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Background/objectives: With breast cancer (BC) survival improving due to optimized therapy, enhancing quality of life has become increasingly important. Both diagnosis and treatment, with their potential side effects, pose risks to mental well-being. Our study aimed to analyze the incidence and potential risk factors for mental disorders in BC patients., Methods: This retrospective analysis used claims data from AOK Baden-Wuerttemberg, including 11,553 BC patients diagnosed via ICD code C50 between 2010 and 2020 and 31,944 age-matched controls. Patients with mental disorders in the 12 months prior to diagnosis were excluded. Mental disorders were categorized into eight groups based on ICD codes: anxiety, obsessive compulsive disorder, adjustment disorder, dissociative disorder, hypochondriac disorder, affective disorder, mania, and other neuroses., Results: Mental disorders were significantly more common in BC patients than in controls (64.2% vs. 38.1%, p < 0.01, OR 2.91, 95%CI [2.79, 3.04]). In particular, hypochondriac, anxiety, affective, and adjustment disorders occurred significantly more often in BC patients. No differences were found for mania, bipolar disease, other neuroses, obsessive compulsive-, or dissociative disorders. Furthermore, endocrine therapy was associated with psychological comorbidities (OR 1.69, p < 0.001, 95%CI [1.53, 1.86]), while primarily metastasized patients (stage C) had a lower risk than adjuvant patients in stage A (OR 0.55, p < 0.0001, 95%CI [0.49, 0.61]). Regarding surgical treatment, mastectomy patients showed lower rates of mental illnesses (61.2%) than those with breast-conserving treatment (71.6%), or especially breast reconstruction (78.4%, p < 0.01). Breast reconstruction was also associated with more hypochondriac ( p < 0.01) and adjustment disorders ( p < 0.01)., Conclusions: So, BC patients experience significantly more mental disorders than controls, particularly when treated with endocrine therapy and breast reconstructive surgery.

Purpose: Breast cancer is a primary cause of cancer-related death among women worldwide. Neoadjuvant chemotherapy (NACT) is a cornerstone treatment for locally advanced, non-metastatic breast cancer. Achieving pathological complete response (pCR) is often used as a surrogate marker for long-term outcomes. This study examines the impact of obesity, defined by a body mass index (BMI) over 30 kg/m 2 , on achieving pCR in patients with early stage breast cancer (eBC) undergoing NACT., Methods: A retrospective analysis was conducted on patients with eBC treated with NACT at the University of Tübingen. The primary objective was to assess the impact of obesity on achieving pCR. Logistic regression analysis was used to determine the association between pre-treatment BMI and pCR, adjusting for covariates such as age, tumor stage, grading, and chemotherapy intensity., Results: The study included 325 patients, with 24% classified as obese. While the univariate logistic regression analysis showed no significant impact of obesity on the odds ratio of achieving pCR, the multivariate analysis, accounting for covariates, demonstrated that obese patients had a significantly higher likelihood of achieving pCR., Conclusion: In this retrospective study, obesity significantly affected the likelihood of achieving pCR in patients with eBC cancer undergoing NACT after adjusting for covariates. While obesity is a known risk factor for breast cancer development and progression, its impact on the efficacy of NACT in terms of achieving pCR was positive in our study. These findings contribute to the ongoing debate in the literature, though the retrospective design and potential uncontrolled factors should be considered., (© 2024. The Author(s).)

Background: Although adequate physical activity has been shown to be beneficial in early breast cancer, evidence in metastatic breast cancer is sparse and contradictory, which could be related to distinct effects of physical activity on the different molecular cancer subtypes. Therefore, we here evaluated the effect of physical activity on progression-free and overall survival (PFS, OS) in metastatic breast cancer, specifically looking at molecular subtypes., Methods: International Physical Activity Questionnaire (IPAQ) questionnaires, filled out by patients enrolled in the prospective PRAEGNANT registry (NCT02338167; n = 1,270) were used to calculate metabolic equivalent task (MET) minutes, which were subsequently categorized into low (n = 138), moderate (n = 995) or high IPAQ categories (n = 137). Cox regression analyses were used to evaluate the impact of IPAQ categories and its interaction with molecular subtypes on PFS and OS., Results: Patient and tumor characteristics were equally distributed across IPAQ categories. HER2pos, HRpos and TNBC were present in 23.1%, 65.7% and 11.2% of patients, respectively. IPAQ scores did not have an impact on PFS and OS in addition to established prognostic factors, either overall or in particular molecular subtypes (PFS: p = 0.33 and OS: p = 0.08, likelihood ratio test). Exploratory analyses showed higher overall survival rates for high IPAQ categories compared to low/moderate IPAQ categories in luminal B-like breast cancer., Conclusions: Self-reported physical activity using the IPAQ questionnaire did not significantly affect PFS or OS in patients suffering from metastatic breast cancer. Nevertheless, some hypothesis-generating differences between molecular subtypes could be observed, which may be interesting to evaluate further., (© 2024. The Author(s).)

Background: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials., Methods: Between 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed., Results: Among 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria., Conclusion: Patient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P.A.F. reports grants from Biontech and Cepheid, personal fees from Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, MSD, Lilly, Pierre Fabre, SeaGen, Roche, Hexal, Agendia, Gilead. C.C.H. received honoraria from AstraZeneca, Daiichi Sankyo, Eisai, Novartis, Pfizer, Roche, Gilead and MSD, and travel grants from Daiichi-Sankyo. N.N. is an employee of Novartis Pharma GmbH. B.A. received honoraria from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Stemline, Teva, Tesaro, Daiichi Sankyo and Pfizer. Received travel grants from AstraZeneca, Roche, Novartis, Celgene, Lilly, Eisai, Stemline, Daiichi Sankyo and Pfizer. Participated in the data safety monitoring board or advisory boards for AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Tesaro, Daiichi Sankyo and Pfizer. S.K. received honoraria from Amgen, Celgene, Daiichi Sankyo, Novartis and Roche. C.T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. H.-C.K. received honoraria from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, TEVA, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, Daiichi Sankyo, Gilead and Zuellig, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, Gilead, AstraZeneca, Zuellig, and Stemline, participated in data safety monitoring or advisory boards for Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen, MSD, Gilead, Daiichi Sankyo, Seagen, Genomic Health/Exact Sciences, Agendia, Lilly and owns stock of Theraclion SA. W.J. has received research grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Celgene and Johnson&Johnson. A.S. reported grants from Celgene, Roche and AbbVie. Personal fees from Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, and Pierre Fabre, and travel grants from Celgene, Roche, Pfizer and AstraZeneca. F.M. received honoraria from Amgen, AstraZeneca, Celgene, Clovis Oncology, CureVac, Eisai, Genomic Health, GSK, Immunomedics, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, PharmaMar, Roche, Seattle Genetics, Tesaro. M.W.S. received honoraria from AstraZeneca, Pfizer, Clovis, Mylan, Roche, Gedeon Richter, Carl Zeiss Meditec, travel support from Pfizer, Carl Zeiss Meditec. C.J. reports personal fees from AstraZeneca, Exact Sciences, Lilly, Novartis and Roche. V.M. received speaker honoraria from AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institut. Consultancy honoraria: Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline. Institutional research support from Novartis, Roche, Seagen, Genentech, AstraZeneca. Travel grants from AstraZeneca, Roche, Pfizer, Daiichi Sankyo, Gilead. C.R. received honoraria from MSD and AstraZeneca, travel expenses from the Swiss Society of Senology and the Swiss Society of Gynecology. P.D. received honoraria from MSD, Pierre Fabre, Novartis, AstraZeneca, Lilly, Gilead, Pfizer, Roche. E.B. received honoraria from Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, Bayer, Ipsen, Bluebird, B. Braun and onkowissen.de for consulting, clinical research management or medical education activities. S.Y.B. has received honoraria from Roche Pharma, Novartis, Pfizer, MSD, Teva, AstraZeneca. T.N.F. has received honoraria from Novartis, Roche, Pfizer, TEVA, Diachii Sankyo, AstraZeneca and MSD. All of the remaining authors have declared that they do not have any conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Germline mutations in BRCA1 and BRCA2 (gBRCA1/2) are required for a PARP inhibitor therapy in patients with HER2-negative (HER2-) advanced breast cancer (aBC). However, little is known about the prognostic impact of gBRCA1/2 mutations in aBC patients treated with chemotherapy. This study aimed to investigate the frequencies and prognosis of germline and somatic BRCA1/2 mutations in HER2- aBC patients receiving the first chemotherapy in the advanced setting. Patients receiving their first chemotherapy for HER2- aBC were retrospectively selected from the prospective PRAEGNANT registry (NCT02338167). Genotyping of 26 cancer predisposition genes was performed with germline DNA of 471 patients and somatic tumor DNA of 94 patients. Mutation frequencies, progression-free and overall survival (PFS, OS) according to germline mutation status were assessed. gBRCA1/2 mutations were present in 23 patients (4.9%), and 33 patients (7.0%) had mutations in other cancer risk genes. Patients with a gBRCA1/2 mutation had a better OS compared to non-mutation carriers (HR: 0.38; 95%CI: 0.17-0.86). PFS comparison was not statistically significant. Mutations in other risk genes did not affect prognosis. Two somatic BRCA2 mutations were found in 94 patients without gBRCA1/2 mutations. Most frequently somatic mutated genes were TP53 (44.7%), CDH1 (10.6%) and PTEN (6.4%). In conclusion, aBC patients with gBRCA1/2 mutations had a more favorable prognosis under chemotherapy compared to non-mutation carriers. The mutation frequency of ~5% with gBRCA1/2 mutations together with improved outcome indicates that germline genotyping of all metastatic patients for whom a PARP inhibitor therapy is indicated should be considered., (© 2024. The Author(s).)

Background With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry. Methods Patients with information available on the first three therapy lines were selected from the German PRAEGNANT registry (NCT02338167). Attrition was determined for each therapy line using competing risk analyses, with the start of the next therapy line or death as endpoints. Additionally, a simple attrition rate was calculated based on the proportion of patients who completed therapy but did not start the next therapy line. Results Competitive risk analyses were performed on 3988 1st line, 2651 2nd line and 1866 3rd line patients. The probabilities of not starting the next therapy line within 5 years after initiation of 1st, 2nd and 3rd line therapy were 30%, 24% and 24% respectively. Patients with HER2-positive disease had the highest risk for attrition, while patients with HRpos/HER2neg disease had the lowest risk. Attrition rates remained similar across molecular subgroups in the different therapy lines. Conclusion Attrition affects a large proportion of patients with aBC, which should be considered when planning novel therapy concepts that specifically address the sequencing of therapies. Taking attrition into account could help understand treatment effects resulting from sequential therapies and might help develop treatment strategies that specifically aim at maintaining quality of life., Competing Interests: Conflict of Interest E. B. has received honoraria from Novartis, Celgene, Eisai, Daiichi Sankyo, Merrimack, AstraZeneca, Riemser, Pfizer, Hexal, Amgen, and onkowissen.de for consulting, clinical research management, or medical education activities. J. E. has received honoraria/travel support from Roche, Celgene, Novartis, Pfizer, Lilly, Pierre Fabre, Teva, and Tesaro, AstraZeneca, Daiichi, Seagen, Gilead, StemLine, ClinSol. P. A. F. has received honoraria from Roche, Pfizer, Novartis, and Celgene; his institution conducts research for Novartis. A. D. H. has received honoraria from Roche, Novartis, Lilly, MSD, AstraZeneca, Seagen, GSK, ExactScience, Riemser, Teva, Onkowissen, Gilead, Menarini Stemline, Pfizer, Amgen, Pierre Fabre and Eisai and travel support from Roche, Novartis, Lilly, AstraZeneca, GSK, Exact Science, Gilead, Menarini Stemline and Pfizer. C. H. has received honoraria from Amgen, Celgene, Oncovis, Roche, and Pfizer. J. H. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer, and travel support from Roche, Celgene, and Pfizer. C. K. has received honoraria from Amgen, Roche, Teva, Novartis, MSD, Axios, and Riemser. H.-C. K. has received honoraria from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, TEVA, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lily, SurgVision, Onkowissen, Gilead, Daiichi Sankyo and MSD, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, Gilead and Menarini Stemline and owns stock of Theraclion SA. M. P. L. has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, Exact Sciences, Agendia, Daiichi-Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Samantree, Endomag, and medac for advisory boards, lectures, and travel support. V. M. Speaker honoraria: AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institut. Consultancy honoraria: Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline. Institutional research support: Novartis, Roche, Seagen, Genentech, AstraZeneca. Travel grants: AstraZeneca, Roche, Pfizer, Daiichi Sankyo, Gilead P. H. has received honoraria, unrestricted educational grants, and research funding from Amgen, Novartis, Hexal and Pfizer. A. S. has received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Zuckschwerdt Verlag GmbH, Georg Thieme Verlag, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH, and promedicis GmbH. H. T. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer, and travel support from Roche, Celgene, and Pfizer. M. W. received speaker honoraria from AstraZeneca, Celgene, Roche, MSD and Novartis. R. W. has received honoraria from Agendia, Amgen, APOGHEVA, Aristo, Astra Zeneca, Celgene, Clovis Oncology, Daiichi-Sankyo, Eisai, Esteve, Exact Sciences, ilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics /Seagen, Sidekick, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, Wiley, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI, MediSeminar. F. A. T. has received speaker and consultancy honoraria from AstraZeneca, Gilead, GSK, MSD, Novartis, Onkowissen, Pfizer, Roche. C. B. W. has received honoraria from Teva, AstraZeneca, Novartis, Pfizer, and Roche D. L. has received honoraria from Amgen, Loreal, Pfizer, Novartis, Eli Lilly, Samsung, Celgene, Astra Zeneca, Teva and GSK H. H. received speaker honorar for: Novartis Pharma GmbH and LEO Pharma GmbH and Grant/Research support from: Novartis Pharma GmbH. M. U. has received honoraria for advisory boards and travel support, payed to the employer from Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Lilly Deutschland, Lilly Int., MSD, Mundipharma, Myriad Genetics, Odonate, Pfizer, Puma Biotechnology, Roche, Sanofi Aventis Deutschland, Teva Pharmaceuticals Ind Ltd, Novartis, Pierre Fabre, Clovis Oncology, and Seattle Genetics W. J. has received honoraria and research grants from Sanofi-Aventis, Novartis, Lilly, Pfizer, Roche, Chugai, AstraZeneca, MSD, and Daiichi Sankyo L. L. M. received honoraria from Amgen, AstraZeneca, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, Roche and Eisai for advisory boards, lectures and travel support. S. Y. B. has received honoraria from Roche, Novartis, Pfizer, MSD, Teva, and AstraZeneca T. N. F. has received honoraria from Novartis, Roche, Pfizer, Teva, Daiichi Sankyo, AstraZeneca, and MSD All remaining authors have declared that they have no conflicts of interest = M. W. B., S. U., C. G., T. L., C. M., D. W., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Breast cancer is the leading cause of cancer-related mortality among women in Germany and worldwide. This retrospective claims data analysis utilizing data from AOK Baden-Wuerttemberg, a major statutory German health insurance provider, aimed to construct and assess a real-world data breast cancer disease model. The study included 27,869 female breast cancer patients and 55,738 age-matched controls, analyzing data from 2010 to 2020. Three distinct breast cancer stages were analyzed: Stage A (early breast cancer without lymph node involvement), Stage B (early breast cancer with lymph node involvement), and Stage C (primary distant metastatic breast cancer). Tumor subtypes were estimated based on the prescription of antihormonal or HER2-targeted therapy. The study established that 77.9% of patients had HR+ breast cancer and 9.8% HER2+; HR+/HER2- was the most common subtype (70.9%). Overall survival (OS) analysis demonstrated significantly lower survival rates for stages B and C than for controls, with 5-year OS rates ranging from 79.3% for stage B to 35.4% for stage C. OS rates were further stratified by tumor subtype and stage, revealing varying prognoses. Distant recurrence-free survival (DRFS) analysis showed higher recurrence rates in stage B than in stage A, with HR-/HER2- displaying the worst DRFS. This study, the first to model breast cancer subtypes, stages, and outcomes using German claims data, provides valuable insights into real-world breast cancer epidemiology and demonstrates that this breast cancer disease model has the potential to be representative of treatment outcomes.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy., Patients and Methods: From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed., Results: 3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88-90%) and five-year OS rates were 95% (95% CI: 94-96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients)., Conclusions: The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies., Competing Interests: Conflict of Interest P. G. received honoraria from Novartis, MSD, and AstraZeneca. K. A. received speaker honoraria from Roche Pharma AG, Pfizer Pharma GmbH and AstraZeneca. C. C. H. received honoraria from Roche, Pfizer, Novartis, AstraZeneca, Gilead, Daiichi Sankyo, Eisai, Gilead and MSD, and received travel grants from Daiichi Sankyo. B. A. received honoraria from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Stemline, Teva, Tesaro, Daiichi Sankyo and Pfizer. Received travel grants from AstraZeneca, Roche, Novartis, Celgene, Lilly, Eisai, Stemline, Daiichi Sankyo and Pfizer. Participated in the data safety monitoring board or advisory boards for AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Tesaro, Daiichi Sankyo and Pfizer. S. K. received honoraria from Amgen, Celgene, Daiichi Sankyo, Novartis and Roche. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. H.-C. K. has received honoraria from Pfizer, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, Daiichi Sankyo, Gilead, Zuellig, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro, Gilead, AstraZeneca, Zuellig, Stemline, participated in data safety monitoring board or advisory boards for Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen, MSD, Gilead, Daiichi Sankyo, Seagen, Genomic Health/Exact Sciences, Agendia, Lilly and owns stock of Theraclion SA. W. J. has received research grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. A. S. reported grants from Celgene, Roche and AbbVie. Personal fees from Cellgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, and Pierre Fabre, and travel grants from Celgene, Roche, Pfizer and AstraZeneca. F. M. received honoraria from Amgen, AstraZeneca, Celgene, Clovis Oncology, CureVac, Eisai, Genomic Health, GlaxoSmithKline, Immunomedics, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, PharmaMar, Roche, Seattle Genetics, Tesaro. M. W. S. received honoraria from AstraZeneca, Pfizer, Clovis, Mylan, Roche, Gedeon Richter, Carl Zeiss Meditec, travel support from Pfizer, Carl Zeiss Meditec. C. J. reports personal fees from AstraZeneca, Exact Sciences, Lilly, Novartis and Roche. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. E. B. received honoraria from Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, Bayer, Ipsen, Bluebird, Braun and onkowissen.de for consulting, clinical research management or medical education activities. S. Y. B. has received honoraria from Roche Pharma, Novartis, Pfizer, MSD, Teva, AstraZeneca. T. N. F. has received honoraria from Novartis, Roche, Pfizer, Teva, Daiichi Sankyo, AstraZeneca and MSD. P. A. F. reports personal fees from Novartis, grants from Biontech, personal fees from Pfizer, personal fees from Daiichi Sankyo, personal fees from AstraZeneca, personal fees from Eisai, personal fees from MSD, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Gilead. C.R. received honoraria from MSD and AstraZeneca, travel expenses from the Swiss Society of Senology and the Swiss Society of Gynecology. All of the remaining authors declare that they do not have any conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Breast conserving resection with free margins is the gold standard treatment for early breast cancer recommended by guidelines worldwide. Therefore, reliable discrimination between normal and malignant tissue at the resection margins is essential. In this study, normal and abnormal tissue samples from breast cancer patients were characterized ex vivo by optical emission spectroscopy (OES) based on ionized atoms and molecules generated during electrosurgical treatment. The aim of the study was to determine spectroscopic features which are typical for healthy and neoplastic breast tissue allowing for future real-time tissue differentiation and margin assessment during breast cancer surgery. A total of 972 spectra generated by electrosurgical sparking on normal and abnormal tissue were used for support vector classifier (SVC) training. Specific spectroscopic features were selected for the classification of tissues in the included breast cancer patients. The average classification accuracy for all patients was 96.9%. Normal and abnormal breast tissue could be differentiated with a mean sensitivity of 94.8%, a specificity of 99.0%, a positive predictive value (PPV) of 99.1% and a negative predictive value (NPV) of 96.1%. For 66.6% patients all classifications reached 100%. Based on this convincing data, a future clinical application of OES-based tissue differentiation in breast cancer surgery seems to be feasible.

Background: The phenotypes of tumor cells change during disease progression, but invasive rebiopsies of metastatic lesions are not always feasible. Here we aimed to determine whether initially HER2-negative metastatic breast cancer (MBC) patients with HER2-positive circulating tumor cells (CTCs) benefit from a HER2-targeted therapy., Methods: The open-label, interventional randomized phase III clinical trial (EudraCT Number 2010-024238-46, CliniclTrials.gov Identifier: NCT01619111) recruited from March 2012 until September 2019 with a follow-up duration of 19.5 months. It was a multicenter clinical trial with 94 participating German study centers. A total of 2137 patients with HER2-negative MBC were screened for HER2-positive CTCs with a final modified intention-to-treat population of 101 patients. Eligible patients were randomized to standard therapy with or without lapatinib. Primary study endpoints included CTC clearance (no CTCs at the end of treatment) and secondary endpoints were progression-free survival, overall survival (OS), and safety., Results: In both treatment arms CTC clearance at first follow-up visit-although not being significantly different for both arms at any time point-was significantly associated with improved OS (42.4 vs 14.1 months; P = 0.002). Patients treated additionally with lapatinib had a significantly improved OS over patients receiving standard treatment (20.5 vs 9.1 months, P = 0.009)., Conclusions: DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of MBC cancer patients to HER2-targeting therapies. The OS benefit could be related to lapatinib, but further studies are required to prove this clinical observation. ClinicalTrials.gov Registration Number: NCT01619111., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)