"Trastuzumab for HER2-Positive Early Breast Cancer". The New England Journal of Medicine. 2005. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients with HER2-positive early-stage breast cancer who have completed locoregional therapy and chemotherapy, does trastuzumab therapy improve disease-free survival?

Bottom Line

A year of trastuzumab therapy after adjuvant chemotherapy significantly improves disease-free survival amongst women with HER2-positive early-stage breast cancer.

Major Points

Guidelines

Trastuzumab is now a standard part of treatment for HER2-positive early breast cancer following primary treatment based on these trial results.

Design

- International, multicenter, randomized, open-label trial
- N=5,081 patients with HER2-positive early-stage invasive breast cancer
- Trastuzumab for 1 year (n=1,694) vs. Observation (n=1,693)
- Enrollment: December 2001 to March 2005
- Mean follow-up: 1 year

Population

- Women with early-stage invasive breast cancer with overexpressed or amplified HER2 after locoregional therapy and at least four cycles of chemotherapy
- Median age: 49 years

Inclusion Criteria
- Histologically confirmed invasive breast cancer with overexpression or amplification of HER2
- Completed locoregional therapy
- At least four cycles of chemotherapy
- Adequate baseline organ function

Exclusion Criteria
- Distant metastases
- Previous invasive breast carcinoma
- Previous neoplasm not involving the breast
- Clinical stage T4 tumor or involvement of supraclavicular nodes
- LVEF < 55%

Interventions

- Trastuzumab: 8 mg/kg IV once, followed by 6 mg/kg IV every three weeks for one year
- Observation: No trastuzumab administration

Outcomes

Primary Outcome
- Disease-free survival, defined as time from randomization to the first occurrence of breast cancer recurrence, contralateral or ipsilateral cancer, second nonbreast cancer, or death from any cause

Secondary Outcomes
- Cardiac safety, overall survival, site of the first disease-free survival event, time to distant recurrence

Criticisms

- Short follow-up period
- Potential long-term risks of cardiotoxicity are unknown
- Unclear if trastuzumab effectively reduces incidence of disease recurrence in the central nervous system

Funding

- Supported by F. Hoffmann–La Roche (Roche), Basel, Switzerland

Further Reading

- [Related articles and publication details provided by The New England Journal of Medicine]