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Published on: June 13, 2014
Management of small HER2 overexpressing tumours
Arnoud Templeton1, Alberto Ocaña, Boštjan Seruga
1Division of Medical Oncology and Hematology, Princess Margaret Hospital, Department of Medicine, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada.
Abstract:
Overexpression of the human epidermal growth factor receptor 2 (HER2) is found in 10-20 % of breast cancers and is associated with a worse prognosis. Several large studies have established the addition of trastuzumab to chemotherapy as the gold standard in early breast cancer that overexpresses HER2. Little is known about the role of such adjuvant treatment in node-negative subcentimeter tumours ('small tumours', pT1a/b) because these patients were generally excluded from the pivotal trials. Only the BCIRG006 study published in 2011 included such tumours if high-risk features were present. Here we review the literature of small HER2-positive tumours and present a meta-analysis of retrospective studies confirming a worse outcome in terms of disease-free survival (hazard ratio 2.6, p < 0.001) and a trend for higher odds of distant recurrence at 5 years (odds ratio [OR] 2.51, p = 0.11). We discuss these findings in the light of the increased risk of grade 3 and 4 cardiac toxicity (OR 7.6, p < 0.001) and other adverse events associated with the use of trastuzumab. Such treatment may well be a valuable option in selected patients with high-risk features but physicians should exercise caution given the small absolute benefits of adjuvant chemotherapy and trastuzumab for patients with small HER2-overexpressing tumours.
Insights
Adjuvant trastuzumab (human epidermal growth factor receptor 2) treatment improves outcomes for HER2-positive breast cancer. However, its benefit in small, node-negative tumors is uncertain, with significant cardiac risks noted.
Area of Science:
- Oncology
- Medical research
Background:
- HER2-overexpressing breast cancer (10-20% of cases) has a poorer prognosis.
- Trastuzumab plus chemotherapy is standard for early HER2-positive breast cancer.
- Small, node-negative HER2-positive tumors (pT1a/b) were often excluded from major trials.
Purpose of the Study:
- To review literature on adjuvant treatment for small HER2-positive breast tumors.
- To perform a meta-analysis on outcomes in this patient group.
- To evaluate the risks and benefits of trastuzumab in this population.
Main Methods:
- Literature review of studies including small HER2-positive tumors.
- Meta-analysis of retrospective studies.
- Assessment of disease-free survival and distant recurrence rates.
- Analysis of cardiac toxicity and adverse events.
Main Results:
- Small HER2-positive tumors show worse disease-free survival (HR 2.6, p < 0.001).
- A trend towards higher 5-year distant recurrence odds (OR 2.51, p = 0.11) was observed.
- Trastuzumab use was associated with increased grade 3/4 cardiac toxicity (OR 7.6, p < 0.001).
Conclusions:
- Adjuvant trastuzumab may benefit selected small HER2-positive tumor patients with high-risk features.
- Physicians should cautiously consider trastuzumab due to small absolute benefits and significant cardiac risks.
- Further research is needed to define optimal treatment strategies for this subgroup.
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