Clinical trial NCT00816244: Study of Statin as Neo-Adjuvant Therapy in Postmenopausal Breast Cancer
Official title: A Phase II Study of Neo-Adjuvant Statin Therapy in Postmenopausal Primary Breast Cancer: A Window-of-Opportunity Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Postmenopausal
Keywords: Breast cancer
Postmenopausal
Neo-adjuvant
Tumor proliferation
Statin
Atorvastatin
Ki67
Translational research
Cell cycle regulators
Gene expression
Genomic profiling
Apoptosis
Window-of-opportunity
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2009-01-01
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to monitor:

* Tumor biological alterations following two weeks of neo-adjuvant statin therapy.
* Effects of statins on tumor proliferation.
* Functional studies on the mevalonate pathway.

Detailed description: Blood samples and three core biopsies are taken after diagnosis. Treatment with atorvastatin at a daily dosis of 80 mg is initiated 14 days before planned surgery. Translational research will be performed from the core biopsy and blood samples taken before surgery and from the specimen from surgery.

Eligibility criteria: Inclusion Criteria:

* Women with primary breast cancer who are candidates for radical surgery.
* Breast tumours clinically ≥ 15 mm, Nx, M0.
* Breast tumours identified on mammography and verified on fine needle aspiration.
* Age \> 18 years.
* Performance status of ECOG ≤ 1.
* Laboratory requirements at the day of diagnosis (t1-):Prior to inclusion a normal renal (serum creatinine) and hepatic (transaminases) function (within normal limits) estimated in blood samples is required.
* Prior to patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
* Negative pregnancy test for pre menopausal women before inclusion in the trial

Exclusion Criteria:

* Ongoing cholesterol lowering therapy (statins, fibrates, ezetimibe).
* Prior breast cancer treatment.
* Current HRT.
* Known liver disease.
* History of hemorrhagic stroke.
* Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions will be discussed with the patient before registration in the trial.
* History of allergic reactions attributed to compounds of similar chemical or biological composition to atorvastatin.

Primary outcomes:
measure: Tumor biological alterations following two weeks of neo-adjuvant statin therapy in postmenopausal breast cancer patients; to evaluate the tumor proliferation using Ki67 as proliferation marker.
timeFrame: After two weeks of treatment with statin therapy.
Secondary outcomes:
measure: Assessments of apoptosis using immunohistochemistry.
timeFrame: After two weeks of treatment with statin therapy.
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: University Hospital, Department of Oncology
Study officials:
affiliation: University Hospital Lund
name: Carsten Rose, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Feldt M, Menard J, Rosendahl AH, Lettiero B, Bendahl PO, Belting M, Borgquist S. The effect of statin treatment on intratumoral cholesterol levels and LDL receptor expression: a window-of-opportunity breast cancer trial. Cancer Metab. 2020 Nov 23;8(1):25. doi: 10.1186/s40170-020-00231-8.
citation: Feldt M, Bjarnadottir O, Kimbung S, Jirstrom K, Bendahl PO, Veerla S, Grabau D, Hedenfalk I, Borgquist S. Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial. J Transl Med. 2015 Apr 29;13:133. doi: 10.1186/s12967-015-0486-0.