Vaccines: Potential Breast Cancer Risk Reduction, Prevention

Vaccines to prevent cancer are of great interest to the cancer community, and with the success of the HPV vaccine in preventing cervical cancer--caused by a virus--interest in preventing disease caused by inherited genes, has soared.

Researchers from the Tumor Vaccine Group at the University of Washington are investigating new ways to stimulate the immune system to prevent invasive or recurrent breast cancer. Stanton and Disis¹ suggest that because preinvasive breast cancer is slow growing and patients (pretreatment) do not have suppressed immune systems, they are good candidates for vaccination. A vaccine must identify antigens that are present in preinvasive disease and should trigger the T-helper type 1 (Th1) cell immune response.

T-lymphocytes are distinguished by the presence of cell surface molecules, CD4 and CD8. T-lymphocytes expressing CD4, produce the most cytokines, which are hormonal messengers responsible for most of the biologic effects in the immune system. The researchers also suggest that a vaccine must identify the heterogeneity of preinvasive breast cancer by targeting multiple immunogenic proteins present in the lesion. Women with high-risk ductal carcinoma in situ (DCIS), preinvasive breast lesions, or are associated with an increased risk of developing invasive breast cancer, would benefit from such a vaccine.

One study showed that the HER2 vaccine was immunogenic and 91% of the subjects had greater than five-fold response to HER2 peptides by IFN-gamma ELISPOT after vaccination. Unfortunately, 84.6% of the patients had residual DCIS, although 55% of patients had a decrease in size of DCIS and the DCIS remaining had lost HER2 expression.²

Animal studies have shown that a multiantigen vaccine targeting neu can stimulate type I CD4+ T-cells, inhibiting tumor progression in mice with preinvasive breast disease.³ Phase II studies will reveal more about the efficacy of such a vaccine, but it looks like these approaches may actually prevent breast cancer when the vaccine is given to patients who have breast lesions but not detectable disease.

References:

• Stanton SE, Disis ML. (2015). Designing vaccines to prevent breast cancer recurrence or invasive disease. Immunotherapy, 7(2): 69-72.
• Czerniecki BJ, Koski GK, Koldovsky U, et al. (2007).Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res., 67(4): 1842–52.
• Disis ML, Gad E, Herendeen DR, et al. (2013). A multi-antigen vaccine targeting neu, IGFBP-2 and IGF-IR prevents tumor progression in mice with pre-invasive breast disease. Cancer Prev Res., 6(12).