Relationship Between Hypoxia and Endocrine Response in Human Breast Cancer

Fudan University

Status: Unknown

Conditions: Breast Cancer; Hypoxia

Treatments: Drug: Letrozole; Other: 18FMISO PET/CT scan

Study type: Observational

Funder types: Other

Identifiers

NCT01814449

20120224.1.1

Details and patient eligibility

About

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

Full 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.

Enrollment: 130 estimated patients

Sex: Female

Ages: 60 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

130 participants in 2 patient groups

Hypoxic Group

Description:

Higher 18FMISO uptake (Target to background Ratio, TBR\>1.2) in Primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy Letrozole was given to the patients.

Treatment:

Other: 18FMISO PET/CT scan

Drug: Letrozole

Non-Hypoxic Group

Description:

Lower 18FMISO uptake (TBR\<1.2)in primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy letrozole was given to the patients.

Treatment:

Other: 18FMISO PET/CT scan

Drug: Letrozole