Article
Oncology
G. Griguolo, G. Serna, T. Pascual, R. Fasani, X. Guardia, N. Chic, L. Pare, S. Pernas, M. Munoz, M. Oliveira, M. Vidal, A. Llombart-Cussac, J. Cortes, P. Galvan, B. Bermejo, N. Martinez, R. Lopez, S. Morales, I Garau, L. Manso, J. Alarcon, E. Martinez, P. Villagrasa, A. Prat, P. Nuciforo
Summary: In HER2+ breast cancer, changes in the density of immune cells in the tumor microenvironment after anti-HER2 treatment, particularly those interacting spatially with tumor cells, are associated with treatment response. Furthermore, patients achieving pathologic complete response show a consistent decrease in stromal tumor-infiltrating lymphocytes (sTILs) post-surgery, while residual tumors often remain inflamed, suggesting a progressive loss of T cell function. Understanding the implications of the resulting immunosuppressive microenvironment is crucial for developing effective strategies for early-stage HER2+ breast cancer therapy.
NPJ PRECISION ONCOLOGY
(2021)
Article
Oncology
Tomas Pascual, Aranzazu Fernandez-Martinez, Maki Tanioka, M. Vittoria Dieci, Sonia Pernas, Joaquin Gavila, Valentina Guarnieri, Javier Cortes, Patricia Villagrasa, Nuria Chic, Maria Vidal, Barbara Adamo, Montserrat Munoz, Gaia Griguolo, Antonio Llombart, Pierfranco Conte, Mafalda Oliveira, Benedetta Conte, Laia Pare, Patricia Galvan, Lisa A. Carey, CharlesM. Perou, Aleix Prat
Summary: In HR+/HER2+ breast cancer, the PAM50-based CES score can predict sensitivity to chemo-endocrine therapy and provide additional prognostic information beyond intrinsic subtype and clinicopathologic characteristics. High CES is associated with lower pCR probability and better DFS.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Susanna Nguy, S. Peter Wu, Cheongeun Oh, Naamit K. Gerber
Summary: The study found that adding HER2 therapy to endocrine therapy did not significantly improve overall survival in non-metastatic ER+/HER2+ breast cancer patients who did not receive chemotherapy.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Oncology
Nicola Cosgrove, Alex J. Eustace, Peter O'Donovan, Stephen F. Madden, Bruce Moran, John Crown, Brian Moulton, Patrick G. Morris, Liam Grogan, Oscar Breathnach, Colm Power, Michael Allen, Janice M. Walshe, Arnold D. Hill, Anna Blumel, Darren O'Connor, Sudipto Das, Malgorzata Milewska, Joanna Fay, Elaine Kay, Sinead Toomey, Bryan T. Hennessy, Simon J. Furney
Summary: This study suggests that age, estrogen receptor status, and level of immune cell infiltration may play important roles in predicting the response to neoadjuvant therapy in HER2-positive breast cancer. Clonal evolution analysis reveals the presence of therapy resistant subclones. APOBEC-associated mutagenesis may mediate the immunogenic phenotype in HER2-negative/HER2-positive subtype.
Article
Oncology
Yifan Xie, Siyu Wu, Ying Zhang, Jianwei Li, Miao Mo, Zhimin Shao, Guangyu Liu
Summary: The study aimed to investigate the optimal number of cycles of neoadjuvant TCH therapy for HER2-positive breast cancer patients and found no significant difference in terms of pathological complete response rate and four-year event-free survival rate between four and six cycles. Negative hormone receptor status and weekly paclitaxel were independent factors for predicting pCR. Four cycles of taxane/carboplatin-based neoadjuvant anti-HER2 therapy may be applied as an optimal treatment duration for screening high-risk HER2-positive breast cancer patients for escalation treatment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Chrystel Isca, Federico Piacentini, Ilenia Mastrolia, Valentina Masciale, Federica Caggia, Angela Toss, Claudia Piombino, Luca Moscetti, Monica Barbolini, Michela Maur, Massimo Dominici, Claudia Omarini
Summary: miRNAs play important roles in breast cancer, especially in HER2-positive breast cancer. They are being studied as potential biomarkers for prognosis and diagnosis. Despite the significant improvement in survival outcomes with anti-HER2 targeted therapies, drug resistance remains a challenge.
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
Yihong Wang, Kamaljeet Singh, Don Dizon, Teresa Graves, Ali Amin, Evgeny Yakirevich
Summary: The study investigated the response of HER2-positive breast cancer patients to neoadjuvant chemotherapy, finding that HER2 protein expression is associated with predicting NAC response and long-term prognosis.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Pathology
Ayaka Katayama, Islam M. Miligy, Sho Shiino, Michael S. Toss, Karim Eldib, Sasagu Kurozumi, Cecily M. Quinn, Nahla Badr, Ciara Murray, Elena Provenzano, Grace Callagy, Cian Martyn, Rebecca Millican-Slater, Colin Purdie, Dave Purnell, Sarah E. Pinder, Tetsunari Oyama, Abeer M. Shaaban, Ian Ellis, Andrew H. S. Lee, Emad A. Rakha
Summary: The response of HER2-positive breast cancer patients to anti-HER2 targeted therapy varies, with HER2 status discordance potentially occurring after neoadjuvant treatment. Results indicate that HER2 IHC 3+ and histological grade 3 are independent predictors of pathological complete response following neoadjuvant anti-HER2 therapy.
Article
Multidisciplinary Sciences
Young-Joon Kang, Se Jeong Oh, Soo Youn Bae, Eun-Kyu Kim, Young-Jin Lee, Eun Hwa Park, Joon Jeong, Heung Kyu Park, Young Jin Suh, Yong-Seok Kim
Summary: This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. It found that age, advanced tumor and lymph node stage, high histological grade, presence of lymphatic and vascular invasion, and hormone receptor-negative status were associated with poor overall survival. Node status had a more significant relationship with long-term prognosis than tumor stage in HER2-positive breast cancer patients.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Kathryn E. Cole, Quan P. Ly, Michael A. Hollingsworth, Jesse L. Cox, Kurt W. Fisher, James C. Padussis, Jason M. Foster, Luciano M. Vargas, James E. Talmadge
Summary: In recent years, immune therapy has shown therapeutic activity for some tumor types, but the optimal combination of immune therapy with standard treatments is still unclear. This study aimed to investigate the impact of preoperative chemotherapy on patient immunity and the combination of chemotherapy and immune therapy. The results showed limited immunological differences in patients 6 weeks after preoperative chemotherapy, supporting rapid immune normalization. Preoperative chemotherapy may decrease the frequency of myeloid derived suppressor cells (MDSCs) in the spleen and increase the frequency of mature T-cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Roberto A. Leon-Ferre, Tina J. Hieken, Judy C. Boughey
Summary: Neoadjuvant chemotherapy has become the preferred approach for most HER2-positive and triple-negative breast cancers, with initial motivations being to decrease surgical extent and advance drug development, recent trials have shown survival advantages from escalating systemic treatment in patients with residual disease.
ANNALS OF SURGICAL ONCOLOGY
(2021)
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=).
Article
Oncology
Elli-Noora Hannikainen, Johanna Mattson, Peeter Karihtala
Summary: Retrospective data analysis of 119 patients with HER2-positive breast cancer treated with neoadjuvant systemic treatment showed that achieving a pathological complete response (pCR) was associated with better prognosis, while moderate immunohistochemical HER2 expression was associated with worse prognosis.
Article
Multidisciplinary Sciences
Stephanie Cabarcas-Petroski, Gabriella Olshefsky, Laura Schramm
Summary: This study analyzed breast cancer datasets and found amplification of MAF1 in breast cancer, which is associated with other genes. MAF1 expression is significantly increased in HER2-positive breast cancer and is related to the prognosis of trastuzumab treatment.
Article
Oncology
Adith Abraham, Carlos H. Barcenas, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Ellis G. Levine, Nancy U. Lin, Beverly Moy, Joyce C. Niland, Antonio C. Wolff, Michael J. Hassett, Sarah Asad, Daniel G. Stover
Summary: We developed a risk prediction model for late relapse of triple negative breast cancer (lrTNBC) using clinicopathologic and sociodemographic features. Our study found that tumor stage at diagnosis and BMI were significantly associated with lrTNBC. This risk prediction model may help identify patients at risk of developing lrTNBC and should be further investigated.
Review
Oncology
Claudette Falato, Francesco Schettini, Tomas Pascual, Fara Braso-Maristany, Aleix Prat
Summary: Traditionally, breast cancer classification has relied on the expression of immunohistochemical bio-markers available in clinical practice. However, intrinsic molecular subtypes based on gene expression have been identified and show different characteristics compared to IHC-based subgroups. Hormone receptor-positive tumors can demonstrate non-luminal biology, which has prognostic value and impacts sensitivity to treatment. Genomic instability, cell plasticity, treatment selective pressure, and tumor microenvironment all contribute to the diversity observed between primary and metastatic breast cancer. This review focuses on hormone receptor-positive/HER2-negative advanced breast cancer and discusses the distribution and clinical behavior of intrinsic subtypes, as well as ongoing clinical trials investigating their predictive and prognostic value for routine care.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Kala Visvanathan, Leslie Cope, Mary Jo Fackler, Michael Considine, Lori Sokoll, Lisa A. Carey, Andres Forero-Torres, James N. Ingle, Nancy U. Lin, Rita Nanda, Anna Maria Storniolo, Suzana Tulac, Neesha Venkatesan, Natalie C. Wu, Sudhakar Marla, Scott Campbell, Michael Bates, Christopher B. Umbricht, Antonio C. Wolff, Saraswati Sukumar
Summary: This study evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay for early assessment of disease progression in women with metastatic breast cancer (MBC). The results showed that high levels of cumulative methylation (CM) were associated with shorter median progression-free survival (PFS) and overall survival (OS) at week 4. The CM levels at week 4 could be used to predict disease progression as early as 3 months after initiating a new treatment.
CLINICAL CANCER RESEARCH
(2023)
Editorial Material
Oncology
Cesar A. Santa-Maria, Antonio C. Wolff
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Susana L. Garcia-Recio, Toshinori J. Hinoue, Gregory L. C. Wheeler, Benjamin J. Kelly, Ana C. A. Garrido-Castro, Tomas Pascual, Aguirre A. M. De Cubas, Youli B. Xia, Brooke M. Felsheim, Marni B. McClure, Andrei A. Rajkovic, Ezgi Karaesmen, Markia A. Smith, Cheng E. Fan, Paula I. Gonzalez J. Ericsson, Melinda E. Sanders, Chad J. Creighton, Jay T. Bowen, Kristen Leraas, Robyn T. Burns, Sara Coppens, Amy L. Wheless, Salma S. Rezk, Amy L. K. Garrett, Joel S. Parker, Kelly K. H. Foy, Hui Shen, Ben H. Park, Ian Krop, Carey F. Anders, Julie Gastier-Foster, Mothaffar F. U. Rimawi, Rita Nanda, Nancy U. Lin, Claudine Isaacs, P. Kelly J. Marcom, Anna Maria Storniolo, Fergus J. Couch, Uma Chandran, Michael Davis, Jonathan C. Silverstein, Alexander G. Ropelewski, Minetta C. Liu, Susan G. L. Hilsenbeck, Larry Norton, Andrea L. C. Richardson, W. Fraser E. Symmans, Antonio C. A. Wolff, Nancy E. V. Davidson, Lisa A. M. Carey, Adrian V. A. Lee, Justin M. W. Balko, Katherine A. R. Hoadley, Peter W. A. Laird, Elaine R. A. Mardis, Tari A. A. King, Charles M. AURORA US Network, Charles M. Perou
Summary: The AURORA US Metastasis Project aimed to identify molecular features associated with metastasis in breast cancer. By analyzing the samples from 55 females with metastatic breast cancer, changes in gene expression subtypes and DNA clonality shifts were observed. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Differences in the tumor microenvironment and immune cell infiltrates were also found in different breast cancer subtypes, providing implications for targeted therapies.
Review
Oncology
Laura Pala, Tommaso De Pas, Eleonora Pagan, Isabella Sala, Chiara Catania, Emma Zattarin, Paolo Arnone, Massimo M. Grassi, Marco Colleoni, Antonio C. Wolff, Javier Cortes, Martine Piccart, Richard D. Gelber, Giuseppe Viale, Vincenzo Bagnardi, Fabio Conforti
Summary: This study conducted a systematic review and meta-analysis of randomized clinical trials to compare the efficacy of limited-extended adjuvant endocrine treatment (ET) and full-extended ET in patients with early-stage breast cancer. The results showed that full-extended ET significantly improved disease-free survival (DFS) in patients with nodal-positive disease, while no significant improvement was observed in other subgroups.
Article
Oncology
Anna Weiss, Olga Martinez-Saez, Adrienne G. Waks, Alison Laws, Monica McGrath, Paolo Tarantino, Leah Portnow, Eric Winer, Maria Rey, Marta Tapia, Aleix Prat, Ann H. Partridge, Sara M. Tolaney, Juan M. Cejalvo, Elizabeth A. Mittendorf, Tari A. King
Summary: This study evaluated the rates of pathologic nodal disease in patients with cT1-cT2N0M0 HER2-positive breast cancer who underwent upfront surgery or neoadjuvant chemotherapy. The results showed that approximately 20% of patients who underwent upfront surgery were pN-positive, and the rate increased to 25% for those with cT1c tumors. These findings suggest the need for further investigation into the use of routine axillary imaging in HER2-positive breast cancer patients.
Correction
Oncology
Javier Garcia-Corbacho, Alberto Indacochea, Azucena E. Gonzalez Navarro, Ivan Victoria, Debora Moreno, David Pesantez, Laura Angelats, Andrea Modrego-Sanchez, Esther Sanfeliu, Oleguer Castillo, Paula Blasco, Laura Mezquita, Nuria Vinolas, Miquel Nogue, Patricia Galvan, Barbara Adamo, Neus Baste, Tamara Sauri, Manel Juan, Aleix Prat, Francesco Schettini
CANCER IMMUNOLOGY IMMUNOTHERAPY
(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
Antonio C. Wolff, Mark R. Somerfield, Mitchell Dowsett, M. Elizabeth H. Hammond, Daniel F. Hayes, Lisa M. McShane, Thomas J. Saphner, Patricia A. Spears, Kimberly H. Allison
Summary: This article is an update on the recommendations for HER2 testing in breast cancer, affirming the 2018 ASCO-CAP recommendations. The article emphasizes a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified, and provides best practice recommendations to distinguish IHC 0 and 1+.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Fara Braso-Maristany, Aleix Prat
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Editorial Material
Oncology
Antonio C. Wolff
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Maria Vittoria Dieci, Pierfranco Conte, Giancarlo Bisagni, Stefania Bartolini, Antonio Frassoldati, Daniele Generali, Federico Piacentini, Gaia Griguolo, Enrico Tagliafico, Fara Braso Maristany, Nuria Chic, Laia Pare, Federica Miglietta, Roberto Vicini, Roberto D'Amico, Sara Balduzzi, Aleix Prat, Valentina Guarneri
Summary: The integration of intrinsic molecular subtypes with stage or HER2DX risk score can predict site-specific metastatic risk in HER2-positive breast cancer, potentially impacting personalized surveillance and preventing site-specific recurrence in clinical trials.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Sara M. Tolaney, Paolo Tarantino, Noah Graham, Nabihah Tayob, Laia Pare, Guillermo Villacampa, Chau Dang, Denise A. Yardley, Beverly Moy, P. Kelly Marcom, Kathy S. Albain, Hope S. Rugo, Matthew J. Ellis, Iuliana Shapira, Antonio C. Wolff, Lisa A. Carey, Romualdo Barroso-Sousa, Patricia Villagrasa, Michelle DeMeo, Molly DiLullo, Jorge Gomez Tejeda Zanudo, Jakob Weiss, Nikhil Wagle, Ann H. Partridge, Adrienne G. Waks, Clifford A. Hudis, Ian E. Krop, Harold J. Burstein, Aleix Prat, Eric P. Winer
Summary: This study reports the long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab, and establishes potential biomarkers to predict prognosis. The results indicate that adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for this population, and the HER2DX genomic tool might help refine the prognosis.
Article
Oncology
Sanne L. de Haas, Dennis J. Slamon, Miguel Martin, Michael F. Press, Gail D. Lewis, Chiara Lambertini, Aleix Prat, Vanesa Lopez-Valverde, Thomas Boulet, Sara A. Hurvitz
Summary: The KRISTINE study investigated the association of biomarkers with clinical outcomes in HER2-positive breast cancer patients. Although no specific subgroup of patients benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm.
BREAST CANCER RESEARCH
(2023)