A phase II neoadjuvant trial of anastrozole, fulvestrant, and gefitinib in patients with newly diagnosed estrogen receptor positive breast cancer

Suleiman Massarweh, Yee L. Tham, Jian Huang, Krystal Sexton, Heidi Weiss, Anna Tsimelzon, Amanda Beyer, Mothaffar Rimawi, Wei Yen Cai, Susan Hilsenbeck, Suzanne Fuqua, Richard Elledge

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27 Scopus citations


Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining 12 patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (P value = 0.01), with a parallel reduction in the expression of the Cyclin D1 (P value = 0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.

Original languageEnglish
Pages (from-to)819-827
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - Oct 2011

Bibliographical note

Funding Information:
Acknowledgments Funded by a grant from Astra Zeneca and NIH grant P50 CA58183. Dr. S Massarweh receives funding from Novartis and Bayer, and Dr. M. Rimawi receives funding from Astra Zeneca and GSK. Presented in part at the 2007 American Society of Clinical Oncology Meeting in Chicago, IL, Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1050. Registered under Clinicaltri-als.gov number NCT00206414.


  • Breast cancer
  • EGFR
  • Endocrine resistance
  • Estrogen receptor
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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