Which HER2 positive early breast cancer patients are candidates for adjuvant trastuzumab?

The SCAN workgroup voted 9 to 3 in support of the adoption of the ESMO guidelines (Supplementary Table 1) for the inclusion of patients for adjuvant trastuzumab. Under these guidelines, adjuvant trastuzumab can be considered for node negative HER2 positive breast cancers under 1 cm, especially if the patient is unresponsive to hormonal therapy as defined by lack of expression of oestrogen and progesterone receptors. For HER2 positive tumours larger than 1 cm or with lymph node involvement, adjuvant trastuzumab is recommended. While distant recurrence risk is significant for patients with small node negative HER2 positive early breast cancers, there is little or conflicting data1,2to suggest a clear demarcation of risk between tumours which are T1a (1 to 5 mm) versus T1b (>5 and up to 10 mm). As such, the workgroup members who are in favour of the ESMO guidelines indicate that ESMO guidelines offer higher flexibility in daily practice compared to the NCCN guidelines in this regard. Support for the ESMO guidelines was not unanimous. One workgroup member expressed that although several retrospective studies have suggested a higher risk of relapse when HER2 is overexpressed, there is no Level I evidence supporting the administration of trastuzumab-based postoperative chemotherapy in small under 1 cm HER2 positive tumours, and preferred the more conservative NICE guidelines15,16with regards to recommending trastuzumab and chemotherapy to this, group of patients. A separate workgroup member supported the NCCN guidelines as it is more specific in its recommendation for T1a versus T1b node negative tumours. The workgroup notes that under the latest NCCN Clinical Practice Guidelines in Oncology Breast Cancer version 2.2015, adjuvant chemotherapy and trastuzumab can be considered for patients with T1a tumours, and as such, there is now less distinction between the ESMO and NCCN recommendations with regard to T1a and T1b HER2 positive breast cancers. The SCAN breast cancer workgroup acknowledges that there is no local efficacy data on adjuvant trastuzumab in early breast cancer. In reviewing the risk benefits, the workgroup considered the pooled analysis of adjuvant trastuzumab which shows a relative reduction in the risk of distant disease recurrence by 40% and a relative reduction in the risk of death by 30%.3-9The main toxicity of concern associated with adjuvant trastuzumab is New York Heart Association (NYHA) class III or IV congestive cardiac failure, the incidence of which varies according to the choice of chemotherapy backbone used. With a non-anthracycline containing adjuvant regimen, this risk is approximately 0.5%5,17but increases to 3% to 4% with a regimen comprising an anthracycline followed by concurrent trastuzumab and taxane.11,12Local data for trastuzumab-induced cardiotoxicity has been presented in which the overall rate of symptomatic decline in left ventricular ejection fraction is 9%. However, the rate of NYHA class III or IV congestive cardiac failure attributable to trastuzumab, independent of cardiac events caused by anthracyclines prior to the use of trastuzumab is not described and the paper has only been presented in abstract form.19