Some types of tumour are more likely than others to recur after surgical removal, and there is evidence indicating that processes triggered by surgery itself stimulate recurrence. However, the reasons why certain tumours recur more often than others are unclear. Human epidermal receptor 2 (HER2) is expressed in 20–25% of breast carcinomas, and these tumours show a high frequency of recurrence. In the August issue of The Lancet, Sylvie Ménard and colleagues investigate the effects of surgery on proliferation of HER2-expressing breast carcinomas, and conclude that the release of specific growth factors triggered by surgery causes the high level of recurrence of these tumours.

The authors showed that overexpression of HER2 correlates with an increased number of proliferative cells in residual tumour tissue that remains after surgery. They also showed a similar effect in vitro by incubating breast-carcinoma cell lines with wound-drainage fluid obtained from patients with breast cancer after surgery. In these experiments, cells that overexpress HER2 showed higher levels of proliferation than other breast-carcinoma lines. Importantly, serum samples taken after surgery stimulated higher levels of proliferation in HER2-expressing cells than samples from the same patients taken before surgery, indicating that processes triggered during surgery cause the HER2-dependent increase in proliferation.

Growth factors are prime candidates for substances released after surgery that might trigger cell proliferation, and Ménard and colleagues found increased levels of epidermal growth factor (EGF)-like growth factors in serum samples taken after removal of breast carcinomas. Antibodies targeted against two of these molecules, transforming growth factor-α and heparin-binding EGF, which are released during wound healing, decreased the proliferative effect of drainage fluid on HER2-expressing cells by up to 50%. This indicates that cellular damage incurred during surgery might trigger growth-factor release and therefore induce proliferation through HER2. In support of this, the authors showed a correlation between the amount of tissue damage after surgery and both the levels of EGF-like factors present in serum and the level of drainage-fluid-induced proliferation.

Trastuzumab, an antibody against HER2, is already used to treat patients with HER2-expressing breast carcinomas. Ménard and colleagues investigated the potential to use this drug to inhibit the proliferation of HER2-expressing cells after surgery, and saw a decrease in proliferation when trastuzumab was added to cells one day before the addition of drainage fluid. This indicates that treatment of patients with HER2-expressing breast carcinomas with trastuzumab before surgery might be an effective way of minimizing the recurrence of this type of tumour.