Tanja Ignatov1,2, Franceska Gorbunow1, Holm Eggemann1, Olaf Ortmann2, Atanas Ignatov3,4. 1. Department of Gynecology and Obstetrics, Otto-von-Guericke University, Magdeburg, Germany. 2. Department of Gynecology and Obstetrics, University Medical Center, Landshuter Str. 65, 93047, Regensburg, Germany. 3. Department of Gynecology and Obstetrics, Otto-von-Guericke University, Magdeburg, Germany. atanas.ignatov@gmail.com. 4. Department of Gynecology and Obstetrics, University Medical Center, Landshuter Str. 65, 93047, Regensburg, Germany. atanas.ignatov@gmail.com.
Abstract
PURPOSE: HER2 expression has been reported to be discordant between primary tumor and metastatic tissue. PATIENTS AND METHODS: HER2 discordance and relation to HER2-targeted treatment was investigated in 227 patients with primary breast cancer. RESULTS: HER2 discordance between primary biopsy and second biopsy after neoadjuvant or adjuvant treatment was observed in 20.7%. This discordance was related only to the use of HER2-targeted treatment: 30 of 33 (90.9%) women with downgraded HER2 expression underwent a HER2-targeted therapy, whereas in the group of patients with concordant HER2 expression, only 32 of 180 (17.8%) received HER2-targeted treatment (p < 0.0001). HER2 discordance was associated with reduced disease-free survival but not overall survival. In a second cohort, including patients with HER2 overexpressing tumors, trastuzumab treatment was associated with change of HER2 expression from positive to negative in 47.3% of cases. Addition of pertuzumab increased the rate of HER2 loss up to 63.2%. Notably, the interval between last HER2-targeted treatment and the time of surgical excision of the tumor after neoadjuvant chemotherapy (NACT) or the biopsy of the metachronous metastasis was associated with a significant change in HER2 expression. The median time between NACT and the time of surgical excision was 23 days (range 5-81 days) for tumors with decreased HER2 expression and 51 days (range 10-179 days) for tumors with concordant HER2 expression. Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively. CONCLUSION: The interval between anti-HER2 treatment and the determination of HER2 in second histology is strongly associated with HER2 expression.
PURPOSE:HER2 expression has been reported to be discordant between primary tumor and metastatic tissue. PATIENTS AND METHODS: HER2 discordance and relation to HER2-targeted treatment was investigated in 227 patients with primary breast cancer. RESULTS:HER2 discordance between primary biopsy and second biopsy after neoadjuvant or adjuvant treatment was observed in 20.7%. This discordance was related only to the use of HER2-targeted treatment: 30 of 33 (90.9%) women with downgraded HER2 expression underwent a HER2-targeted therapy, whereas in the group of patients with concordant HER2 expression, only 32 of 180 (17.8%) received HER2-targeted treatment (p < 0.0001). HER2 discordance was associated with reduced disease-free survival but not overall survival. In a second cohort, including patients with HER2 overexpressing tumors, trastuzumab treatment was associated with change of HER2 expression from positive to negative in 47.3% of cases. Addition of pertuzumab increased the rate of HER2 loss up to 63.2%. Notably, the interval between last HER2-targeted treatment and the time of surgical excision of the tumor after neoadjuvant chemotherapy (NACT) or the biopsy of the metachronous metastasis was associated with a significant change in HER2 expression. The median time between NACT and the time of surgical excision was 23 days (range 5-81 days) for tumors with decreased HER2 expression and 51 days (range 10-179 days) for tumors with concordant HER2 expression. Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively. CONCLUSION: The interval between anti-HER2 treatment and the determination of HER2 in second histology is strongly associated with HER2 expression.
Authors: Victoria A Brentville; Rachael L Metheringham; Ian Daniels; Suha Atabani; Peter Symonds; Katherine W Cook; Mireille Vankemmelbeke; Ruhul Choudhury; Poonam Vaghela; Mohamed Gijon; Ghislaine Meiners; Willem-Jan Krebber; Cornelis J M Melief; Lindy G Durrant Journal: J Immunother Cancer Date: 2020-06 Impact factor: 13.751
Authors: Laura Rey-Vargas; Juan Carlos Mejía-Henao; María Carolina Sanabria-Salas; Silvia J Serrano-Gomez Journal: BMC Cancer Date: 2020-07-18 Impact factor: 4.430
Authors: Allen Li; Jamie M Keck; Swapnil Parmar; Janice Patterson; Marilyne Labrie; Allison L Creason; Brett E Johnson; Molly Downey; George Thomas; Carol Beadling; Laura M Heiser; Annette Kolodzie; Alexander R Guimaraes; Christopher L Corless; Joe W Gray; Gordon B Mills; Raymond C Bergan; Zahi I Mitri Journal: NPJ Precis Oncol Date: 2021-03-26
Authors: Hoyoung M Maeng; Brittni N Moore; Hadi Bagheri; Seth M Steinberg; Jon Inglefield; Kim Dunham; Wei-Zen Wei; John C Morris; Masaki Terabe; Lee C England; Brenda Roberson; Douglas Rosing; Vandana Sachdev; Svetlana D Pack; Markku M Miettinen; Frederic G Barr; Louis M Weiner; Sandhya Panch; David F Stroncek; Lauren V Wood; Jay A Berzofsky Journal: Front Oncol Date: 2021-12-16 Impact factor: 6.244