Abstract P3-05-16: The effect of HER-2/neu inhibition on prolonging clinical benefit with fulvestrant treatment for metastatic estrogen receptor positive breast cancer patients treated with trastuzumab
Authors: Charif Mahmoud , Lower Elyse E , Kennedy Diane , Kumar Harriet , Khan Shugufta , Radhakrishnan Neetu , Zhang Xiaoting 
Published: May 2015

Background: Fulvestrant is a well-established treatment for postmenopausal patients with estrogen receptor (ER) positive metastatic breast cancer, and some patients experience prolonged clinical benefit exceeding one year. HER2 activation is a major cause of endocrine resistance, and cross-talk between HER2/neu and ER coactivator MED1 regulates tamoxifen resistance in breast cancer cells. (Cancer Res 2012 1;72(21):5625-34.). In a xenograft mouse model, suppression of MED1 enhanced tumor growth inhibition by fulvestrant in HER2/neu overexpressing breast cancer cells (PLoS One 20123 30;8(7)). Objective of study: To determine if blocking the HER2/neu receptor with trastuzumab can improve response to fulvestrant. Methods: This was an IRB approved record review of patients from three medical oncologists with biopsy-proven ER+ metastatic breast cancer treated with fulvestrant. Demographic data collected included age at diagnosis, type and stage of cancer, original and metastatic ER, progesterone receptor (PR), and HER2/neu biomarkers, and site(s) of metastasis, and primary local and systemic treatment. All patients with HER2/neu positive primary tumors received trastuzumab. The duration of fulvestrant therapy was calculated. Time to clinical disease progression on fulvestrant was measured as a surrogate for duration of clinical benefit. Based on the median duration of therapy of 425 days, patients were divided into two groups: Short Treatment (&lt; 425 days) versus Prolonged Treatment (&gt;425 days). Results: One hundred metastatic ER+ fulvestrant treated breast cancer patients with documented duration of therapy were identified. There was no difference between the Short and Prolonged Treatment Groups in regards to age, sites of metastases, or use of adjuvant endocrine or chemotherapy. Eighty five patients had recorded HER2/neu tumor status. All 11 of 85 (13%) patients with documented HER2/neu positive primary tumors received trastuzumab. Patients with HER2/neu positive tumors tended to have longer durations of fulvestrant therapy (772 (51-1911) days (median (range)) compared to HER2/neu negative patients (360 (60-2739) days, p=0.059). Only 2 of 45 (4%) tumors from the Short Treatment Group were HER2/neu positive, while 9 of 40 Prolonged Treatment Group patients with documented HER2/neu status were positive (Fisher’s exact test p&lt;0.021). Patients with HER2/neu positive tumors were more likely to experience prolonged responses to therapy with an odds ratio of 6.2 (1.26 to 30.92 95% confidence interval, p=0.0249). Conclusion: Overexpression of HER2/neu in tumors from ER+ metastatic breast cancer patients treated with trastuzumab was associated with a prolonged response to fulvestrant therapy.

Citation Format: Mahmoud Charif, Elyse E Lower, Diane Kennedy, Harriet Kumar, Shugufta Khan, Neetu Radhakrishnan, Xiaoting Zhang. The effect of HER-2/neu inhibition on prolonging clinical benefit with fulvestrant treatment for metastatic estrogen receptor positive breast cancer patients treated with trastuzumab [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-16.