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Purpose: Breast cancer (BC) is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a condition associated with an increased risk of various malignancies, including radiation therapy (RT)-induced malignancies (RIM) within previously irradiated areas. Our study aimed to assess the incidence of RIM in patients with LFS and early-stage BC treated with adjuvant RT, including the effect of RT dose and technique., Methods and Materials: We examined patients with a germline pathogenic/likely pathogenic TP53 variant diagnosed with early-stage BC and monitored by a hereditary cancer team at a single cancer center. The study endpoints included RIM frequency, the association of RIM with the dose and type of RT (2-dimensional [2D] RT, 3-dimensional [3D] RT, and intensity modulated RT [IMRT]), and BC recurrence., Results: We analyzed 48 patients with a median age of 39 years (range, 21-62). The majority (71%) had the TP53 R337H variant, and 87% were unaware of their LFS diagnosis at the time of BC treatment. Treatment modalities included mastectomy (62%), (neo)adjuvant chemotherapy (66%), and RT (62%), with RT being more common after breast-conserving surgery (87% vs 46% with mastectomy, P = .010). Among the 30 patients treated with RT, 10% developed RIM in the irradiated field, consisting of 3 soft tissue malignancies. RT dose (≤40.8 or >40.8 Gy) did not influence RIM occurrence, but the type of RT did. RIM was observed in 100% of cases with 2D RT (2/2), 50% with IMRT (1/2), and 0% with 3D RT (0/16) (P = .004)., Conclusions: Our study underscores a concerning rate of RIM after adjuvant RT, emphasizing the importance of a thorough risk-benefit evaluation before recommending RT, with preference for its avoidance if possible. Although subgroup sizes were limited, the risk of RIM appeared to be influenced by the RT technique, with higher rates observed with 2D RT and IMRT compared with 3D RT. Early TP53 testing is essential to guide the BC treatment plan., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: While general conclusions of historical trials are widely recognized, the nuances regarding precise indications of Sentinel Node Biopsy (SNB) in breast cancer in complex clinical scenarios often remain a source of debate and require further elucidation., Methods: Two reviewers (JFB and GNM) independently searched electronic databases for studies including SNB as the main intervention. Filters were applied to retrieve only clinical trials (randomized or experimental non-randomized); non-oncological outcomes were excluded. The selected studies were considered to construct a narrative review focused on inclusion criteria and survival outcomes, followed by recommendations., Results: Fourteen (n = 14) trials were selected, including eleven (n = 11) randomized trials for upfront surgery, and three (n = 3) single-group clinical trials for surgery following neoadjuvant therapy. All trials for upfront surgery provided long-term survival data for SNB, that was equivalent or non-inferior to axillary dissection, in tumors without palpable adenopathy (caution for larger T3 and T4 tumors) - Grade of recommendation: A. In tumors up to 5 cm, complete axillary dissection is not necessary if up to two sentinel nodes are positive for macrometastasis, and radiation therapy is planned - Grade of recommendation: A. If there are more than two sentinel nodes positive for macrometastasis, or a positive node other than the sentinel one, complete axillary dissection is recommended - Grade of recommendation: A. Following neoadjuvant chemotherapy, considering 10% as an acceptable false negative rate, SNB might be offered for cN0 patients who have remained negative, and for cN1 (caution for cN2) patients become clinically negative; complete axillary dissection might not be necessary if at least two sentinel lymph nodes are retrieved, and there is no residual disease - Grade of recommendation: B., Conclusion: SNB can be performed in most cases of clinically negative nodes. After neoadjuvant chemotherapy, SNB is feasible and may have acceptable performance for cN0 and cN1 tumors, although prospective survival data is still awaited., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Breast cancer (BC) is the most incident tumor and, consequently, any new intervention can potentially promote a considerable budget impact if incorporated. Cost-effectiveness (CE) studies assist in the decision-making process but may be influenced by the country's perspective of analysis and pharmaceutical industry funding., Methods: A systematic review of Medline, Scopus, and Web of Science from January 1st, 2012 to July 8th, 2022 was conducted to identify CE studies of tumor-targeted systemic-therapies for advanced BC. Articles without incremental cost-effectiveness ratio calculations were excluded. We extracted information on the country and class of drug studied, comparator type, authors' conflicts of interest (COI), pharmaceutical industry funding, and authors' conclusions., Results: 71 studies comprising 204 CE assessments were included. The majority of studies were from the United States and Canada (44%), Asia (32%) and Europe (20%). Only 8% were from Latin America and none from Africa. 31% had pharmaceutical industry funding. The most studied drug classes were cyclin-dependent-kinase inhibitors (29%), anti-HER2 therapy (23%), anti-PD(L)1 (11%) and hormone therapy (11%). Overall, 34% of CE assessments had favorable conclusions. Pharmaceutical industry-funded articles had a higher proportion of at least one favorable conclusion (82% vs. 24%, p-value<0.001), European countries analyzed (45% vs. 9%, p-value = 0.003), and CE assessments with same class drug comparators (56% vs. 33%, p-value = 0.004)., Conclusions: Breast cancer CE literature scarcely represents low-and-middle-income countries' perspectives and is influenced by pharmaceutical industry funding which targets European countries', frequently utilizes comparisons within same-drug class, and is more likely to have favorable conclusions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:FLN, MAZM, CMTHF, and AGC have no conflicts of interest to disclose. MCMM has received payment for lectures from Lilly and MSD. The author has received support for attending meetings from Pfizer. LT provides advisory/consulting assistance to MSD, Daiichi Sankyo/Astra Zeneca, Lilly, Pfizer, and Novartis and receives travel accommodation financial support from Gilead, Roche and Astra Zeneca., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Visceral Crisis (VC) in breast cancer is a critical scenario when the burden of metastatic disease results in rapid deterioration of organ functions. There are no widely accepted objective clinical criteria for the definition of VC, and different studies have reported diverse clinical conditions such as visceral crises. Diagnosis of VC is associated with a dismal prognosis and the management of this condition is currently based on limited retrospective evidence and expert opinions. International guidelines have recommended cytotoxic polychemotherapy in the management of VC, to achieve rapid symptomatic control and preserve organ function. Nevertheless, in the case of hormone receptor-positive breast cancer, the role of chemotherapy as the treatment of choice for VC has been recently questioned, since endocrine therapy plus CDK4/6 inhibitors yielded similar response rates, with better quality of life. For HER2-positive and triple-negative breast cancer, combined chemotherapy (plus HER2-directed therapy for HER2-positive) remains a standard option for VC, but novel effective drugs such as antibody-drug conjugates are emerging and their role in the VC context shall soon be elucidated. This review aims to critically discuss the definition, prognosis, management, and future directions regarding the visceral crisis in metastatic breast cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-year treatment period in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-year efficacy results from a prespecified overall survival (OS) interim analysis. In the intent-to-treat population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with hazard ratios of 0.680 (95% CI, 0.599 to 0.772) for IDFS and 0.675 (95% CI, 0.588 to 0.774) for DRFS. This persistence of abemaciclib benefit translated to continuous separation of the curves with a deepening in 5-year absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with rates of 6% and 5.3% at 4 years and 4.8% and 4.1% at 3 years. With fewer deaths in the abemaciclib plus ET arm compared with the ET-alone arm (208 v 234), statistical significance was not reached for OS. No new safety signals were observed. In conclusion, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence beyond the completion of treatment. The increasing absolute improvement at 5 years is consistent with a carryover effect and further supports the use of abemaciclib in patients with high-risk EBC.

Introduction: Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS., Methods: We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS)., Results: Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P < 0.001). Other relevant baseline characteristics and treatment received were similar between groups. 5y-RFS rates were 79.4% in the mTP53 versus 93.6% in the control group (HR 2.43, 95%CI 0.74-8.01, P = 0.143); and were not impacted by the use of adjuvant radiotherapy. 5y-BCSS rates were 92.2% and 98.6%, respectively (HR 1.87, IC95% 0.25-13.48, P = 0.534)., Conclusions: Our results showed no statistically significant difference in BC-related RFS and BCSS between patients with mTP53 and a control group with no pathogenic variant. Larger multicentric studies are warranted to confirm these results., Competing Interests: Declaration of competing interest VP: Speaker fees and/or honoraria for consultancy or advisory functions: AstraZeneca, Daiichi-Sankyo, Novartis; Financial support for educational programs and symposia: Daiichi-Sankyo. RCB: Speaker fees and/or honoraria for consultancy or advisory functions: Daiichi-Sankyo, Nestle; Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo; Institutional Research Funding: Novartis, AstraZeneca. LT: Consulting or Advisory Role: Lilly, Novartis, MSD, AstraZeneca, Daiichi-Sankyo; Educational Support: Pfizer, Lilly, Zodiac, AstraZeneca; Speaker: Novartis, Roche, Pfizer, Zodiac, Lilly, MSD, AstraZeneca, Daichii-Sankyo; Institutional Research Funding: Novartis. DJBHC: Speaker fees and/or honoraria for consultancy or advisory functions: Novartis, Daiichi-Sankyo, AstraZeneca; Financial support for educational programs and symposia: Gilead. AC: Speaker fees and/or honoraria for consultancy or advisory functions: AstraZeneca, Libbs. RGC: Speaker fees and/or honoraria for consultancy or advisory functions: AstraZeneca, MSD, GSK; Financial support for educational programs and symposia: AstraZeneca., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Adjuvant abemaciclib plus endocrine therapy previously showed a significant improvement in invasive disease-free survival and distant relapse-free survival in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2; also known as ERBB2)-negative, node-positive, high-risk, early breast cancer. Here, we report updated results from an interim analysis to assess overall survival as well as invasive disease-free survival and distant relapse-free survival with additional follow-up., Methods: In monarchE, an open-label, randomised, phase 3 trial, adult patients (aged ≥18 years) who had hormone receptor-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence with an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 603 sites including hospitals and academic and community centres in 38 countries. Patients were randomly assigned (1:1) by means of an interactive web-based response system (block size of 4), stratified by previous chemotherapy, menopausal status, and region, to receive standard-of-care endocrine therapy of physician's choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for 2 years (treatment period). All therapies were administered in an open-label manner without masking. High-risk disease was defined as either four or more positive axillary lymph nodes, or between one and three positive axillary lymph nodes and either grade 3 disease or tumour size of 5 cm or larger (cohort 1). A smaller group of patients were enrolled with between one and three positive axillary lymph nodes and Ki-67 of at least 20% as an additional risk feature (cohort 2). This was a prespecified overall survival interim analysis planned to occur 2 years after the primary outcome analysis for invasive disease-free survival. Efficacy was assessed in the intention-to-treat population. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03155997, and is ongoing., Findings: Between July 17, 2017, and Aug 12, 2019, 5637 patients were randomly assigned (5601 [99·4%] were women and 36 [0·6%] were men). 2808 were assigned to receive abemaciclib plus endocrine therapy and 2829 were assigned to receive endocrine therapy alone. At a median follow-up of 42 months (IQR 37-47), median invasive disease-free survival was not reached in either group and the invasive disease-free survival benefit previously reported was sustained: HR 0·664 (95% CI 0·578-0·762, nominal p<0·0001). At 4 years, the absolute difference in invasive disease-free survival between the groups was 6·4% (85·8% [95% CI 84·2-87·3] in the abemaciclib plus endocrine therapy group vs 79·4% [77·5-81·1] in the endocrine therapy alone group). 157 (5·6%) of 2808 patients in the abemaciclib plus endocrine therapy group died compared with 173 (6·1%) of 2829 patients in the endocrine therapy alone group (HR 0·929, 95% CI 0·748-1·153; p=0·50). The most common grade 3-4 adverse events were neutropenia (in 548 [19·6%] of 2791 patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six [0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800 receiving endocrine therapy. There were two treatment-related deaths in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none in the endocrine therapy alone group., Interpretation: Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer. Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients., Funding: Eli Lilly., Competing Interests: Declaration of interests SRDJ reports grants or contracts from Pfizer, Puma Biotechnology, Eli Lilly, AstraZeneca, Novartis, and Roche–Genentech for research funding to institute for laboratory studies and clinical trials; consulting fees from Eli Lilly, AstraZeneca, Puma Biotechnology, Pfizer, Novartis, and Sanofi Genzyme for consulting or an advisory role; and payment or honoraria from Pfizer, Eisai, AstraZeneca, and Roche–Genentech for speaker's bureau. MT reports grants or contracts from Chugai, Takeda, Pfizer, Taiho, JBCRG, KBCRN, Eisai, Eli Lilly, Daiichi-Sankyo, AstraZeneca, Astellas, Shimadzu, Yakult, Nippon Kayaku, AFI technology, Luxonus, Shionogi, GL Science, and Sanwa Shurui for research grants to their department; payment or honoraria from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, Daiichi-Sankyo, AstraZeneca, Eli Lilly, Merck Sharp and Dohme, Exact Science, Novartis, Shimadzu, Yakult, Nippon Kayaku, Devicore Medical Japan, and Sysmex for lecture honoraria or honoraria for lecture chair; participation on a data safety monitoring board or advisory board for Daiichi-Sankyo, Eli Lilly, Bristol Myers Squibb, Athenex Oncology, Bertis, Terumo, and Kansai Medical Net; and other financial or non-financial interest from British Journal of Cancer, Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer, Asian Journal of Surgery, and Asian Journal of Breast Surgery for his role as Associate Editor. JO'S reports consulting fees and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from from AbbVie, Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Athenex, Bayer, Bristol Myers Squibb, Carrick Therapeutics, Celgene Corporation, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Genzyme, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Eli Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Ontada, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche, Samsung Bioepsis, Sandoz, Sanofi, Seagen, Syndax Pharmaceuticals, Taiho Oncology, Takeda, Theralink, and Synthon. MC reports personal payment support from Eli Lilly for the present article, advisory board, and speaker's bureau; payment or honoraria to institution from Novartis; support for attending meetings from Eli Lilly, Novartis, AstraZeneca, and Pfizer; and payment to institution from AstraZeneca, Novartis, Sanofi, Pfizer, Seagen, Gilead, Daiichi Sankyo for participation on a data safety monitoring board or advisory board. C-SH reports research grants to institution from Eli Lilly for the present article; research grants to institution or contracts from Daiichi Sankyo, AstraZeneca, EirGenix, Eli Lilly and Company, Merck Sharp and Dohme, OBI Pharma, Pfizer, Roche, and Novartis; payment or honoraria from Daiichi Sankyo, AstraZeneca, Pfizer, Novartis, Roche, and Eli Lilly for speaker's bureau; support for attending meetings or travel from Astra Zeneca, Pfizer, Roche, and Novartis; and participation on advisory boards from Daiichi Sankyo, AstraZeneca, Eli Lilly, Pfizer, Novartis, and Roche. JH reports institutional grants or contracts from Celgene, Novartis, Hexal, and Eli Lilly; consulting fees paid to self from Eli Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, Merck Sharp and Dohme, Celgene, AbbVie, and Daiichi-Sankyo; honoraria or payments to self for lectures, presentation, speaker's bureaus, manuscript writing, or educational events from Eli Lilly, Novartis, Roche, Pfizer, AstraZeneca, Merck Sharp and Dohme, Celgene, Eisai, Abbvie, Seagen, and Gilead; and support for attending meetings or travel paid to self from Roche, Pfizer, Novartis, Celgene, Daiichi-Sankyo, and Gilead. SMT reports institutional funding for study, consulting work to personal (honorariums), and manuscript preparation from Eli Lilly; institutional grants or contracts from AstraZeneca, Merck, Mektar, Novartis, Pfizer, Genentech–Roche, Gilead, Exelixis, Bristol Myers Squibb, Eisai, Nanostring, Cyclacel, Sanofi, and Seagen; and honoraria payments to self for participation in advisory boards or consulting from AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Genentech–Roche, Gilead, Bristol Myers Squibb, Eisai, Sanofi, Seagen, Daiichi-Sankyo, Athenex, OncoPep, Kyowa Kirin Pharma, CytomX, Certara, Mersana Therapeutics, Ellipses Pharma, 4D Pharma, OncoSec, Infinity Therapeutics, BeyondSpring Pharma, OncXerna, Zymeworks, Zentalis, ARC Therapeutics, Reveal Genomics, Blueprint Medicines, Myovant, Umoja Biopharma, and Menarini–Stemline. MPG reports institutional grants or contracts from Pfizer, Eli Lilly, and Sermonix; consulting fees to institution from Eagle Pharmaceuticals, Eli Lilly, Biovica, Novartis, Sermonix, Pfizer, and ARC Therapeutics; honoraria or payment to self for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Research to Practice, Clinical Education Alliance, Medscape, Total Health Conferencing, Curio Science, and MJH Life Sciences; and support to institution from Eli Lilly, AstraZeneca, Novartis, Biotheranostics, Blueprint Medicines, Sanofi Genzyme, and ARC Therapeutics for participation on a data safety monitoring board or advisory board. HSR reports institutional research support from Pfizer, Novartis, Eli Lilly, Genentech–Roche, OBI, Merck, Gilead Sciences, Daiichi Sankyo, Seattle Genetics, Sermonix, AstraZeneca, and Astellas; travel support to academic meetings from Merck, AstraZeneca, and Gilead; and consulting or advisory support from Puma, NAPO, and Blueprint. ES reports support from Eli Lilly for the present article including investigator fees and medical writing; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from AstraZeneca, Cancérodigest, Curio, Science, Egis, Eli Lilly and Company, Exact Sciences, Gilead, high5md, Merck Sharp and Dohme, Novartis, Pfizer, and Pierre Fabre; support for attending meetings or travel from Egis, Gilead, Novartis, Pfizer, and Roche; participation on a data safety monitoring board or advisory board from AstraZeneca, Egis, Eli Lilly, Exact Sciences, Merck Sharp and Dohme, Novartis, and Pfizer; a leadership or fiduciary role from Stowarzyszenie Różowy Motyl as Chair (unpaid); stock or stock options from AstraZeneca, Eli Lilly, and Pfizer; receipt of equipment, materials, drugs, medical writing, gifts or other services from Astellas, AstraZeneca, and Eli Lilly; and other financial or non-financial interests from Amgen, AstraZeneca, Eli Lilly, Novartis, OBI Pharma, Pfizer, Roche, and Samsung for contracted research. LT reports support from Eli Lilly as the trial sponsor for the study; grants or contracts from Novartis for clinical research; consulting fees from Merck Sharp and Dohme, Eli Lilly, and Novartis for advisory board; payment or honoraria from Merck Sharp and Dohme, Eli Lilly, Pfizer, Daiichi Sankyo, Novartis, and AstraZeneca for medical education; and support for attending meetings or travel from Pfizer and AstraZeneca. LDM reports an institutional research grant from Eli Lilly, Novartis, Roche, Daiichi Sankyo, and Seagen; consulting fees paid to self from Eli Lilly; honoraria or payment to self from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, Merck Sharp and Dohme, Seagen, Gilead, Pierre Fabre, Eisa, Exact Sciences, and Ipsen for lectures, presentations, speaker's bureaus, manuscript writing or educational events; support for attending meetings or travel from Roche, Pfizer, and Eisai; and fees paid to self for participation on a data safety monitoring board or advisory Board from Novartis, Roche, Eli Lilly, Pfizer, Daiichi-Sankyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, AstraZeneca, and Agendia. CS reports research grants from Eli Lilly, and honoraria for lectures from Pfizer and Eli Lilly. RW, AS, MMu, BSA, VA are employees and stock shareholders of Eli Lilly. NH reports support for the present article (medical writing) from Eli Lilly; consulting fees from Gilead, Sandoz, and Seagen; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Amgen, AsraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, Merck Sharp and Dohme, Novartis, Pierre-Fabre, Pfizer, Roche, and Seagen; participation on a data safety monitoring board or advisory board from Roche; and a leadership or fiduciary role with the West German Study Group and ESMO. MMa reports institutional grants from Roche, Novartis, and Puma; consulting fees paid to self from Roche, Eli Lilly, Pfizer, Daiichi-Sankyo, AstraZeneca, and Novartis; payment or honoraria to self for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Roche, Eli Lilly, Astrazeneca, and Pfizer; support paid to self for attending meetings or travel from Daiichi-Sankyo and Roche; and support paid to self for participation on a data safety monitoring board or advisory board from Novartis. PR, PN, GGJ, and IC declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Special histological types (SHT) of triple-negative breast cancer (TNBC) are a heterogeneous group of rare poorly understood diseases. We aimed to evaluate the clinical features, treatment, and outcomes of patients with SHT of TNBC., Methods: We evaluated patients with a SHT of TNBC treated in a cancer center between 2009 and 2020. The endpoints were characterization of clinical and pathological features, pathologic complete response (PCR) rate after neoadjuvant chemotherapy, disease-free survival (DFS), progression-free survival, and overall survival (OS)., Results: The 132 patients included had the following histologies: metaplastic (n=71), medullary pattern (n=14), lobular (n=12), adenoid cystic (n=12), apocrine (n=10), and others (n=13). Metaplastic, lobular, and medullary pattern tumors had higher grade (66.6-85.7% grade 3); adenoid cystic and apocrine had mainly grade 1-2 (70-83.3%). Metaplastic and lobular carcinomas had higher disease stages (47.8% and 58.2% stages III-IV). PCR rates were 10.3% for metaplastic and 33.3% for lobular carcinomas, with 5-year DFS rates of 56% and 51.4%. Medullary pattern carcinomas had a great response to treatment, with PCR rate of 100%, and 5-year DFS rate of 92.8%. Apocrine carcinomas also had favorable prognosis, with no recurrence after early disease treatment, and 5-year DFS rate of 83.3%. Adenoid cystic carcinomas had intermediate prognosis, with 5-year DFS rate of 66.6%., Conclusion: SHT of TNBC encompasses heterogeneous malignancies with distinct behaviors. Lobular and metaplastic carcinomas showed high aggressiveness and poor treatment response, while medullary pattern and apocrine carcinomas had favorable outcomes. Treatment strategies focus on molecular features of each of these diseases are warranted., (Copyright © 2022. Published by Elsevier Inc.)

Importance: Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of relapse, and there is a need to find better therapeutic options for these patients., Objective: To determine the efficacy and safety outcomes for patients with hormone receptor (HR)-positive, ERBB2 (formerly HER2)-, high-risk early breast cancer enrolled in the randomized clinical trial monarchE who received NAC., Design, Setting, and Participants: The monarchE randomized clinical trial was a multicenter, phase 3, open-label study that evaluated adjuvant treatment with abemaciclib plus endocrine therapy (ET) compared with ET alone in patients with HR+, ERBB2-, and node-positive early breast cancer who were at high risk of recurrence. Patients were recruited between July 2017 and August 2019 from 603 sites in 38 countries. This subgroup analysis was performed with primary outcome data, with a cutoff date of July 8, 2020., Intervention: Enrolled patients were randomized (1:1) to receive standard of care ET for at least 5 years with or without treatment with abemaciclib (150 mg, twice daily) for 2 years (treatment period) or until criteria were met for discontinuation., Main Outcomes and Measures: Prior chemotherapy (NAC vs adjuvant vs none) was a stratification factor in monarchE, and and a prespecified exploratory analysis included outcomes in patients who received NAC. The data presented in this article are from the primary outcome analysis (395 invasive disease-free survival [IDFS] events; cutoff date, July 8, 2020; median follow-up 19 months [IQR, 15.6-23.9 months]). Invasive disease-free survival (the primary end point of monarchE) and distant relapse-free survival (DRFS) were evaluated using the Cox proportional hazard model and Kaplan-Meier method., Results: Of the 5637 patients (mean [SD] age, 49.9 [10.6] years; 2046 women [99.5%]; 462 Asian [22.8%], 54 Black [2.7%], and 1473 White participants [70.8%]) enrolled in monarchE, 2056 (37%) received treatment with NAC. In this subgroup, treatment with abemaciclib and ET demonstrated clinically meaningful benefit in IDFS (hazard ratio, 0.61; 95% CI, 0.47-0.80) and DRFS (hazard ratio, 0.61; 95% CI, 0.46-0.81), which corresponded with an absolute improvement of 6.6% in 2-year IDFS rates and 6.7% in 2-year DRFS rates. A consistent treatment benefit was observed across subgroups of pathological breast tumor size or number of positive lymph nodes at surgery., Conclusions and Relevance: In the randomized clinical trial monarchE, treatment with adjuvant abemaciclib combined with ET demonstrated a clinically meaningful improvement in IDFS and DRFS for patients with HR+, ERBB2-, node-positive, high-risk early breast cancer who received NAC before trial enrollment., Trial Registration: ClinicalTrials.gov Identifier: NCT03155997.

Background: A recent Brazilian populational database analysis showed a concerning increase in breast cancer mortality rates among patients under 40 years. We aimed to evaluate the trends in the proportion of new breast cancer cases and deaths occurring in patients younger than 40 years over the last decade in Brazil., Methods: We evaluated all consecutive breast cancer patients treated from 2009 to 2020 in a Brazilian tertiary cancer center. The proportions of new cases and deaths in patients younger than 40 years was compared between two time periods (2015-2020 versus 2009-2014) using Chi-squared test. Linear regression was used to evaluate the trends in the proportion of new cases and deaths in young patients over the years., Results: From 2009 to 2020, a total of 12,569 breast cancer patients started treatment at our institution; 1441 were younger than 40 years. From 2009 to 2014, 9.9% (95% CI 9.2-10.7%) were patients younger than 40 years compared to 12.9% (95% CI 12.1-13.8%) from 2015 to 2020. Similarly, the proportion of deaths among breast cancer patients younger than 40 years increased during the period (2009-2014: 9.6%, 95% CI 7.8-11.6%; 2015-2020: 12.4%, 95% CI 10.9-14%). The linear regression model showed a trend for an increasing proportion of new breast cancer cases occurring in patients under 40 years (P = 0.005). Proportion increased from 7.9% (95% CI 6.2-9.8%) in 2009 to 21.8% (95% CI 19.1-24.8%) in 2020. The trend for the increase in the proportion of deaths in this young population was also observed in the linear regression model (P = 0.01)., Conclusions: The proportion of new breast cancer cases and deaths among patients younger than 40 years has increased in a public Brazilian cancer center over the past decade. These results raise the concern for the need to reconsider primary and secondary prevention strategies for young women., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET)., Methods: A single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239., Results: The study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively., Conclusions: The humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.

The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Sixteen women (age: 47.0 ± 2.0 yr; body mass index: 24.2 ± 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m 2 ) and CY (600 mg/m 2 ) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP; finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs; flow cytometry), a surrogate marker for endothelial damage. MSNA and BP responses were increased ( P < 0.001), whereas CBF and CVC responses were decreased ( P < 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT ( P = 0.03, CHT vs. SL session). No difference in HR response was observed ( P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions. NEW & NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.

Background: In North America and Europe, return-to-work (RTW) rates vary among breast cancer (BC) survivors, from 24% to 66% and from 53% to 82% at 6 and 36 months after diagnosis, respectively. To date, there is a lack of data on RTW rates after BC diagnosis in Latin America. Therefore, the primary objectives of this study were to define RTW rates at 12 and 24 months after BC diagnosis and to identify the factors associated with RTW in this population., Methods: In total, 125 employed women from a single institution with newly diagnosed BC were interviewed by telephone at 6, 12, and 24 months after diagnosis. Those who had inoperable or metastatic disease were excluded., Results: Overall, RTW rates were 30.3% and 60.4% at 12 and 24 months after BC diagnosis, respectively. Most women reported that they received support from their employer, but only 29.1% reported having been offered work adjustments. In multivariate analysis, the factors associated with positive RTW outcomes included higher household income (odds ratio [OR], 17.76; 95% confidence interval [CI], 3.33-94.75; P = .001), breast-conserving surgery (OR, 9.77; 95% CI, 2.03-47.05; P = .004), and work adjustments (OR, 37.62; 95% CI, 2.03-47.05; P = .004). The factors associated with negative RTW outcomes included adjuvant endocrine therapy (OR, 0.11; 95% CI, 0.02-0.74; P = .023), and depression diagnosed after BC (OR, 0.07; 95% CI, 0.01-0.63; P = .017)., Conclusions: RTW rates in the current study were lower than those observed in developed countries but similar to the rates among low-income Americans. Workplace adjustments, higher income, breast-conserving surgery, endocrine therapy, and depression after BC played an important role in the RTW decision., (© 2018 American Cancer Society.)

Background: Weekly paclitaxel has been shown more effective and less toxic than the conventional three-weekly administration. The GEICAM 9906 demonstrated effectiveness and safety of a dose-dense schedule of 100 mg/m(2) of paclitaxel given over 8 weeks (w). This schedule has been adopted at our institution in 2009 for HER2-negative disease, and herein, we present the first off-trial experience and compare its safety profile with that of a historical cohort of patients treated with the conventional 80 mg/m(2) over 12 w schedule., Methods: Retrospective single-center chart review of patients with locally advanced breast cancer treated with (neo)adjuvant paclitaxel-based therapy from 2008 to 2012 with (1) 80 mg/m(2) for 12 w or (2) 100 mg/m(2) for 8 w. Adverse events were graded according to common terminology criteria for adverse events (CTCAE) 4.0., Results: A total of 326 patients were analyzed. Median age was 52 (±10.9). Seventy and 256 patients received schedule (1) and (2), respectively. No significant difference was observed in the incidence of grade (G) 3/4 toxicity: pneumonitis (2.8 vs 0.3 % p = 0.097); neuropathy (2.8 vs 0.7 % p = 0.303); hand-foot syndrome (1.4 vs 0.3 % p = 0.538); anemia (0 vs 0.6 % p = 0.624); and neutropenia (5.7 vs 6.2 % p = 0.408). Also, no significant difference was seen when comparing all grades toxicity. Schedule (2) had higher dose intensity: 97.72 vs 77.07 mg/m(2) per week (p < 0.0001)., Conclusions: Weekly paclitaxel given according to GEICAM 9906 is pragmatic and well tolerated, with safety profile consistent with the conventional schedule. In addition to being convenient to patients, it may also be cost-effective because of a lower number of clinic visits and infusions.

In recent years, a number of new molecules - commonly known as biological therapies - have been approved or are in late stages of regulatory evaluation for the treatment of advanced breast cancer. These innovative compounds have improved treatment efficacy and have probably contributed to the increase in survival length observed in some breast cancer subtypes. However, these agents are not deprived of toxicity, which can impair quality of life and may occasionally be life-threatening. In this article, we reviewed the most common toxicities associated with these drugs and provided a number of practical recommendations on their optimal clinical management., (Copyright © 2013 Elsevier Ltd. All rights reserved.)