The aim of our current study was to analyze whether 18F-labeled Fluoromisonidazole (1-(2-nitro-1-imidazolyl)- 2-hydroxy-3-fluoropropane \[18F-FMISO\]) PET/CT and expression of HIF-1-alpha could predict response of primary endocrine therapy in ER-positive breast cancer
Approximately 30% of ER-positive breast cancer will unfortunately display primary resistance to hormonal therapy, and some may develop acquired resistance to the therapy after initial treatment. Hypoxia is a normal phenomenon in solid tumors that arises, in part, from uncontrolled proliferation and immature blood vessels. Previous studies have demonstrated hypoxia significantly reduced both the growth-promoting effects of estradiol (E2) and the growth-inhibitory effects of an antiestrogen on ER-positive breast cancer cell lines. A recent study comparing neoadjuvant letrozole with letrozole plus metronomic cyclophosphamide found that increased levels of HIF-1a were significantly associated with resistance to treatment. Taken together, these data indicate that hypoxia might be associated with endocrine resistance in breast cancer. With PET/CT, radiolabeled hypoxia-avid compounds can be applied to evaluate oxygenation status in experimental or human tumors. 18F-labeled fluoromisonidazole (1-\[2-nitro- 1-imidazolyl\]-2-hydroxy-3-fluoropropane \[18F-FMISO\]) PET/CT is the most widely used one in the clinic. Studies have demonstrated an excellent correlation between the 18F-FMISO uptake and oxygenation status of several cancers including breast cancer. The major aim of our study was to analyze uptake of 18FFMISO as well as the IHC expression of HIF-1-alpha in ER-positive breast cancers, and to predict the clinical, pathological and biological response of primary endocrine therapy.
Study Type
OBSERVATIONAL
Enrollment
130
The baseline 18F-FMISO PET/CT scans were scheduled before initiation of endocrine therapy. All patients were injected intravenously with 370 MBq of 18F-FMISO and PET/CT static emission scans were conducted at 4 hours after injection.
Patients were assigned to primary endocrine therapy with letrozole 2.5mg daily for at least 4 months.
Cancer Hospital/ Institute, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGClinical Objective Response
Tumor response was evaluated according to the criteria of the World Health Organization. Clinical tumor progression (PD) was defined as an increase of at least 25% in tumor size; stable disease (SD) as an increase of less than 25% or a reduction of less than 50%; partial response (cPR) as a tumor shrinkage greater than 50%; and complete response (cCR) as the complete disappearance of all clinical signs of disease.
Time frame: 4 months
Pathological Response
Including pathological complete response (pCR or Grade 5),pathological partial response (pPR or Grade 3-4) and pathological non-response (NR or Grade 1-2).
Time frame: 4 months
Depression of Ki67 score
A biological response of Ki67 depression was tested on a second core needly biopsy on the primary site of the breast cancer after 3 months of primary endocrine therapy. Ki67\>=15% was regarded as a biological resistance to primary endocrine therapy
Time frame: 3 months
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