¹⁸F-Fluoroestradiol PET to Predict the Response to Neoadjuvant Treatment of Luminal Breast Cancer

TO THE EDITOR: Chae et al. (1) prospectively investigated the ability of pretreatment ¹⁸F-fluoroestradiol PET/CT to predict the pathologic response to neoadjuvant therapy in postmenopausal women with estrogen receptor–positive breast cancer. Of 25 evaluated patients, 12 received neoadjuvant chemotherapy and 13 neoadjuvant endocrine therapy. In the former group, the 2 patients with ¹⁸F-fluoroestradiol–negative tumors and none of the 10 patients with ¹⁸F-fluoroestradiol–avid tumors achieved a pathologic complete response (P = 0.02). In the latter group, all 13 patients had ¹⁸F-fluoroestradiol–avid uptake, but none achieved a pathologic complete response. No difference in pretreatment SUV_max between responders and nonresponders was observed in either group. However, using the Miller–Payne grading system to define response, 5 of 7 neoadjuvant chemotherapy patients with a baseline SUV_max of less than 7.3 achieved a pathologic response, whereas none of the 5 neoadjuvant endocrine therapy patients with an SUV_max of less than 7.3 were responders (P = 0.03). In agreement with another study (2), these results suggest that patients with low tumor ¹⁸F-fluoroestradiol uptake at baseline are more likely to be treated with neoadjuvant chemotherapy than with neoadjuvant endocrine therapy. In patients with a high baseline tumor SUV_max, Chae et al. observed no difference in pathologic response, whatever the treatment group. For these tumors with high ¹⁸F-fluoroestradiol uptake, a second PET examination could potentially be helpful to measure the change in SUV under treatment, in the same way as is sometimes done with ¹⁸F-FDG imaging (3). This could increase the predictive value of ¹⁸F-fluoroestradiol imaging. In the metastatic setting, among 16 patients treated with fulvestrant, baseline ¹⁸F-fluoroestradiol PET was unable to predict the response (4). When a second examination was performed a few weeks after the start of treatment, the change in tumor ¹⁸F-fluoroestradiol uptake was significantly larger in patients having clinical benefit from fulvestrant than in patients with progressive disease (P = 0.025) (4). Another research possibility would be the use of ¹⁸F-FDG imaging in addition to ¹⁸F-fluoroestradiol PET. In estrogen receptor–positive breast cancer, recent studies suggested that ¹⁸F-FDG uptake measured at a single time point before neoadjuvant chemotherapy (5) or before initial surgery (6) was associated with patient survival. A pilot study evaluated the value of ¹⁸F-fluoroestradiol and ¹⁸F-FDG imaging together in predicting the response of various breast cancer phenotypes to neoadjuvant chemotherapy. The ratio of ¹⁸F-fluoroestradiol SUV to ¹⁸F-FDG SUV showed great value in predicting the response (P = 0.002) (2). However, the small number of patients in this study (n = 18) was a limitation. Moreover, luminal tumors were mixed with estrogen receptor–negative breast cancer. In the metastatic setting, the recent study from Kurland et al. showed that information from baseline ¹⁸F-fluoroestradiol and ¹⁸F-FDG imaging can be used together to separate patients into 3 groups with different prognoses (7).

In conclusion, although the study from Chae et al. suggests that baseline ¹⁸F-fluoroestradiol PET could be of interest to predict the response to neoadjuvant therapy in estrogen receptor–positive breast cancer patients, the predictive value seems to have some limitations. Performing a second ¹⁸F-fluoroestradiol PET examination during treatment or complementing the ¹⁸F-fluoroestradiol examination with a ¹⁸F-FDG PET examination could potentially improve the predictive power and deserves to be evaluated prospectively in a large study.

• © 2017 by the Society of Nuclear Medicine and Molecular Imaging.