Tumor-Specific Expression of Vascular Endothelial Growth Factor Receptor 2 but Not Vascular Endothelial Growth Factor or Human Epidermal Growth Factor Receptor 2 Is Associated With Impaired Response to Adjuvant Tamoxifen in Premenopausal Breast Cancer

Abstract

Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor-positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.

Vascular endothelial growth factor receptor 2 and downstream p38 mitogen-activated protein kinase are possible candidate markers of intrinsic resistance to adjuvant endocrine treatment in steroid receptor positive breast cancer

“…VEGFR2 is less studied and the data concerning the prognostic and predictive role contradictory. In accordance to our results, a previous study including a large number of premenopausal patients randomized to tamoxifen for two years or no adjuvant endocrine therapy, showed that high VEGFR2 expression were correlated with reduced survival [24]. On the contrary, the same group could not demonstrate that VEGFR2…”

MTA1, a transcriptional activator of breast cancer amplified sequence 3

“…Based on above studies, BCAS3 and MTA1 status was assessed in a patient cohort consisting of 380 premenopausal breast cancer patients (18). The expression of BCAS3 and MTA1 was first evaluated from 0 (negative) to 4 (strongest intensity) but were later divided into three groups, 0-1, 2, and 3-4, as illustrated in Fig.…”

Dual Inhibition of PI3K and mTOR Mitigates Compensatory AKT Activation and Improves Tamoxifen Response in Breast Cancer

“…Preclinical and clinical data showed that VEGF levels in tumor tissue were related with worse response to endocrine therapy (21,22). Retrospective clinical data showed that decreasing VEGF level may restore sensitivity and improve efficacy to hormonal therapy (22). Phase III LEA study showed that there was a trend of longer progression-free survival in patients treated with bevacizumab and hormone therapy in HR-positive advanced breast cancer (23).…”

“…In breast cancer, studies have shown that VEGF receptor and mTOR inhibitors show similar but also distinct effects on tumor vascular biology, which has implications for their clinical activity alone or in combination. Preclinical and clinical data showed that VEGF levels in tumor tissue were related with worse response to endocrine therapy (21,22). Retrospective clinical data showed that decreasing VEGF level may restore sensitivity and improve efficacy to hormonal therapy (22).…”