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
Medicine, Research & Experimental
Myrto Moutafi, Charles J. Robbins, Vesal Yaghoobi, Aileen Fernandez, Sandra Martinez-Morilla, Vasiliki Xirou, Yalai Bai, Yan Song, Patricia Gaule, Joseph Krueger, Kenneth Bloom, Salisha Hill, Daniel C. Liebler, Regan Fulton, David L. Rimm
Summary: The efficacy of the antibody drug conjugate Trastuzumab deruxtecan (T-DXd) in HER2 low breast cancer patients suggests the need for revision of the conventional HER2 assays. In this study, an optimized dynamic range for unamplified HER2 detection in breast cancer was determined and a quantitative assay to stratify HER2 expression in unamplified cases was designed. The application of this assay to a large number of breast cancer cases demonstrated its potential for selecting optimal patients for T-DXd treatment.
LABORATORY INVESTIGATION
(2022)
Article
Oncology
Luciana de Moura Leite, Marcelle Goldner Cesca, Monique Celeste Tavares, Debora Maciel Santana, Erick Figueiredo Saldanha, Paula Tavares Guimaraes, Daniella Dias Silva Sa, Maria Fernanda Evangelista Simoes, Rafael Lima Viana, Francisca Giselle Rocha, Simone Klog Loose, Sinara Figueiredo Silva, Rafaela Pirolli, Camilla Albina Zanco Fogassa, Bruna Raphaeli Silva Mattos, Fernando Augusto Batista Campos, Solange Moraes Sanches, Vladmir Claudio Cordeiro de Lima, Noam Falbel Ponde
Summary: Our study does not support HER2-low as a biologically distinct subtype of breast cancer, showing no prognostic value on survival outcomes and no predictive effect for pathological complete response after conventional neoadjuvant chemotherapy.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
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
Multidisciplinary Sciences
Yuson Wang, Xiaoyan Liu, Keda Yu, Shouping Xu, Pengfei Qiu, Xinwen Zhang, Mozhi Wang, Yingying Xu
Summary: Neoadjuvant therapy (NAT) is recommended for patients with HER2+ BC who have a poor prognosis. The tumor immune microenvironment plays a significant role in the efficacy of NAT, but the relationship between tumor-infiltrating lymphocytes and the response to NAT in HER2+ BC is not yet clear. Our study classified the immune infiltration status of 295 patients into immune-rich and immune-poor phenotypes, with the immune-rich phenotype being significantly associated with pCR. We identified 10 genes that were correlated with both pCR and the immune phenotype, and constructed a generalized non-linear model that successfully predicted response to NAT.
Article
Multidisciplinary Sciences
Sandra Orru, Emanuele Pascariello, Barbara Pes, Vincenzo Rallo, Raffaele Barbara, Marta Muntoni, Francesca Notari, Gianfranco Fancello, Cristina Mocci, Maria Rosaria Muroni, Paolo Cossu-Rocca, Andrea Angius, Maria Rosaria De Miglio
Summary: In this study, the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in HER2+ breast cancer patients receiving trastuzumab-based neoadjuvant chemotherapy was evaluated. The study found that a high tumoral pathological complete response rate is associated with a high percentage of infiltrating immune cells and right-sided tumors, which reduce distant metastasis and improve survival. HER2 protein expression levels and tumor laterality emerge as strong predictors of tumoral pathological complete response.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Chau Dang, Michael S. Ewer, Suzette Delaloge, Jean-Marc Ferrero, Ramon Colomer, Luis de la Cruz-Merino, Theresa L. Werner, Katherine Dadswell, Mark Verrill, Daniel Eiger, Sriparna Sarkar, Sanne Lysbet de Haas, Eleonora Restuccia, Sandra M. Swain
Summary: The BERENICE study assessed the cardiac safety of neoadjuvant-adjuvant therapy for high-risk, HER2-positive early breast cancer. The study confirmed that pertuzumab-trastuzumab-based therapies are the standard of care for this patient population, with no new cardiac issues reported.
Article
Oncology
Sheau Wen Lok, Richard De Boer, Sally Baron-Hay, Peter Button, Bianca Devitt, Benjamin C. Forster, Peter Fox, Michael Harold, Sahisha Ketheeswaran, Ganessan Kichenadasse, Belinda E. Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter Gibbs
Summary: This study analyzed the safety and effectiveness data of pertuzumab in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia. The results revealed that pertuzumab showed effectiveness in surgical outcomes and the safety data align with previous clinical trials, without any new safety concerns.
INTERNATIONAL JOURNAL OF CANCER
(2023)
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
Amy S. Clark, Christina Yau, Denise M. Wolf, Emanuel F. Petricoin, Laura J. van't Veer, Douglas Yee, Stacy L. Moulder, Anne M. Wallace, A. Jo Chien, Claudine Isaacs, Judy C. Boughey, Kathy S. Albain, Kathleen Kemmer, Barbara B. Haley, Hyo S. Han, Andres Forero-Torres, Anthony Elias, Julie E. Lang, Erin D. Ellis, Rachel Yung, Debu Tripathy, Rita Nanda, Julia D. Wulfkuhle, Lamorna Brown-Swigart, Rosa Gallagher, Teresa Helsten, Erin Roesch, Cheryl A. Ewing, Michael Alvarado, Erin P. Crane, Meredith Buxton, Julia L. Clennell, Melissa Paoloni, Smita M. Asare, Amy Wilson, Gillian L. Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B. Matthews, Scott Berry, Ashish Sanil, Michelle Melisko, Jane Perlmutter, Hope S. Rugo, Richard B. Schwab, W. Fraser Symmans, Nola M. Hylton, Donald A. Berry, Laura J. Esserman, Angela M. DeMichele
Summary: HER2-targeted therapy significantly improves outcomes in early breast cancer patients. Two HER2-targeted combinations have shown promising efficacy in early breast cancer patients at high risk of recurrence, potentially aiding in identifying patients who can safely reduce cytotoxic chemotherapy without compromising outcomes.
NATURE COMMUNICATIONS
(2021)
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
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
Eric M. Lander, Katherine C. Rappazzo, Li-Ching Huang, Jiun-Ruey Hu, Heidi Chen, Yu Shyr, Vandana G. Abramson
Summary: This novel study investigates the relationship between HER2 amplification and pathologic complete response (pCR) following neoadjuvant anti-HER2 dual therapy without chemotherapy. The results show a positive association between the HER2/CEP17 FISH ratio and pCR.
Editorial Material
Oncology
Alicia F. C. Okines, Nicholas C. Turner
Summary: HER2 amplification heterogeneity is linked to resistance to trastuzumab emtansine in the neoadjuvant setting, highlighting the significance of determining whether varying HER2-positive cancer types require distinct treatment approaches.
Review
Oncology
S. Morganti, G. Bianchini, A. Giordano, M. Giuliano, G. Curigliano, C. Criscitiello
Summary: Since its approval in 2006, adjuvant trastuzumab for 1 year has been the standard care for early-stage HER2-positive breast cancer. However, the optimal duration of treatment has been uncertain, and there have been doubts about the standard 12-month duration. A recent meta-analysis presented at the ESMO meeting showed the non-inferiority of 6-month trastuzumab, but this conclusion should be interpreted with caution considering the limitations of the analysis and the use of alternative treatment strategies. Therefore, we believe that 1-year trastuzumab should remain the standard of care.