Combining trastuzumab (Herceptin) with hormonal therapy in breast cancer: what can be expected and why?

Hormonal therapy and the humanised anti-HER2 monoclonal antibody trastuzumab (Herceptin) represent one of the oldest and one of the newest treatment modalities for breast cancer, respectively. Recent data have suggested that HER2 overexpression is associated with resistance to hormonal therapy and there is considerable preclinical evidence to support the existence of interaction or 'cross talk' between HER2 and estrogen-receptor (ER) signalling pathways in breast cancer. Preclinical data also demonstrate that adding trastuzumab to hormonal therapy results in greater antitumour activity than either agent alone. The existence of an inverse relationship between ER expression and HER2 overexpression has also been well established clinically. Thus, a range of clinical trials are now ongoing to determine whether the addition of trastuzumab to hormonal therapy will provide breast cancer patients with benefits in clinical practice. This review describes the rationale for these trials and discusses the potential of therapeutic regimens combining trastuzumab with hormonal therapy.