David B Page1, Hannah Wen2, Edi Brogi2, Dana Dure2, Dara Ross2, Kateri J Spinelli3, Sujata Patil2, Larry Norton2, Clifford Hudis2, Heather L McArthur4. 1. Providence Cancer Center, Earle A. Chiles Research Institute, 4805 NE Glisan St., Suite 6N40, Portland, OR, 97213, USA. David.Page2@providence.org. 2. Memorial Sloan Kettering Cancer Center, 300 E 66th Street, New York, NY, 10065, USA. 3. Providence Cancer Center, Earle A. Chiles Research Institute, 4805 NE Glisan St., Suite 6N40, Portland, OR, 97213, USA. 4. Cedars-Sinai Medical Center, 8700 Beverly Blvd, AC 1042B, Los Angeles, CA, 90048, USA. heather.mcarthur@cshs.org.
Abstract
PURPOSE: HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment. METHODS: From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0. RESULTS: Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH. CONCLUSIONS: In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.
PURPOSE:HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment. METHODS: From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0. RESULTS: Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH. CONCLUSIONS: In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.
Authors: Gábor Cserni; Monika Francz; Balázs Járay; Endre Kálmán; Ilona Kovács; Tibor Krenács; Erika Tóth; Nóra Udvarhelyi; László Vass; András Vörös; Ana Krivokuca; Karol Kajo; Katarína Kajová Macháleková; Janina Kulka Journal: Pathol Oncol Res Date: 2022-06-27 Impact factor: 2.874
Authors: Ayaka Katayama; Jane Starczynski; Michael S Toss; Abeer M Shaaban; Elena Provenzano; Cecily M Quinn; Grace Callagy; Colin A Purdie; Rebecca Millican-Slater; David Purnell; Leena Chagla; Tetsunari Oyama; Sarah E Pinder; Steve Chan; Ian Ellis; Andrew H S Lee; Emad A Rakha Journal: Histopathology Date: 2022-08-08 Impact factor: 7.778