TBCRC 008: Early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer

Roisin M. Connolly, Jeffrey P. Leal, Matthew P. Goetz, Zhe Zhang, Xian C. Zhou, Lisa K. Jacobs, Joyce Mhlanga, H. O. Joo, John Carpenter, Anna Maria Storniolo, Stanley Watkins, John H. Fetting, Robert S. Miller, Kostandinos Sideras, Stacie C. Jeter, Bridget Walsh, Penny Powers, Jane Zorzi, Judy C. Boughey, Nancy E. DavidsonLisa A. Carey, Antonio C. Wolff, Nagi Khouri, Edward Gabrielson, Richard L. Wahl, Vered Stearns

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes.

Methods: Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR.

Results: In an intent-to-treat analysis (n 5 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n 5 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P 5 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3-22.7; P 5 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not.

Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18FFDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatmentselection biomarker.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Fluorodeoxyglucose F18
Breast Neoplasms
Placebos
Carboplatin
Therapeutics
Histone Deacetylase Inhibitors
Epigenomics
Estrogen Receptors
Nanoparticles
Area Under Curve
Neoplasms
Breast
Biomarkers
Lymph Nodes
Odds Ratio
vorinostat
human ERBB2 protein
Confidence Intervals
Biopsy
Drug Therapy

Keywords

  • F-FDG PET
  • Biomarker
  • Breast cancer
  • Neoadjuvant
  • Vorinostat

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

TBCRC 008 : Early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer. / Connolly, Roisin M.; Leal, Jeffrey P.; Goetz, Matthew P.; Zhang, Zhe; Zhou, Xian C.; Jacobs, Lisa K.; Mhlanga, Joyce; Joo, H. O.; Carpenter, John; Storniolo, Anna Maria; Watkins, Stanley; Fetting, John H.; Miller, Robert S.; Sideras, Kostandinos; Jeter, Stacie C.; Walsh, Bridget; Powers, Penny; Zorzi, Jane; Boughey, Judy C.; Davidson, Nancy E.; Carey, Lisa A.; Wolff, Antonio C.; Khouri, Nagi; Gabrielson, Edward; Wahl, Richard L.; Stearns, Vered.

In: Journal of Nuclear Medicine, Vol. 56, No. 1, 01.01.2015, p. 31-37.

Research output: Contribution to journalArticle

Connolly, RM, Leal, JP, Goetz, MP, Zhang, Z, Zhou, XC, Jacobs, LK, Mhlanga, J, Joo, HO, Carpenter, J, Storniolo, AM, Watkins, S, Fetting, JH, Miller, RS, Sideras, K, Jeter, SC, Walsh, B, Powers, P, Zorzi, J, Boughey, JC, Davidson, NE, Carey, LA, Wolff, AC, Khouri, N, Gabrielson, E, Wahl, RL & Stearns, V 2015, 'TBCRC 008: Early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer', Journal of Nuclear Medicine, vol. 56, no. 1, pp. 31-37. https://doi.org/10.2967/jnumed.114.144741
Connolly, Roisin M. ; Leal, Jeffrey P. ; Goetz, Matthew P. ; Zhang, Zhe ; Zhou, Xian C. ; Jacobs, Lisa K. ; Mhlanga, Joyce ; Joo, H. O. ; Carpenter, John ; Storniolo, Anna Maria ; Watkins, Stanley ; Fetting, John H. ; Miller, Robert S. ; Sideras, Kostandinos ; Jeter, Stacie C. ; Walsh, Bridget ; Powers, Penny ; Zorzi, Jane ; Boughey, Judy C. ; Davidson, Nancy E. ; Carey, Lisa A. ; Wolff, Antonio C. ; Khouri, Nagi ; Gabrielson, Edward ; Wahl, Richard L. ; Stearns, Vered. / TBCRC 008 : Early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer. In: Journal of Nuclear Medicine. 2015 ; Vol. 56, No. 1. pp. 31-37.
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abstract = "Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes.Methods: Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR.Results: In an intent-to-treat analysis (n 5 62), overall pCR was 27.4{\%} (vorinostat, 25.8{\%}; placebo, 29.0{\%}). In a pooled analysis (n 5 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0{\%} vs. 32.9{\%}; P 5 0.003). Patients with 50{\%} or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95{\%} confidence interval, 1.3-22.7; P 5 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not.Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18FFDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatmentselection biomarker.",
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author = "Connolly, {Roisin M.} and Leal, {Jeffrey P.} and Goetz, {Matthew P.} and Zhe Zhang and Zhou, {Xian C.} and Jacobs, {Lisa K.} and Joyce Mhlanga and Joo, {H. O.} and John Carpenter and Storniolo, {Anna Maria} and Stanley Watkins and Fetting, {John H.} and Miller, {Robert S.} and Kostandinos Sideras and Jeter, {Stacie C.} and Bridget Walsh and Penny Powers and Jane Zorzi and Boughey, {Judy C.} and Davidson, {Nancy E.} and Carey, {Lisa A.} and Wolff, {Antonio C.} and Nagi Khouri and Edward Gabrielson and Wahl, {Richard L.} and Vered Stearns",
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TY - JOUR

T1 - TBCRC 008

T2 - Early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer

AU - Connolly, Roisin M.

AU - Leal, Jeffrey P.

AU - Goetz, Matthew P.

AU - Zhang, Zhe

AU - Zhou, Xian C.

AU - Jacobs, Lisa K.

AU - Mhlanga, Joyce

AU - Joo, H. O.

AU - Carpenter, John

AU - Storniolo, Anna Maria

AU - Watkins, Stanley

AU - Fetting, John H.

AU - Miller, Robert S.

AU - Sideras, Kostandinos

AU - Jeter, Stacie C.

AU - Walsh, Bridget

AU - Powers, Penny

AU - Zorzi, Jane

AU - Boughey, Judy C.

AU - Davidson, Nancy E.

AU - Carey, Lisa A.

AU - Wolff, Antonio C.

AU - Khouri, Nagi

AU - Gabrielson, Edward

AU - Wahl, Richard L.

AU - Stearns, Vered

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes.Methods: Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR.Results: In an intent-to-treat analysis (n 5 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n 5 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P 5 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3-22.7; P 5 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not.Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18FFDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatmentselection biomarker.

AB - Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes.Methods: Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1-3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR.Results: In an intent-to-treat analysis (n 5 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n 5 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P 5 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3-22.7; P 5 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not.Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18FFDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatmentselection biomarker.

KW - F-FDG PET

KW - Biomarker

KW - Breast cancer

KW - Neoadjuvant

KW - Vorinostat

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