Abstract PD05-04: The Potential of Using Discordance of Estrogen PET (FES-PET) and Glucose PET (FDG-PET) Scans and Pathologic Characteristics Including HER2 and Ki67 To Predict for Hormone Insensitivity in Women with Metastatic Breast Cancer
Authors: Tonkin KS , Joy AA , Basi SK , Fenton D , Amanie J , Mackey JR , Tankel K , Deschenes J , Mcewan S. 
Published: April 2011

Abstract
Background: We investigated utility of pre-treatment estrogen PET scans using 16α[18F]-fluoroestradiol PET (FES-PET) to predict hormone sensitivity in ER positive metastatic breast cancer. We evaluated FES discordance to routine [18F]-fluorodeoxy-D-glucose (FDG) PET and to pathologic characteristics of the primary including grade, ER/PgR levels, HER2 and Ki67 to assess prediction to hormone therapy response. Materials and Methods: Scans were performed prior to 1st, 2nd or 3rd line hormone therapy. Image review was double blinded to treatment and outcome using standard uptake values (SUV) and a tumor present scale from 1=def neg to 5=def pos. Clinicians were aware of FDG results but not FES. Standard radiological investigations were done per clinician choice. We established the percentage of metastatic sites that retained hormone sensitivity (FES positive) and compared this to the total number of FDG positive sites for each patient. Primary tumors were tested by immunochemistry for ER (SP1) PgR (PgR 636), HER2 (CerB-II) and Ki67 (MIB-1). Where HER2 was 2+ or 3+ CISH (CAP/ASCO guidelines) was also used. All tumors underwent pathology assessment (CAP-approved protocol). Results: N=38 mean age 53. Adjuvant chemo and hormones were given in 63.2%. At initial diagnosis 42.1% were stage 2, 21% were stage 4. 58% had visceral disease. 39.5%, 44.7% and 15.8% were starting 1st,2nd and 3rd line hormones. 53% (N=20) had discordance where FES showed fewer lesions in visceral/soft tissue/nodes/bone than FDG. Response to hormones was unsuccessful in the site of discordance in 50% (N=10). Of these N= 5 in liver +/− lung/nodes/bone N=1 in lung and N=4 in bone. Another 25% (N=5) had early progression but not in the discordant site. For 25% disease remained stable, mainly bone only disease where discordance was in non-bone sites and only bone scans were done for follow up. Overall all 7 HER2 positive cases (and 6 of 7 did not respond to hormones) and 6 of 7 grade 3 cases were in the discordant group (p=0.01 for HER2 and p=0.05 for grade 3 in the discordant group compared to the rest of the patients). There was no relationship between the level of ER positivity and FES scan discordance or response. Ki67 N=22 so far correlates only with HER2 (p=0.027). Of the 18 patients with no discordance of FES and FDG 14 had either SD or better responses. In 21% (N=8) FDG also revealed unsuspected visceral disease that required change to chemotherapy in N=4. Discussion: FES can help predict response to hormonal therapy for metastatic ER positive breast cancer. Not all lesions can be biopsied so optimum determination of hormonal response has not been established. Since HER2 + patients form a large group of non-responders these presumed luminal B patients may not be suitable for hormonal therapy even though they have ER+ primary disease. In 75% of women where there is discordance of FDG and FES the FES scan can predict early progression of disease on hormones.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-04.