Abstract P6-01-05: Potential biomarkers of response to primary antiangiogenic and hormonal therapy in post-menopausal women with hormone-positive, HER2-negative primary breast cancer
Authors: Verdaguer Helena , Morales Serafin , Navarro Valentí , Martinez Lopez Alba , Petit Anna , Climent Fina , Casanovas Oriol , Pernas Sònia 
Published: May 2015

Abstract
Introduction The role of antiangiogenic therapy in primary hormonal therapy in HER2-negative ER-positive early breast cancer is unknown. Potential biomarkers of response to antiangiogenic therapy are lacking. A phase I clinical trial was conducted with sunitinib and exemestane given at conventional dose (25 mg/d) during 6 months, before surgery. 18 patients were enrolled, 15 in dose level 0 of sunitinib (25 mg/d) and 3 in dose level 1 (37.5 mg/d). Results were presented in SABCS 2011. Main toxicities were: asthenia (50%), leucopenia (28%, all grade 2), diarrhea (28%), mucositis (22%), and hypertension (22%). 10 patients achieved radiological partial response (56%) and 8 patients stable disease (44%). 7 patients (38.89%) obtained a pathological downstaging. Potential biomarkers of response to antiangiogenic therapy are presented.
Materials and methods Tissue samples were obtained by fine-needle aspiration or core needle biopsy before starting treatment, one month after and at surgery. All samples were formalin-fixed paraffin-embedded. Ki67, phospho-ERK and mean vessel density (by CD34), were analyzed by immunostaining. At the same time points, plasma levels of angiopoietin 2 (ANG2), soluble VEGFR2 and VEGF were analyzed by ELISA. Basal levels and its changes over time were evaluated and correlated with clinical outcomes.
Results Changes in Ki67 were observed, with a median value of 16.44%pre surgery and 12.78% post surgery (p=0.062). A significant decrease in mean vessel density was not observed.
Basal levels of plasmatic biomarkers are shown in the next table:
Basal levels of plasmatic biomarkers SDPRpPath DownstNo Path DownstpANG 22396+/-6503455+/-13940.083184+/-16102818+/-7680.6VEGF110+/-12577+/-660.5794+/-6388+/-1210.9VEGFR210570+/-22512110+/-43940.3512140+/-432110980+/-31960.55
Values of biomarkers are average in ng/ml ± Standard Deviation. Differences analyzed by student's t-test.
Abreviations: SD= stable disease. PR= partial response. p = p value. Path. Downst.= Pathological downstaging.
Furthermore, there was a significant decrease in VEGFR2 mean levels after one month of treatment (p=0.0046): 12284±3449 ng/ml at baseline; 8148±3216 ng/ml at one month and 7732±3052 ng/ml at 6 months. Differences between basal and one month determination were significant (p&lt;0.01), but no differences were seen between 1 month and 6 months, showing a relevant early decrease of VEGFR2 plasma levels. In contrast, levels of VEGF did not change significantly over time and had no association with clinical outcomes.
Conclusions Baseline ANG2 levels have a promising predictive value of response in this phase I trial of neoadjuvant combination of sunitinib plus exemestane. There is a significant early decrease in VEGFR2 with treatment with sunitinib. These results should be validated in further studies to improve the selection of patients for antiangiogenic+hormonal therapy.
Citation Format: Helena Verdaguer, Serafin Morales, Valentí Navarro, Alba Martinez Lopez, Anna Petit, Fina Climent, Oriol Casanovas, Sònia Pernas. Potential biomarkers of response to primary antiangiogenic and hormonal therapy in post-menopausal women with hormone-positive, HER2-negative primary breast cancer [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 P6-01-05.