Philip H Petra

Publications (2)26.11 Total impact

• Article: Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer.

  Hannah M Linden, Brenda F Kurland, Lanell M Peterson, Erin K Schubert, Julie R Gralow, Jennifer M Specht, Georgiana K Ellis, Thomas J Lawton, Robert B Livingston, Philip H Petra, Jeanne M Link, Kenneth A Krohn, David A Mankoff
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  ABSTRACT: To determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-estrogen receptor (ER) binding differ between types of standard endocrine therapy. The ER has been a highly successful target for breast cancer treatment. ER-directed treatments include lowering ligand concentration by using aromatase inhibitors (AI) and blocking the receptor with agents like tamoxifen (TAM) or fulvestrant (FUL). We measured regional estrogen-ER binding by using positron emission tomography with (18)F-fluoroestradiol (FES PET) prior to and during treatment with AI, TAM, or FUL in a series of 30 metastatic breast cancer patients. FES PET measured in vivo estrogen binding at all tumor sites in heavily pretreated women with metastatic bone soft tissue-dominant breast cancer. In patients with uterus (n = 16) changes in uterine FES uptake were also measured. As expected, tumor FES uptake declined more markedly on ER blockers (TAM and FUL, average 54% decline) compared with a less than 15% average decline on estrogen-depleting AIs (P < 0.001). The rate of complete tumor blockade [FES standardized uptake value (SUV) ≤1.5] following TAM (5/5 patients) was greater than the blockade rate following FUL (4/11; 2-sided mid P = 0.019). Percent FES SUV change in the uterus showed a strong association with tumoral change (ρ = 0.63, P = 0.01). FES PET can assess the in vivo pharmacodynamics of ER-targeted agents and may give insight into the activity of established therapeutic agents. Imaging revealed significant differences between agents, including differences in the efficacy of blockade by different ER antagonists in current clinical use.
  Clinical Cancer Research 07/2011; 17(14):4799-805. · 7.74 Impact Factor
• Article: Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer.

  Hannah M Linden, Svetlana A Stekhova, Jeanne M Link, Julie R Gralow, Robert B Livingston, Georgiana K Ellis, Philip H Petra, Lanell M Peterson, Erin K Schubert, Lisa K Dunnwald, Kenneth A Krohn, David A Mankoff
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  ABSTRACT: In breast cancer, [(18)F]fluoroestradiol (FES) positron emission tomography (PET) correlates with estrogen receptors (ER) expression and predicts response to tamoxifen. We tested the ability of FES-PET imaging to predict response to salvage hormonal treatment in heavily pretreated metastatic breast cancer patients, predominantly treated with aromatase inhibitors. Initial FES uptake measurements in 47 patients with ER-positive tumors were correlated with subsequent tumor response to 6 months of hormonal treatment. Most patients had bone dominant disease and prior tamoxifen exposure. Response was compared to initial FES-PET uptake, measured qualitatively and quantitatively using standardized uptake value (SUV) and estradiol-binding flux. Eleven of 47 patients (23%) had an objective response. While no patients with absent FES uptake had a response to treatment, the association between qualitative FES-PET results and response was not significant (P = .14). However, quantitative FES uptake and response were significantly associated; zero of 15 patients with initial SUV less than 1.5 responded to hormonal therapy, compared with 11 of 32 patients (34%) with SUV higher than 1.5 (P < .01). In the subset of patients whose tumors did not overexpress HER2/neu, 11 of 24 patients (46%) with SUV higher than 1.5 responded. Quantitative FES-PET can predict response to hormonal therapy and may help guide treatment selection. Treatment selection using quantitative FES-PET in our patient series would have increased the rate of response from 23% to 34% overall, and from 29% to 46% in the subset of patients lacking HER2/neu overexpression. A multi-institutional collaborative trial would permit definitive assessment of the value of FES-PET for therapeutic decision making.
  Journal of Clinical Oncology 07/2006; 24(18):2793-9. · 18.37 Impact Factor