Is there a qualitative interaction between adjuvant trastuzumab and size of the primary tumor in breast cancer?
Abstract:
Benefit of adjuvant trastuzumab in breast cancer has been reported in four randomized trials of phase III, and these results are consistent in showing improvement in disease-free survival (DFS). Current evidence for homogeneity of this DFS benefit in subgroups of patients with the different size of the primary HER2-positive tumor treated according to the HERA trial is reviewed. It is evident that current published evidence is insufficient to rule out that there is a cohort of patients with HER2-positive disease who do not achieve a reduction in the risk of recurrence by adjuvant treatment with trastuzumab after completion of previous adjuvant chemo- and radiotherapy. An alternative interpretation of results of the HERA trial currently available in two primary reports (1-year, and 2-year median follow- up, respectively) is discussed. The risk factors of central nervous system (CNS) metastases in breast cancer and problem of CNS metastases in HER2-positive tumors are briefly reviewed. A hypothesis on the relations between brain metastases, their risk factors, the size of the primary tumor, and their impact on the DFS in patients with HER2-positive tumors treated with adjuvant trastuzumab is proposed based on the results of the HERA trial. Altogether, some direct evidence is presented here based on the published results of the HERA trial, and still more indirect evidence based on the information on related topics in literature, to show that current clinical practice of adjuvant trastuzumab in mono-therapy, which is based on assumption that there is a homogeneous benefit as for disease-free survival for all sizes of primary HER2-positive tumors above 1 cm, may not be based on such firm evidence as is commonly presented.