INTRODUCTION: Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer. METHODS: Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017. Pretreatment and posttreatment specimens were analyzed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by Ret expression by immunohistochemistry. RESULTS: Ten patients were enrolled. There was no statistically significant difference in ERK activation compared with placebo (P=0.45); however, ERK activation was reduced 74% compared with pretreatment biopsy with vandetinib treatment (P=0.005) without a significant reduction in the placebo group (-29%, P=0.55). Mean change in Ki-67 after vandetanib treatment was +0.3% compared with +2.0% in placebo treated patients, P=0.72. Mean change in TUNEL was +0.48 apoptotic nuclei per HPF in the vandetanib arm compared with +1.02 in the placebo arm, P=0.32. In vandetanib treated patients, Ki-67 was reduced 0.3% in RET-positive tumors compared with increased 1.0% in RET-negative tumors, P=0.43 and TUNEL was increased 0.77 in RET-positive tumors and 0.2 in RET-negative tumors, P=0.21. CONCLUSIONS: In this pilot study, no statistically significant differences on prespecified markers were seen with vandetanib compared with placebo. In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in Ret expressing tumors.
INTRODUCTION: Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer. METHODS: Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017. Pretreatment and posttreatment specimens were analyzed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by Ret expression by immunohistochemistry. RESULTS: Ten patients were enrolled. There was no statistically significant difference in ERK activation compared with placebo (P=0.45); however, ERK activation was reduced 74% compared with pretreatment biopsy with vandetinib treatment (P=0.005) without a significant reduction in the placebo group (-29%, P=0.55). Mean change in Ki-67 after vandetanib treatment was +0.3% compared with +2.0% in placebo treated patients, P=0.72. Mean change in TUNEL was +0.48 apoptotic nuclei per HPF in the vandetanib arm compared with +1.02 in the placebo arm, P=0.32. In vandetanib treated patients, Ki-67 was reduced 0.3% in RET-positive tumors compared with increased 1.0% in RET-negative tumors, P=0.43 and TUNEL was increased 0.77 in RET-positive tumors and 0.2 in RET-negative tumors, P=0.21. CONCLUSIONS: In this pilot study, no statistically significant differences on prespecified markers were seen with vandetanib compared with placebo. In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in Ret expressing tumors.
Authors: Philip M Spanheimer; Allison W Lorenzen; James P De Andrade; Mikhail V Kulak; Jennifer C Carr; George W Woodfield; Sonia L Sugg; Ronald J Weigel Journal: Ann Surg Oncol Date: 2015-05-14 Impact factor: 5.344
Authors: T Sørlie; C M Perou; R Tibshirani; T Aas; S Geisler; H Johnsen; T Hastie; M B Eisen; M van de Rijn; S S Jeffrey; T Thorsen; H Quist; J C Matese; P O Brown; D Botstein; P E Lønning; A L Børresen-Dale Journal: Proc Natl Acad Sci U S A Date: 2001-09-11 Impact factor: 11.205
Authors: Pedram Razavi; Matthew T Chang; Guotai Xu; Chaitanya Bandlamudi; Dara S Ross; Neil Vasan; Yanyan Cai; Craig M Bielski; Mark T A Donoghue; Philip Jonsson; Alexander Penson; Ronglai Shen; Fresia Pareja; Ritika Kundra; Sumit Middha; Michael L Cheng; Ahmet Zehir; Cyriac Kandoth; Ruchi Patel; Kety Huberman; Lillian M Smyth; Komal Jhaveri; Shanu Modi; Tiffany A Traina; Chau Dang; Wen Zhang; Britta Weigelt; Bob T Li; Marc Ladanyi; David M Hyman; Nikolaus Schultz; Mark E Robson; Clifford Hudis; Edi Brogi; Agnes Viale; Larry Norton; Maura N Dickler; Michael F Berger; Christine A Iacobuzio-Donahue; Sarat Chandarlapaty; Maurizio Scaltriti; Jorge S Reis-Filho; David B Solit; Barry S Taylor; José Baselga Journal: Cancer Cell Date: 2018-09-10 Impact factor: 31.743
Authors: S N Holden; S G Eckhardt; R Basser; R de Boer; D Rischin; M Green; M A Rosenthal; C Wheeler; A Barge; H I Hurwitz Journal: Ann Oncol Date: 2005-05-19 Impact factor: 32.976
Authors: Katalin Boér; István Láng; Antonio Llombart-Cussac; Inger Andreasson; Guillermo L Vivanco; Nick Sanders; Gillian M Pover; Elizabeth Murray Journal: Invest New Drugs Date: 2010-09-10 Impact factor: 3.850
Authors: Andrea Morandi; Lesley-Ann Martin; Qiong Gao; Sunil Pancholi; Alan Mackay; David Robertson; Marketa Zvelebil; Mitch Dowsett; Ivan Plaza-Menacho; Clare M Isacke Journal: Cancer Res Date: 2013-05-06 Impact factor: 12.701
Authors: Rachel A Freedman; Rebecca S Gelman; Carey K Anders; Michelle E Melisko; Heather A Parsons; Anne M Cropp; Kelly Silvestri; Christine M Cotter; Kathryn P Componeschi; Juan M Marte; Roisin M Connolly; Beverly Moy; Catherine H Van Poznak; Kimberly L Blackwell; Shannon L Puhalla; Rachel C Jankowitz; Karen L Smith; Nuhad Ibrahim; Timothy J Moynihan; Ciara C O'Sullivan; Julie Nangia; Polly Niravath; Nadine Tung; Paula R Pohlmann; Robyn Burns; Mothaffar F Rimawi; Ian E Krop; Antonio C Wolff; Eric P Winer; Nancy U Lin Journal: J Clin Oncol Date: 2019-03-12 Impact factor: 44.544
Authors: Erica L Mayer; Steven J Isakoff; Giannoula Klement; Sean R Downing; Wendy Y Chen; Keri Hannagan; Rebecca Gelman; Eric P Winer; Harold J Burstein Journal: Breast Cancer Res Treat Date: 2012-09-23 Impact factor: 4.872
Authors: Philip M Spanheimer; Anthony R Cyr; Matthew P Gillum; George W Woodfield; Ryan W Askeland; Ronald J Weigel Journal: Ann Surg Date: 2014-04 Impact factor: 12.969