Relationship Between Hypoxia and Endocrine Response in Human Breast Cancer

Breast Cancer Clinical Trial

Official title:

Department of Breast Surgery And Department of Nuclear Medicine, Fudan University Shanghai Cancer Center,

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01814449
• Other study ID #: 20120224.1.1
• Status: Recruiting
• Phase: N/A
• First received: March 16, 2013
• Last updated: March 19, 2013
• Start date: March 2012
• Est. completion date: May 2014

Study information

• Verified date: March 2013
• Source: Fudan University
• Contact: Guangyu Liu, M.D.
• Phone: 86-21-64175590
• Email: liugy123[@]yahoo.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Observational [Patient Registry]

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: May 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years to 90 Years

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Hypoxia

Intervention

Other:
• 18FMISO PET/CT scan
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.

Drug:
• Letrozole
Patients were assigned to primary endocrine therapy with letrozole 2.5mg daily for at least 4 months.

Locations

Country	Name	City	State
China	Cancer Hospital/ Institute, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Disease free survival	An early recurrence of the disease during adjuvant endocrine therapy was also regarded as a resistance to endocrine therapy	5 years	No
Primary	Clinical 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.	4 months	No
Secondary	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).	4 months	No
Secondary	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	3 months	No