Review
Oncology
Joohyun Hong, Yeon Hee Park
Summary: Significant progress has been made in the treatment of HER2-positive breast cancer, especially with the development of targeted therapies. Different treatment approaches are applied based on the risk level and presence of residual disease, including adjuvant trastuzumab, pertuzumab, paclitaxel, and other drugs. Ongoing trials are exploring the combination of novel agents and de-escalation of treatment in the neoadjuvant setting, aiming to achieve better outcomes.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)
Review
Oncology
Veronique Debien, Evandro de Azambuja, Martine Piccart-Gebhart
Summary: Triple-positive breast tumors overexpress HER2 and are positive for HR expression. ER expression affects the response to anti-HER2 and associated systemic therapies. Optimizing dual anti-HER2 blockade is important for disease control in triple-positive tumors.
CANCER TREATMENT REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Maria Gaibar, Apolonia Novillo, Alicia Romero-Lorca, Diego Malon, Beatriz Anton, Amalia Moreno, Ana Fernandez-Santander
Summary: This study aimed to investigate the correlation between copy number variations (CNVs) in several genes related to the PI3K/AKT pathway and the efficacy of anti-HER2 neoadjuvant treatment in early HER2-positive breast cancer patients. The findings suggest that patients with FGFR1 amplification might benefit less from anti-HER2 antibody therapy.
Article
Oncology
Elisa Agostinetto, Lieveke Ameye, Samuel Martel, Philippe Aftimos, Noam Ponde, Christian Maurer, Sarra El-Abed, Yingbo Wang, Malou Vicente, Saranya Chumsri, Judith Bliss, Judith Kroep, Marco Colleoni, Fausto Petrelli, Lucia Del Mastro, Alvaro Moreno-Aspitia, Martine Piccart, Marianne Paesmans, Evandro de Azambuja, Matteo Lambertini
Summary: PREDICT underestimates overall survival in HER2-positive early breast cancer patients treated with effective chemotherapy and anti-HER2 targeted therapies. The underestimation is especially significant in patients with hormone receptor negative-disease, nodal involvement, and large tumor size.
Article
Oncology
Yong-Seok Kim, Der Sheng Sun, Juneyoung Ahn, Yongseon Kim, Jung-Sook Yoon, Hye Sung Won
Summary: This study provides insights into the genetic alterations associated with disease recurrence in early stage HER2-positive breast cancer, highlighting the activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment as risk factors for recurrence. These findings can aid in the development of effective risk-adapted therapeutic strategies.
Editorial Material
Oncology
Giuseppe Curigliano
Summary: The monarchE and PALLAS trials investigating adjuvant treatment with CDK4/6 inhibitors abemaciclib and palbociclib in hormone receptor-positive, HER2-negative early stage breast cancer patients have shown opposing results, despite similar efficacy in the metastatic setting. Potential reasons for this disparity are discussed.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Ljubica Vazdar, Ivo Darko Gabric, Ivan Kruljac, Hrvoje Pintaric, Robert Separovic, Lora Stanka Kirigin Bilos, Mirjana Pavlovic, Ana Tecic Vuger, Mario Stefanovic
Summary: The study identified risk factors for trastuzumab-induced cardiotoxicity, including advanced age, lower body mass index, left breast involvement, N3 status, diabetes, and a family history of coronary artery disease. However, there was no association found between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Otto Metzger Filho, Giuseppe Viale, Shayna Stein, Lorenzo Trippa, Denise A. Yardley, Ingrid A. Mayer, Vandana G. Abramson, Carlos L. Arteaga, Laura M. Spring, Adrienne G. Waks, Eileen Wrabel, Michelle K. DeMeo, Aditya Bardia, Patrizia Dell'Orto, Leila Russo, Tari A. King, Kornelia Polyak, Franziska Michor, Eric P. Winer, Ian E. Krop
Summary: Intratumor heterogeneity, particularly the fraction of ERBB2 nonamplified cancer cells, is strongly correlated with resistance to HER2-targeted therapies and could potentially aid in optimizing treatment selection for HER2-positive breast cancer patients.
Article
Oncology
Apolonia Novillo, Maria Gaibar, Alicia Romero-Lorca, Diego Malon, Beatriz Anton, Amalia Moreno, Ana Fernandez-Santander
Summary: In this study, the potential biomarkers of a good response to anti-HER2 treatment in HER2-positive breast cancer patients were identified as the SNPs rs1058808 (HER2Ala1170Pro) and rs2070096 (BARD1Thr351=).
Review
Oncology
Olga Martinez-Saez, Adrienne G. Waks
Summary: In the past 20 years, there have been significant advancements in the treatment of HER2-positive breast cancer. However, identifying which patients can receive de-intensified treatment remains a challenge. Various biomarkers have been proposed to better understand the clinical and biological heterogeneity of HER2-positive breast cancer. Integrating these factors will be crucial in determining the true risk and individualized treatment strategy for each patient.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2023)
Article
Oncology
J. Bergh, K. Pritchard, S. Swain, D. Cameron, K. Albain, S. Anderson, R. Arriagada, J. Bartlett, E. Bergsten-Nordstrom, J. Bliss, R. Bradley, E. Brain, J. Braybrooke, L. Carey, M. Clarke, R. Coleman, J. Cuzick, N. Davidson, L. Del Mastro, A. Di Leo, J. Dignam, D. Dodwell, M. Dowsett, F. Duane, B. Ejlertsen, P. Francis, R. Gelber, M. Gnant, M. Goetz, P. Goodwin, R. Gray, P. Halpin-Murphy, D. Hayes, C. Hill, R. Jagsi, W. Janni, Z. Liu, S. Loibl, E. MacKinnon, E. Mamounas, G. Mannu, M. Martin, P. McGale, H. Mukai, V Nekljudova, L. Norton, Y. Ohashi, H. Pan, R. Peto, M. Piccart, L. Pierce, P. Poortmans, V Raina, D. Rea, M. Regan, J. Robertson, E. Rutgers, D. Slamon, T. Spanic, J. Sparano, G. Steger, C. Taylor, G. Tang, M. Toi, A. Tutt, G. Viale, X. Wang, T. Whelan, N. Wilcken, N. Wolmark
Summary: The study demonstrates that adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer significantly reduces the risk of breast cancer recurrence and death, with worthwhile proportional reductions irrespective of recorded patient and tumor characteristics.
Article
Oncology
Nadia Harbeck
Summary: The availability of HER2-targeted therapy has greatly improved patient outcomes in HER2-positive early breast cancer. Neoadjuvant therapy has become standard of care for stage II or III tumors, and the status of pathological complete response (pCR) after surgery can be used to tailor adjuvant systemic therapy. For non-pCR patients, 14 cycles of adjuvant T-DM1 have become a new standard, while low-risk patients can benefit from 12 weeks of adjuvant paclitaxel + trastuzumab.
Article
Oncology
Nora Tabea Sibert, Simone Wesselmann, Clara Breidenbach, Jens Blohmer, Barbara Brueckner, Gerhard Gebauer, Marina dos Santos Guilherme, Andreas Hartkopf, Christoph Lindner, Susanne Peschel, Lorenz Rieger, Friedemann Schad, Paul Strecker, Julia Ferencz, Sebastian Dieng, Elisabeth C. Inwald, Christoph Kowalski, Olaf Ortmann
Summary: In certified Breast Cancer Centers (BCCs) in Germany, guideline-concordant recommendation of trastuzumab has been increasing since 2006. The recommendation for trastuzumab for HER2-positive breast cancer patients in BCCs is significantly associated with patients' age and the recommendations for other additional therapy strategies, apart from surgery.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Nadia Harbeck, Harold J. Burstein, Sara A. Hurvitz, Stephen Johnston, Gregory A. Vidal
Summary: The heterogeneity of hormone receptor (HR)-positive, HER2-negative early breast cancers highlights the importance of personalized treatment approaches. Patients with high-risk features have an elevated risk for recurrence despite standard care. Adding cyclin-dependent kinase 4 and 6 inhibitors to endocrine therapy shows promise in improving outcomes for this difficult to treat patient population.
Review
Oncology
Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani, Monali Ray
Summary: HER2-positive breast cancer is aggressive and has a poor prognosis. Standard chemotherapy with HER2 blockers can improve outcomes and increase the suitability for breast-conserving surgery. It is crucial to identify patients who should receive systemic cancer treatment and decide the most appropriate option for each case.
Review
Oncology
Alberto Servetto, Fabiana Napolitano, Carmine De Angelis, Pietro De Placido, Mario Giuliano, Grazia Arpino, Sabino De Placido, Roberto Bianco, Luigi Formisano
Summary: The development of CDK4 and CDK6 inhibitors has shown significant clinical benefits in the treatment of ER+ HER2- metastatic breast cancer, but resistance remains a challenge. Next Generation Sequencing methods have been used to identify predictive biomarkers of response or resistance, revealing genomic alterations and gene expression profiles associated with resistance.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Oncology
Carmine De Angelis, Xiaoyong Fu, Maria Letizia Cataldo, Agostina Nardone, Resel Pereira, Jamunarani Veeraraghavan, Sarmistha Nanda, Lanfang Qin, Vidyalakshmi Sethunath, Tao Wang, Susan G. Hilsenbeck, Matteo Benelli, Ilenia Migliaccio, Cristina Guarducci, Luca Malorni, Lacey M. Litchfield, Jiangang Liu, Joshua Donaldson, Pier Selenica, David N. Brown, Britta Weigelt, Jorge S. Reis-Filho, Ben H. Park, Sara A. Hurvitz, Dennis J. Slamon, Mothaffar F. Rimawi, Valerie M. Jansen, Rinath Jeselsohn, C. Kent Osborne, Rachel Schiff
Summary: The study found that aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i, and transcriptomic and proteomic analysis revealed that acquired resistance to palbociclib is linked to activation of the IFN pathway.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Xian Wang, Jamunarani Veeraraghavan, Chia-Chia Liu, Xixi Cao, Lanfang Qin, Jin-Ah Kim, Ying Tan, Suet Kee Loo, Yiheng Hu, Ling Lin, Sanghoon Lee, Martin J. Shea, Tamika Mitchell, Shunqiang Li, Matthew J. Ellis, Susan G. Hilsenbeck, Rachel Schiff, Xiao-Song Wang
Summary: NLK was identified as a novel actionable kinase target in endocrine-resistant breast cancer, modulating endocrine resistance through phosphorylation of ER and its coactivator SRC-3. Coadministration of VX-702 and everolimus demonstrated significant therapeutic effects in cell line- and patient-derived xenograft tumor models.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jamunarani Veeraraghavan, Carolina Gutierrez, Vidyalakshmi Sethunath, Sepideh Mehravaran, Mario Giuliano, Martin J. Shea, Tamika Mitchell, Tao Wang, Sarmistha Nanda, Resel Pereira, Robert Davis, Kristina Goutsouliak, Lanfang Qin, Carmine De Angelis, Irmina Diala, Alshad S. Lalani, Chandandeep Nagi, Susan G. Hilsenbeck, Mothaffar F. Rimawi, C. Kent Osborne, Rachel Schiff
Summary: The combination of neratinib and trastuzumab showed better efficacy in HER2+ breast cancer compared to pertuzumab plus trastuzumab or lapatinib plus trastuzumab. This combination treatment also accelerated complete response. Further clinical testing is warranted to evaluate the efficacy of neratinib plus trastuzumab with or without chemotherapy in the neoadjuvant setting for HER2+ breast cancer.
Editorial Material
Oncology
Katherine G. Sanchez, Julie R. Nangia, Rachel Schiff, Mothaffar F. Rimawi
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Grazia Arpino, Juan de la Haba Rodriguez, Jean -Marc Ferrero, Sabino De Placido, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F. Rimawi
Summary: The addition of pertuzumab to trastuzumab and an aromatase inhibitor significantly improved progression-free survival in patients with previously untreated HER2-positive and hormone receptor-positive breast cancer. The treatment effect of pertuzumab may be enhanced in patients who do not require chemotherapy.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Jamunarani Veeraraghavan, Carolina Gutierrez, Carmine De Angelis, Robert Davis, Tao Wang, Tomas Pascual, Pier Selenica, Katherine Sanchez, Hiroaki Nitta, Monesh Kapadia, Anne C. Pavlick, Patricia Galvan, Brent Rexer, Andres Forero-Torres, Rita Nanda, Anna M. Storniolo, Ian E. Krop, Matthew P. Goetz, Julie R. Nangia, Antonio C. Wolff, Britta Weigelt, Jorge S. Reis-Filho, Susan G. Hilsenbeck, Aleix Prat, C. Kent Osborne, Rachel Schiff, Mothaffar F. Rimawi
Summary: The study aims to explore a multiparameter classifier to identify HER2+ breast cancer patients who can benefit from reducing chemotherapy. By analyzing samples from two clinical trials, the study found that the classifier can accurately predict the pathologic complete response rate to anti-HER2 therapy, thereby guiding treatment decisions.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
William J. Gradishar, Ruth O'Regan, Mothaffar F. Rimawi, Jeffrey L. Nordstrom, Minori K. Rosales, Hope S. Rugo
Summary: Several anti-HER2 agents have been approved for third-line treatment and beyond, but there is currently no recommended treatment strategy for this stage. Although these agents improve disease outcomes, metastatic HER2-positive breast cancer remains incurable and effective therapies are needed in later lines of treatment. This review focuses on the development of margetuximab-cmkb, a novel, Fc-engineered, anti-HER2 monoclonal antibody, and its role in the systemic treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.
Review
Oncology
Hope S. Rugo, Christine L. Crossno, Yaron B. Gesthalter, Kristen Kelley, Heather B. Moore, Mothaffar F. Rimawi, Kelly E. Westbrook, Saundra S. Buys
Summary: Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate targeting HER2 in previously treated metastatic/unresectable breast cancer patients. It demonstrated improved progression-free survival compared to ado-trastuzumab emtansine and physician's choice chemotherapy in HER2-positive and HER2-low patients. However, T-DXd is associated with interstitial lung disease (ILD), necessitating monitoring and management strategies to be implemented in clinical practice.
JCO ONCOLOGY PRACTICE
(2023)
Meeting Abstract
Oncology
Carmine De Angelis, Jamunarani Veeraraghavan, Vidyalakshmi Sethunath, Lieveke Ameye, Marianne Paesmans, Sarra El-Abed, Anup Choudhury, Sylvia Napoleone, Saranya Chumsri, Martine J. Piccart-Gebhart, Alvaro Moreno-Aspitia, Henry Leonidas Gomez, Giuseppe Viale, Susan G. Hilsenbeck, Mothaffar F. Rimawi, C. Kent Osborne, Evandro De Azambuja, Rachel Schiff
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Jamunarani Veeraraghavan, Ragini Mistry, Sarmistha Nanda, Vidyalakshmi Sethunath, Martin Shea, Tamika Mitchell, Meenakshi Anurag, Michael A. Mancini, Fabio Stossi, C. Kent Osborne, Mothaffar F. Rimawi, Rachel Schiff
Meeting Abstract
Oncology
Vidyalakshmi Sethunath, Xiaoyong Fu, Pamela L. Luna, Sarmistha Nanda, Martin Shea, Jamunarani Veeraraghavan, Carmine De Angelis, Huizhong Hu, Chad Shaw, Mothaffar Rimawi, C. Kent Osborne, Rachel Schiff
Article
Oncology
Chia-Chia Liu, Jamunarani Veeraraghavan, Ying Tan, Jin-Ah Kim, Xian Wang, Suet Kee Loo, Sanghoon Lee, Yiheng Hu, Xiao-Song Wang
Summary: A novel tumor-specific chimeric transcript RAD51AP1-DYRK4 was identified in luminal B breast tumors, with its overexpression associated with aggressiveness. Ectopic expression of RAD51AP1-DYRK4 activated the MEK/ERK pathway, enhancing cell motility and sensitivity to MEK inhibitors. This discovery may lead to new therapeutic opportunities for aggressive breast tumors overexpressing RAD51AP1-DYRK4 fusion.
CLINICAL CANCER RESEARCH
(2021)