Inhibitory effect of lomustine on the growth of spontaneous HER2-positive mammary tumors in transgenic mice

Background. In patients with HER2-positive breast cancer (HER2+ BC), as a result of targeted anti-HER2 therapy, the remission period is significantly prolonged. However, resistance to therapy often develops, especially in relation to brain metastases. In the search for effective additional drugs in combination therapy, it is advisable to study the antitumor effect of lomustine (CCNU) in HER2+ BC. Lomustine is not targeted, but is used to treat brain metastases, because it is known as one of the standard remedies for glioblastomas. Aim. Evaluate the inhibitory activity of lomustine on the growth of spontaneous HER2+ BC in female FVB/N mice. Materials and methods. Transgenic mice HER2+ aged 5–6 months were used, from which seven pairs of animals were selected (for control and treatment with lomustine) with spontaneous mammary tumors of the same size in each pair. Lomustine was administered once at a dose of 50 mg/kg (orally by gavage) followed by a 30-day follow-up. The criteria for evaluating the antitumor effect were ITG % (inhibition of tumor growth), as well as TGI (tumor growth index), calculated by the ratio of the area (S) under the kinetic curve of tumor growth in the group of animals treated with lomustine (SE ) to control (SC ). With such a comparison in the control, TGI will always be 100 %. Results. During the observation period, the volume of ВС in the control (solvent administration) increased 8-fold, while in mice treated with lomustine, the tumors regressed significantly. ITG after treatment with lomustine was 78–92 % (p = 0.007–0.0006, to control). The total mean S significantly differed by 5.6 times when comparing the control and lomustine groups and TGI in mice in the lomustine group was 18.8 %, while in the control it was 100 % (p = 0,0006). Conclusion. Lomustine exhibits a pronounced inhibitory effect on the growth of spontaneous HER2+ ВС in FVB/N transgenic mice. The results indicate the advisability of using lomustine in patients with HER2+ ВС complicated by cerebral metastases.