Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research

Conditions

Breast Cancer, Heart Failure

Keywords

trastuzumab, cardiac MRI, beta-blocker, biomarkers, angiotensin converting enzyme inhibitor, cardiotoxicity, HER2 positive

Brief summary

While trastuzumab has been shown to prevent recurrences of breast cancer, some women may also experience damage to their heart muscle (including heart failure) as a result of their treatment. The investigators hope to learn if standard medications used in heart failure can prevent heart damage caused by trastuzumab in women with breast cancer. The investigators would also like to know if there are any ways to detect this damage earlier using magnetic resonance imaging (MRI) and blood tests.

Detailed description

We propose a randomized, placebo-controlled, double-blind study evaluating the efficacy of an ACE-inhibitor (perindopril) or a beta blocker (bisoprolol) for the prevention of LV remodeling among women with early breast cancer scheduled for chemotherapy and one year of trastuzumab. Participants will undergo cardiac MRI at baseline and 3 and 12 months, replacing the usual MUGA, as well as a post-treatment cardiac MRI at 24 months to evaluate long-term effect.

Related papers

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Abstract PD5-03: Prophylactic beta blockade preserves left ventricular ejection fraction in HER2-overexpresssing breast cancer patients receiving trastuzumab: Primary results of the MANTICORE randomized controlled trial

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Abstract S1-05: Prophylactic beta blockade preserves left ventricular ejection fraction in HER2-overexpresssing breast cancer patients receiving trastuzumab: Primary results of the MANTICORE randomized controlled trial

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Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101--Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI.

Pituskin E, Haykowsky M, Mackey JR, Thompson RB, Ezekowitz J, Koshman S, Oudit G, Chow K, Pagano JJ, Paterson I.

2011-07-2762 citations

10.1186/1471-2407-11-318

Interventions

DRUGperindopril OR bisoprolol OR placebo

perindopril- oral daily titrated does from 2mg up to 8mg bisoprolol- oral daily titrated dose from 2.5mg up to 10mg

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

DIAGNOSTIC

Masking

DOUBLE (Caregiver, Investigator)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Histologic diagnosis of HER2 positive breast carcinoma * Eligible to receive trastuzumab * Age \> 18 years * Able to give informed consent * No contraindications to MRI

Exclusion criteria

* Known contraindication to beta-blocker therapy * Known contraindication to ACEI therapy * Current treatment with ACEI or beta blocker for other indication * History of heart failure, cardiomyopathy or baseline LVEF \< 50%

Design outcomes

Primary

Measure	Time frame
The primary objective is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular (LV) remodeling among women with HER2+ early breast cancer.	3.5 years

Countries

Canada

Outcome results

None listed