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Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.
N Engl J Med
January 2025
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) - both in Pittsburgh; AGO-B and Helios Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie-Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) - all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); Orlando Health Cancer Institute, Orlando, FL (E.P.M.); Hospital Universitario La Paz-Instituto de Investigación del Hospital Universitario La Paz, Madrid (A.R.); L'Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier (V.D.), Institut Bergonié, INSERM Unité 1312, and Université de Bordeaux UFR Sciences Médicales, Bordeaux (H.R.B.) - all in France; Providence Cancer Institute, Portland, OR (A.K.C.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and Oncology 2, Istituto Oncologico Veneto IRCCS, Padua (V.G.), and the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (E.R.C.) - all in Italy; Stanford University School of Medicine, Stanford, CA (I.L.W.); the National Cancer Institute, Mexico City (C.A.-S.); Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the All-Ireland Cooperative Oncology Research Group (J.P.C.), and the Oncology Unit, Cancer Clinical Trials and Research Unit, Beaumont RCSI Cancer Centre, and Cancer Trials Ireland (B.T.H.) - all in Dublin; Fudan University Shanghai Cancer Center, Shanghai, China (Z.S.); Institute for Oncology and Radiology of Serbia, Belgrade (L.S.); Grupo Médico Ángeles, Guatemala City, Guatemala (H.C.-S.); Roche Products, Welwyn Garden City, United Kingdom (A.K., A.S.); and F. Hoffmann-La Roche, Basel, Switzerland (C.L., T.B., B.N., E.R.).
Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.
Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.
The History of Breast Cancer Early Detection: 1865 - 2020.
Breast Cancer (Dove Med Press)
December 2024
Department of Breast Surgical Oncology, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, USA.
Early detection is a relative newcomer in medicine, with its efficacy relying not only on therapy but also on the availability of evidence supporting the advantage of treatment at an earlier stage. Late 19th century histologic evidence that cancer begins as a single primary focus and Halsted's centrifugal theory of stepwise spread (breast, regional nodes, and systemic distribution) provided the rationale for both en bloc surgery and the lifesaving benefit of early detection. Clinicians soon noticed exceptions to this ordered timeline, and pathologists identified histological features that questioned its primacy; however, Bernard Fisher spearheaded the initial challenge.
View Article and Find Full Text PDFMolecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.
Cell Rep Med
November 2024
German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg, Germany. Electronic address:
Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.
View Article and Find Full Text PDFBreast cancer radiobiology: The renaissance of whole breast radiation fractionation (Review).
Mol Clin Oncol
December 2024
Department of Radiation Oncology, King Hussein Cancer Center, Amman 11941, Jordan.
Breast cancer radiotherapy has evolved significantly, driven by decades of research into fractionation schedules aimed at optimizing treatment efficacy and minimizing toxicity. Initial trials such as NSABP B-06 and EBCTCG meta-analyses established the benefits of adjuvant whole-breast irradiation in reducing local recurrence and improving survival rates. The linear-quadratic (LQ) model provided a framework to understand tissue response to radiation, highlighting the importance of the α/β ratio in determining fractionation sensitivity.
View Article and Find Full Text PDFA 7-Gene Biosignature for Ductal Carcinoma in situ of the Breast Identifies Subpopulations of HER2-positive Patients With Distinct Recurrence Rates After Breast-Conserving Surgery and Radiation Therapy.
Clin Breast Cancer
September 2024
PreludeDx, Laguna Hills, CA.
Purpose: A subpopulation of women with ductal carcinoma in situ (DCIS) remains at risk for in-breast recurrence (IBR) following breast-conserving surgery (BCS) and radiation therapy (RT). The NSABP B-43 trial evaluated the role of concurrent RT and trastuzumab in patients with HER2-positive DCIS but did not reach the prespecified endpoint. We hypothesized that a 7-gene biosignature (DCISionRT) with its Residual Risk subtype (RRt) could identify 2 groups of HER2(3+) patients with significantly different IBR risks after BCS plus RT.
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