours, Olivier Tredan, Christelle Jouannaud, Olivier Rigal, Marion Fournier, Patrick Soulie, Maria Alice Franzoi, Lucia Del Mastro, Ann H. Partridge, Fabrice Andre, Ines Vaz-Luis, Antonio Di Meglio. Attitudes and factors influencing contraception use over time in premenopausal women with early breast cancer in the prospective CANTO study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-20.

Background: Mobile health (mHealth) applications (app) and remote monitoring demonstrated tangible value in terms of improving dose delivery, quality of life and mitigating the severity of acute treatment-related side effects, both in the metastatic setting and during the active phase of treatment in patients (pts) with early-stage solid tumors. However, the value of mHealth in ‘after primary treatment’ survivorship phase is less studied. Most BC pts have hormone receptor-positive disease and are eligible for adjuvant ET for 5-10 years. ET is associated with multiple side effects that negatively impact quality of life and treatment adherence. A prior survey among French survivors suggested that pts are willing to use digital companion app to help them in the after-cancer experience. In this setting, we developed a digital companion for survivors of BC receiving ET. Objectives: In this study, we explored acceptability, representations, levers, and barriers to a multimodal mHealth intervention among BC pts treated with ET. Methods: This was a qualitative study based on 3 focus groups (FG) with survivors of BC receiving adjuvant ET. The multimodal mHealth intervention had the following features: measure (symptom reporting), understand, and appease (information on interventions to relieve the symptom). FG were conducted via videoconference, lasted approximately 60-90 min, were recorded and transcribed for analysis. A content, thematic analysis was performed. All participants provided oral informed consent and socio-demographic information. Results: 17 BC survivors from diverse professional and socio-economic background participated. Mean age was 48.5 years (range: 32-61). There was a consensus regarding the acceptability and perception of usefulness of an app during treatment with adjuvant ET. A feeling of loneliness during this period was also expressed. Emergent themes cited included: a) positive representations i) satisfaction with the educational support with language and the level of information of the app judged as appropriate and reliable; ii) hope in the role of the app as a companion to alleviate the loneliness; iii) vehicle to enhance family interaction; iv) tool to boost engagement towards their treatment. b) concerns associated with i) fear of human contact replacement ii) fear of loss of interest over time, particularly in the setting of a 5-10 year journey. Pts were pro-active in providing feedback regarding innovative features that could be integrated: i) including interest on the use of biosensors (step counting, nutritional tracking); ii) to receive personalized encouragement messages and iii) updated information regarding scientific advances related to the treatment of early breast cancer. Most participants found the app to be aesthetically pleasing and easy to use. Conclusions: Findings from this qualitative study are promising regarding the acceptability and perception of usefulness of a personalized app for the mitigation of ET side effects in the adjuvant setting. It highlights the need of personalized educational material, but also maintenance of ‘bi-directional’ communication with health professionals. Optimization of the tool is ongoing and updated FG results will be presented. This tool will be tested in a randomized controlled trial starting in Q1/2022, which will evaluate its effectiveness. Quotes from participantsThemes emergedParticipants’ quotes from focus groupsSatisfaction with educational support‘’Today we find everything on the internet, bad and good things, we cannot know what is true and what is fake. (⋯) If an app can give us reliable information, good, summarized information, this would be great!’’Satisfaction with educational support; Hope in the role of the app to alleviate loneliness“I didn’t even know we had so many side-effects linked to endocrine therapy. Now I understand that it’s true, it’s not something from my head. It’s related to the treatment and it’s really nice to have this support.”Alleviation of loneliness‘’I often feel lonely, sometimes is difficult to have contact with the doctor.’’, ‘’We feel lonely, even our family cannot understand.’’Alleviation of loneliness‘’We need to exchange with people that lived the same situation.’’, “We go to forums, chats, Instagram⋯”, ‘’We realize that we are not alone, that we are not the only ones with the symptoms.’’Fear of human contact replacement‘’It is a good addition, but it will never replace the relationship that we have with our doctor.’’Fear of loss of interest over time‘’It is a good app to start endocrine therapy⋯ How to make the app interesting and useful during several years of treatment?’’ Citation Format: Elise Martin, Antonio Di Meglio, Pietro Lapidari, Daniele Presti, Davide Soldato, Léna Degousee, Marion Aupomerol, Barbara Pistilli, Léonor Fasse, Diane Boinon, Florian Scotte, Gwenn Menvielle, Agnès Dumas, Céline Lazorthes, Jonathan Benhamou, Matthieu Pozza, Raphaëlle Martin-Neuville, Nicolas Helleringer, Jeanne Eelkema, Fabrice Andre, Ines Vaz-Luis, Maria Alice Franzoi. A multimodal and personalized digital companion to help survivors of breast cancer (BC) manage side effects of adjuvant endocrine therapy (ET): A qualitative exploration [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-27.

Background: Prior studies demonstrated that premenopausal obese women with BC have a poorer prognosis than non-obese patients (pts). We examined time trends in the prevalence of overweight and obesity among young women diagnosed with early BC and assessed the impact of baseline BMI and weight changes in disease outcomes. Patients and methods: Multicenter retrospective cohort study including young women (≤40yrs) diagnosed with stage I-III BC during 2000-2016 treated in two large Belgian hospitals. Data on baseline characteristics, treatment, and survival outcomes were collected. Pts were classified according to baseline BMI into underweight ( Table 1.- Impact of Baseline BMI and weight changes on disease outcomesOverall survival (OS)4 BMI categories (baseline)Hazard ratio2 BMI categories (baseline)Hazard ratioNormal weightReferenceUnderweight/normal weight (BMI Citation Format: Maria Alice Franzoi, Kevin Punie, Annouschka Laenen, Boudewijn Dullens, Celia Fernandes Costa, Patrick Neven, Hans Wildiers, Matteo Lambertini, Evandro de Azambuja. Impact of baseline body mass index (BMI) and weight changes after diagnosis in young women with early breast cancer (BC): A multicenter retrospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-11.

Background: Our prior analysis of the MONARCH2/3 trials showed no difference in progression-free survival rates according to BMI in patients treated with abemaciclib and endocrine therapy for hormone receptor-positive, HER2-negative advanced breast cancer (Franzoi et al, JNCI 2021). However, a statistically inferior overall response rate with abemaciclib and endocrine therapy was observed in patients with BMI ≥25. In the present study, we examined the impact of baseline BMI on mean KI67% changes, achievement of complete cell cycle arrest (CCCA) and clinical and radiological responses in patients included in the phase II NEOMONARCH trial, which randomized patients to receive a 2-week initial treatment with either abemaciclib, letrozole, or abemaciclib and letrozole followed by 14 weeks of the combination of abemaciclib and letrozole as neoadjuvant therapy for hormone receptor-positive, HER2-negative early-stage breast cancer patients. Patients and methods: This is an exploratory, individual patient-level, post-hoc analysis of the NEOMONARCH study. Data was assessed through a research proposal submission in the Vivli platform. Patients were classified according to baseline BMI into underweight/normal weight (BMI Citation Format: Maria Alice Franzoi, Matteo Lambertini, Marcello Ceppi, Marco Bruzonne, Evandro de Azambuja. Implications of body mass index (BMI) on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-07.

Background: The poor prognostic value of young age at diagnosis appears to vary according to breast cancer (BC) subtype, although this has been studied mainly in hormone receptor-positive (HR+) disease, with limited data in HER2-positive BC and short follow-up. Limited evidence exists on the benefit of anti-HER2 therapy in young women with BC. Considering that age has historically been a rationale for overtreatment, further research efforts to better investigate the prognostic and predictive value of age are needed. This exploratory analysis conducted within the APHINITY trial aimed to investigate the prognostic and predictive value of young age in patients with HER2-positive early BC treated with modern chemotherapy and concurrent anti-HER2 targeted treatment. Methods: APHINITY (NCT01358877) is an international, placebo-controlled, double-blind randomized phase III trial in patients with HER2-positive early BC investigating the benefit of adding pertuzumab to adjuvant chemotherapy plus trastuzumab. For the purpose of the present analysis, 40 years of age at enrolment was used as the cut-off to distinguish between young (≤40 years) and older (>40 years) cohorts. Invasive disease-free survival (IDFS) was the primary endpoint. IDFS irrespective of treatment arm and the benefit of adding pertuzumab were evaluated in all patients by comparing the young and older cohorts and then according to centrally-assessed hormone receptor status. Univariate and multivariable Cox proportional hazard models were used to assess the prognostic and predictive value of age on IDFS as a continuous and dichotomous variable (≤40 years and >40 years). A STEPP analysis was also conducted to illustrate possible treatment-effect heterogeneity based on age as a continuous factor. Results: Out of 4,804 patients in the ITT population, 768 (16.0%) were ≤40 years at enrollment. Patients in the young cohort were less overweight/obese (29.3% vs. 50.4%), underwent mastectomy more frequently (63.2% vs. 52.6%), had higher rates of node positive (66.4% vs. 61.8%) and HR+ (71.7% vs. 64.9%) BC as compared to those in the older cohort (all p Citation Format: Matteo Lambertini, Shona Fielding, Sibylle Loibl, Wolfgang Janni, Emma Clark, Maria Alice Franzoi, Debora Fumagalli, Carmela Caballero, Luca Arecco, Sharon Salomoni, Noam F Ponde, Francesca Poggio, Hee Jeong Kim, Cynthia Villarreal-Garza, Olivia Pagani, Shani Paluch-Shimon, Alberto Ballestrero, Lucia Del Mastro, Martine Piccart, Jose Bines, Ann H. Partridge, Evandro de Azambuja. Effect of young age at diagnosis on clinical outcomes and efficacy of anti-HER2 targeted therapy in patients with HER2-positive early breast cancer: Results from the APHINITY trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-42.

Background/methods: Although the prognosis of metastatic breast cancer (BC) has improved, some patients still develop high burden metastases or visceral crisis (VC) and polychemotherapy is commonly used in these cases. Data reporting the real effectiveness of this strategy are scanty. Therefore, the outcomes of patients with metastatic BC treated with platinum-based chemotherapy (P-ChT) at the Jules Bordet Institute during the period of January 2008 and December 2018 were retrospectively reviewed. The presence of VC was defined according to ABC 4 criteria. Results 441 patients were identified: visceral metastases were observed in 430 (97.5%) while 261 (59.2%) presented VC. As for metastatic BC subtype, 255 (57.8%) had ER-positive/HER2-negative, 41 (9.3%) ER-positive/HER2-positive, 34 (7.7%) ER-negative/HER2-positive and 111 (25.1%) triple-negative BC. Median number of prior treatment lines was 3.8 (0–12). Median OS with P-ChT in the entire cohort was 6.13 months. Patients with VC had lower OS than patients without VC (8.6 vs 3.7 months; p 3 previous treatment lines (HR 2.27; 95% CI 1.53–3.21). Of the 261 patients with VC, 106 (40.5%) presented a resolution of the VC which correlated with better OS (9.3 vs 2.0 months, HR 0.27; 95% CI 0.21–0.36). Conclusion Patients who overcome VC benefit from P-ChT with OS similar to patients without VC. In this analysis, hyperbilirubinemia, poor ECOG and >3 previous treatment lines were significant prognostic factors in the overall study population., Highlights • Outcomes of pts with advanced BC treated with platinum-based chemotherapy at our Institution were reviewed. • Our results highlight the poor prognosis of pts with BC and visceral crisis (VC). • Hyperbilirubinemia, poor ECOG PS, and >3 prior treatment lines may be factors associated with inferior OS. • Prospective studies in pts with VC are needed to provide better guidance towards treatment decisions.

Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects models. The study is registered with the PROSPERO registration number CRD42020158324. Results: Overall, 39 studies were included. Out of the 8,265,713 young women included in these studies, 8,093,401 were from the general population, 57,739 had cancers other than BC, 114,573 had BC. Among the 114,573 BC patients, 7,505 had a pregnancy after BC diagnosis and 107,068 did not. Compared to women from the general population, BC patients had 60% reduced chances of having a pregnancy following anticancer treatment completion (RR 0.40, 95% CI 0.32-0.49). Among other cancer patients, only women with prior cervical cancer had lower pregnancy rates (RR 0.33, 95% CI 0.31-0.35) than BC patients. Compared to the general population, BC survivors had significantly increased risks of low birth weight (OR 1.50, 95% CI 1.31-1.73), small for gestational age (OR 1.16, 95% CI 1.01-1.33), preterm delivery (OR 1.45, 95% CI 1.11-1.88) and caesarean section (OR 1.14, 95% CI 1.04-1.25). No significant increased risk of congenital abnormalities (OR 1.63, 95% CI 0.89-2.98) or other pregnancy or delivery complications (spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage) was observed. Prior chemotherapy exposure or short pregnancy interval (defined as Pregnancy after BC was not associated with a negative impact on patients’ outcomes. Compared to BC patients without subsequent pregnancy, those with pregnancy after BC had better OS (HR 0.56, 95% CI 0.46-0.67) and DFS (HR 0.73, 95% CI 0.56-0.94). Similar results were observed in the studies correcting for the potential “healthy mother effect” (OS: HR 0.52, 95% CI 0.42-0.65; DFS: HR 0.74, 95% CI 0.58-0.96). No detrimental prognostic effect of pregnancy after BC was observed in patients with hormone-receptor positive disease (DFS: HR 1.10, 95% CI 0.73-1.66), while better outcomes were observed for those with hormone-receptor negative disease (DFS: HR 0.72, 95% CI 0.55-0.95). The safety of pregnancy after BC was observed irrespective of BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval and pregnancy outcomes. Conclusions: This large meta-analysis provides solid evidence on the safety of pregnancy after prior BC diagnosis. The increased risk of fetal and obstetrical complications (but not of congenital abnormalities) calls for ensuring a closer monitoring of these pregnancies. The significantly reduced chances of conceiving as compared to the general population and other cancer patients should raise further awareness on the need to improve the oncofertility counseling of young BC patients wishing to complete their family planning following anticancer treatment completion. Citation Format: Eva Blondeaux, Marta Perachino, Marco Bruzzone, Richard A. Anderson, Evandro De Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Jr., Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori, Matteo Lambertini. Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-09.

Background: The number of people living with HIV is increasing worldwide thanks to the use of effective antiretroviral therapy. As these individuals get older, their risk of being diagnosed with cancer increases, including non-AIDS defining cancers such as breast cancer (BC). Most reports reveal that HIV+ patients (pts) with BC tend to be younger than HIV-uninfected (HIV-) pts. However, epidemiological data is yet conflicting regarding tumor stage at diagnosis, distribution of BC subtypes and overall survival (OS) of HIV+ pts as compared to HIV- pts. This meta-analysis aims to assess differences of baseline clinicopathological characteristics and OS of HIV+ vs HIV- BC pts. Methods: We performed a systematic review using MEDLINE, Scielo, and conference abstracts up to June 10, 2019, with no language restrictions. Cohort studies and consecutive series comparing baseline characteristics (age, stage at diagnosis or BC subtypes) and/or OS of HIV+ vs HIV- BC pts were included. BC subtypes were defined according to 2 classifications: 1) “classic” immunohistochemical (IHC) subtypes (ER+/HER2-; HER2+; triple-negative BC); 2) surrogate intrinsic subtypes as per the St. Gallen Consensus (luminal A-like, luminal B-like, HER2-enriched and basal-like). Summary risk estimates (pooled mean ratios [pMR] and odds ratios [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. OS data were pooled as hazard ratios (HR) and 95% CI and modeled using a random effects model. The main endpoints were age (as a continuous variable), stage at diagnosis (early [0-II] vs late [III-IV]), distribution of BC subtypes and OS (using both adjusted and unadjusted HR). Subgroup analysis of each endpoint was performed according to region of the world. Results: A total of 16 studies (4 from North America and 12 from Sub-Saharan Africa [SSA]) published from 2005-2019 were included in this meta-analysis (with 1,764 HIV+ and 1,330,122 HIV- pts). HIV+ pts were younger than HIV- pts (pooled mean age of 41.1 vs 50.5 years, respectively; pMR 0.82, 95% CI 0.76-0.90, p < 0.001) and had a 45% increased risk of presenting with late stage disease (pOR 1.45, 95% CI 1.25-1.68, p < 0.001). There were no differences regarding distribution of BC subtypes, both by the “classic” IHC or by the St. Gallen classification. Overall, HIV+ pts had a 91% increased risk of dying as compared to HIV- pts (adjusted HR for OS: 1.91, 95% CI 1.06-3.45, p = 0.031 and unadjusted HR for OS: HR 1.47, 95% CI 1.10-1.95, p = 0.008). Subgroup analysis of OS according to region of the world showed that, in North America, HIV+ pts had a significantly increased risk of dying as compared to HIV- pts (adjusted HR 2.96, 95% CI 1.06-8.25, p = 0.038). In SSA, the increased mortality risk among HIV+ pts was also significant (adjusted HR 1.59, 95% CI 1.26-2.00, p < 0.001). Sensitivity analysis showed similar findings. Conclusion: This meta-analysis provides for the first time a comprehensive comparison of baseline characteristics and survival outcomes between HIV+ vs HIV- BC pts. Our results consistently demonstrate that HIV+ pts are diagnosed with BC at a younger age and at a more advanced stage. Additionally, even after adjusting for known prognostic factors, HIV+ pts have a worse OS as compared to HIV- pts, not only in developing countries (SSA) but also and particularly in developed countries (North America). There were no apparent differences in terms of distribution of BC subtypes. These results should raise the awareness of clinicians and policy makers regarding the detection and survival gap among HIV+ BC pts. This underserved population should be the focus of more research efforts, in order to better understand the reasons behind these disparities, which can be related to the HIV infection itself, to a more aggressive BC biology, and/or to a lower access to timely diagnosis and effective treatment. Citation Format: Mariana Brandão, Marco Bruzzone, Maria Alice Franzoi, Claudia De Angelis, Daniel Eiger, Rafael Caparica, Martine Piccart-Gebhart, Laurence Buisseret, Marcello Ceppi, Evandro de Azambuja, Matteo Lambertini. Characteristics and survival outcomes of HIV-positive breast cancer patients: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-03.

Background Young age at breast cancer (BC) diagnosis has historically been a rationale for overtreatment. Limited data with short follow-up exist on the prognostic value of age at diagnosis in HER2-positive BC and the benefit of anti-HER2 therapy in young patients. Methods APHINITY (NCT01358877) is an international, placebo-controlled, double-blind randomized phase III trial in HER2-positive early BC patients investigating the addition of pertuzumab to adjuvant chemotherapy plus trastuzumab. The prognostic and predictive value of age on invasive disease-free survival (IDFS) as continuous and dichotomous variable (aged 40 years or younger and older than 40 years) was assessed. A subpopulation treatment effect pattern plot analysis was conducted to illustrate possible treatment-effect heterogeneity based on age as a continuous factor. Results Of 4804 included patients, 768 (16.0%) were aged 40 years or younger at enrollment. Median follow-up was 74 (interquartile range = 62-75) months. Young age was not prognostic either as dichotomous (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.84 to 1.33) or continuous (HR = 1.00, 95% CI = 1.00 to 1.01) variable. Lack of prognostic effect of age was observed irrespective of hormone receptor status and treatment arm. No statistically significant interaction was observed between age and pertuzumab effect (Pinteraction = 0.61). Adding pertuzumab improved IDFS for patients in the young (HR = 0.86, 95% CI = 0.56 to 1.32) and older (HR = 0.75, 95% CI = 0.62 to 0.92) cohorts. Similar results were observed irrespective of hormone receptor status. Subpopulation treatment effect pattern plot analysis confirmed the benefit of pertuzumab in 6-year IDFS across age subpopulations. Conclusions In patients with HER2-positive early BC treated with modern anticancer therapies, young age did not demonstrate either prognostic or predictive value, irrespective of hormone receptor status.

Geographic location and national income may influence access to innovation in healthcare. We aimed to study if geographical location and national income influenced the timelines to activate the global phase III APHINITY trial, evaluating adjuvant pertuzumab in patients with HER2-positive early breast cancer.Time from regulatory authority (RA) submission to approval (RAA), time to Ethics Committee/Institutional Review Board (EC/IRB) approval, time from study approval by EC/IRB to first randomised patient and from first to last randomised patient were collected. Analyses were conducted grouping countries by geographical region or economic income classification.Forty-one countries (of 42) had data available regarding all relevant timelines. No statistical difference was observed between the time to RAA and geographical region (Geographical location and income classification did not appear to be the major drivers influencing time for clinical trial activation. Wide variability in activation timelines within geographical regions and income groups exists and is worthy of further investigation.

Introdução: A hipodermóclise é uma via de infusão em pacientes com câncer nos casos em que os acessos oral e endovenoso não estão disponíveis. Considerando a sua utilidade no controle dos sintomas no final de vida, faz-se importante ampliar o conhecimento e a divulgação das experiências quanto aos seus benefícios. Relato de caso: Trata-se de dois relatos de caso de pacientes com câncer, nos quais a hipodermóclise foi utilizada para administração de medicamentos. Conclusão: Essa prática apresentou-se como uma via segura, minimamente invasiva e eficaz no tratamento sintomático dos pacientes com câncer em cuidados paliativos.

Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic carcinoma, a relatively uncommon but devastating complication of many malignancies. Although only 5% of patients with breast cancer develop leptomeningeal involvement, it remains the most common etiology of LC. It can occur as a late-stage complication of systemic progression or present as the first sign of metastatic disease, with or without parenchymal brain metastases. Lobular carcinomas have a higher propensity to metastasize into the meninges when compared to ductal carcinoma, especially the triple-negative subtype, which usually is associated with a shorter interval between metastatic breast cancer diagnosis and the development of LC. Prognosis remains poor, with median survival of 4 months for patients receiving state-of-the-art treatment. The main factors associated with survival are performance status at diagnosis, CSF protein level and triple-negative subtype. Headache is commonly the first clinical presentation of LC, and the diagnostic workup usually requires CSF-cytological analysis and or/MRI. The current management of LC consists of a combination of intra-CSF chemotherapy, systemic therapy, radiotherapy and/or best-supportive care. The standard intra-CSF chemotherapy regimen is methotrexate. Radiotherapy is used for relieving obstruction points on CSF-outflow channels due to ependymal nodules, tumor deposits or bulky disease. Objective responses have been reported with intrathecal administration of trastuzumab for HER2-positive disease, yet this strategy is still under investigation. Further prospective trials are needed to better address the impact of these treatment modalities on overall survival and quality of life.

BACKGROUND: Breast cancer (BC) in young women is uncommon and often more aggressive. There are disparities in terms of screening coverage, diagnostic features and access to optimal treatment among young BC patients worldwide. To better understand this scenario through real world data we performed a sub-analysis of AMAZONA III study. METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2950 women newly diagnosed with invasive BC in Brazil during the period of January 2016 to March 2018 within 22 sites. Of them, 2888 patients had valid data regarding age at diagnosis and complete baseline information. For the purpose of comparisons of epidemiologic and clinicopathologic features at the time of diagnosis of BC, patients were divided in two groups: women aged ≤40 years (Group 1) and >40 years (Group 2). Quantitative variables were expressed with mean, while categorical variables were described as their count and percentage and compared using the chi-square test. RESULTS: Of 2888 women, 486 (17%) were ≤40 years of age. No differences were found between ethnicity, performance status, body mass index, personal income, health insurance and family history of cancer between the two groups. Young women had higher educational level (p Breast cancer features by age groups at diagnosis in Brazilian women.InformationGroup 1 (≤40 years)Group 2 (> 40 years)p-valueN: 2888486 (16.83%)2402 (83.17%) Stage at diagnosis p< 0.001I76 (19.2%)541 (27.8%) II156 (39.4%)816 (41.9%) III146 (36.8%)489 (25.1%) IV19 (4.6%)101 (5.2%) Tumor size p< 0.001T1114 (27.1%)749 (36.9%) T2141 (33.6%)764 (37.6%) T3101 (24.1%)282 (13.9%) T464 (15.2%)235 (11.6%) Tumor grade p < 0.001Grade 146 (10.7%)381 (17.9%) Grade 2198 (46.2%)1150 (52.0%) Grade 3185 (43.1%)641 (30.1%) Molecular Subtype p < 0.001Luminal A106 (30.6%)957 (51.3%) Luminal B - HER 2 negative55 (15.8%)212 (11.4%) Luminal B- HER 2 positive79 (22.8%)298 (16.0%) HER 2 positive27 (7.8%)135 (7.2%) Triple negative80 (23.0%)264 (14.1%) Citation Format: Franzoi MA, Rosa D, Barrios C, Bines J, Cronemberger E, Queiroz G, Cordeiro de Lima VC, Junior R, Couto J, Emerenciano K, Resende H, Crocamo S, Reinert T, Van Evyl B, Neron Y, Dybal V, Lazaretti N, Costamilan RdC, de Andrade D, Mathias C, Zerwes Vacaro G, Borges G, Silva K, Werutsky G, Morelle A, Sampaio Filho CA, Mano M, Zaffaroni F, Simon S, Liedke PE. Advanced stage at diagnosis and worse clinicopathologic features in young woman with breast cancer. A sub-analysis of Brazilian population through the AMAZONA III study (GBECAM 0115) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-27.

ImportanceAs life span has increased among patients with cancer, survivorship has become an important component of breast cancer care. Among survivorship concerns, adequate contraceptive counseling is needed for premenopausal patients who are not seeking to become pregnant.ObjectiveTo examine contraceptive use and chosen methods and to assess factors associated with contraceptive use over time in patients with early breast cancer.Design, Setting, and ParticipantsThe Cancer Toxicity (CANTO) study was a multicenter nationwide prospective cohort study that enrolled women diagnosed with stage I to stage III breast cancer in France between March 2012 and December 2017. This analysis included 2900 premenopausal women who were 50 years of age or younger at diagnosis. Data were analyzed from July 2020 to July 2022.ExposuresContraceptive use and method at diagnosis, shortly after the end of primary treatment (year 1), and during follow-up (year 2).Main Outcomes and MeasuresContraceptive use and methods were longitudinally evaluated at diagnosis, year 1, and year 2 after breast cancer diagnosis. Multivariable logistic regression models were used to assess the associations of clinical, socioeconomic, treatment, adverse effect, and patient-reported outcome variables with contraceptive use after diagnosis.ResultsA total of 2900 patients (mean [SD] age, 43.1 [5.6] years) were included in the analysis; 2050 of 2894 women (70.8%) received chemotherapy, and 2305 of 2880 women (80.0%) received endocrine therapy. After diagnosis, 1182 of 2625 patients (45.0%) at year 1 and 1553 of 2363 patients (65.7%) at year 2 reported consulting with a gynecologist in the previous year. At diagnosis, 1487 of 2744 patients (54.2%) reported contraceptive use, with most patients (921 of 1470 women [62.7%]) using hormonal methods. The use of contraception significantly decreased after diagnosis (911 of 2342 patients [38.9%] at year 1 and 808 of 1961 patients [41.2%] at year 2; P Conclusions and RelevanceFindings from this study support the importance of raising awareness and improving targeted contraceptive counseling for premenopausal women with early breast cancer.

Background: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer. Methods: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model. Results: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03–4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49–0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23–6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93–7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69–7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33–4.10; p < 0.001). Conclusions: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer., SCOPUS: ar.j, info:eu-repo/semantics/published

Background There are limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer, especially in patients treated with endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitors. Methods A pooled analysis of individual patient-level data from MONARCH 2 and 3 trials was performed. Patients were classified according to baseline BMI into underweight ( Results This analysis included 1138 patients (757 received abemaciclib + ET and 381 placebo + ET). There was no difference in PFS between BMI categories in either group, although normal-weight patients presented a numerically higher benefit with abemaciclib + ET (Pinteraction = .07). Normal and/or underweight patients presented higher overall response rate in the abemaciclib + ET group compared with overweight and/or obese patients (49.4% vs 41.6%, odds ratio = 0.73, 95% confidence interval = 0.54 to 0.99) as well as higher neutropenia frequency (51.0% vs 40.4%, P = .004). Weight loss was more frequent in the abemaciclib + ET group (odds ratio = 3.23, 95% confidence interval = 2.09 to 5.01). Conclusions Adding abemaciclib to ET prolongs PFS regardless of BMI, showing that overweight or obese patients also benefit from this regimen. Our results elicit the possibility of a better effect of abemaciclib in normal and/or underweight patients compared with overweight and/or obese patients. More studies analyzing body composition parameters in patients under treatment with cyclin-dependent kinase 4/6 inhibitors may further clarify this hypothesis.

BACKGROUND As women living with HIV (WLWH) become older, their risk of developing breast cancer increases. Nonetheless, literature is conflicting regarding tumor stage, distribution of subtypes and overall survival among WLWH vs. HIV-negative women with breast cancer. We assessed differences in clinicopathological characteristics and overall survival between these two groups. METHODS Systematic review and meta-analysis using MEDLINE, Scopus, ISI Web of Knowledge, LILACS, SciELO and conference abstracts up to 1 January 2020. Cross-sectional/cohort studies comparing baseline characteristics (stage and/or subtypes) and/or overall survival of WLWH vs. HIV-negative women with breast cancer were included. We performed random-effects meta-analyses to estimate summary statistics and subgroup analyses according to region of the world. RESULTS Eighteen studies [4 from North America, 14 from sub-Saharan Africa (SSA)] were included, with 3174 WLWH and 2 394 598 HIV-negative women. WLWH from North America and SSA were more likely to present with stage III/IV disease compared with HIV-negative women - pooled odds ratio (pOR) 1.76 [95% confidence interval (CI):1.58-1.95] and pOR 1.23 (95% CI: 1.06-1.42), respectively. WLWH from SSA were also less likely to have estrogen receptor-positive/HER2-negative tumors (pOR 0.81; 95% CI: 0.66-0.99). After adjustment, WLWH had worse overall survival compared with HIV-negative women, both in North America [pooled adjusted hazard ratio (aHR) 2.45; 95% CI: 1.11-5.41] and SSA (aHR 1.43; 95% CI: 1.06-1.92). CONCLUSION Compared with HIV-negative women, WLWH are diagnosed with breast cancer at a more advanced stage and have a worse overall survival. These results should raise awareness regarding the detection and survival gap among WLWH with breast cancer and further studies are needed to decipher the reasons behind these disparities.

Background: Obesity is a risk factor for breast cancer (BC) development, recurrence, and death. In view of this, we aimed to investigate the clinical value of obesity in BC patients treated with anti-HER2 therapies in the NeoALTTO trial, which randomized 455 patients to neo-adjuvant lapatinib, trastuzumab, or their combination plus paclitaxel. Methods: Patients were classified according to their basal body mass index (BMI) into underweight (< 18.5 kg/m2), normal (≥ 18.5; < 25 kg/m2), overweight (≥ 25; < 30 kg/m2), and obese (≥ 30 kg/m2) WHO categories. Univariate and multivariate logistic regression analyses were performed using BMI as a categorical variable. Pathological complete response (pCR) and event-free survival (EFS) were the NeoALTTO primary and secondary outcomes, respectively. Results: Among 454 patients analyzed, 14 (3%), 220 (48%), 137 (30%), and 83 (18%) were classified as underweight, normal weight, overweight, and obese, respectively; 231 (51%) and 223 (49%) had hormone receptor (HR)-positive and HR-negative primary tumors; 160 (35%) achieved pCR. In the overall patient population, no association was found between BMI groups and pCR, as we reported pCR rates of 57.1%, 35%, 30.7%, and 39.8% in underweight, normal weight, overweight, and obese cases, respectively. In contrast, in HR-positive tumors, overweight or obesity was generally associated with decreased likelihood of achieving a pCR independently of other clinical variables, including planned surgery, nodal status, and tumor size (odds ratio [OR] = 0.55, 95%CI 0.30–1.01, as compared to normal or underweight; p = 0.053); notably, no differential effect of BMI with respect to pCR was observed in HR-negative cases (odds ratio [OR] = 1.30, 95%CI 0.76–2.23, as compared to normal or underweight; p = 0.331), resulting in a statistically significant interaction between BMI and HR status (p = 0.036). There was no association between BMI and EFS neither in the overall nor in the HR-positive population, but this analysis was under-powered. Conclusions: NeoALTTO patients overweight or obese at baseline and with HR-positive primary BC appeared less likely to achieve pCR after neo-adjuvant anti-HER2 therapies. This finding paves the way to future research in targeting the interplay between HER2/HR signaling and metabolism., SCOPUS: ar.j, info:eu-repo/semantics/published

Immunotherapy emerged as a new treatment modality for breast cancer, and its use is approved in combination with chemotherapy for first-line therapy in metastatic triple-negative breast cancer overexpressing PD-L1. As immune checkpoint inhibitors alone have modest clinical activity in advanced breast cancer, there is a growing interest in combinatorial modalities, and particularly for their rapid development in the early disease setting. The plethora of ongoing immunotherapy trials in early breast cancer comes at a time when solid data in advanced disease are still imperfect. This review offers a perspective on the efforts to establish the efficacy and safety of immunotherapeutic agents in early breast cancer.

Older patients now form between 30 and 40% of breast cancer (BC) patients. Managing older patients with BC is particularly challenging due to the limited availability of high-quality evidence. In this review we discuss the available evidence on the efficacy and safety of anti-HER2 agents in older patients with HER2-positive BC is presented, with a particular look at the latest results of promising new agents such trastuzumab-deruxtecan. The data suggest that older patients can expect similar efficacy when using standard regimens, with higher toxicity, particular cardiac toxicity and diarrhea. Anti-HER2 agents should thus be used in most older patients most as per standard of care as long as adequate follow-up is available to manage toxicities.

Treatment de-escalation in early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been attempted in order to decrease costs and toxicities. One of the strategies pursued is decreasing trastuzumab treatment duration, with mixed results thus far. Trastuzumab-associated cardiotoxicity, however, may be more frequent with 12 months of trastuzumab compared with shorter treatment lengths. Therefore, we have conducted a meta-analysis to address this question. Materials and methods A meta-analysis of trials testing 12 months of adjuvant trastuzumab versus shorter regimens, reporting cardiac outcomes in patients with HER2-positive BC was performed with the random effects model with inverse variance weighting. Results Clinical cardiac dysfunction associated with 12 months of trastuzumab versus shorter trastuzumab regimens, including 11 250 patients, showed a pooled OR (pOR) of 1.90 (95% CI 1.37 to 2.64; p value, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Knowledge regarding risk of treatment-induced premature ovarian insufficiency (POI) is crucial for appropriate oncofertility counseling. While the gonadotoxicity of anthracycline- and cyclophosphamide-based chemotherapy (CT) in young breast cancer (BC) patients (pts) is well established, the impact of anti-HER2 agents remains largely unknown and limited conflicting evidence exists for taxanes. Anti-Mullerian hormone (AMH) is an established biomarker of ovarian reserve; its measurements during systemic therapies may aid in diagnosis and prediction of POI. The NeoALTTO trial represented a unique setting to explore the acute gonadotoxicity of anti-HER2 therapy alone and in combination with weekly paclitaxel in pts not previously exposed to any other potentially gonadotoxic anticancer treatment. Methods: NeoALTTO (NCT00553358) is a multicenter, open-label, randomized phase III neoadjuvant trial in HER2-positive early BC pts randomized to receive lapatinib (L), trastuzumab (T), or their combination (L+T) alone for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery.The present analysis included only premenopausal women aged ≤45 years with available frozen serum samples at baseline (i.e. before administering any anticancer treatment), at week 2 (i.e. “biological window” of anti-HER2 therapy alone) and/or at surgery (i.e. after completion of paclitaxel plus anti-HER2 therapy). Central AMH testing was performed at Erasme Hospital (Brussels, Belgium) with the Roche Elecsys® AMH Plus assay (LoD=0.010 ng/ml). AMH levels during anti-HER2 therapy alone and then combined with paclitaxel were assessed as a measure of treatment impact on ovarian reserve. The impact of different anti-HER2 agents (T and/or L), pts’ age and baseline AMH levels on treatment gonadotoxicity were also investigated. Results: The present analysis included 130 pts with a median age of 38 years (IQR: 33-42 years), of whom 86 (66.2%) were ≤40 years. At baseline, median AMH levels were 1.29 ng/mL (IQR 0.56 - 2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median value: 1.10 ng/mL, IQR 0.45 - 2.09 ng/mL, p Citation Format: Matteo Lambertini, Marcello Ceppi, Richard A. Anderson, David A. Cameron, Marco Bruzzone, Maria Alice Franzoi, Claudia Massarotti, Sarra El-Abed, Yingbo Wang, Christophe Lecocq, Paolo Nuciforo, Rebecca Rolyance, Lajos Pusztai, Joohyuk Sohn, Jacopo Ligato, Maria Maddalena Latocca, Luca Arecco, Barbara Pistilli, Kathryn J. Ruddy, Alberto Ballestrero, Lucia Del Mastro, Fedro A. Peccatori, Ann H. Partridge, Cristina Saura, Michael Untch, Martine Piccart, Serena Di Cosimo, Evandro de Azambuja, Isabelle Demeestere. Impact of anti-HER2 therapy alone and in association with weekly paclitaxel on the ovarian reserve of young women with HER2-positive early breast cancer: Biomarker analysis of the NeoALTTO trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-05.

PURPOSE: Breast cancer (BC) in young women is uncommon and tends to present with more aggressive characteristics. To better understand and characterize this scenario in Brazil through real-world data, we performed a subanalysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973). METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2,950 women newly diagnosed with invasive BC in Brazil from January 2016 until March 2018 at 22 sites. Valid data were obtained from 2,888 patients regarding age at diagnosis and complete baseline information. To compare epidemiologic and clinicopathological features at the time of diagnosis, patients with BC were divided into two groups according to age: ≤ 40 years and > 40 years. Quantitative variables were described as means, and categorical variables were described as frequencies and percentages and compared using the Pearson's χ2 test. RESULTS: Of 2,888 women diagnosed with BC, 486 (17%) were ≤ 40 years old. Young women had higher educational level, most were employed and a significant number were married (P < .001 for all associations). Younger patients were more symptomatic at BC diagnosis (P < .001), and they also presented more frequently with stage III, T3/T4, grade 3 tumors, HER-2-positive, luminal B, and triple-negative subtypes. CONCLUSION: Brazilian women younger than age 40 years have unfavorable clinicopathological features of BC at diagnosis, with more aggressive subtypes and advanced stage when compared with older women. These differences are not explained by socioeconomic or ethnic imbalances. The causes of a higher prevalence of BC among young women in Brazil deserve additional investigation., SCOPUS: ar.j, info:eu-repo/semantics/published

TPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]

Background Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. On March 8th 2019, the Food and Drug Administration approved anti–PD-L1 antibody, atezolizumab, in combination with chemotherapy for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC. Trial design ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated May 4th 2018, and approximately 430 sites are expected to open globally in 30 countries. This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinical trial identification NCT03498716. Legal entity responsible for the study This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Funding Roche. Disclosure M. Ignatiadis: Advisory / Consultancy: Celgene, Novartis, Pfizer, Seattle Genetics, Tesaro; Research grant / Funding (institution): Roche, Menarini Silicon Biosystems, Janssen Diagnostics, Pfizer; Travel / Accommodation / Expenses: Pfizer,Bayer. H.L. McArthur: Advisory / Consultancy: LIlly, Amgen, Immunomedics, Pfizer, Genentech, BMS, Genomic Health, Merck, spectrum pharmaceuticals; Research grant / Funding (institution): BMS, Lilly, Merck, Ziopharm Oncology. J. Martinez: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.. C. Lai: Full / Part-time employment: Roche/Genentech; Shareholder / Stockholder / Stock options: Roche/Genentech. T. Goulioti: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.; Shareholder / Stockholder / Stock options: GlaxoSmithKline; Spouse / Financial dependant: GlaxoSmithKline, UCB. A. Bouhlel: Full / Part-time employment: Roche. V. Balta: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.. G. Viale: Honoraria (self): MSD Oncology; Advisory / Consultancy: Dako, Roche/genentech, Astellas Pharma, Novartis; Research grant / Funding (self): Roche/genentech; Research grant / Funding (institution): Ventana Medical Systems, Dako/Agilent Technologies; Travel / Accommodation / Expenses: Roche, Celgene. D.A. Nguyen: Shareholder / Stockholder / Stock options: Roche/Genentech; Full / Part-time employment: Roche/Genentech. R.D. Gelber: Research grant / Funding (institution): Roche, Novartis, Pfizer, Merck, Celgene, Ferring, Ipsen, AstraZeneca. M. Piccart: Officer / Board of Directors: Radius; Advisory / Consultancy: AstraZeneca, Lilly, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Camel-IDS, Crescendo Biologics, Periphagen, Huya, Debiopharm, PharmaMar, G1 Therapeutics, Menarini, Seattle Genetics, Immunomedics, Oncolytics; Research grant / Funding (institution): AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche-Genentech, Synthon, Radius, Servier. E.P. Winer: Honoraria (self): Genentech, Leap, Carrick Therapeutics, Lilly, Seattle Genetics, GSK. All other authors have declared no conflicts of interest.