Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients

Brenda F. Kurland, Vijayakrishna K. Gadi, Jennifer M. Specht, Kimberly H. Allison, Robert B Livingston, Eve T. Rodler, Lanell M. Peterson, Erin K. Schubert, Xiaoyu Chai, David A. Mankoff, Hannah M. Linden

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background In breast cancer endocrine therapy, post-therapy Ki-67 assay of biopsy material predicts recurrence-free survival but is invasive and prone to sampling error. [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) has shown an early agonist or 'flare' response to tamoxifen and estradiol, but has not been tested in response to estrogen-lowering aromatase inhibitors (AIs). We hypothesized that decreased agonistic response to AIs would result in early FDG uptake decline. We also measured early response to trastuzumab (T), another targeted agent for breast cancer with differing mechanisms of action. Our study was designed to test for an early decline in FDG uptake in response to AI or T and to examine association with Ki-67 measures of early response. Methods Patients with any stage of newly diagnosed or recurrent breast cancer were eligible and enrolled prior to initiation (or resumption) of AI or T therapy. FDG PET and tissue biopsy were planned before and after 2 weeks of AI or T therapy, with pretreatment archival tissue permitted. Cutoffs of ≥20% decline in standardized uptake value (SUV) as FDG PET early response and ≤5% post-treatment expression as Ki-67 early response were defined prior to analysis. Results Forty-two patients enrolled, and 40 (28 AI, 12 T) completed serial FDG-PET imaging. Twenty-two patients (17 AI, 5 T) had newly diagnosed disease, and 23 (14 AI, 9 T) had metastatic disease (5 newly diagnosed). Post-treatment biopsy was performed in 25 patients (63%) and was either refused or not feasible in 15. Post-treatment biopsy yielded tumor in only 17/25 cases (14 AI, 3 T). Eleven of 14 AI patients with post-therapy tissue showed FDG PET early response, and there was 100% concordance of PET and post-therapy Ki-67 early response. For the T group, 6/12 showed an FDG PET early response, including 2/3 patients with post-therapy biopsy, all with Ki-67 >5%. Conclusions Substantial changes in FDG PET SUV occurred over 2 weeks of AI therapy and were associated with low post-therapy proliferation. SUV decline was seen in response to T, but few tissue samples were available to test association with Ki-67. Our results support further investigation of FDG PET as a biomarker for early response to AI therapy.

Original languageEnglish (US)
JournalEJNMMI Research
Volume2
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Aromatase Inhibitors
Feasibility Studies
Positron-Emission Tomography
Breast Neoplasms
Biopsy
Therapeutics
Trastuzumab
Selection Bias
Fluorodeoxyglucose F18
Tamoxifen
Cell- and Tissue-Based Therapy
Estradiol
Estrogens
Biomarkers

Keywords

  • Aromatase inhibitor
  • Breast cancer
  • Early response
  • FDG PET
  • Ki-67
  • Pharmacodynamic response
  • Trastuzumab

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients. / Kurland, Brenda F.; Gadi, Vijayakrishna K.; Specht, Jennifer M.; Allison, Kimberly H.; Livingston, Robert B; Rodler, Eve T.; Peterson, Lanell M.; Schubert, Erin K.; Chai, Xiaoyu; Mankoff, David A.; Linden, Hannah M.

In: EJNMMI Research, Vol. 2, No. 1, 2012.

Research output: Contribution to journalArticle

Kurland, BF, Gadi, VK, Specht, JM, Allison, KH, Livingston, RB, Rodler, ET, Peterson, LM, Schubert, EK, Chai, X, Mankoff, DA & Linden, HM 2012, 'Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients', EJNMMI Research, vol. 2, no. 1. https://doi.org/10.1186/2191-219X-2-34
Kurland, Brenda F. ; Gadi, Vijayakrishna K. ; Specht, Jennifer M. ; Allison, Kimberly H. ; Livingston, Robert B ; Rodler, Eve T. ; Peterson, Lanell M. ; Schubert, Erin K. ; Chai, Xiaoyu ; Mankoff, David A. ; Linden, Hannah M. / Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients. In: EJNMMI Research. 2012 ; Vol. 2, No. 1.
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title = "Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients",
abstract = "Background In breast cancer endocrine therapy, post-therapy Ki-67 assay of biopsy material predicts recurrence-free survival but is invasive and prone to sampling error. [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) has shown an early agonist or 'flare' response to tamoxifen and estradiol, but has not been tested in response to estrogen-lowering aromatase inhibitors (AIs). We hypothesized that decreased agonistic response to AIs would result in early FDG uptake decline. We also measured early response to trastuzumab (T), another targeted agent for breast cancer with differing mechanisms of action. Our study was designed to test for an early decline in FDG uptake in response to AI or T and to examine association with Ki-67 measures of early response. Methods Patients with any stage of newly diagnosed or recurrent breast cancer were eligible and enrolled prior to initiation (or resumption) of AI or T therapy. FDG PET and tissue biopsy were planned before and after 2 weeks of AI or T therapy, with pretreatment archival tissue permitted. Cutoffs of ≥20{\%} decline in standardized uptake value (SUV) as FDG PET early response and ≤5{\%} post-treatment expression as Ki-67 early response were defined prior to analysis. Results Forty-two patients enrolled, and 40 (28 AI, 12 T) completed serial FDG-PET imaging. Twenty-two patients (17 AI, 5 T) had newly diagnosed disease, and 23 (14 AI, 9 T) had metastatic disease (5 newly diagnosed). Post-treatment biopsy was performed in 25 patients (63{\%}) and was either refused or not feasible in 15. Post-treatment biopsy yielded tumor in only 17/25 cases (14 AI, 3 T). Eleven of 14 AI patients with post-therapy tissue showed FDG PET early response, and there was 100{\%} concordance of PET and post-therapy Ki-67 early response. For the T group, 6/12 showed an FDG PET early response, including 2/3 patients with post-therapy biopsy, all with Ki-67 >5{\%}. Conclusions Substantial changes in FDG PET SUV occurred over 2 weeks of AI therapy and were associated with low post-therapy proliferation. SUV decline was seen in response to T, but few tissue samples were available to test association with Ki-67. Our results support further investigation of FDG PET as a biomarker for early response to AI therapy.",
keywords = "Aromatase inhibitor, Breast cancer, Early response, FDG PET, Ki-67, Pharmacodynamic response, Trastuzumab",
author = "Kurland, {Brenda F.} and Gadi, {Vijayakrishna K.} and Specht, {Jennifer M.} and Allison, {Kimberly H.} and Livingston, {Robert B} and Rodler, {Eve T.} and Peterson, {Lanell M.} and Schubert, {Erin K.} and Xiaoyu Chai and Mankoff, {David A.} and Linden, {Hannah M.}",
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T1 - Feasibility study of FDG PET as an indicator of early response to aromatase inhibitors and trastuzumab in a heterogeneous group of breast cancer patients

AU - Kurland, Brenda F.

AU - Gadi, Vijayakrishna K.

AU - Specht, Jennifer M.

AU - Allison, Kimberly H.

AU - Livingston, Robert B

AU - Rodler, Eve T.

AU - Peterson, Lanell M.

AU - Schubert, Erin K.

AU - Chai, Xiaoyu

AU - Mankoff, David A.

AU - Linden, Hannah M.

PY - 2012

Y1 - 2012

N2 - Background In breast cancer endocrine therapy, post-therapy Ki-67 assay of biopsy material predicts recurrence-free survival but is invasive and prone to sampling error. [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) has shown an early agonist or 'flare' response to tamoxifen and estradiol, but has not been tested in response to estrogen-lowering aromatase inhibitors (AIs). We hypothesized that decreased agonistic response to AIs would result in early FDG uptake decline. We also measured early response to trastuzumab (T), another targeted agent for breast cancer with differing mechanisms of action. Our study was designed to test for an early decline in FDG uptake in response to AI or T and to examine association with Ki-67 measures of early response. Methods Patients with any stage of newly diagnosed or recurrent breast cancer were eligible and enrolled prior to initiation (or resumption) of AI or T therapy. FDG PET and tissue biopsy were planned before and after 2 weeks of AI or T therapy, with pretreatment archival tissue permitted. Cutoffs of ≥20% decline in standardized uptake value (SUV) as FDG PET early response and ≤5% post-treatment expression as Ki-67 early response were defined prior to analysis. Results Forty-two patients enrolled, and 40 (28 AI, 12 T) completed serial FDG-PET imaging. Twenty-two patients (17 AI, 5 T) had newly diagnosed disease, and 23 (14 AI, 9 T) had metastatic disease (5 newly diagnosed). Post-treatment biopsy was performed in 25 patients (63%) and was either refused or not feasible in 15. Post-treatment biopsy yielded tumor in only 17/25 cases (14 AI, 3 T). Eleven of 14 AI patients with post-therapy tissue showed FDG PET early response, and there was 100% concordance of PET and post-therapy Ki-67 early response. For the T group, 6/12 showed an FDG PET early response, including 2/3 patients with post-therapy biopsy, all with Ki-67 >5%. Conclusions Substantial changes in FDG PET SUV occurred over 2 weeks of AI therapy and were associated with low post-therapy proliferation. SUV decline was seen in response to T, but few tissue samples were available to test association with Ki-67. Our results support further investigation of FDG PET as a biomarker for early response to AI therapy.

AB - Background In breast cancer endocrine therapy, post-therapy Ki-67 assay of biopsy material predicts recurrence-free survival but is invasive and prone to sampling error. [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) has shown an early agonist or 'flare' response to tamoxifen and estradiol, but has not been tested in response to estrogen-lowering aromatase inhibitors (AIs). We hypothesized that decreased agonistic response to AIs would result in early FDG uptake decline. We also measured early response to trastuzumab (T), another targeted agent for breast cancer with differing mechanisms of action. Our study was designed to test for an early decline in FDG uptake in response to AI or T and to examine association with Ki-67 measures of early response. Methods Patients with any stage of newly diagnosed or recurrent breast cancer were eligible and enrolled prior to initiation (or resumption) of AI or T therapy. FDG PET and tissue biopsy were planned before and after 2 weeks of AI or T therapy, with pretreatment archival tissue permitted. Cutoffs of ≥20% decline in standardized uptake value (SUV) as FDG PET early response and ≤5% post-treatment expression as Ki-67 early response were defined prior to analysis. Results Forty-two patients enrolled, and 40 (28 AI, 12 T) completed serial FDG-PET imaging. Twenty-two patients (17 AI, 5 T) had newly diagnosed disease, and 23 (14 AI, 9 T) had metastatic disease (5 newly diagnosed). Post-treatment biopsy was performed in 25 patients (63%) and was either refused or not feasible in 15. Post-treatment biopsy yielded tumor in only 17/25 cases (14 AI, 3 T). Eleven of 14 AI patients with post-therapy tissue showed FDG PET early response, and there was 100% concordance of PET and post-therapy Ki-67 early response. For the T group, 6/12 showed an FDG PET early response, including 2/3 patients with post-therapy biopsy, all with Ki-67 >5%. Conclusions Substantial changes in FDG PET SUV occurred over 2 weeks of AI therapy and were associated with low post-therapy proliferation. SUV decline was seen in response to T, but few tissue samples were available to test association with Ki-67. Our results support further investigation of FDG PET as a biomarker for early response to AI therapy.

KW - Aromatase inhibitor

KW - Breast cancer

KW - Early response

KW - FDG PET

KW - Ki-67

KW - Pharmacodynamic response

KW - Trastuzumab

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