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Objective: Women with locally advanced breast cancer (LABC) or inoperable local recurrence often suffer from a significantly reduced quality of life (QOL) due to local tumor-associated pain, bleeding, exulceration, or malodorous discharge. We aimed to further investigate the benefit of radiotherapy (RT) for symptom relief while weighing the side-effects. Materials and methods: Patients who received symptom-oriented RT for palliative therapy of their LABC or local recurrence in the Department of Radiation Oncology at Heidelberg University Hospital between 2012 and 2021 were recorded. Clinical, pathological, and therapeutic data were collected and the oncological and symptomatic responses as well as therapy-associated toxicities were analyzed. Results: We retrospectively identified 26 consecutive women who received palliative RT with a median total dose of 39 Gy or single dose of 3 Gy in 13 fractions due to (impending) exulceration, pain, local hemorrhage, and/or vascular or plexus compression. With a median follow-up of 6.5 months after initiation of RT, overall survival at 6 and 12 months was 60.0% and 31.7%, and local control was 75.0% and 47.6%, respectively. Radiation had to be discontinued in 4 patients due to oncological clinical deterioration or death. When completed as initially planned, symptom improvement was achieved in 95% and WHO level reduction of analgesics in 28.6% of patients. In 36% (16%) of patients, local RT had already been indicated >3 months (>6 months) before the actual start of RT, but was delayed or not initiated among others in favor of drug alternatives or systemic therapies. RT-associated toxicities included only low-grade side-effects (CTCAE I°-II°) with predominantly skin erythema and fatigue even in the context of re-RT. Conclusion: Palliative RT in symptomatic LABC or locoregional recurrence is an effective treatment option for controlling local symptoms with only mild toxicity. It may thus improve QOL and should be considered early in palliative patient care management.

Introduction: In the adjuvant setting for cervical cancer, classical risk factors for postoperative radiochemotherapy have been established. However, data on laboratory changes during therapy and the prognostic value of serological markers are limited and further knowledge is needed to optimize the toxic trimodal regimen. Methods: We retrospectively identified 69 women who underwent weekly postoperative radiochemotherapy with 40 mg/m 2 of cisplatin for cervical cancer between 2010 and 2021 at a single center. Laboratory parameters were recorded before, at each cycle and after radiochemotherapy. Kaplan-Meier and log-rank analyses were used to calculate and compare survival, groups were compared using the Mann–Whitney U , χ 2 , and variance tests. Results: With a median follow-up of 17.7 months, the 1- and 5-year local control rates were 94.0% and 73.7%, respectively, with significantly better rates for more chemotherapy cycles and negative resection margins. Only 68.1% of patients completed all cycles. The most common reasons for early discontinuation were persistent asymptomatic leukopenia in women aged ≤ 50 years, and limiting infections in women aged > 50 years. Leukopenia was more likely to occur after the third cycle. Significantly worse survival was observed for post-radiochemotherapy elevated C-reactive-protein and lactate dehydrogenase levels, low pre-radiochemotherapy nutritional index, and raised C-reactive-protein-levels; the latter were also predictable for local control. The Glasgow prognostic score did not reliably predict survival. Conclusion: Incomplete application of simultaneous chemotherapy leads to inferior local control, and age-dependent limiting factors should be identified at an early stage. In addition to classical risk factors, serological markers (C-reactive-protein, lactate dehydrogenase, nutritional index) show prognostic significance.

BACKGROUND:Locoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI). METHODS:Prospective clinical data from 456 patients treated between 2003 and 2011 was analyzed. The Kaplan-Meier method was used to examine the probabilities of locoregional recurrence, local recurrence and distant metastases according to individual prognosis score, stratified by type of surgery (breast conserving therapy or mastectomy). The possible confounding of the relationship between recurrence risk and MDAPI by established risk factors was accounted for in multiple survival regression models. To define the clinical utility of the MDAPI we analyzed its performance to predict locoregional recurrence censoring patients with prior or simultaneous distant metastases. RESULTS:Mastectomized patients (42% of the patients) presented with more advanced tumor stage, lower tumor grade, hormone-receptor positive disease and consequently lower pathological complete response rates. Only a few patients presented with high-risk scores (2,7% MDAPI≥3). All patients with high-risk MDAPI score (MDAPI ≥3) who developed locoregional recurrence were simultaneously affected by distant metastases. CONCLUSION:Our data do not support a clinical utility of the MDAPI to guide local therapy.

Purpose: Breast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC., Methods: A retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003-2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes., Results: A total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p < 0.1). Analyses of BC subtypes demonstrated that NLR was significantly higher in the pCR- compared with the non-pCR group (3.304 vs. 2.379, respectively; p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043)., Conclusion: NLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC., (© 2022. The Author(s).)

Background: Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients., Methods: After surgery, patients were randomised to receive either subcutaneous trastuzumab into the thigh or into the abdominal wall (AW). Patient preferences were evaluated using validated questionnaires (PINT). Primary objectives of this multicentre, non-blinded, randomised substudy of the GAIN-2 study were to investigate pharmacokinetics of the injection into the thigh versus AW and to determine patients' preferences of either administration site versus the previously received intravenous application., Results: 226 patients were randomised and 219 patients (thigh: N = 110; AW: N = 109) formed the modified intent-to-treat (mITT). Overall, 83.5% (out of N = 182 with information about patients' preference) preferred subcutaneous over previous intravenous application or had no preference. Preference was similar between both administration sites (thigh: 80.6%; AW: 86.5; p = 0.322). Pharmacokinetic analysis included 30 patients. Geometric means of C max and AUC 0-21d were higher in thigh than in AW group (geometric mean ratio with body weight adjustment: C max : 1.291, 90%-CI 1.052-1.584; AUC 0-21d : 1.291, 90%-CI 1.026-1.626). Safety profile was in line with previous reports of subcutaneous trastuzumab., Conclusion: Subcutaneous trastuzumab into the thigh showed an approximately 30% higher bioavailability. Injections were well tolerated and preferred over intravenous administration. The subcutaneous injection into the thigh should remain the standard of care., Competing Interests: Declaration of competing interest MR reports travel support from AstraZeneca, Celgene, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Seagen, Somatex and Roche. MU reports personal fees for lectures and/or consultancy from Abbvie, Amgen, Astra Zeneca, BMS, Celgene, Daiji Sankyo, Gilead, GSK, Lilly, MSD Merck, Mundipharma, Myriad Genetics, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi Aventis, Saegen. MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen outside the submitted work. Institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen; has a patent for EP2390370 B1 issued and a patent for EP2951317 B1issued. SL reports other from Amgen, other from BMS, grants and other from Celgene, grants, non-financial support and other from Roche, during the conduct of the study; grants and other from Abbvie, grants and other from AstraZeneca, other from Eirgenix, other from GSK, grants, non-financial support and other from Gilead, other from Lilly, other from Merck, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, non-financial support and other from Seagen, grants, non-financial support and other from Daiichi-Sankyo, other from Sanofi, outside the submitted work; In addition; has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending, and a patent Digital Ki67 Evaluator with royalties paid. ES reports honoraria from Pfizer, Roche, AstraZeneca, MSD, Gilead, Daiichi-Sankyo, Novartis, Seagen, Lilly, Pierre Fabre. SaS reports grants and non-financial support from F. Hoffman-La Roche, grants from BMS (Celgene), Amgen, during the conduct of the study; personal fees from Abbvie, outside the submitted work. CJ reports Honoraria from Amgen, AstraZeneca, Roche, Lilly, Novartis, Pfizer, Exact Sciences, Pierre-Fabré, Molecular Health. FM reports personal fees from Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, GenomicHealth, CureVac, EISAI outside the submitted work. CD reports stock and other ownership interest from Sividon Diagnostics (until 2016); consulting or advisor role from MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Merck, Roche, Lilly; research funding from Myriad Genetics, Roche; patents, royalties or other intellectual property from VMScope digital pathology software, patent applications WO2015114146A1 and WO2010076322A1-therapy response, patent application WO2020109570A1-immunotherapy. No other potential conflict of interest relevant to this article was reported., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Circulating miRNAs can provide valid prognostic and predictive information for breast cancer diagnosis and subsequent management. They may comprise quintessential biomarkers that can be obtained minimally invasively from liquid biopsy in metastatic breast cancer patients. Therefore, they would be clinically crucial for monitoring therapy response, with the goal of detecting early relapse. This study investigated miRNA expression in patients with early and/or late relapse, and the predictive value for assessing overall (OS) and progression-free survival (PFS)., Methods: Forty-seven patients with metastatic breast cancer from the University Women's Hospital Heidelberg were enrolled in this study. Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 was analyzed by RT-qPCR before a new line of systemic therapy and after the first cycle of a respective therapy. Tumor response was assessed every 3 months using the RECIST criteria. Statistical analysis focused on the relation of miR-200s expression and early vs. late cancer relapse in relation to systemic treatment. The association of miRNAs with PFS and OS was investigated., Results: Before starting a new line of systemic therapy, miR-429 (p = 0.024) expression was significantly higher in patients with early relapse (PFS ≤ 4 months) than in patients with late relapse (PFS > 4 months). After one cycle of systemic therapy, miR-200a (p = 0.039), miR-200b (p = 0.003), miR-141 (p = 0.017), and miR-429 (p = 0.010) expression was higher in early than in late progressive cancer. In addition, 4 out of 5 miR-200 family members (miR-200a, miR-200b, miR-141, and miR-429) predicted PFS (p = 0.048, p = 0.008, p = 0.026, and p = 0.016, respectively). Patients with heightened miRNA levels showed a significant reduction in OS and PFS., Conclusion: Circulating miR-200s were differentially expressed among patients with late and/or early relapse. 4 of 5 members of the miR-200 family predicted significantly early relapse after systemic treatment. Our results encourage the use of circulating miR-200s as valuable prognostic biomarkers during metastatic breast cancer therapy., (© 2022. The Author(s).)

The extracellular circulating microRNA (miR)-200 regulates epithelial-mesenchymal transition and, thus, plays an essential role in the metastatic cascade and has shown itself to be a promising prognostic and predictive biomarker in metastatic breast cancer (MBC). Expression levels of the plasma miR-200 family were analyzed in relationship to systemic treatment, circulating tumor cells (CTC) count, progression-free survival (PFS), and overall survival (OS). Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429, and CTC status (CTC-positive ≥ 5 CTC/7.5 mL) was assessed in 47 patients at baseline (BL), after the first completed cycle of a new line of systemic therapy (1C), and upon the progression of disease (PD). MiR-200a, miR-200b, and miR-141 expression was reduced at 1C compared to BL. Upon PD, all miR-200s were upregulated compared to 1C. At all timepoints, the levels of miR-200s were elevated in CTC-positive versus CTC-negative patients. Further, heightened miR-200s expression and positive CTC status were associated with poorer OS at BL and 1C. In MBC patients, circulating miR-200 family members decreased after one cycle of a new line of systemic therapy, were elevated during PD, and were indicative of CTC status. Notably, increased levels of miR-200s and elevated CTC count correlated with poorer OS and PFS. As such, both are promising biomarkers for optimizing the clinical management of MBC.

Background: The development of anti-HER2 antibody-drug conjugates opens new therapeutic options for patients with breast cancer, including patients with low expression of HER2. To characterise this new breast cancer subtype, we have compared the clinical and molecular characteristics of HER2-low-positive and HER2-zero breast cancer, including response to neoadjuvant chemotherapy and prognosis., Methods: In this pooled analysis of individual patient data, we evaluated a cohort of 2310 patients with HER2-non-amplified primary breast cancer that were treated with neoadjuvant combination chemotherapy in four prospective neoadjuvant clinical trials (GeparSepto, NCT01583426; GeparOcto, NCT02125344; GeparX, NCT02682693; Gain-2 neoadjuvant, NCT01690702) between July 30, 2012, and March 20, 2019. Central HER2 testing was done prospectively before random assignment of participants in all trials. HER2-low-positive status was defined as immunohistochemistry (IHC) 1+ or IHC2+/in-situ hybridisation negative and HER2-zero was defined as IHC0, based on the American Society of Clinical Oncology/College of American Pathologists guidelines. Disease-free survival and overall survival data were available for 1694 patients (from all trials except GeparX) with a median follow-up of 46·6 months (IQR 35·0-52·3). Bivariable and multivariable logistic regression models and Cox-proportional hazards models were performed based on a predefined statistical analysis plan for analysis of the endpoints pathological complete response, disease-free survival, and overall survival., Findings: A total of 1098 (47·5%) of 2310 tumours were HER2-low-positive and 1212 (52·5%) were HER2-zero. 703 (64·0%) of 1098 patients with HER2-low-positive tumours were hormone receptor positive, compared with 445 (36·7%) of 1212 patients with HER2-zero tumours (p<0.0001). HER2-low-positive tumours had a significantly lower pathological complete response rate than HER2-zero tumours (321 [29·2%] of 1098 vs 473 [39·0%] of 1212, p=0·0002). Pathological complete response was also significantly lower in HER2-low-positive tumours versus HER2-zero tumours in the hormone receptor-positive subgroup (123 [17·5%] of 703 vs 105 [23·6%] of 445, p=0·024), but not in the hormone receptor-negative subgroup (198 [50·1%] of 395 vs 368 [48·0%] of 767, p=0·21). Patients with HER2-low-positive tumours had significantly longer survival than did patients with HER2-zero tumours (3-year disease-free survival: 83·4% [95% CI 80·5-85·9] vs 76·1% [72·9-79·0]; stratified log-rank test p=0·0084; 3-year overall survival: 91·6% [84·9-93·4] vs 85·8% [83·0-88·1]; stratified log-rank test p=0·0016). Survival differences were also seen in patients with hormone receptor-negative tumours (3-year disease-free survival: 84·5% [95% CI 79·5-88·3] vs 74·4% [70·2-78.0]; stratified log-rank test p=0·0076; 3-year overall survival: 90·2% [86·0-93·2] vs 84·3% [80·7-87·3], stratified log-rank test p=0·016), but not in patients with hormone receptor-positive tumours (3-year disease-free survival 82·8% [79·1-85·9] vs 79·3% [73·9-83·7]; stratified log-rank test p=0·39; 3-year overall survival 92·3% [89·6-94·4] vs 88·4% [83·8-91·8]; stratified log-rank test p=0·13)., Interpretation: Our results show that HER2-low-positive tumours can be identified as new subgroup of breast cancer by standardised IHC, distinct from HER2-zero tumours. HER2-low-positive tumours have a specific biology and show differences in response to therapy and prognosis, which is particularly relevant in therapy-resistant, hormone receptor-negative tumours. Our results provide a basis for a better understanding of the biology of breast cancer subtypes and the refinement of future diagnostic and therapeutic strategies., Funding: German Cancer Aid (Deutsche Krebshilfe)., Competing Interests: Declaration of interests CD reports grants from European Commission H2020, German Cancer Aid Translational Oncology, German Breast Group, during the conduct of the study; personal fees from Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Molecular Health, and Merck, and grants from Myriad, outside the submitted work. CD is the cofounder of Sividon diagnostics. CD has a patent VMScope digital pathology software with royalties paid, a patent WO2020109570A1-cancer immunotherapy pending, and a patent WO2015114146A1 and WO2010076322A1-therapy response issued. AS reports grants from Celgene, Roche, and AbbVie; personal fees from Roche, AstraZeneca, Celgene, Novartis, MSD, Tesaro, Lilly, and Roche, outside the submitted work. TL receives payment or honoraria from Tesaro, MSD, Roche, Novartis, Pfizer, Amgen, Clovis, and Lilly; receives support for travel costs from Roche, Pfizer, MSD, Celgene, and Clovis; reports participation on an Advisory Board from Roche, Tesaro, Amgen, MSD, Pfizer, Lilly, Myriad, Esai, and GSK, outside the submitted work. J-UB reports personal fees from AstraZeneca, Exact Sciences, Amgen, MSD Oncology, Lilly, Novartis, Sysmex, Roche, and Sonoscape, outside the submitted work. PW reports personal fees from Amgen, AstraZeneca, MSD, Novartis, Pfizer, PharmaMar, Roche, Teva, Eisai, Clovis, and Tesaro, outside the submitted work. HT reports consulting fees and travel costs from Pierre Fabre, Pfizer Pharma, Mundipharma, ClinSol, Novartis, Lilly, Grünenthal, Vifor, AstraZeneca, Mylan, and AMGEN; payment or honoraria from Vifor, Novartis, AstraZeneca, ClinSol, Mundipharma, Lilly, and Amgen; participation on an Advisory Board from Novartis, Bristol Myers Squibb, AstraZeneca, Molecular Health, Pfizer, Roche, Grünenthal, and Mylan; and is part of a leadership or fiduciary role in Arbeitskreis klinische Studien. ASCO, BNHO, DGHO, DKG, ESMO, Deutsche Gesellschaft für Senelogie. CJ receives payment or honoraria from Roche, AstraZeneca, Novartis, Lilly, Exact Sciences, and Pierre Fabre; recieves support for travel costs from Roche and AstraZeneca, reports participation on an Advisory Board from Roche, Lilly, and AstraZeneca. MR reports consulting fees from Roche, Novartis, Lilly, and Somatex; receives payment or honoraria from Novartis, Roche, Lilly, Somatex, and AstraZeneca; recieves support for travel costs from Novartis, Pfizer, and Celgene. EFS receives payment or honoraria from AstraZeneca, Pfizer, Celgene, Roche, and Amgen; support for travel costs from Amgen, AstraZeneca, Celgene, Clovis Oncology, Eisai, Erbe, Gedeon, Richter, Genomic Health, Jenapharm, Johnson Johnson, KLS Martin, Matramed, Medac, Mentor, Novartis, Pfizer, Pharma Mar, MSD, Roche, Samsung, Storz, Tewa, Vifor, Medconcept, and Thieme; is part of a leadership or fiduciary role of University of Saarland, Germany, society for German Gynecological Endoscopy. CH reports personal fees from Pfizer, Roche, Novartis, Lilly, AstraZeneca, Celgene, outside the submitted work. PAF reports personal fees from Novartis, Pfizer, Daiichi-Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seattle Genetics, Roche, and Hexal, and grants from Biontech and Cepheid, during the conduct of the study. KL receives payment from Roche, Pfizer, MSD, Novartis, Lilly, and Genomic Health, support for travel costs from Roche, and reports participation on an Advisory Board from Roche, MSD, and Esai. JH reports research grants to institution from Celgene, Novartis, and Hexal; consulting fees from Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, and Abbvie; receives payment from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, and Abbvie; recieves support for travel costs from Roche, Pfizer, Novartis, Celgene, and Daiichi. TR reports consulting fees from Pfizer, honoraria for presentations from AstraZeneca and receives payment from Pfizer, Roche, and Novartis. MS reports grants from AstraZeneca, BioNtech, Eisai, German Breast Group, Genentech, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, and Roche; consulting fees from AstraZeneca, Eisai, Lilly, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen; receives payment or honoraria from AstraZeneca, Novartis, Pfizer, Roche, and SeaGen; support for travel costs from Pfizer and Roche; has planned patents, issued or pending from EP 2951317 B1 and EP 2390370 B1; reports participation on an Advisory Board from AstraZeneca, Eisai, Lilly, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen; medical writing support from Roche. WJ reports grants and personal fees from Sanofi-Aventis, Novartis, Lilly, Pfizer, Roche, Chugai, AstraZeneca, MSD, and Daiichi Sankyo, during the conduct of the study. ES reports consulting fees from Roche and AstraZeneca; receives payment or honoraria from Roche, Pfizer, Novartis, and Astra Zeneca; support for travel costs from Roche, Pfizer, and Daiko. SSe reports reimbursement of travel costs from Novartis and personal fees from Roche, Mundipharma, and Amgen, outside the submitted work. MU reports personal fees and non-financial support from Abbvie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly Int, MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, Roche Pharma, Sanofi Aventis Deutschland, TEVA Pharmaceuticals, Novartis, and Clovis Oncology; personal fees from Bristol Myers Squibb, Lilly Deutschland, PUMA Biotechnology, Pierre Fabre, Seattle Genetics, outside the submitted work. SL reports grants or fundings from Amgen, AstraZeneca, Celgene, Novartis, Immunomedics, Pfizer, Roche, DSI Trevor, Vifor, Abbvie, Cepheid, Seagen, and VM Scope; receives payment or honoraria from AstraZeneca, Roche, Novartis, Pfizer, Prime/Medscape, Puma, and Samsung; has planned patents, issued or pending from EP14153692.0; reports participation on an Advisory Board from Amgen, AstraZeneca, DSI, Roche, Merck, Pfizer, BMS, SeaGen, Eirgenix, Celgene, Abbvie, Lilly, GlaxoSmithKline, and Pierre Fabre; is part of a leadership or fiduciary role from BIG. All other authors report no conflicts of interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with superior survival. This association is strongest in triple-negative breast cancer (TNBC). The CPS + EG system, based on pre-treatment clinical (CS) and post-treatment pathological stage (PS), oestrogen-receptor status (E) and grade (G), leads to a refined estimate of prognosis after NACT in all-comers and hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here, we investigate if CPS + EG scoring provides a superior estimate of prognosis in TNBC to select patients for postneoadjuvant therapy., Methods: We calculated the CPS + EG score for 1795 patients with TNBC from 8 prospective German trials. Five-year disease-free survival (DFS) and overall survival estimates were calculated using the Kaplan-Meier method., Results: In TNBC, patients with pCR (ypT0/is ypN0, n = 822, 45.8%) had a 5-year DFS of 86%, whereas patients with residual American Joint Committee on Cancer stage I disease (n = 383; 21.3%) had a 5-year DFS of 77.5%.CPS + EG led to superior prognostic information compared with that provided by the clinical stage, but it was inferior to the prognostic information provided by the pathological stage (c-index statistics, p < 0.001). CPS + EG did not discriminate prognosis within the two best prognostic groups (score 1 and 2; n = 362; 37.2%). In contrast, pCR status added prognostic information beyond CPS + EG. Patients with a CPS + EG score of 3 had a 5-year DFS rate of 64% overall, but those with pCR had a 5-year DFS rate of 84%, and those without pCR had a 5-year DFS rate of only 49.7%., Conclusions: In TNBC, CPS + EG scoring provided inferior prognostic information compared with the pathological stage and was unable to identify patients without pCR and with a sufficiently good prognosis, who could avoid postneoadjuvant therapy. pCR remains the strongest and most clinically useful prognostic factor after NACT. Other biologic factors beyond pCR are needed in TNBC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial., Methods: From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations., Results: Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line., Conclusion: The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Carlo FremdHonoraria: Roche, Pfizer, Celgene, AstraZeneca, Amgen Consulting or Advisory Role: Roche, Pfizer Travel, Accommodations, Expenses: Celgene, RocheLaura MichelHonoraria: AstraZeneca, Roche, Eisai, LillyDaniela RichterTravel, Accommodations, Expenses: IlluminaPeter HorakHonoraria: IpsenAlbrecht StenzingerConsulting or Advisory Role: AstraZeneca, Novartis, Bristol Myers Squibb, Bayer, Illumina, Thermo Fisher Scientific, Janssen, Lilly, Seattle Genetics, Takeda, AGCT Speakers' Bureau: Bristol Myers Squibb, AstraZeneca, MSD, Roche, Bayer, Illumina, Thermo Fisher Scientific, Novartis Research Funding: Chugai Pharma, Bristol Myers Squibb, BayerChristoph SpringfeldConsulting or Advisory Role: Celgene, Servier, Eisai, Roche, MSD, Bayer Travel, Accommodations, Expenses: Celgene, ServierKatharina SmetanayHonoraria: Celgene, Roche, Pfizer Travel, Accommodations, Expenses: CelgeneAthanasios MavratzasHonoraria: Roche, Eisai Europe, Pfizer Travel, Accommodations, Expenses: Roche, Eisai, PfizerFlorian SchuetzHonoraria: Roche, Pfizer, MSD Oncology, Amgen, AstraZeneca Consulting or Advisory Role: MSD OncologyStefan FröhlingHonoraria: PharmaMar, Roche, Lilly, Amgen Consulting or Advisory Role: Bayer, Illumina, Roche Research Funding: AstraZeneca, PharmaMar, Pfizer, Roche Travel, Accommodations, Expenses: PharmaMar, Roche, Lilly, AmgenHans-Peter SinnHonoraria: NanoString Technologies, Roche Pharma AG Research Funding: Roche Pharma AG Travel, Accommodations, Expenses: NanoString TechnologiesDirk JägerConsulting or Advisory Role: Roche/Genentech, Bristol Myers Squibb, BioNTech AG, AmgenAndreas SchneeweissHonoraria: Roche Pharma AG, Celgene, AstraZeneca, Pfizer, Novartis, MSD Oncology, Lilly, Tesaro Research Funding: Roche Pharma AG, Celgene, Abbvie, Molecular Partners Expert Testimony: Roche, AstraZeneca Travel, Accommodations, Expenses: Roche, Celgene No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

Due to its rarity, there are no randomized trials investigating the outcome of adjuvant radiotherapy in MBC. This study reports on patient and tumor characteristics of 41 consecutive MBC patients treated between 1990 and 2018 and on clinical outcomes after surgical resection of tumors and adjuvant radiotherapy of the chest wall or breast. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and toxicity were evaluated. After a median follow-up of 80 months (95% CI: 14.6-213.8 months) there was only one recurrence, in a patient's locoregional lymph nodes 17 months after start of radiotherapy, resulting in an LC rate of 100% at 5 years and a 5-year LRC rate of 97.4% (standard deviation (SD): 0.025). Five-year DFS and OS rates were 64.6% (SD: 0.085) and 57.2% (SD: 0.082), respectively. Adjuvant radiotherapy was tolerated well without high-grade (CTCAE grade > II) adverse events. After tumor resection and adjuvant radiotherapy, LC and LRC rates in MBC patients are excellent and comparable to results found for female breast cancer (FBC) patients. However, as patients are often diagnosed with locally advanced, higher-risk tumors, distant recurrences remain the major failure pattern.

Purpose: In the ACOSOG Z0011 trial, completing axillary lymph node dissection (cALND) did not benefit patients with T1-T2 cN0 early breast cancer and 1-2 positive sentinel lymph nodes (SLN) undergoing breast-conserving surgery (BCT). This paper reports cALND rates in the clinical routine for patients who had higher (T3-T4) tumor stages and/or underwent mastectomy but otherwise met the ACOSOG Z0011 eligibility criteria. Aim of this study is to determine cALND time trends and non-sentinel axillary metastases (NSAM) rates to estimate occult axillary tumor burden., Methods: Data were included from patients treated in 179 German breast cancer centers between 2008 and 2015. Time-trend rates were analyzed for cALND of patients with T3-T4 tumors separated for BCT and mastectomy and regarding presence of axillary macrometastases or micrometastases., Results: Data were available for 188,909 patients, of whom 19,009 were identified with 1-2 positive SLN. Those 19,009 patients were separated into 4 cohorts: (1) Patients with T1-T2 tumors receiving BCT (ACOSOG Z0011 eligible; n = 13,741), (2) T1-T2 with mastectomy (n = 4093), (3) T3-T4 with BCT (n = 269), (4) T3-T4 with mastectomy (n = 906). Among patients with T3-T4 tumors, cALND rates declined from 2008 to 2015: from 88.2 to 62.6% for patients receiving mastectomy and from 96.6 to 58.1% in patients receiving BCT. Overall rates for any NSAM after cALND for cohorts 1-4 were 33.4%, 42.3%, 46.9%, 58.8%, respectively., Conclusions: The cALND rates have decreased substantially in routine care in patients with 'extended' ACOSOG Z0011 eligibility criteria. Axillary tumor burden is higher in these patients than in the ACOSOG Z0011 trial.

Purpose: Some reproductive factors are well-known general risk factors for breast cancer (BC). On the other hand, BC subtypes also have a high prognostic value. Correlations, however, that link these risk factors to the development of a particular one of the different BC subtypes are still poorly understood. The primary objective of our study was to assess the influence of different reproductive factors (duration of breastfeeding, parity, and age at first childbirth) on pathological BC subtypes. Secondarily, we correlated body mass index (BMI), age at primary diagnosis, and smoking behavior with tumor subclasses., Patients and Methods: We performed a retrospective chart review of 1082 patients with BC who had been treated for postmenopausal BC at the Heidelberg University Hospital during the period 2009-2014. For statistical analysis, different types of correlation analysis as well as a logistic regression model were used., Results: Relating to the primary objective, we found that patients with luminal-like BC had significantly fewer children than patients with triple-negative or HER2-positive subtype tumors (P = 0.027). Concerning the duration of breastfeeding, patients with a luminal A-like tumor had a significantly lower mean nursing period than patients with other subtypes (P = 0.012). Furthermore, patients who did breastfeed presented with a significantly lower number of hormone receptor-positive tumors (estrogen receptor-positive, P = 0.04; progesterone receptor-positive, P = 0.017) but the highest rate of HER2-overexpressing malignancies (P = 0.011). Moreover, late first childbirth was associated with the occurrence of luminal tumors (OR 0.952; P = 0.041). Regarding our secondary aim, higher BMI (P = 0.031) and higher age at primary diagnosis (P = 0.038) were both found to be significantly associated with luminal-like BC., Conclusion: The results suggest a correlation of the occurrence of luminal-like BC subtypes with low parity and short or no duration of breastfeeding. Prospective investigations are needed for further confirmation and to evaluate the molecular basis of our findings.

This study examines the in vitro antimicrobial and antioxidant activities of the methanolic extracts of three Salvia species from Tunisia: Salvia aegyptiaca L., S. argentea L. and S. verbenaca Ssp. clandestina L. Pugsley. The extracts inhibited the growth of dermatophytes and of bacteria responsible for unpleasant odours to varying degrees; the pathogenic yeasts Candida albicans and Cryptococcus neoformans, the filamentous fungi Aspergillus fumigatus and selected dog otitis bacteria were all resistant to each of the extracts. The extracts were screened for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) test systems, and gave positive results in both tests. The extracts of S. aegyptiaca were the most active in both tests, followed by those of S. verbenaca, then S. argentea. These results confirm the antimicrobial and antioxidant activities of the genus Salvia and underline the potential of these plants either as natural preservatives or in pharmaceutical applications.