Feasibility and Predictability of Perioperative PET and Estrogen Receptor Ligand in Patients with Invasive Breast Cancer

Abstract

The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator for both disease-free and overall survival. 16α-¹⁸F-fluoro-17β-estradiol (¹⁸F-FES) with PET is a noninvasive test for evaluation of ER expression and has been used for predicting response to endocrine therapy in patients with ER-positive metastatic breast cancer. The purpose of this study was to correlate ¹⁸F-FES PET and ER expression in patients with primary, operable breast cancer. Methods: Forty-eight patients were prospectively enrolled in an institutional review board–approved protocol and signed an informed consent form. All patients had undergone ¹⁸F-FES PET preoperatively. Clinical characteristics, tumor characteristics, and treatment outcomes were recorded. Immunohistochemical analysis for ER and PgR percentage expression (46 surgical, 2 core biopsy specimens) was performed. ¹⁸F-FES PET standardized uptake value (SUV) of the breast lesion was correlated with percentage immunohistochemistry ER and PgR expression. ¹⁸F-FES PET SUV was quantified, with a value of 1.5 or more considered positive, and ER and progesterone receptor (PgR) was quantified, with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was available for 44 patients (42 surgical, 2 core biopsy specimens). We used a microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and PGR) were compared with ¹⁸F-FES PET SUV (Spearman rank correlation). Tumor size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol level, body mass index (BMI), and lean BMI were compared with ¹⁸F-FES PET uptake using univariate and multivariate analysis. Results: Forty-eight patients completed our protocol, and 2 patients did not undergo surgery because bone metastases were identified preoperatively on ¹⁸F-FES PET. Eighty-three percent of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one patients underwent a sentinel node biopsy. Twenty-one patients had nodal involvement. ¹⁸F-FES PET identified 5 patients with axillary nodal uptake (median SUV, 3.0; range, 1.7–6.9). These 5 patients had ER-positive breast cancer, and all had more than 4 positive nodes at the time of axillary node dissection. ¹⁸F-FES PET SUV was associated with immunohistochemistry ER expression. The sensitivity and specificity of the ¹⁸F-FES PET for the breast lesion were 0.85 and 0.75, respectively. Estrogen and progesterone gene expression (ESR1, ESR2, and PGR) was not associated with ¹⁸F-FES PET SUV (Spearman rank correlation). We found a significant correlation between ¹⁸F-FES PET SUV and tumor size (P = 0.0015) but not with ductal histology, grade, HER2-neu overexpression, PgR, estradiol, BMI, or lean BMI (logistic regression). ER expression (P < 0.001) and tumor size (P < 0.0001) were significant on multivariate regression analysis. Conclusion: ¹⁸F-FES PET SUV correlated with ER immunohistochemistry expression but not gene expression in our patients with early breast cancer. We found that size of primary tumor was significantly associated with ¹⁸F-FES PET SUV. ¹⁸F-FES PET is highly predictive for metastatic disease and helped in the identification of patients with metastatic disease in a preoperative setting.