Adding Sunitinib to Tamoxifen Shows Preclinical Promise for ER-Positive Breast Cancer

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(ChemotherapyAdvisor) – Adding sunitinib to tamoxifen antiestrogen therapy might prove to be a promising treatment strategy for estrogen receptor (ER)-positive breast cancer, according to a preclinical animal and cell line study presented at the 66th Annual Society of Surgical Oncology (SSO) Cancer Symposium in National Harbor, MD in National Harbor, MD.

Sunitinib significantly reduced tumor MCF-7 cell proliferation and induced apoptosis “with effects that were additive with tamoxifen,” reported Philip M. Spanheimer, MD, of the University of Iowa, Iowa City, IA, and coauthors.

“In preclinical animal studies, sunitinib treatment significantly reduced MCF-7 xenograft tumorigenesis. Furthermore, sunitinib inhibited ERK1/2 activation in primary human breast cancers with more pronounced effects in ER-positive tumors,” Dr. Spanheimer and coauthors reported. “Together, these results indicate that combination therapy with antiestrogens and a RET inhibitor may offer a novel treatment strategy in breast cancer.”

Sunitinib is a small molecule RET proto-oncogene inhibitor. The team administered sunitinib to mice bearing MCF-7 ER-positive breast cancer xenografts, and studied in vitro RET expression in primary breast tumor tissue samples treated with glial cell line derived neurotropic factor (GDNF) to activate ERK1/2 and tumor cell proliferation, the coauthors reported.

Sunitinib reduced MCF-7 cell proliferation, S-phase, and GDNF induction, they found.

“Treatment with both sunitinib and tamoxifen demonstrated additive effects to decrease proliferation (P<0.001), S phase (P=0.007), and Ki-67 (P=0.01) and induce CC3 (P=0.001),” they reported. “Athymic mice treated with sunitinib had reduced MCF-7 xenograft formation at 3 weeks compared to control mice (33% vs. 100%; P=0.05).”

Among 12 primary human tumor samples, the mean expression of RET receptor in ER-positive tumors was 14 times higher than in ER-negative samples (P=0.04) “and 20-fold higher than patient-matched normal breast tissue (P=0.02),” they noted.

The abstract (#15) for this presentation is available at the 66th Annual SSO Cancer Symposium's website.

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