Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial ¹⁸F-FDG PET was predictive of time to skeletal-related events (tSRE) and time to progression (TTP). ¹⁸F-NaF PET improves bone metastasis detection compared with bone scanning. We prospectively tested ¹⁸F-FDG PET and ¹⁸F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (MBC). Methods: Patients with bone-dominant MBC were imaged with ¹⁸F-FDG PET and ¹⁸F-NaF PET before starting new therapy (scan1) and again at a range of times centered around approximately 4 mo later (scan2). Maximum standardized uptake value (SUV_max) and lean body mass adjusted standardized uptake (SUL_peak) were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and ¹⁸F-FDG PET and ¹⁸F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) were also applied. Survival curves for mPERCIST compared response categories of complete response+partial response+stable disease versus progressive disease for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher ¹⁸F-FDG SUL_peak at scan2 predicted shorter time to tSRE (P = <0.001) and TTP (P = 0.044). Higher ¹⁸F-FDG SUV_max at scan2 predicted a shorter time to tSRE (P = <0.001). A multivariable model using ¹⁸F-FDG SUV_max of the index lesion at scan1 plus the difference in SUV_max of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by ¹⁸F-FDG PET mPERCIST, tSRE and TTP were longer in responders (complete response, partial response, or stable disease) than in nonresponders (progressive disease) (P = 0.007, 0.028, respectively), with a trend toward improved survival (P = 0.1). An increase in the uptake between scans of up to 5 lesions by ¹⁸F-NaF PET was associated with longer OS (P = 0.027). Conclusion: Changes in ¹⁸F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial ¹⁸F-NaF PET was associated with OS but was not useful for predicting TTP or tSRE in bone-dominant MBC.

Purpose: This study evaluated the ability of¹⁸F-Fluorodeoxyglucose (FDG) and¹⁸F-Fluorothymidine (FLT) imaging with positron emission tomography (PET) to measure early response to endocrine therapy from baseline to just prior to surgical resection in estrogen receptor positive (ER+) breast tumors.Methods: In two separate studies, women with early stage ER+ breast cancer underwent either paired FDG-PET (n = 22) or FLT-PET (n = 27) scans prior to endocrine therapy and again in the pre-operative setting. Tissue samples for Ki-67 were taken for all patients both prior to treatment and at the time of surgery.Results: FDG maximum standardized uptake value (SUVmax) declined in 19 of 22 lesions (mean 17% (range −45 to 28%)). FLT SUVmax declined in 24 of 27 lesions (mean 26% (range −77 to 7%)). The Ki-67 index declined in both studies, from pre-therapy (mean 23% (range 1 to 73%)) to surgery [mean 8% (range < 1 to 41%)]. Pre- and post-therapy PET measures showed strong rank-order agreement with Ki-67 percentages for both tracers; however, the percent change in FDG or FLT SUVmax did not demonstrate a strong correlation with Ki-67 index change or Ki-67 at time of surgery.Conclusions: A window-of-opportunity approach using PET imaging to assess early response of breast cancer therapy is feasible. FDG and FLT-PET imaging following a short course of neoadjuvant endocrine therapy demonstrated measurable changes in SUVmax in early stage ER+ positive breast cancers. The percentage change in FDG and FLT-PET uptake did not correlate with changes in Ki-67; post-therapy SUVmax for both tracers was significantly associated with post-therapy Ki-67, an established predictor of endocrine therapy response.

Aim: This study examines the combination of FES-PET and FDG-PET as complementary imaging for detection of metastatic ILC. Methods: We retrospectively evaluated FES and FDG uptake in patients with metastatic ILC from an estrogen receptor (ER) positive primary tumor. We classified lesions into three categories (FES high/FDG low, FES high/FDG high, FES low/FDG low) using SUVmax cut-off values of 1.5 for FES and 5.0 for FDG. Qualitative evaluation included examination of the difference in the extent of disease between FES and FDG. Results: Of the 38 patients, 82% had FES uptake in all tumor sites identified by FDG, with 18% lacking FES uptake in at least one lesion. Mean (range) SUVmax for FES and FDG was 4.0 (0.67–10.6) and 4.6 (1.3–12.5), respectively. The majority of ILC patients (25/38), had lesions with FES high/FDG low uptake, consistent with the strongly ER + indolent nature of ILC. Patients with disease classified as FES high/FDG low had longer median overall survival (OS) (3.2 years) and progression-free survival (PFS) (1.5 years) than FES high/FDG high (OS = 2.1 years and PFS = 0.46 years). The median overall OS for all patients was 3.0 years (95% CI 2.5, 4.8) and PFS of 1.3 years (95% CI 0.6, 2.5). 8 patients (21%) had qualitatively more extensive disease by FES-PET. Conclusions: Our findings suggest that both FES-PET and FDG-PET can identify metastatic ILC and be useful in detecting the pattern and extent of disease. The imaging combination provides additional information for prognosis and clinical decision making, balancing suitability for endocrine therapy and aggressiveness/indolence of disease.