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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

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Abstract

Purpose

To assess whether the early metabolic response evaluated by 18F-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.

Study design

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 (SUVmax) 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.

Results

The average decreases in SUVmax 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.

Conclusion

Cell-cycle response monitored by the Ki67 labeling index correlates with metabolic response monitored by tumor SUVmax. Monitoring of tumor SUVmax using FDG PET/CT may be feasible to predict cell-cycle response to neoadjuvant endocrine therapy of primary breast cancer.

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Acknowledgments

This work was supported by grants for the promotion of Defense Medicine from the Ministry of Defense, Japan, and from the Department of Breast Oncology of the International Medical Center at Saitama Medical University. The authors would like to thank Takaaki Suzuki for providing data related to previously published studies.

Conflict of interest statement

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Shigeto Ueda, Jiro Omata, Tomoyuki Moriya & Junji Yamamoto

  2. Breast Oncology Service, Tokorozawa Ichou Hospital, 1-7-25 Nishi-tokorozawa, Tokorozawa, Saitama, Japan

    Toshiaki Saeki, Akihiko Osaki & Takashi Shigekawa

  3. Department of Breast Oncology, Saitama Medical University, 38 Morohongo, Moroyama, Saitama, 350-0495, Japan

    Akihiko Osaki

  4. Department of Breast Oncology, Saitama Medical University, International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    Shigeto Ueda, Toshiaki Saeki & Takashi Shigekawa

  5. Tokorozawa PET Diagnostic Imaging Clinic, 7-5 Higashi-Sumiyoshi, Tokorozawa, Saitama, 359-1124, Japan

    Jiro Ishida, Katsumi Tamura & Yoshiyuki Abe

  6. Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

    Hitoshi Tsuda

  7. Headquarter Clinic, Mutual Aid Association, Ministry of Defense, 5-1 Honmura-chou, Ichigaya, Shinjuku-ku, Tokyo, Japan

    Shigeto Ueda

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  1. Shigeto Ueda
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  2. Hitoshi Tsuda
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Corresponding author

Correspondence to Hitoshi Tsuda.

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Ueda, S., Tsuda, H., Saeki, T. et al. 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. Breast Cancer 18, 299–308 (2011). https://doi.org/10.1007/s12282-010-0212-y

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  • DOI: https://doi.org/10.1007/s12282-010-0212-y

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