TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

J Clin Oncol. 2019 Mar 20;37(9):714-722. doi: 10.1200/JCO.2018.78.7986. Epub 2019 Feb 5.


Purpose: Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT).

Patients and methods: Patients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%.

Results: Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed.

Conclusion: Early changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

Trial registration: ClinicalTrials.gov NCT01937117.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Radiopharmaceuticals / administration & dosage
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / deficiency
  • Single Photon Emission Computed Tomography Computed Tomography
  • Time Factors
  • Trastuzumab / administration & dosage*
  • Trastuzumab / adverse effects
  • Trastuzumab / metabolism
  • Treatment Outcome
  • United States


  • Antibodies, Monoclonal, Humanized
  • Radiopharmaceuticals
  • Receptors, Estrogen
  • Fluorodeoxyglucose F18
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • pertuzumab
  • Trastuzumab

Associated data

  • ClinicalTrials.gov/NCT01937117