Early metabolic response to neoadjuvant letrozole, measured by FDG PET/CT, is correlated with a decrease in the Ki67 labeling index in patients with hormone receptor-positive primary breast cancer: A pilot study

Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Breast Cancer (Impact Factor: 1.59). 10/2011; 18(4):299-308. DOI: 10.1007/s12282-010-0212-y
Source: PubMed


To assess whether the early metabolic response evaluated by (18)F-fluorodeoxy-glucose positron emission combined with computed tomography (FDG PET/CT) predicts the morphological, pathological, and cell-cycle responses to neoadjuvant endocrine therapy of hormone receptor-positive primary breast cancer.
Eleven patients (12 tumors) with estrogen receptor-positive (Allred score 7 or 8) primary breast cancer were enrolled. All patients received a daily dose (2.5 mg) of letrozole for 12 weeks followed by surgery. Sequential FDG PET/CT scans were performed before treatment (baseline), at 4 weeks after the initiation of endocrine therapy (PET2), and prior to surgery (PET3). Tumors showing a 40% or more reduction and those showing a less than 40% reduction in the standardized uptake value maximum (SUV(max)) at PET2 compared with the baseline PET were defined as metabolic responders and metabolic nonresponders, respectively. Change in tumor size as measured by ultrasound (morphological response), pathological response, and change in the Ki67 labeling index in tumor tissue (cell-cycle response) during the neoadjuvant letrozole therapy were compared between the metabolic responders and nonresponders.
The average decreases in SUV(max) at PET2 compared with the baseline PET in the metabolic responders (n = 6) and the metabolic nonresponders (n = 6) were 60.9% (±21.3 SD) and 14.2% (±12.0 SD), respectively. At PET3 compared with the baseline PET, the metabolic responders showed a significantly higher decrease of 64.5% (±18.7 SD) (p = 0.0004), whereas the nonresponders showed a nonsignificant decrease of 16.7% (±14.1 SD) (p = 0.06). The morphological and pathological responses after letrozole therapy did not differ between the metabolic responders and nonresponders. The metabolic responders showed a marked decrease in the Ki67 labeling index at 2 weeks after the initiation of treatment (62.9%, ±35.9 SD, p = 0.04) and at surgery (91.7%, ±10.7 SD, p = 0.03) compared with the baseline values. In contrast, metabolic nonresponders showed no significant change in the Ki67 index either after 2 weeks of therapy or at surgery.
Cell-cycle response monitored by the Ki67 labeling index correlates with metabolic response monitored by tumor SUV(max). Monitoring of tumor SUV(max) using FDG PET/CT may be feasible to predict cell-cycle response to neoadjuvant endocrine therapy of primary breast cancer.

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    • "Other diagnostic techniques such as FDG-PET, which measures the uptake of labeled glucose into a tumor, are thus better suited to evaluate biological activity at a given point in time and are currently evaluated [26], [27]. An alternative to evaluate the presence of viable tumor cells is by measuring the readily available immunohistochemical analysis of the nuclear antigen Ki67 [28]. There is now increasing interest in the nuclear proliferation antigen Ki67, since allows to distinguish the relatively chemo-resistant luminal A from the more sensitive luminal B breast cancer subtype [29]. "
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    Full-text · Article · Jun 2013 · PLoS ONE
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    • "In order to gain insights into mechanisms by which LOX-PP inhibits tumor growth in vivo, we first evaluated relative expression levels of Ki-67 by immunohistochemistry in harvested tumors. Ki-67 is a marker for cell proliferation, and is expressed in all phases of the cell cycle except G0, and is a predictive and prognostic marker for breast cancer [27], [28], [29], [30], [31]. A higher number of Ki-67 immunopositive cells were observed in sections injected with PBS or implanted with empty beads compared to rLOX-PP injection or rLOX-PP/alginate beads implantation, as seen in representative sections (Figure 4A and 4B). "
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