18F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer.

OBJECTIVES: This study assesses 18F-FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer. METHODS: In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent 18F-FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery.18F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI). RESULTS: A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, 18F-FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, 18F-FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9-20%). CONCLUSIONS: 18F-FDG-PET/CT revealed distant metastases in 14% (95% CI: 9-20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9-24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with 18F-FDG-PET/CT at the time of initial diagnosis.

(18)F-FDG-PET/CT for systemic staging of newly diagnosed triple-negative breast cancer.

PURPOSE: National Comprehensive Cancer Network guidelines recommend (18)F-FDG-PET/CT, in addition to standard staging procedures, for systemic staging of newly diagnosed stage III breast cancer patients. However, factors in addition to stage may influence PET/CT utility. As breast cancers that are negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (triple-negative breast cancer, or TNBC) are more aggressive and metastasize earlier than other breast cancers, we hypothesized that receptor expression may be one such factor. This study assesses (18)F-FDG-PET/CT for systemic staging of newly diagnosed TNBC. METHODS: In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with TNBC who underwent (18)F-FDG-PET/CT in 2007-2013 prior to systemic or radiation therapy. Initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery, if performed prior to (18)F-FDG-PET/CT. (18)F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases, as well as unsuspected synchronous malignancies. Kaplan Meier survival estimates were calculated for initial stage IIB patients stratified by whether or not stage 4 disease was detected by (18)F-FDG-PET/CT. RESULTS: A total of 232 patients with TNBC met inclusion criteria. (18)F-FDG-PET/CT revealed unsuspected distant metastases in 30 (13 %): 0/23 initial stage I, 4/82 (5 %) stage IIA, 13/87 (15 %) stage IIB, 4/23 (17 %) stage IIIA, 8/14 (57 %) stage IIIB, and 1/3 (33 %) stage IIIC. Twenty-six of 30 patients upstaged to IV by (18)F-FDG-PET/CT were confirmed by pathology, with the remaining four patients confirmed by follow-up imaging. In addition, seven unsuspected synchronous malignancies were identified in six patients. Initial stage 2B patients who were upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival compared to initial stage 2B patients who were not (3-year Kaplan Meier estimate 0.33, 95 % CI 0.13-0.55 versus 0.97, CI 0.76-0.93, p < .0001). CONCLUSION: F-FDG-PET/CT revealed distant metastases in 15 % of patients with stage IIB TNBC. Stage IIB patients upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival than those who were not, consistent with (18)F-FDG-PET/CT detecting an increased burden of disease. This study provides further evidence that populations of patients with stage IIB breast cancer, such as TNBC, should be considered for systemic staging with (18)F-FDG-PET/CT at the time of initial diagnosis.

Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers.

UNLABELLED: (18)F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ((18)F-fluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins have been shown to be upregulated in breast malignancies by microarray and immunohistochemical analysis, so we hypothesized that (18)F-fluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of (18)F-fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). METHODS: Twenty-seven women with a new diagnosis of locally advanced IDC (n = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of (18)F-fluciclovine. The SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of (18)F-fluciclovine PET/CT were compared with those of (18)F-FDG PET/CT, when available, using the concordance correlation coefficient. RESULTS: All locally advanced breast cancers were (18)F-fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, (18)F-fluciclovine-avid axillary nodes were seen in 20. (18)F-fluciclovine detected pathologically proven extraaxillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients underwent (18)F-FDG PET/CT for comparison with (18)F-fluciclovine. Concordance for metabolic tumor volume between (18)F-fluciclovine and (18)F-FDG was strong (concordance correlation coefficient, 0.89; 95% confidence interval, 0.73-0.96), but concordance for SUVmax was weak (concordance correlation coefficient, 0.04; 95% confidence interval, -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated (18)F-fluciclovine avidity (median SUVmax, 6.1; range, 4.5-10.9) greater than (18)F-FDG avidity (median SUVmax, 3.7; range, 1.8-6.0). Primary IDCs (n = 10) had a lower (18)F-fluciclovine avidity (median SUVmax, 6.8; range, 3.6-9.9) than (18)F-FDG avidity (median SUVmax, 10; range, 3.3-43.5). CONCLUSION: (18)F-fluciclovine PET/CT demonstrates potential for imaging of both IDC and ILC, including the detection of unsuspected extraaxillary nodal metastases. The low concordance for SUVmax between (18)F-fluciclovine and (18)F-FDG suggests that these tracers measure different biologic phenomena within the tumor. The apparently higher uptake of (18)F-fluciclovine in ILC requires confirmation in a larger cohort.