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.
Keywords: 18F-FDG PET/CT; Breast cancer; Estrogen receptor; Human epidermal growth factor receptor 2; Progesterone receptor; Triple negative.