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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.)

Invasive lobular carcinoma (ILC) is the second most frequent type of breast cancer (BC) and its peculiar morphology is mainly driven by inactivation of CDH1, the gene coding for E-cadherin cell adhesion protein. ILC-specific therapeutic and disease-monitoring approaches are gaining momentum in the clinic, increasing the importance of accurate ILC diagnosis. Several essential and desirable morphologic diagnostic criteria are currently defined by the World Health Organization, the routine use of immunohistochemistry (IHC) for E-cadherin is not recommended. Disagreement in the diagnosis of ILC has been repeatedly reported, but interpathologist agreement increases with the use of E-cadherin IHC. In this study, we aimed to harmonize the pathological diagnosis of ILC by comparing 5 commonly used E-cadherin antibody clones (NCH-38, EP700Y, Clone 36, NCL-L-E-cad [Clone 36B5], and ECH-6). We determined their biochemical specificity for the E-cadherin protein and IHC staining performance according to type and location of mutation on the CDH1 gene. Western blot analysis on mouse cell lines with conditional E-cadherin expression revealed a reduced specificity of EP700Y and NCL-L-E-cad for E-cadherin, with cross-reactivity of Clone 36 to P-cadherin. The use of IHC improved interpathologist agreement for ILC, lobular carcinoma in situ, and atypical lobular hyperplasia. The E-cadherin IHC staining pattern was associated with variant allele frequency and likelihood of nonsense-mediated RNA decay but not with the type or position of CDH1 mutations. Based on these results, we recommend the indication for E-cadherin staining, choice of antibodies, and their interpretation to standardize ILC diagnosis in current pathology practice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Neoadjuvant chemotherapy is standard of care in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), irrespective of the hormone receptor status. Trastuzumab-emtansine (T-DM1), antibody-drug conjugate, is highly effective in HER2+ EBC; however, no survival data are available for de-escalated antibody-drug conjugate-based neoadjuvant therapy without conventional chemotherapy., Patients and Methods: In the WSG-ADAPT-TP (ClinicalTrials.gov identifier: NCT01779206) phase II trial, 375 centrally reviewed patients with hormone receptor-positive (HR+)/HER2+ EBC (clinical stage I-III) were randomly assigned to 12 weeks of T-DM1 with or without endocrine therapy (ET) or trastuzumab + ET once every 3 weeks (ratio 1:1:1). Adjuvant chemotherapy (ACT) omission was allowed in patients with pathologic complete response (pCR). In this study, we report the secondary survival end points and biomarker analysis. Patients who received at least one dose of study treatment were analyzed. Survival was analyzed using the Kaplan-Meier method, two-sided log-rank statistics, and Cox regression models stratified for nodal and menopausal status. P values < .05 were considered statistically significant., Results: T-DM1, T-DM1 + ET, and trastuzumab + ET induced similar 5-year invasive disease-free survival (iDFS; 88.9%, 85.3%, 84.6%; P log-rank = .608) and overall survival rates (97.2%, 96.4%, 96.3%; P log-rank = .534). Patients with pCR versus non-pCR had improved 5-year iDFS rates (92.7% v 82.7%; hazard ratio, 0.40 [95% CI, 0.18 to 0.85]). Among the 117 patients with pCR, 41 did not receive ACT; 5-year iDFS rates were similar in those with (93.0% [95% CI, 84.0 to 97.0]) and without ACT (92.1% [95% CI, 77.5 to 97.4]; P log-rank = .848). Translational research revealed that tumors with PIK3CA wild type, high immune marker expression, and luminal-A tumors (by PAM50) had an excellent prognosis with de-escalated anti-HER2 therapy., Conclusion: The WSG-ADAPT-TP trial demonstrated that pCR after 12 weeks of chemotherapy-free de-escalated neoadjuvant therapy was associated with excellent survival in HR+/HER2+ EBC without further ACT. Despite higher pCR rates for T-DM1 ± ET versus trastuzumab + ET, all trial arms had similar outcomes because of mandatory standard chemotherapy after non-pCR. WSG-ADAPT-TP demonstrated that such de-escalation trials in HER2+ EBC are feasible and safe for patients. Patient selection on the basis of biomarkers or molecular subtypes may increase the efficacy of systemic chemotherapy-free HER2-targeted approaches.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed., Competing Interests: Declaration of interests DEO-L reports honoraria from BMUC and unrestricted grants from Janssen for consensus nuclear medicine meetings in 2020 and 2022, outside the submitted work. LF reports grants from Bristol Myers Squibb and Banque Publique d’Investissement; honoraria for lectures from GE Healthcare, Fujifilm, and Median Technologies; support for attending meetings from Guerbet; participation on a safety monitoring board with Pandas Prodige; and research collaborations with Philips, Ariana Pharma, Evolucare, and Dassault Systems, outside the submitted work. EL reports royalties or licences from Springer, outside the submitted work. DK reports grants from Merck and honoraria from Merck Sharp & Dohme and Pfizer, outside the submitted work. SK reports an advisory role and study material from Novartis, Amgen, Somatex, Daiichi Sankyo, Gilead, AstraZeneca, Pfizer, Eli Lilly, MSD, and Roche for the submitted work; consulting fees from Eli Lilly and MSD; honoraria from AstraZeneca, Eli Lilly, and Pfizer; support for attending meetings from Roche, Daiichi Sankyo, and Eli Lilly; participation on boards with Novartis, Amgen, Somatex, pfm medical, MSD, Daiichi Sankyo, Seagen, Gilead Science, Agendia, Exact Science, Roche, Sonoscape, Eli Lilly, AstraZeneca, and Pfizer; and leadership in other boards with AGO, WSG, and ESMO, outside the submitted work. IM reports honoraria supported by Eli Lilly, Novartis, Pfizer, Seagen, Gilead, and Accuray, outside the submitted work. WMHO reports grants from Pfizer and AstraZeneca, travel grants from Daiitchi, and participation on an advisory board with GE, outside the submitted work. KH reports personal fees from Bayer, Sofie Biosciences, SIRTEX, Adacap, Curium, Endocyte, IPSEN, Siemens Healthineers, GE Healthcare, Amgen, Novartis, Y-mAbs, Aktis Oncology, Theragnostics, Pharma15, Debiopharm, AstraZeneca, and Janssen; non-financial support from ABX; and grants and personal fees from BTG, outside the submitted work. FC reports honoraria from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck Sharp, Meus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, priME Oncoloy, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, and Touchime, and support for attending meetings from Pfizer and Roche, outside the submitted work. BL reports participation on boards for AstraZeneca, Pfizer, Eli Lilly, Daiichi-Sankyo, Novartis, Pierre Fabre, Breast International Group Executive Committee, EORTC Breast Cancer Group, and Swedish Association of Breast Oncologists, outside the submitted work. WK reports consulting fees from Mint Medical and honoraria from Bristol Myers Squibb, outside the submitted work. CD reports consulting fees from Terumo, Sitex, and PSI CRO; honoraria from Ipsen; and a chairing role for EORTC Imaging Group, outside the submitted work. ES reports royalties from Springer; honoraria from Cancerodigest, Curio Science, Egis, Eli Lilly, Exact Sciences, Gilead, high5md, MSD, Novartis, and Pfizer; support for attending meetings from Egis, Gilead, Novartis, Pfizer, and Roche; participation on boards with AstraZeneca, Eli Lilly, Exact Sciences, Novartis, Oncompass Medicine, and Stowarzyszenie Rozowy Motyl; stock options from AstraZeneca, Eli Lilly, and Pfizer; receipt of equipment from AstraZeneca and Eli Lilly; and interests with Amgen, AstraZeneca, Eli Lilly, Novartis, OBI Pharma, Pfizer, Roche, and Samsung, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Partner involvement in the decision-making process concerning breast reconstruction (BR) after a breast cancer diagnosis may be very supportive for the patient. So far, no study evaluates partner satisfaction with the outcome after BR and the relationship to patient satisfaction. The aim of this study was to assess and compare partner satisfaction of BR with autologous tissue (ABR) and prosthetic implants (IBR), respectively, and compare it to patient-reported outcomes., Patients and Methods: All patients undergoing ABR and IBR between January 2014 and December 2020 were asked to participate with their partners. Patient and partner satisfaction with breast reconstruction, overall outcome as well as patient's perceived and self-reported psychosocial well-being were evaluated using the Breast-Q and a modified partner questionnaire, respectively., Results: Fifty-three couples participated (IBR: n=30, ABR: n = 23). Patient and partner satisfaction with breast (r = 0.552), outcome (r = 0.465) as well as patient's perceived and self-report psychosocial well-being (r = 0.495) were highly correlated with partners scoring significantly higher (p<0.001). In terms of partner satisfaction, both reconstructive procedures achieved satisfactory results. ABR scored higher in terms of softness of breast and how natural the breast feels to touch whereas IBR was rated superior evaluating the breast size., Conclusion: Both reconstructive procedures achieve satisfactory results in terms partner satisfaction whereas patient's psychosocial well-being was highly overestimated by their partners. Hence, partner inclusion in the regular psycho-oncological support might further sensitize them of the high psychological burden of a breast cancer diagnosis and therefore stabilize patients private support system., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. The Author(s).)

Introduction: Failure of an implant-based breast reconstruction often requires a change to an autologous procedure (salvage autologous breast reconstruction [Salv-ABR]). The aim of this study was to compare surgical and patient-reported outcomes of Salv-ABR to immediate or delayed-immediate ABR (I/DI-ABR), which has hardly been addressed in the existing literature., Methods: All patients undergoing Salv- or I/DI-ABR between January 2014 and December 2020 were asked to participate in this study. Complication rates, the aesthetic outcome (5-point Likert scale), and quality of life (EORTC QLQ-C30 and -BR23, Breast-Q, Center for Epidemiology Studies Depression Scale) were compared between both procedures., Results: Seventy patients participated in the study (Salv-ABR: n = 23; mean ± SD age, 53.5 ± 9.1 years; follow-up, 28.6 ± 18.5 month; I/DI-ABR: n = 45, mean ± SD age: 50.2 ± 7.3 years; follow-up, 32.8 ± 18.5 month). Main indication for Salv-ABR was a major capsular contracture (n = 14 [60.1%]). Early unplanned reoperation rates were significantly increased in the Salv-ABR (56.5% vs 14.9%; P < 0.01). Patients with I/DI-ABR showed a significantly improved overall aesthetic outcome (2.7 ± 0.9 vs 3.3 ± 0.7; P < 0.01) and scored significantly higher in several subscales of EORTC QLQ-C30/BR23 (Global Health Status, Role Functioning, Body Image; P < 0.05) and the Breast-Q (Psychosocial Well-being, Satisfaction with Breast; P < 0.05) compared with patients with Salv-ABR., Conclusions: Salvage ABR is associated with a higher complication rate, compromised aesthetic outcome, and quality of life compared with I/DI-ABR. This should be considered and discussed with the patient when planning any kind of reconstructive breast surgery., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Efficacy and quality of life (QoL) are key criteria for therapy selection in metastatic breast cancer (MBC). In hormone receptor positive (HR +) human epidermal growth factor receptor 2 negative (HER2 -) MBC, addition of targeted oral agents such as everolimus or a cycline-dependent kinase 4/6 (CDK 4/6) inhibitor (e.g., palbociclib, ribociclib, abemaciclib) to endocrine therapy substantially prolongs progression-free survival and in the case of a CDK 4/6i also overall survival. However, the prerequisite is adherence to therapy over the entire course of treatment. However, particularly with new oral drugs, adherence presents a challenge to disease management. In this context, factors influencing adherence include maintaining patients' satisfaction and early detection/management of side effects. New strategies for continuous support of oncological patients are needed. An eHealth-based platform can help to support therapy management and physician-patient interaction., Methods: PreCycle is a multicenter, randomized, phase IV trial in HR + HER2 - MBC. All patients (n = 960) receive the CDK 4/6 inhibitor palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant) according to national guidelines. PreCycle evaluates and compares the time to deterioration (TTD) of QoL in patients supported by eHealth systems with substantially different functionality: CANKADO active vs. inform. CANKADO active is the fully functional CANKADO-based eHealth treatment support system. CANKADO inform is a CANKADO-based eHealth service with a personal login, documentation of daily drug intake, but no further functions. To evaluate QoL, the FACT-B questionnaire is completed at every visit. As little is known about relationships between behavior (e.g., adherence), genetic background, and drug efficacy, the trial includes both patient-reported outcome and biomarker screening for discovery of forecast models for adherence, symptoms, QoL, progression free survival (PFS), and overall survival (OS)., Discussion: The primary objective of PreCycle is to test the hypothesis of superiority for time to deterioration (TTD) in terms of DQoL = "Deterioration of quality of life" (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in patients merely receiving eHealth-based information (CANKADO inform). EudraCT Number: 2016-004191-22., (© 2023. The Author(s).)

Background: Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient's pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow., Methods: A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab., Results: At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00)., Conclusion: This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT., (© 2023. The Author(s).)

Purpose: To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer., Materials and Methods: Baseline and postendocrine Ki67 (Ki67 post ) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67 post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental ( v control) arm; secondary end points included distant DFS, overall survival, and translational research., Results: Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was -3.3%, establishing prespecified noninferiority ( P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% ( P < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, P < .001)., Conclusion: WSG-ADAPT-HR+/HER2- demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.

Background: Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy., Methods: Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models., Results: AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89-1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80-1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86-1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77-1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3-4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology., Conclusion: For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy., (© 2022. The Author(s).)

Background: Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6i) have significantly improved clinical outcomes in patients with advanced hormone receptor-positive (HR+) breast cancer and have demonstrated favourable antitumour immune responses in preclinical studies., Methods: Here, we investigated peripheral immune responses to ribociclib in patients with metastatic HR+ breast cancer as a preplanned exploratory subanalysis of the RIBECCA trial (NCT03096847). Peripheral blood mononuclear cells were subjected to immune cell profiling, gene expression analysis of immune-related signatures, and deep T cell receptor profiling before treatment started and after 12 weeks of treatment with ribociclib., Results: Gene expression analysis revealed an upregulation of signatures associated with an activated adaptive immune system and a decrease in immunosuppressive cytokine signalling during treatment with ribociclib. Profiling of peripheral immune cell subpopulations showed a decrease in Treg cell frequencies, which was associated with treatment response. Furthermore, induction of CD4+ naive T cells could be seen, whereas effector and memory T cell populations remained largely unchanged. Correspondingly, T cell repertoire diversity remained mostly unchanged during treatment, although an increase in clonality could be observed in single patients., Conclusions: We show that treatment with ribociclib has significant effects on the peripheral innate and adaptive immune response in patients with HR+ breast cancer. Our data suggest that these effects lead to an activation of an already existing immune response rather than a de novo induction and make a strong case for future combination strategies of CDK4/6i with immunotherapies to enhance the adaptive immune response in HR+ breast cancer., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SB, TD, PF, TF, WJ, SK, AS, MS and DL are members of the RIBECCA trial consortium and received speaker and advisory board honoraria from Novartis for work related to the RIBECCA study. CAP received speaker honoraria from Novartis for work unrelated to this manuscript. UK received speaker and advisory board honoraria from Novartis for work unrelated to this manuscript. The other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: We assessed the value of breast ultrasound (US) performed at week 3 and 6 and at the end (EOT) of neoadjuvant therapy (NAT) for prediction of pathologic complete response (pCR, ypT0/is ypN0) in patients with HR+/HER2+, HR-/HER2-or HR-/HER2+ early breast cancer enrolled in the WSG-ADAPT subtrials., Methods: US was performed at week 3 and 6 of NAT and at EOT in 401, 517, and 553 patients, respectively. Tumors with complete or partial response by US (RECIST 1.1) were classified as responders and those with stable or progressive disease as non-responders., Results: pCR rate was higher in US responders than in non-responders. US tended to yield the highest positive predictive value in HR-/HER2+ (69%) and HR-/HER2-tumors (65%) at week 3, and the highest negative predictive value in HR+/HER2+ tumors at week 6 and at EOT (88.9% and 86.9%, respectively) and in HR-/HER2-tumors at EOT (87.9%). Multivariable analysis of patients with US at week 3 and 6 identified tumor subtype (HR-/HER2+ vs HR+/HER2+; odds ratio (OR) 2.77, 95%CI 1.45-5.29, and OR 4.17, 95%CI 2.26-7.68, respectively) and each 10% change in lesion dimension on US from baseline (OR 1.15, 95%CI 1.08-1.24, and OR 1.25, 95%CI 1.16-1.35, respectively) as parameters associated with pCR., Conclusions: Our data support the use of week 3 and EOT US for prediction of pCR in response-guided NAT and in planning of breast-conserving surgery. Change in tumor diameter on US as a continuous variable could be a valuable alternative to categorical RECIST 1.1 criteria., Competing Interests: Declaration of competing interest Dr. Graeser reports personal fees from AstraZeneca, non-financial support from Daiichi Sanyko, outside the submitted work. Dr. Harbeck reports ownership interest for WSG Study Group, personal fees from Amgen, AstraZeneca, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Zodiac Pharma, consulting/advisory role for Agendia, AstraZeneca, Celgene, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Sandoz, Seattle Genetics, West German Study Group (Institution), grants from Lilly (Institution), Merck Sharp & Dohme (Institution), Novartis (Institution), Pfizer (Institution), Roche/Genentech (Institution), outside the submitted work. Dr. Gluz reports ownership interest for WSG Study Group, personal fees from Genomic Health, Roche, Celgene, Pfizer, Novartis, NanoString Technologies, AstraZeneca, consulting/advisory role for Celgene, Exact Sciences, Lilly, MSD Brazil, Novartis pharma SAS, Pfizer Pharmaceuticals Israel, Roche, grants from Roche, outside the submitted work. Dr. Wuerstlein reports non-financial support and consulting/advisory role for Agendia, Amgen, Aristo, Astra Zeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Daiichi-Sankyo, Esai, Genomic Health, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Seattle Genetics, Tesaro Bio, Teva, outside the submitted work. Dr. zu Eulenburg has nothing to disclose. Dr. Schumacher reports grants from Roche (Institution), Novartis (Institution), Boehringer (Institution), outside the submitted work. Dr. Grischke has nothing to disclose. Dr. Forstbauer reports personal fees, non-financial support and consulting/advisory role for Roche, Celgene, Amgen, outside the submitted work. Dr. Dimpfl has nothing to disclose. Dr. Braun reports personal fees from AstraZeneca, Exact Sciences, Novartis, Pfizer, Roche, Teva, consulting/advisory role for AstraZeneca, Exact Sciences, Novartis, Puma, Roche, non-financial support from AstraZeneca, Celgene, Medac, Novartis, Roche, outside the submitted work. Dr. Christgen has nothing to disclose. Dr. Kreipe reports personal fees from Roche, Novartis, AstraZeneca, Genomic Health, consulting/advisory role for AstraZeneca, Genomic Health, Novartis pharma SAS, Roche Pharma AG, non-financial support from AstraZeneca, Genomic Health, Novartis pharma SAS, Roche Pharma AG, outside the submitted work. Dr. Potenberg has nothing to disclose. Dr. von Schumann has nothing to disclose. Dr. Aktas reports personal fees from Pfizer, Roche Pharma, Novartis Pharma, AstraZeneca, Amgen, Tesaro Bio Germany, PharmaMar, Eisei, consulting/advisory role for Novartis Pharma, Roche Pharma, Pfizer, Tesaro Bio, non-financial support from AstraZeneca, Amgen, Roche Pharma, Pfizer, Novartis Pharma, Tesaro Bio Germany, PharmaMar, Eisei, outside the submitted work. Dr. Kolberg-Liedtke reports ownership interest for Theraklion (Institution), Phaon Scientific (Institution), personal fees from Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, SonoScape, Pfizer (Institution), Novartis (Institution), Roche (Institution), Genomic Health (Institution), Amgen (Institution), AstraZeneca (Institution), Riemser (Institution), Carl Zeiss MediTec (Institution), TEVA Pharmaceuticals Industries (Institution), Theraklion (Institution), Janssen-Cilag (Institution), GlaxoSmithKline (Institution), LIV Pharma (Institution), consulting/advisory role for Roche, Novartis, Pfizer, Celgene, Phaon Scientific, Pfizer (Institution), Novartis (Institution), SurgVision (Institution), CarlZeissMeditec (Institution), Amgen (Institution), Onkowissen (Institution), grants from Roche, Novartis, Pfizer, non-financial support from Roche, Daiichi Sankyo, Novartis, Carl Zeiss Meditec (Institution), LIV Pharma (Institution), Novartis (Institution), Amgen (Institution), Pfizer (Institution), Daiichi Sankyo (Institution), outside the submitted work. Dr. Kümmel reports ownership interest for West German Study Group, consulting/advisory role for Roche, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, SOMATEX Medical Technologies, Daiichi Sankyo, pfm medical, Pfizer, MSD, Lilly, Sonoscape, non-financial support from Roche, Daiichi Sankyo, Sonoscope, outside the submitted work. Dr. Nitz reports other from West German Study Group, personal fees from Agendia, Amgen, Celgene, Genomic Health, NanoString Technologies, Novartis pharma SAS, Pfizer Pharmaceuticals Israel, Roche/Genentech, Teva, other from Genomic Health, Roche, grants from Agendia (Institution), Amgen (Institution), Celgene (Institution), Genomic Health (Institution), NanoString Technologies (Institution), Roche (Institution), Sanofi (Institution), non-financial support from Genomic Health, Pfizer Pharmaceuticals Israel, Roche, outside the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cancer registries usually assess data of conventional treatments and/or patient survival. Beyond that, little is known about the influence of other predictors of treatment response related to the use of complementary therapies (CM) and lifestyle factors affecting patients' quality and quantity of life., Methods: INTREST is a prospective cohort study collecting register data at multiple German certified cancer centers, which provide individualized, integrative, in- and outpatient breast cancer care. Patient-reported outcomes and clinical cancer data of anticipated N = 715 women with pTNM stage I-III breast cancer are collected using standardized case report forms at the time of diagnosis, after completing neo-/adjuvant chemotherapy, after completing adjuvant therapy (with the exception of endocrine therapy) as well as 1, 2, 5, and 10 years after baseline. Endpoints for multivariable prediction models are quality of life, fatigue, treatment adherence, and progression-based outcomes/survival. Predictors include the study center, sociodemographic characteristics, histologic cancer and comorbidity data, performance status, stress perception, depression, anxiety, sleep quality, spirituality, social support, physical activity, diet behavior, type of conventional treatments, use of and belief in CM treatments, and participation in a clinical trial. Safety is recorded following the Common Terminology Criteria for Adverse Events., Discussion: This trial is currently recruiting participants. Future analyses will allow to identify predictors of short- and long-term response to integrative breast cancer treatment in women, which, in turn, may improve cancer care as well as quality and quantity of life with cancer., Trial Registration: German Clinical Trial Register DRKS00014852 . Retrospectively registered at July 4th, 2018.

Background: The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94·7% (95% CI 92·5-96·2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age., Methods: MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18-70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0-1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinical-pathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005-002625-31. Recruitment is complete and further long-term follow-up is ongoing., Findings: Between Feb 8, 2007, and July 11, 2011, 6693 patients were enrolled. On Feb 26, 2020, median follow-up was 8·7 years (IQR 7·8-9·7). The updated 5-year distant metastasis-free survival rate for patients with high clinical risk and low genomic risk receiving no chemotherapy (primary test population, n=644) was 95·1% (95% CI 93·1-96·6), which is above the predefined non-inferiority boundary of 92%, supporting the previous analysis and proving MINDACT as a positive de-escalation trial. Patients with high clinical risk and low genomic risk were randomly assigned to receive chemotherapy (n=749) or not (n=748); this was the intention-to-treat population. The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6-93·8) for chemotherapy versus 89·4% (86·8-91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48-0·92). An exploratory analysis confined to the subset of patients with hormone receptor-positive, HER2-negative disease (1358 [90.7%] of 1497 randomly assigned patients, of whom 676 received chemotherapy and 682 did not) shows different effects of chemotherapy administration on 8-year distant metastasis-free survival according to age: 93·6% (95% CI 89·3-96·3) with chemotherapy versus 88·6% (83·5-92·3) without chemotherapy in 464 women aged 50 years or younger (absolute difference 5·0 percentage points [SE 2·8, 95% CI -0·5 to 10·4]) and 90·2% (86·8-92·7) versus 90·0% (86·6-92·6) in 894 women older than 50 years (absolute difference 0·2 percentage points [2·1, -4·0 to 4·4]). The 8-year distant metastasis-free survival in the exploratory analysis by nodal status in these patients was 91·7% (95% CI 88·1-94·3) with chemotherapy and 89·2% (85·2-92·2) without chemotherapy in 699 node-negative patients (absolute difference 2·5 percentage points [SE 2·3, 95% CI -2·1 to 7·2]) and 91·2% (87·2-94·0) versus 89·9% (85·8-92·8) for 658 patients with one to three positive nodes (absolute difference 1·3 percentage points [2·4, -3·5 to 6·1])., Interpretation: With a more mature follow-up approaching 9 years, the 70-gene signature shows an intact ability of identifying among women with high clinical risk, a subgroup, namely patients with a low genomic risk, with an excellent distant metastasis-free survival when treated with endocrine therapy alone. For these women the magnitude of the benefit from adding chemotherapy to endocrine therapy remains small (2·6 percentage points) and is not enhanced by nodal positivity. However, in an underpowered exploratory analysis this benefit appears to be age-dependent, as it is only seen in women younger than 50 years where it reaches a clinically relevant threshold of 5 percentage points. Although, possibly due to chemotherapy-induced ovarian function suppression, it should be part of informed, shared decision making. Further study is needed in younger women, who might need reinforced endocrine therapy to forego chemotherapy., Funding: European Commission Sixth Framework Programme., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Prediction of histological tumor size by post-neoadjuvant therapy (NAT) ultrasound and magnetic resonance imaging (MRI) was evaluated in different breast cancer subtypes., Methods: Imaging was performed after 12-week NAT in patients enrolled into three neoadjuvant WSG ADAPT subtrials. Imaging performance was analyzed for prediction of residual tumor measuring ≤10 mm and summarized using positive (PPV) and negative (NPV) predictive values., Results: A total of 248 and 588 patients had MRI and ultrasound, respectively. Tumor size was over- or underestimated by < 10 mm in 4.4% and 21.8% of patients by MRI and in 10.2% and 15.8% by ultrasound. Overall, NPV (proportion of correctly predicted tumor size ≤10 mm) of MRI and ultrasound was 0.92 and 0.83; PPV (correctly predicted tumor size > 10 mm) was 0.52 and 0.61. MRI demonstrated a higher NPV and lower PPV than ultrasound in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive and in HR-/HER2+ tumors. Both methods had a comparable NPV and PPV in HR-/HER2- tumors., Conclusions: In HR+/HER2+ and HR-/HER2+ breast cancer, MRI is less likely than ultrasound to underestimate while ultrasound is associated with a lower risk to overestimate tumor size. These findings may help to select the most optimal imaging approach for planning surgery after NAT., Trial Registration: Clinicaltrials.gov , NCT01815242 (registered on March 21, 2013), NCT01817452 (registered on March 25, 2013), and NCT01779206 (registered on January 30, 2013).

Background: The impact of neoadjuvant chemotherapy (NACT) on surgical outcomes following immediate breast reconstruction (IBR) remains unclear. While it is generally considered safe practice to perform an IBR post NACT, reported complication rates in published data are highly variable with the majority of studies including fewer than 50 patients in the NACT and IBR arm. To evaluate this further, we conducted a systematic review and meta-analysis on the effect of NACT on autologous and implant based immediate breast reconstructions. We aimed to assess for differences in the post-operative course following IBR between patients who received NACT with those who did not., Methods: PubMed, EMBASE, and Cochrane Library were searched from 1995 to Sept 2, 2020 to identify articles that assessed the impact of NACT on IBR. All included studies assessed outcomes following IBR. Only studies comparing reconstructed patients receiving NACT to a control group of women who did not receive NACT were included. Unadjusted relative risk of outcomes between patients who received or did not receive NACT were synthesized using a fixed-effect meta-analysis. The evidence was assessed using the Newcastle Ottawa Scale scores and GRADE. Primary effect measures were risk ratios (RRs) with 95% confidence intervals., Results: A total 17 studies comprising 3249 patients were included in the meta-analyses. Overall, NACT did not increase the risk of complications after immediate breast reconstructions (risk ratio [RR]: 0.91, 95% CI 0.74 to 1.11, p = 0.34). There was a moderate, but not significant, increase in flap loss following NACT compared with controls (RR: 1.23, 95% CI 0.70 to 2.18, p = 0.47; I 2  = 0%). Most notably, there was a statistically significant increase in implant/expander loss after NACT (RR: 1.54, 95% CI 1.04 to 2.29, p = 0.03; I 2  = 34%). NACT was not shown to significantly increase the incidence of hematomas, seromas or wound complications, or result in a significant delay to commencing adjuvant therapy (RR: 1.59, 95% CI 0.66 to 3.87, p = 0.30)., Conclusion: Immediate breast reconstruction after NACT is a safe procedure with an acceptable post-operative complication profile. It may result in a slight increase in implant loss rates, but it does not delay commencing adjuvant therapy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: Subcutaneous Herceptin (HER SC) has been shown to be equally effective and safe compared to intravenous Herceptin (HER i.v.) application in early HER2-positive breast cancer (HER2+ BC). However, real-world data from the subcutaneous application are currently limited., Patients and Methods: Based on a non-interventional study (NIS), data from routine clinical use of HER SC have been gathered between 2013 and 2018 in 135 hospitals and open-care practices throughout Germany., Results: A total of 265 patients were recruited in the neo-adjuvant and 605 patients in the adjuvant setting. Primary effectiveness endpoint in the neoadjuvant treatment setting was pathological complete response rate, which was achieved in 41.5%. Primary endpoint in the adjuvant setting was disease free survival rate after 2 years (94.9%). Safety results from the study were comparable to the well-known safety profile of HER i.v. including preferred terms, incidence, severity, including cardiac events. No new safety signals were detected., Conclusion: Effectiveness and safety of HER SC were comparable to data from HER i.v. in early HER2+ BC., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Breast cancer is one of the leading cancers in women in the Western world. Cancer treatment, especially chemotherapy, is often associated with physical and psychosocial side effects., Objective: To improve the quality of life and manage side effects, a new integrative mind-body-medicine group concept for breast cancer patients receiving chemotherapy was developed and pilot tested., Methods: Breast cancer patients participated in a 66 hours mind-body-medicine group program tailored to the needs of cancer patients during chemotherapy. The program was integrated into standard care encompassing mindfulness training, yoga, moderate exercise, nutrition, complementary self-help strategies, cognitive restructuring, and acupuncture. Quality of life (EORTC QLQ-C30), depression and anxiety (HADS), stress (PSS-10), and fatigue (BFI) were assessed before and after the program, as well as satisfaction and safety. Analyses were carried out on exploratory basis with paired samples t-tests., Results: Fifty-seven female patients, aged 51.3±10.5 years, with breast cancer diagnoses were enrolled. After completing the program, global EORTC quality of life was improved (D=9.5; 95%-CI=[2.9|16.1]; p=.005), although the EORTC-symptom scales assessing fatigue (D=9.9; 95%-CI=[1|18.8]; p=.030), nausea (D=7.1; 95%- CI=[0.6|13.6]; p=.031), and dyspnea (D=12.5; 95%-CI=[2.9|22.1]; p=.011) were found to be increased. Stress (D=-3.5; 95%-CI=[-5|-2.1]; p=.000), anxiety (D=-3.8; 95%-CI=[-4.9|-2.7]; p=.000) and depression (D=-3.9; 95%-CI=[-4.9|-2.8]; p=.000) were also found to be significantly reduced. Regarding the severity of (D=0.2; 95%- CI=[-0.8|0.5]; p=.644) and the impairment due to fatigue (D=0.1; 95%-CI=[-0.8|0.6]; p=.696), no significant worsening was observed. Patients were satisfied with the program. No serious adverse events were reported., Conclusion: Breast cancer patients benefit from an integrative mind-body-medicine group program during chemotherapy regarding the quality of life and psychological symptoms. Randomized controlled trials are warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that patients with a favorable response to NACT might not benefit from RT after mastectomy., Methods: A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%)., Results: The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval [CI] 9.0-22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7-14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27-1.0; p = 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis., Conclusions: Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.

Purpose: The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)-paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes., Methods: Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m 2 (after study amendment, 125 mg/m 2 ) or weekly sb-paclitaxel 80 mg/m 2 followed in both arms by four times epirubicin 90 mg/m 2 plus cyclophosphamide 600 mg/m 2 every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year., Results: A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease-free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m 2 compared with NAB-paclitaxel 150 mg/m 2 ., Conclusion: The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m 2 compared with NAB-paclitaxel 150 mg/m 2 .

Background: Distortion of taste sensations is a common chemotherapy-induced side effect; however, treatment evidence is limited. Pilot data indicated that acupuncture might be able to improve symptoms of dysgeusia. Thus, the aim of this study is to investigate the effects and side effects of hypoglossal acupuncture in the treatment of dysgeusia in patients with breast cancer undergoing chemotherapy., Methods/design: The study is a randomized controlled trial comparing a single verum acupuncture treatment with two active comparators: sham acupuncture and dietary recommendations. Sample size calculation revealed a total of 75 patients pending an alpha of 0.05, a power of 0.8, and an estimated effect size of 0.80. Patients with breast cancer undergoing platinum- or taxane-based chemotherapy will be included if they present with phantogeusia (abnormal taste sensations without an external oral stimulus) with an intensity of 4 points or above on an 11-point numeric rating scale (NRS). The primary outcome is phantogeusia; secondary outcomes include parageusia (abnormal taste of food), hypogeusia (reduced taste sensations), hypergeusia (increased taste sensations), xerostomia (dry mouth), stomatitis, appetite, and functional impairment. All outcomes will be assessed at baseline and prior to the next chemotherapy administration using an 11-point NRS for each. All adverse events will be recorded., Discussion: The results of this study will demonstrate the extent to which hypoglossal acupuncture may influence the intensity of and functional impairment due to chemotherapy-induced dysgeusia., Trial Registration: Clinical Trials.gov, NCT02304913 . Registered on 19 November 2014.

Background: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients., Methods: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT., Results: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment., Conclusions: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process., Trial Registration: Clinical Trials Number: CFEM345DDE19.

Purpose: Addition of alpelisib to fulvestrant significantly extended progression-free survival in PIK3CA -mutant, hormone receptor-positive (HR + ) advanced/metastatic breast cancer in the phase III SOLAR-1 study. The combination of alpelisib and letrozole also had promising activity in phase I studies of HR + advanced/metastatic breast cancer. NEO-ORB aimed to determine whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting. Patients and Methods: Postmenopausal women with HR + , human epidermal growth factor receptor 2-negative, T1c-T3 breast cancer were assigned to the PIK3CA -wild-type or PIK3CA -mutant cohort according to their tumor PIK3CA status, and randomized (1:1) to 2.5 mg/day letrozole with 300 mg/day alpelisib or placebo for 24 weeks. Primary endpoints were objective response rate (ORR) and pathologic complete response (pCR) rate for both PIK3CA cohorts., Results: In total, 257 patients were assigned to letrozole plus alpelisib (131 patients) or placebo (126 patients). Grade ≥3 adverse events (≥5% of patients) in the alpelisib arm were hyperglycemia (27%), rash (12%), and maculo-papular rash (8%). The primary objective was not met; ORR in the alpelisib versus placebo arm was 43% versus 45% and 63% versus 61% in the PIK3CA -mutant and wild-type cohorts, respectively. pCR rates were low in all groups. Decreases in Ki-67 were similar across treatment arms and cohorts. In PIK3CA -mutant tumors, alpelisib plus letrozole treatment induced a greater decrease in phosphorylated AKT versus placebo plus letrozole., Conclusions: In contrast to initial results in advanced/metastatic disease, addition of alpelisib to 24-week neoadjuvant letrozole treatment did not improve response in patients with HR + early breast cancer., (©2019 American Association for Cancer Research.)

The E-VITA study evaluated the efficacy and tolerability of two schedules of eribulin and lapatinib in patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer. This multicenter, open-label phase II trial, randomly assigned patients with trastuzumab-pretreated HER-2-positive metastatic breast cancer to lapatinib 1000 mg daily with eribulin 1.23 mg/m (equivalent to 1.4 mg/m eribulin mesylate) days 1+8 every 21 days (split-dose arm) or eribulin 1.76 mg/m (equivalent to 2.0 mg/m eribulin mesylate) day 1 every 21 days (3-weekly arm). Time to progression and tolerability were defined as primary end points; no sample size calculation for formal comparison of efficacy data has been performed. Secondary end points included objective response rate, clinical benefit rate, and overall survival. Overall, 43 patients of a planned number of 80 patients were recruited. At a median follow-up of 28.7 months, the median time to progression was 8.1 months [95% confidence interval (CI): 4.8-9.4] in the split-dose arm and 6.5 months (95% CI: 4.6-13.4) in the 3-weekly arm. Objective response rate was 52.4% (95% CI: 31.0-73.7) in the split-dose arm and 45.0% (95% CI: 23.2-66.8) in the 3-weekly arm, and clinical benefit rate was 71.4% (95% CI: 52.1-90.8) and 75.0% (95% CI: 56.0-94.0), respectively. Overall survival was also similar in both arms. The most frequent grade 3-4 adverse events were neutropenia (58.5%) and leukopenia (39.0%). The combination of eribulin and lapatinib showed an acceptable safety profile with less toxicity observed in the eribulin 1.23 mg/m day 1+8 group. This might be an alternative regimen when other treatment options are exhausted. Therefore, further clinical studies are warranted.

Purpose: Evidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients., Methods: The prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test., Results: In a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively)., Conclusions: This analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

Purpose: This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathologic tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen receptor (ER)-positive/HER2-negative breast cancer. We also compared the prognostic power of the mEPclin with that of the CPS-EG score. Experimental Design: A total of 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. The mEPclin score was computed using a modified algorithm and predefined cut-off values were used to classify each patient at low or high risk. Primary endpoint was disease-free survival (DFS). Results: A higher continuous mEPclin score was significantly associated with increased risk of relapse [HR, 2.16; 95% confidence interval (CI), 1.86-2.51; P < 0.001] and death (HR, 2.28; 95% CI, 1.90-2.75; P < 0.001). Similarly, patients classified at high risk by dichotomous mEPclin showed significantly poorer DFS and overall survival compared with those at low risk. In contrast with CPS-EG, the mEPclin remained significantly prognostic for DFS in multivariate analysis (HR, 2.13; 95% CI, 1.73-2.63; P < 0.001). Combining CPS-EG and other clinicopathological variables with mEPclin yielded a significant improvement of the prognostic power for DFS versus without mEPclin (c-indices: 0.748 vs. 0.660; P < 0.001). Conclusions: The mEPclin score independently predicted the risk of distance recurrence and provided additional prognostic information to the CPS-EG score to assess more accurately the prognosis after NACT in the luminal non-pCR patient population. Therefore, this approach can be used to select patients for additional post-neoadjuvant therapies. Clin Cancer Res; 24(14); 3358-65. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Background: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment., Patients and Methods: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses., Results: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84)., Conclusions: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration., Clinical Trials Number: CFEM345DDE19., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Many women with early-stage, hormone receptor-positive breast cancer may not benefit from adjuvant chemotherapy. Gene expression tests can reduce chemotherapy over- and undertreatment by providing prognostic information on the likelihood of recurrence and, with Oncotype DX, predictive information on chemotherapy benefit. These tests are currently not reimbursed by German healthcare payers. An analysis was conducted to evaluate the budget impact of gene expression tests in Germany., Materials and Methods: Costs of gene expression tests and medical and non-medical costs associated with treatment were assessed from healthcare payer and societal perspectives. Costs were estimated from data collected at a university hospital and were combined with decision impact data for Oncotype DX, MammaPrint, Prosigna and EndoPredict (EPclin). Changes in chemotherapy use and budget impact were evaluated over 1 year for 20,000 women., Results: Chemotherapy was associated with substantial annual costs of EUR 19,003 and EUR 84,412 per therapy from the healthcare payer and societal perspective, respectively. Compared with standard care, only Oncotype DX was associated with cost savings to healthcare payers and society (EUR 5.9 million and EUR 253 million, respectively). Scenario analysis showed that both women at high clinical but low genomic risk and low clinical but high genomic risk were important contributors to costs., Conclusions: Oncotype DX was the only gene expression test that was estimated to reduce costs versus standard care in Germany. The reimbursement of Oncotype DX testing in standard clinical practice in Germany should be considered., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Hormone receptor (HR)-positive breast cancer (BC) shows a poor response to neoadjuvant chemotherapy (NACT). New treatment targets like the Cyclin D1-CDK4/CDK6 complex are promising adjuvant/post-neoadjuvant therapeutic strategies. Evaluating Cyclin D1 overexpression in residual tumor could recognize those patients that benefit most from such post-neoadjuvant treatment. In this study, we determined Cyclin D1 expression in residual BC after NACT. Secondary aims were to correlate Cyclin D1 expression levels with clinicopathological parameters and to assess its prognostic value after NACT., Methods: We retrospectively assessed the nuclear expression of Cyclin D1 on tissue microarrays with residual tumor from 284 patients treated in the neoadjuvant GeparTrio (n = 186) and GeparQuattro (n = 98) trials. Evaluation was performed with a standardized immunoreactive score (IRS) after selecting a cut-off value., Results: A high expression level (IRS ≥ 6) of Cyclin D1 was found in 37.3% of the assessed specimens. An increased Cyclin D1 expression was observed in HR-positive tumors, compared to HR-negative tumors (p = 0.02). Low Cyclin D1 levels correlated with clinical tumor stage 1-3 (p = 0.03). Among patients with HR-positive/Her2-negative tumors and high Cyclin D1 expression, a better disease-free survival (DFS) was graphically suggested, but not significant (p = 0.21)., Conclusion: Our study demonstrates a measurable nuclear expression of Cyclin D1 in post-neoadjuvant residual tumor tissue of HR-positive BC. Cyclin D1 expression was not prognostic for DFS after NACT. Our results and defined cut-off suggest that the marker can be used to stratify tumors according to protein expression levels. Based on this, a prospective evaluation is currently performed in the ongoing Penelope-B trial.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole., Patients and Methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT., Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit)., Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs., (© 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.)

Background: Tumour-infiltrating lymphocytes (TILs) are predictive for response to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer, but their role in luminal breast cancer and the effect of TILs on prognosis in all subtypes is less clear. Here, we assessed the relevance of TILs for chemotherapy response and prognosis in patients with TNBC, HER2-positive breast cancer, and luminal-HER2-negative breast cancer., Methods: Patients with primary breast cancer who were treated with neoadjuvant combination chemotherapy were included from six randomised trials done by the German Breast Cancer Group. Pretherapeutic core biopsies from 3771 patients included in these studies were assessed for the number of stromal TILs by standardised methods according to the guidelines of the International TIL working group. TILs were analysed both as a continuous parameter and in three predefined groups of low (0-10% immune cells in stromal tissue within the tumour), intermediate (11-59%), and high TILs (≥60%). We used these data in univariable and multivariable statistical models to assess the association between TIL concentration and pathological complete response in all patients, and between the amount of TILs and disease-free survival and overall survival in 2560 patients from five of the six clinical trial cohorts., Findings: In the luminal-HER2-negative breast cancer subtype, a pathological complete response (pCR) was achieved in 45 (6%) of 759 patients with low TILs, 48 (11%) of 435 with intermediate TILs, and 49 (28%) of 172 with high TILs. In the HER2-positive subtype, pCR was observed in 194 (32%) of 605 patients with low TILs, 198 (39%) of 512 with intermediate TILs, and 127 (48%) of 262 with high TILs. Finally, in the TNBC subtype, pCR was achieved in 80 (31%) of 260 patients with low TILs, 117 (31%) of 373 with intermediate TILs, and 136 (50%) of 273 with high TILs (p<0·0001 for each subtype, χ 2 test for trend). In the univariable analysis, a 10% increase in TILs was associated with longer disease-free survival in TNBC (hazard ratio [HR] 0·93 [95% CI 0·87-0·98], p=0·011) and HER2-positive breast cancer (0·94 [0·89-0·99], p=0·017), but not in luminal-HER2-negative tumours (1·02 [0·96-1·09], p=0·46). The increase in TILs was also associated with longer overall survival in TNBC (0·92 [0·86-0·99], p=0·032), but had no association in HER2-positive breast cancer (0·94 [0·86-1·02], p=0·11), and was associated with shorter overall survival in luminal-HER2-negative tumours (1·10 [1·02-1·19], p=0·011)., Interpretation: Increased TIL concentration predicted response to neoadjuvant chemotherapy in all molecular subtypes assessed, and was also associated with a survival benefit in HER2-positive breast cancer and TNBC. By contrast, increased TILs were an adverse prognostic factor for survival in luminal-HER2-negative breast cancer, suggesting a different biology of the immunological infiltrate in this subtype. Our data support the hypothesis that breast cancer is immunogenic and might be targetable by immune-modulating therapies. In light of the results in luminal breast cancer, further research investigating the interaction of the immune system with different types of endocrine therapy is warranted., Funding: Deutsche Krebshilfe and European Commission., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome., Methods: Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression., Results: The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS., Conclusion: ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.

Background: The aim of this meta-analysis was to systematically update the evidence for mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) in women with breast cancer., Material and Methods: In October 2016, PubMed, Scopus, and Central were searched for randomized controlled trials on MBSR/MBCT in breast cancer patients. The primary outcome was health-related quality of life. Secondary outcomes were fatigue, sleep stress, depression, anxiety, and safety. For each outcome, standardized mean differences (SMD/Hedges' g) and 95% confidence intervals (CI) were calculated. Risk of bias was assessed by the Cochrane risk of bias tool., Results: The Literature search identified 14 articles on 10 studies that included 1709 participants. The overall risk of bias was unclear, except for risk of low attrition bias and low other bias. Compared to usual care, significant post-intervention effects of MBSR/MBCT were found for health-related quality of life (SMD = .21; 95%CI = [.04-.39]), fatigue (SMD = -.28; 95%CI = [-.43 to -.14]), sleep (SMD = -.23; 95%CI = [-.40 to -.05]), stress (SMD = -.33; 95%CI = [-.61 to -.05]), anxiety (SMD = -.28; 95%CI = [-.39 to -.16]), and depression (SMD = -.34; 95%CI = [-.46 to -.21]). Up to 6 months after baseline effects were significant for: anxiety (SMD = -.28; 95%CI = [-.47 to -.09]) and depression (SMD = -.26; 95%CI = [-.47 to -.04]); and significant for anxiety (SMD = -.21; 95%CI = [-.40 to -.03]) up to 12 months after baseline. Compared to other active interventions, significant effects were only found post-intervention and only for anxiety (SMD = -.45; 95%CI = [-.71 to -.18]) and depression (SMD = -.39; 95%CI = [-.65 to -.14]). However, average effects were all below the threshold of minimal clinically important differences. Effects were robust against potential methodological bias. Adverse events were insufficiently reported., Conclusions: This meta-analysis revealed evidence for the short-term effectiveness and safety of mindfulness-based interventions in women with breast cancer. However, their clinical relevance remains unclear. Further research is needed.

Aim: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer., Methods: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel. Primary end-point was pathological complete response (pCR) rate; key secondary end-point was objective response rate (ORR) at 6 weeks. Exploratory end-points were evaluation of Ki67 levels and change in tumour infiltrating lymphocytes (TILs) in intermediate biopsies at day 15., Results: Recruitment was suspended mainly due to liver toxicity after enrolment of 50 of the planned 256 patients. In each arm (buparlisib n = 25; placebo n = 25) 21 patients (84%) had wild type PIK3CA and 4 patients (16%) had mutant PIK3CA. Overall, pCR rate was similar between buparlisib and placebo arms (32.0% versus 40%; one-sided P = 0.811). A trend towards higher ORR (68.8% versus 33.3%; P = 0.053) and a significant decrease in Ki67 (75% versus 26.7%; P = 0.021) was observed in buparlisib versus placebo arm in the ER+ subgroup (P interaction  = 0.03)., Conclusions: Addition of the pan-PI3K inhibitor buparlisib to taxane-trastuzumab-based therapy in HER2+ early breast cancer was not feasible. However, the higher ORR and Ki67 reduction in the ER+, HER2+ subgroup indicates a potential role for PI3K-targeted therapy in this setting and may warrant further investigation with better-tolerated second-generation PI3K inhibitors., Trial Registration Identifier: NCT01816594., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Previous research has found that yoga can enhance quality of life and ease menopausal symptoms of breast cancer survivors. The study examined whether self-esteem mediated the effects of yoga on quality of life, fatigue and menopausal symptoms, utilizing validated outcome measures., Study Design: This is a secondary analysis of a randomized controlled trial comparing the effects of yoga with those of usual care in 40 breast cancer survivors who suffered from menopausal symptoms. All participants completed all 3 assessments (week 0, week 12, and week 24) and provided full data., Main Outcome Measures: Outcomes were measured using self-rating instruments. Mediation analyses were performed using SPSS., Results: Self-esteem mediated the effect of yoga on total menopausal symptoms (B=-2.11, 95% BCI [-5.40 to -0.37]), psychological menopausal symptoms (B=-0.94, 95% BCI [-2.30 to -0.01]), and urogenital menopausal symptoms (B=-0.66, 95% BCI [-1.65 to -0.15]), quality of life (B=8.04, 95% BCI [3.15-17.03]), social well-being (B=1.80, 95% BCI [0.54-4.21]), emotional well-being (B=1.62, 95% BCI [0.70-3.34]), functional well-being (B=1.84, 95% BCI [0.59-4.13]), and fatigue (B=4.34, 95% BCI [1.28-9.55]). Self-esteem had no effect on somatovegetative menopausal symptoms (B=-0.50, 95% BCI n.s.) or on physical well-being (B=0.79, 95% BCI n.s.)., Conclusions: Findings support the assumption that self-esteem plays a vital role in the beneficial effect of yoga and that yoga can have long-term benefits for women diagnosed with breast cancer and undergoing menopausal transition., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The GENEVIEVE study compared the pathological complete response (pCR) rate (ypT0/is ypN0/+) in patients with operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) treated with either cabazitaxel or paclitaxel., Methods: GENEVIEVE was a prospective, multicentre, randomised, open-label, phase II study comparing the efficacy and the safety of four 3-weekly cycles cabazitaxel versus 12 weeks of paclitaxel given as neoadjuvant treatment. Primary end-point was the pCR rate defined as the complete absence of invasive carcinoma on histological examination of the breast irrespective of lymph node involvement (ypT0/is, ypN0/+) after the taxane treatment. Patients could receive an anthracycline-based therapy thereafter., Results: Overall, 333 patients were randomised and started treatment with 74.7% and 83.2% of patients completing treatment in the cabazitaxel and paclitaxel arms, respectively. Patients in cabazitaxel arm had a significantly lower pCR rate compared to the paclitaxel arm (1.2% versus 10.8%; p = 0.001). A total of 42 (25.3%) patients in the cabazitaxel arm and 17 (10.2%) in the paclitaxel arm had at least one serious adverse event (p < 0.001). Dose reductions were observed in 9.6% patients in the cabazitaxel arm compared to 11.4% in the paclitaxel arm (p = 0.721). Main reason for dose reductions was non-haematological toxicities in 3.0% versus 7.8% (p = 0.087), respectively., Conclusions: The GENEVIEVE study showed no short-term effect of cabazitaxel in triple-negative or luminal B/HER2-negative primary BC, while there seemed to be no differences in drug exposure and patient compliance between the two arms., Clinical Trials Registration: ClinicalTrials.gov NCT01779479., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine., Methods: The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine., Results: Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (<50 years, 74.1%; 50-60 years, 54.1%; >65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources., Conclusions: This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.

Purpose: The GeparSepto study demonstrated that the use of nab-paclitaxel instead of paclitaxel prior to anthracycline-based chemotherapy could lead to a significantly increased pCR rate, especially in the triple negative subpopulation. We report efficacy and safety for patients treated with two different doses of nab-paclitaxel in comparison to weekly solvent-formulated paclitaxel., Methods: Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m 2 (nP150) weekly, after study amendment 125 mg/m 2 (nP125) weekly or solvent-based paclitaxel 80 mg/m 2 (P80) weekly followed by epirubicin 90 mg/m 2 and cyclophosphamide 600 mg/m 2 on day 1 for four 3-week cycles., Results: 229 patients received nP150, 377 nP125. Baseline characteristics were fairly balanced between these two sequential cohorts as well as compared to 601 patients receiving P80 except for hormone receptor status, HER2 status, and Ki67. Taxane treatment was discontinued in 26.8% (nP150), 16.6% (nP125), and 13.3% of (P80) patients, respectively. Median relative total dose intensity (mRTDI) based on 125 mg/m 2 for nP was 103% with nP150, 95% with nP125, 99% with P80 before and 98% with P80 after the amendment. PSN grade 3-4 was observed in 14.5% of patients with nP150, 8.1% of patients with nP125 (p = 0.018), and 2.7% of patients with P80. Overall pCR before the amendment was 33.6% after nP150 and 23.5% after P80 (OR 1.65 [95% CI 1.10-2.50]; p = 0.022); pCR after the amendment was 41.4% after nP125, and 32.4% after P80 (1.48 [95% CI 1.10-1.99]; p = 0.013)., Conclusions: Nab-paclitaxel 125 mg/m 2 was associated with a better safety profile and compliance without compromising the efficacy compared to nab-paclitaxel 150 mg/m 2 .

Purpose: Patients with bilateral breast cancer (BBC) are usually excluded from participating in clinical trials and little is known about the response and outcome of BBC to neoadjuvant chemotherapy compared to unilateral BC (UBC)., Methods: We prospectively captured the information on patients with BBC in our database treated within four neoadjuvant chemotherapy trials and collected retrospectively the rate of pathological complete response (pCR) defined as ypT0 ypN0, ypT0/is ypN0, ypT0 ypNX, clinical and histologic parameters. Synchronous carcinoma in the contralateral breast was considered as the non-indicator lesion. Patients with UBC only treated within the same neoadjuvant trials performed the control group., Results: From the 6727 patients treated within 4 German neoadjuvant trials 119 (1.8%) patients have been identified with the diagnosis of BBC. The pCR rate (ypT0 ypN0) was 12.6% in the non-indicator lesion group versus 10.9% the indicator lesion group versus 20.9% for patients with unilateral disease (p = 0.003). There were more advanced tumor stages and positive axillary lymph nodes in the indicator lesion than in the nonindicator lesion or in UBC. In 52.5% the molecular subtype was identical between indicator and non-indicator lesion with more triple negative and HER2 positive BC in the group of UBC. The disease free survival rate (DFS) was 25.8% for patients with UBC versus 39.6% for patients with BBC., Conclusion: The selection for the indicator lesion was based on tumor size, nodal status and inclusion criteria. Patients with BBC patients had a lower pCR rate and a lower DFS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort., Patients and Methods: Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0., Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline., Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR., (© The Author 2016. 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.)

Background: With the growing importance of neoadjuvant systemic therapy (NST) the assessment of post neoadjuvant axillary status is of increasing importance especially in patients who presented initially with suspicious nodes (cN1). This study aims to investigate the predictive value of palpation and axillary ultrasound of formerly cN1 patients following NST., Patients and Methods: The SENTINA trial (SENTinel NeoAdjuvant) is a 4-arm prospective multicenter study designed to evaluate the role of sentinel node biopsy (SLNB) in the context of neoadjuvant systemic treatment (NST) of breast cancer patients., Results: 1240 patients from 103 institutions entered the trial. 715 (arm C n = 592; arm D n = 123) patients, who presented initially cN1 underwent clinical evaluation of lymph node status following NST. Palpation alone demonstrated a sensitivity of 8.3%, specifity of 94.8% and a negative predictive value (NPV) of 46.6%. Ultrasound alone revealed a sensitivity of 23.9%, specificity 91.7%, and a NPV of 50.3%.The investigators combined classification (palpation and ultrasound) resulted in a sensitivity of 24.4%, specificity 91.4%, and a NPV of 50.3%. Investigators classified the axilla nodes as being unsuspicious (cN0) following NST in 592/715 patients; of them 298 (50.3%) were pN0, 151 (25.5%) had 1-2 histologically involved nodes and 143 (24.2%) had >2 histologically involved nodes., Conclusion: The diagnostic accuracy of ultrasound and palpation following NST is unacceptably low and additional tools for evaluation of the axillary lymph node status following NST are urgently needed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Pegylated liposomal doxorubicin (PLD) has shown to be as effective as conventional doxorubicin in the treatment of metastatic breast cancer but provides a lower risk of cardiotoxicity. This phase 2 study in heavily pretreated patients with metastatic breast cancer was initiated to evaluate a biweekly instead of a 4-week schedule of PLD in order to obtain a more flexible and tolerable regimen., Patients and Methods: A total of 25 patients with 2 or more prior lines of chemotherapy for metastatic disease were treated with PLD (25 mg/m 2 ) at 2-week intervals for a maximum of 12 courses. Pretreatment with anthracyclines was allowed as long as the cumulative doxorubicin dose at study entry was below 400 mg/m 2 . Most patients were pretreated with anthracyclines, taxanes, vinorelbine, alkylating agents, and capecitabine., Results: The clinical benefit rate, ie, objective response or stable disease, for at least 6 months was 22.7% for all patients and 22.2% in anthracycline- and taxane-pretreated patients, respectively. Median duration of clinical benefit and median time to progression were 12.5 months (95% confidence interval [CI], 10.1-32.3) and 7 weeks (95% CI, 5.4-8.6), respectively. Median overall survival was 9.6 months (95% CI, 5.4-13.9). One- and 2-year survival rates were 38% and 4%, respectively. Myelosuppression was low, with no grade 3 or 4 neutropenia or thrombocytopenia. Most common nonhematologic toxicities were nausea, alopecia, asthenia, and hand-foot syndrome. The low rate of hematologic toxicity and hand-foot syndrome is clinically noteworthy., Conclusion: Biweekly PLD is an easily manageable schedule with a favorable toxicity profile. Efficacy was moderate in heavily pretreated patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: TP53 mutations are frequent in breast cancer, however their clinical relevance in terms of response to chemotherapy is controversial., Methods: 450 pre-therapeutic, formalin-fixed, paraffin-embedded core biopsies from the phase II neoadjuvant GeparSixto trial that included HER2-positive and triple negative breast cancer (TNBC) were subjected to Sanger sequencing of exons 5-8 of the TP53 gene. TP53 status was correlated to response to neoadjuvant anthracycline/taxane-based chemotherapy with or without carboplatin and trastuzumab/lapatinib in HER2-positive and bevacizumab in TNBC. p53 protein expression was evaluated by immunohistochemistry in the TNBC subgroup., Results: Of 450 breast cancer samples 297 (66.0%) were TP53 mutant. Mutations were significantly more frequent in TNBC (74.8%) compared to HER2-positive cancers (55.4%, P < 0.0001). Neither mutations nor different mutation types and effects were associated with pCR neither in the whole study group nor in molecular subtypes (P > 0.05 each). Missense mutations tended to be associated with a better survival compared to all other types of mutations in TNBC (P = 0.093) and in HER2-positive cancers (P = 0.071). In TNBC, missense mutations were also linked to higher numbers of tumor-infiltrating lymphocytes (TILs, P = 0.028). p53 protein overexpression was also linked with imporved survival (P = 0.019)., Conclusions: Our study confirms high TP53 mutation rates in TNBC and HER2-positive breast cancer. Mutations did not predict the response to an intense neoadjuvant chemotherapy in these two molecular breast cancer subtypes.

Background: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer., Patients and Methods: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival., Results: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified., Conclusion: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Tumour documentation is essential for quality assurance of oncological therapies and as a source of reliable information about the in- and outpatient care. The documentation effort and the associated resource consumption were analysed for the example of breast cancer., Material and Methods: The different steps in the care of patients with primary breast cancer in a standardised disease situation were defined from initial diagnosis to the end of the follow-up. After the pilot phase, a multicentre validation (n=7 centres) was performed with the support of the Federal Ministry of Health. The documentation time points were horizontally collected and analysed with regard to amount, duration and personnel expenses., Results: 57% of the documentation costs are caused by the physicians. Regarding the different centres, documentation costs were calculated between € 352.82 and € 1 084.08 per patient from diagnosis to completion of aftercare. Non-certified centres had a reduced documentation effort and thus lower costs., Conclusions: The results demonstrate the need for a reduction of the documentation effort - particularly for physicians - the most expensive profession in the health system. A quality improvement is expected from the certification with its special requirements. In this context, there is a justified demand for an adequate remuneration of the documentation effort for certified centres. Furthermore, it is necessary to reduce the number of variables for quality assurance and to define them centrally. A comprehensive multi-disciplinary documentation should be achieved. Investments in a single data set and interface enhancements of existing documentation systems should be realised., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: In metastatic breast cancer, nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel. The GeparSepto (GBG 69) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response compared with weekly solvent-based paclitaxel, both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment., Method: In a phase 3 randomised trial, we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and randomly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype, Ki67 and SPARC expression. Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2) (after study amendment, 125 mg/m(2)) on days 1, 8, and 15 for four 3-week cycles, or solvent-based intravenous paclitaxel 80 mg/m(2) on days 1, 8, and 15 for four 3-week cycles. Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m(2) plus intravenous cyclophosphamide 600 mg/m(2) on day 1 for four 3-week cycles. Patients with HER2-positive tumours received concurrent trastuzumab 6 mg/kg (loading dose 8 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) on day 1 of every 3-week cycle. Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles. This report is the final analysis of the primary endpoint, pathological complete response (ypT0 ypN0), analysed for all patients who started treatment (modified intention to treat). We used a closed test procedure to test for non-inferiority, with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95% CI for the OR was above 0·858 (OR equivalent to pathological complete response [33%] minus a 10% non-inferiority margin [3·3%]; 29·7%). We planned to test for superiority only in case of a positive non-inferiority test, using an α of 0·05. Safety was assessed in all patients who received study drug. The trial is registered with ClinicalTrials.gov, number NCT01583426., Findings: Between July 30, 2012, and Dec 23, 2013, we randomly assigned 1229 women, of whom 1206 started treatment (606 with nab-paclitaxel and 600 with solvent-based paclitaxel). The nab-paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m(2) due to increased treatment discontinuation and sensory neuropathy in this group. Pathological complete response occurred more frequently in the nab-paclitaxel group (233 [38%, 95% CI 35-42] patients) than in the solvent-based paclitaxel group (174 [29%, 25-33] patients; OR 1·53, 95% CI 1·20-1·95; unadjusted p=0·00065). The incidence of grade 3-4 anaemia (13 [2%] of 605 patients in the nab-paclitaxel group vs four [1%] of patients in the solvent-based paclitaxel group; p=0·048) and peripheral sensory neuropathy grade 3-4 (63 [10%] patients receiving any nab-paclitaxel dose; 31 [8%] of patients starting with 125 mg/m(2) and 32 [15%] of patients starting with 150 mg/m(2); vs 16 [3%] in the solvent-based paclitaxel group, p<0·001) was significantly higher for nab-paclitaxel than for solvent-based paclitaxel. Overall, 283 (23%) patients were noted to have at least one serious adverse event (based on study drug received), 156 (26%) in the nab-paclitaxel group and 127 (21%) in the solvent-based paclitaxel group (p=0·057). There were three deaths (during epirubicin plus cyclophosphamide treatment) in the nab-paclitaxel group (due to sepsis, diarrhoea, and accident unrelated to the trial) versus one in the solvent-based paclitaxel group (during paclitaxel treatment; cardiac failure)., Interpretation: Substituting solvent-based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline-based chemotherapy. These results might lead to an exchange of the preferred taxane, solvent-based paclitaxel, for nab-paclitaxel in therapy for primary breast cancer., Funding: Celgene, Roche., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Pathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS+EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients and compares the results to a cohort of unselected patients., Methods: The CPS+EG score was calculated for 6637 unselected patients and 2454 patients with HR+/HER2- tumours who received anthracycline/taxane-based NACT within 8 prospective German trials., Results: Five-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR+/HER2- subgroup, respectively. The CPS+EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS+EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS+EG score to the HR+/HER2- subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population., Conclusions: In HR+/HER2- patients, the CPS+EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy (NACT) is widely used as an efficient breast cancer treatment. Ideally, a pathological complete response (pCR) can be achieved. Up to date, there is no reliable way of predicting a pCR. For the first time, we explore the ability of minimal invasive biopsy (MIB) techniques to diagnose pCR in patients with clinical complete response (cCR) to NACT in this study. This question is of high clinical relevance because a reliable pCR prediction could have direct implications for clinical practice., Methods: In all, 164 patients were included in this review-board approved, multicenter pooled analysis of prospectively assembled data. Core-cut (CC)-MIB or vacuum-assisted (VAB)-MIB were performed after NACT and before surgery. Negative predictive values (NPV) and false-negative rates (FNR) to predict a pCR in surgical specimen (diagnose pCR through MIB) were the main outcome measures., Results: Pathological complete response in surgical specimen was diagnosed in 93 (56.7%) cases of the whole cohort. The NPV of the MIB diagnosis of pCR was 71.3% (95% CI: (63.3%; 79.3%)). The FNR was 49.3% (95% CI: (40.4%; 58.2%)). Existence of a clip marker tended to improve the NPV (odds ratio 1.98; 95% CI: (0.81; 4.85)). None of the mammographically guided VABs (n=16) was false-negative (FNR 0%, NPV 100%)., Conclusions: Overall accuracy of MIB diagnosis of pCR was insufficient to suggest changing clinical practice. However, subgroup analyses (mammographically guided VABs) suggest a potential capacity of MIB techniques to precisely diagnose pCR after NACT. Representativity of MIB could be a crucial factor to be focused on in further analyses.

Breast cancer is the most common carcinosis with the largest number of mortalities in women. Its therapy comprises a wide spectrum of different treatment modalities a breast oncologist decides about for the individual patient case. These decisions happen according to medical guide lines, current scientific publications and experiences acquired in former cases. Clinical decision making therefore involves the time-consuming search for possible therapy options and their thorough testing for applicability to the current patient case.This research work addresses breast cancer therapy planning as a multi-criteria sequential decision making problem. The approach is based on a data model for patient cases with therapy descriptions and a mathematical notion for therapeutic relevance of medical information. This formulation allows for a novel decision support concept, which targets at eliminating observed weaknesses in clinical routine of breast cancer therapy planning.

Background: Breast cancer survivors have only very limited treatment options for menopausal symptoms. The objective of this trial was to evaluate the effects of a 12-week traditional Hatha yoga and meditation intervention on menopausal symptoms in breast cancer survivors., Methods: Patients were randomly assigned either to a 12-week yoga and meditation intervention or to usual care. The primary outcome measure was total menopausal symptoms (Menopause Rating Scale [MRS] total score). Secondary outcome measures included MRS subscales, quality of life (Functional Assessment of Cancer Therapy-Breast), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), depression, and anxiety (Hospital Anxiety and Depression Scale). Outcomes were assessed at week 12 and week 24 after randomization., Results: In total, 40 women (mean age ± standard deviation, 49.2 ± 5.9 years) were randomized to yoga (n = 19) or to usual care (n = 21). Women in the yoga group reported significantly lower total menopausal symptoms compared with the usual care group at week 12 (mean difference, -5.6; 95% confidence interval, -9.2 to -1.9; P = .004) and at week 24 (mean difference, -4.5; 95% confidence interval, -8.3 to -0.7; P = .023). At week 12, the yoga group reported less somatovegetative, psychological, and urogenital menopausal symptoms; less fatigue; and improved quality of life (all P < .05). At week 24, all effects persisted except for psychological menopausal symptoms. Short-term effects on menopausal symptoms remained significant when only women who were receiving antiestrogen medication (n = 36) were analyzed. Six minor adverse events occurred in each group., Conclusions: Yoga combined with meditation can be considered a safe and effective complementary intervention for menopausal symptoms in breast cancer survivors. The effects seem to persist for at least 3 months., (© 2015 American Cancer Society.)