Abstract
PurposeThis study evaluated the ability of 18F-Fluorodeoxyglucose (FDG) and 18F-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.MethodsIn 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.ResultsFDG 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.ConclusionsA 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.
Highlights
Adjuvant endocrine therapy improves outcomes for estrogen-receptor positive (ER+) breast cancer [1,2,3]
Serial biopsy studies have shown a decrease in proliferative index (Ki-67) following as little as 2 weeks of successful neoadjuvant endocrine therapy [10]; in the IMPACT study, proliferation dropped at 2 weeks and remained low for the subsequent 10 weeks in the majority of patients [11]
We prospectively evaluated early response to neoadjuvant aromatase inhibitor (AI) therapy using baseline and pre-surgery FDG- and FLT-positron emission tomography (PET) imaging in two different protocols, in conjunction with tissue Ki-67 assay in earlystage ER+ tumors under the hypothesis that one or both tracer imaging approaches would produce results similar to Ki-67 biopsy levels
Summary
Adjuvant endocrine therapy improves outcomes for estrogen-receptor positive (ER+) breast cancer [1,2,3]. 25–50% of women with early stage breast cancer (stages I and II) will experience tumor recurrence [4]. Pre-operative or neoadjuvant ’window’ studies provide short exposures to systemic therapy between cancer diagnosis and surgery, potentially providing early insight into tumor sensitivity and resistance [5,6,7]. Serial biopsy studies have shown a decrease in proliferative index (Ki-67) following as little as 2 weeks of successful neoadjuvant endocrine therapy [10]; in the IMPACT study, proliferation dropped at 2 weeks and remained low for the subsequent 10 weeks in the majority of patients [11]. Post-therapy Ki-67 levels following 2 weeks of neoadjuvant endocrine therapy have been shown to predict progression-free survival [12], but the requirement for biopsy, and often serial biopsies, results in limited clinical use
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