Clinical trial NCT01814449: Relationship Between Hypoxia and Endocrine Response in Human Breast Cancer
Official title: Department of Breast Surgery And Department of Nuclear Medicine, Fudan University Shanghai Cancer Center,
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
Hypoxia
Keywords: Breast cancer
Hypoxia
Hypoxia related gene
Endocrine therapy
Treatment resistance
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2013-03-20
Enrollment: 130
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Postmenopausal women who had ER-a-positive breast cancer at stages II-IV and had never received prior endocrine therapy were considered eligible for this study.

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Postmenopausal female
2. With primary invasive ER positive breast cancer pathologically approved by core needle biopsy
3. The target lesion must be measurable and maximum diameter should be over 2cm.
4. Require and accept Endocrine therapy
5. Never treated with endocrine therapy before
6. Patients must have an ECOG performance status of 0 to 2
7. Leucocyte count must be ≥ 3.0\*10\^9/L and platelet count must be ≥ 40\*10\^9/L; AST/SGOT or ALT/AGPT must be \< 2 times the ULN; serum creatinine must be \< 2 times the ULN

Exclusion Criteria:

1. Patients with brain and liver metastasis
2. Previous history of severe heart dysfunction (above Class III), infection, osteoporosis, bone related event or disease in endocrine system
3. Combination of other anticancer therapy, with the exception of biphosphonate

Primary outcomes:
measure: Clinical Objective Response
timeFrame: 4 months
Secondary outcomes:
measure: Pathological Response
timeFrame: 4 months
measure: Depression of Ki67 score
timeFrame: 3 months
Other outcomes:
measure: Disease free survival
timeFrame: 5 years
Locations:
city: Shanghai
country: China
facility: Cancer Hospital/ Institute, Fudan University
state: Shanghai
Study officials:
affiliation: Cancer Hospital/Institute,Fudan University
name: Guangyu Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: