Search

Background: Primary and acquired endocrine resistance remains a major issue in the treatment of hormone receptor positive breast cancer. Acquired resistance often results from estrogen receptor 1 (ESR1) mutations leading to estrogen independent estrogen receptor activation. Selective estrogen receptor degraders (SERDs) induce degradation of this receptor, thereby overcoming this resistance. The intramuscular administration and modest efficacy of fulvestrant, the first SERD, triggered development of oral, more potent SERDs. This narrative review gives an overview of the current evidence regarding this new drug class., Methods: Medline/PubMed and Embase database were screened using a systematic search strategy. We assessed the San Antonio Breast Cancer Symposium abstract reports, the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) meeting resources by applying the following terms: 'SERD', 'giredestrant', 'elacestrant', 'imlunestrant', 'amcenestrant', 'camizestrant' and 'rintodestrant'., Clinicaltrials: gov was consulted to include ongoing trials., Results: The search retrieved 1191 articles. After screening, 108 articles were retained. In the phase 3 EMERALD trial, elacestrant demonstrated benefit in progression free survival (PFS) in second line metastatic disease in postmenopausal women or men, leading to Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for the ESR1 mutated population. This PFS advantage was more pronounced among patients who had priorly received at least 12 months of a cyclin-dependent kinases 4/6 inhibitor (CDK4/6i). In the phase 2 SERENA-2 trial, camizestrant improved PFS as second line treatment. However, trials of giredestrant and amcenestrant failed to show PFS benefit in second line metastatic setting. In the preoperative setting, several oral SERDs resulted in a significant reduction of tumoral proliferation. Furthermore, many trials are still in progress., Conclusion: Oral SERDs constitute an exciting new drug class. Ongoing and future research will further refine the role of these drugs next to standard endocrine treatments and targeted therapies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [For Dr. Mathilde Gheysen: no conflicts of interest. For Dr. Kevin Punie: his institute received research grants from MSD and Sanofi. He received speaker fees and honoraria for consultancy and advisory board functions from Astra Zeneca, Eli Lilly, Exact Sciences, Focus Patient, Gilead, Medimix, MSD, Novartis, Pfizer, Roche, Sanofi, Seagen. He also received speaker fees and honoraria for consultancy and advisory board functions to institution: Astra Zeneca, Eli Lilly, Exact Sciences, Gilead, MSD, Novartis, Pfizer, Roche, Seagen. Travel grants from Astra Zeneca, Gilead, Novartis, Pfizer, PharmaMar, Roche. For Prof. Dr. Patrick Neven: in the last 12 months, his institution received fees for his activities in consultancy (Pfizer, Novartis, Eli Lilly, Roche, Astrazeneca), in advisory Boards (Astrazeneca, Pfizer, Novartis, Lilly, Roche, Medscape, Gilead, Menarini) and lecturing & attendance at scientific exchange meetings. For Prof. Dr. Hans Wildiers: his institution received financial compensation on his behalf for advisory boards, lecture fees and/or consultancy fees from Daiichi Sankyo, Gilead, Lilly, Pfizer, Novartis, MSD, Relay Therapeutics, PSI, Augustine Therapeutics, Astra Zeneca, Roche. He received travel support from Gilead, Daiichi Sankyo, Pfizer]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Burnout in health care professionals (HCPs) results from exposure to psychosocial risks at work. Left unaddressed, burnout can lead to chronic health problems, increased staff turnover, reduced work hours, absenteeism, and early retirement from clinical practice, thus impacting patient care. The European Society for Medical Oncology (ESMO) Resilience Task Force (RTF) was established in December 2019 to support the well-being of oncology HCPs globally. This ESMO RTF position paper aims to provide a set of recommendations to optimise well-being and mitigate burnout in oncology, and to help individuals and institutions maintain the delivery of optimal cancer care., Design: Recommendations were developed by a diverse multinational panel of interprofessional experts based on the key findings from three previously reported ESMO RTF surveys., Results: Several recurrent work-related psychosocial risks in oncology were identified; in particular, concerns about workload and professional development. The need for flexible work patterns, continued use of virtual resources, well-being resources, and targeted support for at-risk groups were highlighted as key considerations to safeguard HCPs' health and prevent burnout. In total, 11 recommendations relating to three priority themes were developed: (i) information and training; (ii) resources; (iii) activism and advocacy., Conclusion: Optimising the well-being of oncology HCPs is essential for the provision of high-quality, sustainable care for patients globally. The ESMO RTF will continue its mission and is rolling out several initiatives and activities to support the implementation of these recommendations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Until recently, treatment options for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and resistance to endocrine therapy were limited to chemotherapy. This real-world study describes treatment patterns and outcomes in patients treated with chemotherapy in the United States before approval of antibody-drug conjugates., Patients and Methods: This retrospective, observational study included adults with HR+/HER2- mBC from the ConcertAI Patient360™ Breast Cancer dataset who initiated their first chemotherapy in the metastatic setting between January 2011 and June 2021. Treatment patterns were described; real-world overall survival, time to next treatment or death, and real-world progression-free survival were evaluated for all eligible patients and patients treated with subsequent chemotherapy. Index dates were the start date of each chemotherapy treatment., Results: Among 1545 eligible patients, 76% were white, 12% had Eastern Cooperative Oncology Group performance status ≥2, 38% had de novo mBC, and median age was 61 years (range, 52-69 years). Within the index period, capecitabine was used the most as the first chemotherapy agent and decreased in later treatments, while the use of eribulin increased between first and fourth chemotherapies. Median (95% confidence interval) real-world overall survival was 23.3 months (21.3-25.4 months) from start of first chemotherapy, time to next treatment or death was 6.5 months (5.9-7.1 months), and real-world progression-free survival was 6.9 months (6.4-7.6 months); median times from second, third, and fourth chemotherapies decreased with each additional chemotherapy treatment., Conclusions: This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes., Patients and Methods: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]., Results: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype)., Conclusions: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection., Methods: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out., Results: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage., Conclusions: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Approximately 10% of breast cancers are associated with the inheritance of a pathogenic variant (PV) in one of the breast cancer susceptibility genes. Multiple breast cancer predisposing genes, including TP53, are responsible for the increased breast cancer risk. Tumor protein-53 (TP53) germline PVs are associated with Li-Fraumeni syndrome, a rare autosomal dominant inherited cancer predisposition syndrome associated with early-onset pediatric and multiple primary cancers such as soft tissue and bone sarcomas, breast cancer, brain tumors, adrenocortical carcinomas and leukemias. Women harboring a TP53 PV carry a lifetime risk of developing breast cancer of 80-90%. The aim of the present narrative review is to provide a comprehensive overview of the criteria for offering TP53 testing, prevalence of TP53 carriers among patients with breast cancer, and what is known about its prognostic and therapeutic implications. A summary of the current indications of secondary cancer surveillance and survivorship issues are also provided. Finally, the spectrum of TP53 alteration and testing is discussed. The optimal strategies for the treatment of breast cancer in patients harboring TP53 PVs poses certain challenges. Current guidelines favor the option of performing mastectomy rather than lumpectomy to avoid adjuvant radiotherapy and subsequent risk of radiation-induced second primary malignancies, with careful consideration of radiation when indicated post-mastectomy. Some studies suggest that patients with breast cancer and germline TP53 PV might have worse survival outcomes compared to patients with breast cancer and wild type germline TP53 status. Annual breast magnetic resonance imaging (MRI) and whole-body MRI are recommended as secondary prevention., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Eva Blondeaux reports research grant (to the Institution) from Gilead to pursue research effort in the field of TP53 pathogenic variants. Kevin Punie reports honoraria for consultancy/advisory roles from Astra Zeneca, Eli Lilly, Exact Sciences, Focus Patient, Gilead Sciences, MSD, Novartis, Pfizer, Roche, Seagen; honoraria for consultancy/advisory roles paid to my institution from Astra Zeneca, Eli Lilly, Exact Sciences, Gilead, MSD, Novartis, Pfizer, Roche, Seagen. Research funding paid to my institution from Sanofi and MSD. Stock options: Need Inc. Travel support: Astra Zeneca, Novartis, Pfizer, PharmaMar, Roche. Carmine De Angelis reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, and GSK, Travel Grants from Gilead and research support (to the Institution) from Novartis outside the submitted work. Sabine C. Linn reports an advisory role for AstraZeneca and Daiichi Sankyo Europe GmbH (paid to the institution), travel and accommodation expenses from Daiichi Sankyo Europe GmbH, and research support (to the institution) from Genentech/Roche, AstraZeneca, Bristol Myers Squibb, Tesaro (now GSK), Merck, Immunomedics (now Gilead), Eurocept Pharmaceuticals, Agendia, and Novartis. Mara Cruellas reports speaker honoraria from Roche and Astrazeneca. Shani Paluch-Shimon reports - advisory Board consultancy, speaker’s bureau: AstraZeneca, Pfizer, Novartis, Lilly, Roche, MSD, Exact Sciences. Gilead. Travel: Roche. Research Funding: Pfizer. Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo and Takeda, Travel Grants from Gilead and research support (to the Institution) from Gilead outside the submitted work. All the other authors declare no conflict of interest.’, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection., Methods: Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test., Results: A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P = 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P = 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%)., Conclusion: Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction in COVID-related mortality in our cohort of patients with solid cancer, highlighting that treatment continuation should be strived for, especially in the curative setting., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

New therapy options have changed the treatment landscape of early-stage triple-negative breast cancer (TNBC) in recent years. Most patients are candidates for neoadjuvant chemotherapy, which helps to downstage the tumor and tailor adjuvant systemic therapy based on pathologic response. Capecitabine, pembrolizumab, and olaparib have been incorporated into the armamentarium of adjuvant treatment for selected patients. The KEYNOTE-522 trial, that demonstrated the benefit of pembrolizumab, given in addition to neoadjuvant chemotherapy and adjuvantly after surgery, represented a paradigm shift for early-stage TNBC treatment. Pembrolizumab was continued in the adjuvant setting irrespective of response to neoadjuvant therapy, and other adjuvant therapies were not administered in the trial. Many questions were then raised on the selection of adjuvant therapy regimens for patients with residual disease (RD). Prior to the routine use of immune-checkpoint inhibitors (ICI), the value of adjuvant capecitabine for patients with RD after neoadjuvant polychemotherapy was demonstrated. Given the poor prognosis of some patients with RD after neoadjuvant chemo-immunotherapy, while the survival advantage of adding capecitabine during the adjuvant phase of pembrolizumab is unknown, it does appear safe and can be considered. Regarding patients harboring germline BRCA mutations with RD after neoadjuvant ICI-containing regimens, the combination of olaparib with pembrolizumab can be an option based on existing safety data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To examine the relationship between baseline elevated CA 15.3 (>30 kU/L) and the prevalence of primary or secondary metastatic disease in breast cancer., Methods: We performed a retrospective, single-center cohort study on patients with newly diagnosed breast cancer and baseline CA 15.3> 30 kU/L, diagnosed between 2000-2015. Information on tumor characteristics, pre-treatment CA 15.3, staging results, treatment approach, disease recurrence and death were collected from individual medical files. For every tumor subtype, the optimal cut-off value of CA 15.3 for determining primary metastatic disease is determined., Results: Eight hundred ninety-four patients with baseline CA15.3 > 30 kU/L were included of which 38% were diagnosed with primary metastatic disease while 15% subsequently developed secondary metastatic disease, with a median follow-up of 74 months. LuminalHER2 tumors had the highest proportion of primary metastatic disease (48%), Triple Negative tumors had the highest proportion of secondary metastatic disease (24%) (p=0.008). A higher CA 15.3 value corresponds to higher risk of both primary and secondary metastatic disease (p<0.001). For the determination of primary metastatic disease, optimal cut-off values for CA 15.3 range between 44 kU/L (Triple Negative) and 59 kU/L (Luminal B)., Conclusion: In patients with newly diagnosed breast cancer and baseline elevated CA 15.3>30 kU/L, 38% presents with primary metastatic disease and 15% develops secondary metastatic disease, with a median follow-up of 74 months. Our results can help clinicians to identify patients at risk of primary or secondary metastatic disease via information on tumor subtype and baseline CA 15.3., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers., Design: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials., Results: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC., Conclusion: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 has had a significant impact on the well-being and job performance of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration set out to investigate and monitor well-being since COVID-19 in relation to work, lifestyle and support factors in oncology professionals 1 year on since the start of the pandemic., Methods: An online, anonymous survey was conducted in February/March 2021 (Survey III). Key outcome variables included risk of poor well-being or distress (expanded Well-Being Index), feeling burnout (single item from expanded Well-Being Index), and job performance since COVID-19. Longitudinal analysis of responses to the series of three surveys since COVID-19 was carried out, and responses to job demands and resources questions were interrogated. SPSS V.26.0/V.27.0 and GraphPad Prism V9.0 were used for statistical analyses., Results: Responses from 1269 participants from 104 countries were analysed in Survey III: 55% (n = 699/1269) female, 54% (n = 686/1269) >40 years, and 69% (n = 852/1230) of white ethnicity. There continues to be an increased risk of poor well-being or distress (n = 464/1169, 40%) and feeling burnout (n = 660/1169, 57%) compared with Survey I (25% and 38% respectively, P < 0.0001), despite improved job performance. Compared with the initial period of the pandemic, more participants report feeling overwhelmed with workload (45% versus 29%, P < 0.0001). There remain concerns about the negative impact of the pandemic on career development/training (43%), job security (37%). and international fellowship opportunities (76%). Alarmingly, 25% (n = 266/1086) are considering changing their future career with 38% (n = 100/266) contemplating leaving the profession., Conclusion: Oncology professionals continue to face increased job demands. There is now significant concern regarding potential attrition in the oncology workforce. National and international stakeholders must act immediately and work closely with oncology professionals to draw up future-proof recovery plans., Competing Interests: Disclosure KHJL is currently funded by the Wellcome-Imperial 4i Clinical Research Fellowship, and reports speaker honorarium from Janssen, outside the submitted work. KP’s institution received speaker fees or honoraria for consultancy/advisory roles from AstraZeneca, Eli Lilly, Gilead Sciences, Medscape, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Pierre Fabre, Hoffmann La Roche, Mundipharma, PharmaMar, Seagen, Teva, and Vifor Pharma; KP’s institution received research grants from MSD and Sanofi; KP received travel support from AstraZeneca, Novartis, Pfizer, PharmaMar, and Roche; all outside the submitted work. CO reports research funding and honoraria from Roche; travel grant and honoraria from medac Pharma and Ipsen Pharma; and travel grant from PharmaMar; outside the submitted work. EÉ reports speaker honoraria, travel support and advisory board: Bayer, Roche, Servier, Amgen, Pierre-Fabre, Sanofi Aventis, MSD, and Merck Serono; outside the submitted work. TA reports personal fees from Pierre Fabre and CeCaVa; personal fees and travel grants from Bristol Myers Squibb (BMS); grants, personal fees, and travel grants from Novartis; and grants from NeraCare, Sanofi, and SkylineDx; all outside the submitted work. PG reports personal fees from Roche, MSD, BMS, Boerhinger-Ingelheim, Pfizer, AbbVie, Novartis, Lilly, AstraZeneca, Janssen, Blueprint Medicines, Takeda, Gilead, and ROVI, outside the submitted work. ML acted as a consultant for Roche, AstraZeneca, Lilly, and Novartis, and received honoraria from Theramex, Roche, Novartis, Takeda, Pfizer, Sandoz, and Lilly, outside the submitted work. CBW reports speaker honoraria, travel support, and participation in advisory boards: Bayer, BMS, Celgene, GlaxoSmithKline (GSK), Merck, Rafael, RedHil, Roche, Servier, Shire/Baxalta, Sirtex, and Taiho, as well as research support from Roche, outside the submitted work. JBAGH reports personal fees for advisory role in Neogene Tx; grants and fees paid to institution from BMS, MSD, Novartis, BioNTech, Amgen; and fees paid to institution from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, Vaximm; outside the submitted work. CH reports being Director of a private company Hardy People Ltd, outside the submitted work. SB reports research grant (institution) from AstraZeneca, Tesaro, and GSK; honoraria for advisory boards or lectures from Amgen, AstraZeneca, Genmab, Immunogen, Mersana, MSD, Merck Serono, OncXerna, Pfizer, Roche, Shattuck Labs, Clovis, Takeda outside the submitted work. KM, KK, MOC, ET, BD, and GM have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants., Patients and Methods: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy., Results: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group., Conclusion: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing., Competing Interests: Disclosure EdA has acted as a scientific advisory board member and has received honoraria from Roche/Genentech, Novartis, Seattle Genetics, Zodiacs, Libbs, Pierre Fabre, and Lilly; has received travel grants from Roche/GNE and GlaxoSmithKline (GSK)/Novartis; and has received research grants through his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier, outside the submitted work. FAP has acted as consultant for Ipsen, Roche Diagnostic, and Merck outside the submitted work. CRJ has acted as a scientific advisory board member and her institution has received honoraria from Bristol Myers Squibb (BMS), Theramex, and Roche; and her institution has received speaker's fees from Theramex and BMS, outside the submitted work. AS has acted as a consultant for Eli Lilly, Pfizer, Novartis, and Roche; has received speaker's fees from Teva, Roche, Pfizer, and Novartis; has received travel grants from Neopharm, Celgene, and Medison; and has received grant support from Novartis and Roche, outside the submitted work. CVG has acted as a consultant, as a scientific advisory board member, and has received speaker's fees from Roche, Novartis, Pfizer, Lilly, and Merck Sharp & Dohme (MSD); and has received research funding from AstraZeneca, Roche, and Pfizer, outside the submitted work. OCC has acted as a scientific advisory board member for Ascires Sistemas Genómicos; and has received grant support from Roche Diagnostics, Neomedic, and Takeda, outside the submitted work. KP has acted as a scientific advisory board member for AstraZeneca, Eli Lilly, Gilead Sciences, MSD, Novartis, Pierre Fabre, Roche, Teva, and Vifor Pharma; has acted as a consultant for AstraZeneca, Novartis, Pfizer, and Roche; has received speaker's fees from Eli Lilly, Medscape, MSD, Mundi Pharma, Novartis, Pfizer, and Roche; has received travel grants from AstraZeneca, Novartis, Pfizer, PharmaMar, and Roche, outside the submitted work. FP has acted as a scientific advisory board member and has received speaker's fees from Amgen, AstraZeneca, Daichi-Sankyo, Eisai, Eli Lilly, Ipsen, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Seagen, and Takeda; has received travel grants from Celgene, GlaxoSmithKline, and Roche; and has received research funding from AstraZeneca, Eisai, and Roche, outside the submitted work. ARF has received honoraria from Bayer, Daiichi Sankyo, Novartis, and Roche; and has received travel grants from Roche, outside the submitted work. JB has acted as consultant for AstraZeneca and Pfizer outside the submitted work. ID has acted as a scientific advisory board member and received grant from Roche; has received speaker's fees from Novartis; and has received travel grants from Theramex and Ferring, outside the submitted work. ML has acted as a consultant for Roche, Lilly, AstraZeneca, Exact Sciences, and Novartis; and has received honoraria from Sandoz, Roche, Lilly, Pfizer, Novartis, Ipsen, and Takeda, outside the submitted work. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes., Patients and Methods: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline., Results: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations., Conclusions: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup., Competing Interests: Disclosure AB: consultancy/advisory role with Biotheranostics Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Daiichi Sanyo/AstraZeneca, Puma, Philips, Eli Lilly, and Foundation Medicine; research funding from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics; travel/accommodations/expenses from Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, and Sanofi. SMT: research funding from Bristol Myers Squibb, Eisai, Immunomedics, Genentech/Roche, Pfizer, Novartis, Nektar, Merck, AstraZeneca, Eli Lilly, and Exelixis. KP: consultancy/advisory role with AstraZeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Hoffmann-La Roche, Vifor Pharma, and European Centre for Clinical Research Training; speaker’s bureau with Eli Lilly, Mundipharma, Novartis, Pfizer, and Hoffmann-La Roche; research funding from Sanofi; expert testimony for Hoffmann-La Roche; travel/accommodations/expenses from AstraZeneca, Novartis, Pfizer, PharmaMar, and Hoffmann-La Roche. DL: consultancy/advisory role with Novartis, Merck Sharp & Dohme (MSD), and Roche. MO: research funding from Immunomedics, Roche, Genentech, PUMA Biotechnology, AstraZeneca, Seattle Genetics, Boehringer Ingelheim, and Novartis; expenses from Roche, Genentech, PUMA Biotechnology, AstraZeneca, Seattle Genetics, and Novartis; non-financial support from Roche, Pierre Fabre, Eisai, GP Pharma, Grünenthal, and Novartis. KK: employment (spouse) with Array Biopharma, Pfizer, and Grail; consultancy/advisory role with Immunomedics, Pfizer, Eisai, Eli Lilly, Amgen, and AstraZeneca; institutional research funding from Immunomedics, Novartis, Incyte, Genentech/Roche, Eli Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zentalis Pharmaceuticals, and CytomX Therapeutics; research funding (spouse) from Array Biopharma, Pfizer, and Grail. AZ: consultancy roles with Novartis and Pfizer. PA: travel/accommodations/expenses from Boehringer Ingelheim, MacroGenics, Amvure, Synthon, Servier, G1 Therapeutics, Roche, Novartis, Amgen, Radius, MSD, and Pfizer. SS: advisory role with Immunomedics, Novartis, and Biotheranostics. EH: consultancy/advisory role with Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Eli Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, and SeaGen; institutional research funding from OncoMed, Genentech/Roche, Zymeworks, Rgenix, ArQule, Clovis, Silverback Therapeutics, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Torque, Black Diamond, Karyopharm, Infinity Pharmaceuticals, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Fochon, Molecular Templates, Onconova Therapeutics, Dana-Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, SeaGen, Puma Biotechnology, Compugen, TapImmune, Eli Lilly, Pfizer, H3 Biomedicine, Takeda, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, MacroGenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, Merck, PharmaMar, Olema, Polyphor, Immunogen, Plexxikon, Amgen, Akesobio Australia, and Shattuck Labs. PS: consultancy role with Immunomedics. ECG: consultancy role with Pfizer, Roche, AstraZeneca, Novartis, and Eli Lilly; speaker’s bureau with Roche, Pfizer, and Eli Lilly. TT: consultancy/advisory role with Genentech/Roche, Pfizer, AstraZeneca, Merck, Puma Biotechnology, Advaxis, Celgene, Innocrin Pharma, Genomic Health, Bristol Myers Squibb, Samsung, Athenex, Aduro Biotech, Halozyme, Daiichi Sankyo, Ionis, and Seattle Genetics; speaker’s bureau with Roche/Genentech; research funding from Eisai, Pfizer, Novartis, Innocrin Pharma, AstraZeneca, Astellas Pharma, Immunomedics, Genentech/Roche, Daiichi Sankyo, Carrick Pharm.JO: consultancy/advisory role with AbbVie, Agendia, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, Genentech, Immunomedics, Jounce Therapeutics, Eli Lilly, Merck, Novartis, Pfizer, Puma Biotechnology, Roche, and Seattle Genetics. JC: consultancy/advisory role with Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceuticals, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Eli Lilly, Servier, MSD, GlaxoSmithKline (GSK), Leuko, Bioasis, and Clovis Oncology; speaker’s bureau for Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Eli Lilly, MSD, and Daiichi Sankyo; institutional research funding from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardant Health, MSD, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; ownership interest in MedSIR. LV: consultancy role with Berg Pharma, Seattle Genetics, Polyphor, Immunomedics, and Osmol Therapeutics; speaker’s bureau with Eisai; contracted research with Roche, OncoTherapy Science, Arvinas, Genentech, Seattle Genetics, and Immunomedics. VD: consultancy/advisory role with Roche/Genentech, Novartis, Eli Lilly, Pfizer, AstraZeneca, Eisai, AbbVie, MSD, Daiichi Sankyo, and Seattle Genetics; speaker’s bureau for Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, and Daiichi Sankyo; travel/accommodations/expenses from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, and Daiichi Sankyo. LAC: royalties (spouse) from Falcon Therapeutics; research funding from Innocrin Pharma, Syndax, Immunomedics, Novartis, and NanoString Technologies; institutional research funding from Sanofi-Aventis, Novartis, G1 Therapeutics, Genentech/Roche, and GSK. HSR: consultancy/advisory role with Samsung and Puma; research funding from Pfizer, Novartis, Eli Lilly, Genentech/Roche, MacroGenics, OBI, Merck, Eisai, Immunomedics, Daiichi, Seattle Genetics, and Odonate; travel/accommodations/expenses from Daiichi, Mylan, Pfizer, Merck, AstraZeneca, Novartis, and MacroGenics. DMG: intellectual property rights/patent holder at Immunomedics; ownership interest with Immunomedics; other interests with Center for Molecular Medicine & Immunology. QH, MO, LMI: employment with Immunomedics. SAH: research funding from Ambrx, Amgen, Arvinas, Bayer, Daiichi Sankyo, Genentech/Roche, GSK, Immunomedics, Eli Lilly, MacroGenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, Sanofi, Seattle Genetics, and Dignitana; ownership interest with NKMax. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Most current guidelines do not recommend the serial analysis of tumour marker CA 15.3 in the follow-up of asymptomatic patients treated for early breast cancer (EBC). These guidelines are based on small-scale studies carried out in an era with more limited treatment options than today. In our large academic centre, serial measurements of CA 15.3 are used routinely in the follow-up of EBC, whereas imaging for distant metastases is only carried out on indication., Patients and Methods: In this retrospective single-centre study, patients were included if they were treated for EBC between 1 January 2000 and 1 January 2018, diagnosed with secondary metastatic disease at least 6 months after initial surgery and had CA 15.3 available at the time of diagnosis of metastases. The primary objective was to evaluate the proportion of patients in whom metastatic disease was discovered by an increasing CA 15.3. Information on the method of metastases detection, CA 15.3 evolution and survival was collected after approval of the ethics committee., Results: At the moment of diagnosis of metastases, 451 of 730 included patients (62%) had CA 15.3 levels above the upper limit of normal (>30 kU/l). In 269 patients (37%), an increasing CA 15.3 was the first sign that led to the diagnosis of metastases. This was most frequent in luminal A-like tumours (48%) and in liver (45%) and bone (41%) localisation of metastases. By contrast, reported symptoms triggered the diagnosis of metastatic disease in 48% of the patients. Median overall survival was significantly longer when the relapse was discovered by CA 15.3 elevation versus those discovered by another trigger (abnormal clinical examination or history, abnormal laboratory tests or an incidental finding) (35 versus 22 months; P = 0.0027)., Conclusion: When CA 15.3 is systematically used in the follow-up of EBC patients, the diagnosis of metastatic disease is made in 37% by a CA 15.3 increase., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Two new antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor payload have recently emerged in the breast cancer (BC) treatment landscape. Sacituzumab govitecan-hziy (SG) is a first-in-class anti-trophoblast cell-surface antigen 2 ADC approved for pretreated metastatic triple-negative breast cancer (mTNBC) and trastuzumab deruxtecan (T-DXd) gained approval for human epidermal growth factor receptor-2 (HER2)-positive advanced BC (aBC). We aim to provide a contemporary review and the current clinical trial landscape of SG and T-DXd in BC., Materials and Methods: We conducted a literature search from Medline database through PubMed, major conference proceedings [abstracts from European Society for Medical Oncology (Breast) Congress, American Society of Clinical Oncology annual meeting, San Antonio Breast Cancer Symposium] and ClinicalTrials.gov with search terms 'sacituzumab govitecan', 'IMMU-132', 'trastuzumab deruxtecan' and 'DS-8201a' up to 21 March 2021., Results: We assessed 293 records for eligibility, of which 153 were included in this review after screening and exclusion. For SG, efficacy and safety data are available from a phase III trial in pretreated mTNBC and from a phase I/II basket study in mTNBC and hormone receptor-positive/HER2-negative aBC. Thirteen trials with pending primary analysis are ongoing with SG as single agent or in combination, of which 11 are enrolling (2/11 in the early setting). For T-DXd, efficacy/safety data are available as single agent in pretreated HER2-positive (phase Ib and phase II) and in HER2-low aBC (phase Ib), and in combination with nivolumab in HER2-low/positive aBC (phase Ib). Of 23 ongoing trials with T-DXd, 12 are open for enrollment and 3 phase III trials have completed recruitment. The distinct safety profiles of both drugs and their management are discussed., Conclusion: Given their robust single-agent activity, SG and T-DXd are expected to substantially impact treatment standards, both in and far beyond the currently approved indications. Several trials are investigating new treatment settings for both drugs, including a transition to earlier lines and combinations with other anticancer treatments such as immune checkpoint inhibitors., Competing Interests: Disclosure PN's institution received honoraria for advisory boards and research funding from AstraZeneca, Amgen, Eli Lilly, Novartis, Pfizer and Roche (all outside the submitted work). HW received travel support from Roche and Pfizer (all outside the submitted work), institution received consulting fees and honoraria from AstraZeneca, Biocartis, Lilly, Novartis, Pfizer, PUMA Biotechnology, Roche, Sirtex and Daiichii-Sankyo and unrestricted research grants from Roche and Novartis. KP received travel support from AstraZeneca, Pfizer, PharmaMar and Roche (all outside the submitted work), institution received honoraria for advisory/consultancy roles for AstraZeneca, Eli Lilly, Gilead Sciences, Novartis, Pfizer, Pierre Fabre, Roche, Teva and Vifor Pharma; speaker fees for Eli Lilly, Medscape, MSD, Mundi Pharma, Novartis, Pfizer and Roche; and research funding from Sanofi. EA has declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Quality indicators (QIs) for the management of breast cancer (BC) have been published in Europe and internationally. In Belgium, a task force was established to select measurable process indicators of systemic treatment for BC, focusing on appropriateness of delivered care. The objective of this study was to evaluate the results of the selected QIs, both nationally and among individual centres., Patients and Methods: Female Belgian residents with unilateral primary invasive BC diagnosed between 2010 and 2014 were selected from the Belgian Cancer Registry database. The national number enabled linkage with the national reimbursement database, which contains information on all reimbursed medical procedures. A total of 12 process indicators were measured on the population and hospital level. Intercentre variability was assessed by median results and interquartile ranges., Results: A total of 48  872 patients were included in the study. QIs concerning specific BC subtypes only applied to patients diagnosed in 2014 (n = 9855). Clinical stage (cStage) I patients (n = 17 116) were staged with positron emission tomography/computed tomography. Among patients who were pT1aN0 human epidermal growth factor receptor 2 (HER2) positive (n = 47), 25.5% (n = 12) received adjuvant trastuzumab. Among patients with de novo metastatic luminal A/B-like HER2-negative BC (n = 295), 17.3% (n = 51) received upfront chemotherapy. (Neo)adjuvant chemotherapy was administered in 52.4% (n = 12 592) of operated women with cStage I-III, in 37.0% (n = 1270) of operated women with cStage I-III luminal A/B-like HER2-negative BC, and in 19.1% of operated women with cStage I luminal A/B-like HER2-negative BC. In the population of operated patients with cStage I-III, of those younger than 70 years that started adjuvant endocrine therapy (n = 3591), 81.7% (n = 2932) continued treatment for ≥4.5 years. Among patients in cStage I-III older than 70 years (n = 8544), 19.0% (n = 1622) received (neo)adjuvant chemotherapy, whereas among patients with cStage I-III luminal A/B-like HER2-negative BC (n = 1388), 13.0% (n = 181) received (neo)adjuvant chemotherapy. In patients with cStage I-II luminal A/B-like HER2-negative BC older than 70 years (n = 1477), 11.6% (n = 171) were not operated and received upfront endocrine treatment., Conclusion: Well-considered QIs using population-based data can evaluate quality of care and expose disparities among treatment centres. Their use in daily practice should be implemented in all centres treating BC., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has resulted in significant changes to professional and personal lives of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration aimed to provide contemporaneous reports on the impact of COVID-19 on the lived experiences and well-being in oncology., Methods: This online anonymous survey (July-August 2020) is the second of a series of global surveys launched during the course of the pandemic. Longitudinal key outcome measures including well-being/distress (expanded Well-being Index-9 items), burnout (1 item from expanded Well-being Index), and job performance since COVID-19 were tracked., Results: A total of 942 participants from 99 countries were included for final analysis: 58% (n = 544) from Europe, 52% (n = 485) female, 43% (n = 409) ≤40 years old, and 36% (n = 343) of non-white ethnicity. In July/August 2020, 60% (n = 525) continued to report a change in professional duties compared with the pre-COVID-19 era. The proportion of participants at risk of poor well-being (33%, n = 310) and who reported feeling burnout (49%, n = 460) had increased significantly compared with April/May 2020 (25% and 38%, respectively; P < 0.001), despite improved job performance since COVID-19 (34% versus 51%; P < 0.001). Of those who had been tested for COVID-19, 8% (n = 39/484) tested positive; 18% (n = 7/39) felt they had not been given adequate time to recover before return to work. Since the pandemic, 39% (n = 353/908) had expressed concerns that COVID-19 would have a negative impact on their career development or training and 40% (n = 366/917) felt that their job security had been compromised. More than two-thirds (n = 608/879) revealed that COVID-19 has changed their outlook on their work-personal life balance., Conclusion: The COVID-19 pandemic continues to impact the well-being of oncology professionals globally, with significantly more in distress and feeling burnout compared with the first wave. Collective efforts from both national and international communities addressing support and coping strategies will be crucial as we recover from the COVID-19 crisis. In particular, an action plan should also be devised to tackle concerns raised regarding the negative impact of COVID-19 on career development, training, and job security., Competing Interests: Disclosure KHJL is currently funded by the Wellcome-Imperial 4i Clinical Research Fellowship, and reports speaker honorarium from Janssen, outside the submitted work. KP’s institution received speaker fees or honoraria for consultancy/advisory roles from AstraZeneca, Eli Lilly, Gilead Sciences, Medscape, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Pierre Fabre, Hoffmann La Roche, Mundipharma, PharmaMar, Teva, Vifor Pharma; KP’s institution received a research grant from Sanofi; KP received travel support from AstraZeneca, Novartis, Pfizer, PharmaMar and Roche; all outside the submitted work. CO reports research funding and honoraria from Roche; travel grant and honoraria from Medac Pharma and Ipsen Pharma; and travel grant from PharmaMar; outside the submitted work. TA reports personal fees from Pierre Fabre and CeCaVa; personal fees and travel grants from Bristol-Myers Squibb (BMS); grants, personal fees, and travel grants from Novartis; and grants from Neracare, Sanofi, and SkylineDx; all outside the submitted work. PG reports personal fees from Roche, MSD, BMS, Boerhinger-Ingelheim, Pfizer, AbbVie, Novartis, Lilly, AstraZeneca, Janssen, Blueprint Medicines, Takeda, Gilead, and ROVI, outside the submitted work. ML acted as a consultant for Roche, AstraZeneca, Lilly, and Novartis, and received honoraria from Theramex, Roche, Novartis, Takeda, Pfizer, Sandoz, and Lilly, outside the submitted work. CBW reports speaker honoraria, travel support, and advisory board: Bayer, BMS, Celgene, Roche, Servier, Shire/Baxalta, RedHil, and Taiho; speaker honoraria from Ipsen; and advisory board in GlaxoSmithKline (GSK), Sirtex, and Rafael; outside the submitted work. JBAGH reports personal fees for advisory role in Neogene Tx; grants and fees paid to institution from BMS, MSD, Novartis, BioNTech, Amgen; and fees paid to institution from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, Vaximm; outside the submitted work. CH reports being Director of a private company Hardy People Ltd., outside the submitted work. SB reports research grant (institution) from AstraZeneca, Tesaro, and GSK; honoraria from Amgen, AstraZeneca, MSD, GSK, Clovis, Genmab, Merck Serono, Mersana, Pfizer, Seattle Genetics, and Tesaro; outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on well-being has the potential for serious negative consequences on work, home life, and patient care. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration set out to investigate well-being in oncology over time since COVID-19., Methods: Two online anonymous surveys were conducted (survey I: April/May 2020; survey II: July/August 2020). Statistical analyses were performed to examine group differences, associations, and predictors of key outcomes: (i) well-being/distress [expanded Well-being Index (eWBI; 9 items)]; (ii) burnout (1 item from eWBI); (iii) job performance since COVID-19 (JP-CV; 2 items)., Results: Responses from survey I (1520 participants from 101 countries) indicate that COVID-19 is impacting oncology professionals; in particular, 25% of participants indicated being at risk of distress (poor well-being, eWBI ≥ 4), 38% reported feeling burnout, and 66% reported not being able to perform their job compared with the pre-COVID-19 period. Higher JP-CV was associated with better well-being and not feeling burnout (P < 0.01). Differences were seen in well-being and JP-CV between countries (P < 0.001) and were related to country COVID-19 crude mortality rate (P < 0.05). Consistent predictors of well-being, burnout, and JP-CV were psychological resilience and changes to work hours. In survey II, among 272 participants who completed both surveys, while JP-CV improved (38% versus 54%, P < 0.001), eWBI scores ≥4 and burnout rates were significantly higher compared with survey I (22% versus 31%, P = 0.01; and 35% versus 49%, P = 0.001, respectively), suggesting well-being and burnout have worsened over a 3-month period during the COVID-19 pandemic., Conclusion: In the first and largest global survey series, COVID-19 is impacting well-being and job performance of oncology professionals. JP-CV has improved but risk of distress and burnout has increased over time. Urgent measures to address well-being and improve resilience are essential., Competing Interests: Disclosure SB reports research grant (institution) from AstraZeneca, Tesaro, and GSK; honoraria from Amgen, AstraZeneca, MSD, GSK, Clovis, Genmab, Immunogen, Merck Serono, Mersana, Pfizer, Seattle Genetics, Roche and Tesaro outside the submitted work. KHJL is currently funded by the Wellcome-Imperial 4i Clinical Research Fellowship, and reports speaker honorarium from Janssen outside the submitted work. KP reports personal fees from Astra Zeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Hoffmann La Roche, Mundi Pharma, and PharmaMar; and other fees paid to institution from Vifor Pharma, TEVA, and Sanofi outside the submitted work. CO reports research funding and honoraria from Roche; travel grant and honoraria from Medac Pharma and Ipsen Pharma; and travel grant from PharmaMar outside the submitted work. ML acted as a consultant for Roche, AstraZeneca, Lilly, and Novartis, and received honoraria from Theramex, Roche, Novartis, Takeda, Pfizer, Sandoz, and Lilly outside the submitted work. CBW reports speaker honoraria, travel support, and serving on the advisory board in Bayer, BMS, Celgene, Roche, Servier, Shire/Baxalta, RedHill, and Taiho; speaker honoraria from Ipsen; and advisory board in GSK, Sirtex, and Rafael outside the submitted work. PG reports personal fees from Roche, MSD, BMS, Boehringer Ingelheim, Pfizer, AbbVie, Novartis, Lilly, AstraZeneca, Janssen, Blueprint Medicines, Takeda, Gilead, and ROVI outside the submitted work. TA reports personal fees from Pierre Fabre and CeCaVa; personal fees and travel grants from BMS; grants, personal fees, and travel grants from Novartis; and grants from NeraCare, Sanofi, and SkylineDx outside the submitted work. JBAGH reports personal fees for advisory role in Neogene Tx; grants and fees paid to institution from BMS, MSD, Novartis, BioNTech, Amgen; and fees paid to institution from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm outside the submitted work. CH reports private company Hardy People Ltd. outside the submitted work. The remaining authors have declared no conflicts of interest., (Copyright © 2021 ESMO. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure KP’s institution received honoraria for advisory/consultancy roles for Astra Zeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Hoffmann/La Roche and Vifor Pharma (paid to institution, outside the submitted work); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer, Hoffmann/La Roche and Teva (paid to institution, outside the submitted work); research funding from Sanofi (paid to institution, outside the submitted work). KP received travel support from Astra Zeneca, Novartis, Pfizer, PharmaMar and Hoffmann/La Roche. AM has no conflicts of interest to disclose.

Competing Interests: Disclosure ML acted as a consultant for Roche, Novartis, Lilly and AstraZeneca, and received honoraria from Theramex, Takeda, Roche, Lilly, Pfizer, Novartis and Sandoz outside the submitted work. KP's institution received honoraria for advisory/consultancy roles for Astra Zeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Hoffmann/La Roche and Vifor Pharma (paid to institution, outside the submitted work); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer, Hoffmann/La Roche and Teva (paid to institution, outside the submitted work); research funding from Sanofi (paid to institution, outside the submitted work). KP received travel support from Astra Zeneca, Novartis, Pfizer, PharmaMar and Hoffmann/La Roche.

Background: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC., Methods: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m 2 every week for 12 weeks followed by doxorubicin at 60 mg/m 2 and cyclophosphamide at 600 mg/m 2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing., Findings: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group)., Interpretation: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile., Funding: F Hoffmann-La Roche/Genentech., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer., Methods: We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis)., Results: A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (<60 years) and 2.27 (95% CI 1.41 to 3.64) among patients without other comorbidities. Severe event occurrence was similar in both groups (36.7% vs 28.8%; aOR 1.10; 95% CI 0.95 to 1.29)., Conclusions: This population-based analysis demonstrates that solid cancer is an independent adverse prognostic factor for in-hospital mortality among patients with COVID-19. This adverse effect was more pronounced among younger patients and those without other comorbidities. Patients with solid cancer should be prioritised in vaccination campaigns and in tailored containment measurements., Competing Interests: Competing interests: EdA: honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen and Zodiac; travel grants from Roche/GNE and GSK/Novartis; research grants to his institution from Roche/GNE, AstraZeneca, GSK/Novartis and Servier. MB: speaker honoraria and travel grants from Roche/GNE; research grants to her institution from Roche/GNE, AstraZeneca, GSK/Novartis and Servier. HW: his institution received consulting fees and honoraria from AstraZeneca, Biocartis, Lilly, Novartis, Pfizer, PUMA Biotechnology, Roche, Sirtex, Daiichi; his institution received unrestricted research grants from Roche and Novartis; he received travel support from Roche and Pfizer. AL: no conflicts of interest to disclose. SA: speaker fees from BMS, AstraZeneca, Roche, Sanofi and Novartis; travel grants from Pfizer, Roche; advisory board fee from Sanofi and Pierre Fabre. CF: advisory board fee from Lilly. JC: advisory board and lectures from Amgen, Servier, Bayer, Novartis, Pfizer, Celgen, Ipsen (paid to institution); travel grants from Roche, Pfizer, Amgen, Novartis. WL: honoraria and/or advisory board from BMS, MSD, Novartis, IPSEN and Bayer; travel support from Roche, MSD and IPSEN. JV: no conflicts of interest to disclose. AR: honoraria and/or advisory board from Sanofi, BMS, Novartis, Pierre Fabre, Roche; travel support from Roche, BMS, MSD. PV: honoraria and/or advisory board from Roche, Novartis, Pfizer, Lilly, MSD, Merus; travel grants from Roche, AstraZeneca, MSD and Pfizer; speaker fees from Pfizer and Roche (paid to institution). JCG: advisory board and lectures from Ipsen, BMS, Janssen, Bayer, AstraZeneca. WD: honoraria and/or advisory board from Amgen, Pierre Fabre. DVB: no conflicts of interest to disclose JD: no conflicts of interest to disclose. SR: consulting fees and honoraria from J&J, Roche, Pfizer, AstraZeneca, Novartis, Bayer, MSD, BMS, Ipsen; research grants from Roche, BSM and MSD; travel grants from Ipsen, Pfizer, Bayer. TG: no conflicts of interest to disclose. KP: honoraria for advisory/consultancy roles for AstraZeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Hoffmann/La Roche and Vifor Pharma (paid to institution); speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer and Hoffmann/La Roche (paid to institution); research funding from Sanofi (paid to institution); travel support from AstraZeneca, Novartis, Pfizer, PharmaMar and Hoffmann/La Roche., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period., Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States)., Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade., Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)