Is there a case for anti-HER2 therapy without chemotherapy in early breast cancer?

Abstract

Trastuzumab in combination with chemotherapy is now standard of care for patients with early HER2-positive cancers larger than 1 cm. Some patients however may not need or simply may not want chemotherapy with its associated toxicities. For example patients with small (<1 cm.Tla.b) node-negative (NO) HER2-positive cancers were largely excluded from all the large randomized adjuvant trastuzumab trials on the basis of perceived excellent prognosis, yet recently several retrospective studies have suggested that this is not always the case and more active adjuvant treatment including anti-HER2 therapy may be warranted. Subset analysis of one trastuzumab trial (HERA) demonstrated that patients with 1-2 cm cancers derived at least as much clinical benefit from 1-year of adjuvant trastuzumab with chemotherapy as the overall cohort and 2 retrospective audits have confirmed this. Anti-HER2 therapy including both trastuzumab and lapatinib alone has established clinical efficacy in metastatic disease, with response rates of up to 35% and with some long term remissions. Combination anti-HER2 therapy with trastuzumab/lapatinib and with trastuzumab/pertuzumab have also been shown to have efficacy as second line treatment inpatients after trastuzumab. Trastuzumab and Lapatinib have each been shown to improve time to progression and response rate when given with anastrazole and letrozole respectively as first line treatment for metastatic ER-positive HER2-positive disease. In neoadjuvant trials the combination of trastuzumab and pertuzumab without chemotherapy have achieved pathological complete remission rates in a significant minority of patients, suggesting that a subgroup exists for whom anti-HER2 therapy alone may be as effective as with additional chemotherapy. Trials and prospective studies are now warranted to investigate this issue further in selected patients and these must be accompanied by tissue collection to try to identify predictive biomarkers. Meanwhile there is already enough circumstantial evidence to justify anti-HER2 therapy alone in selected patients for whom chemotherapy is contraindicated.