As I’ve mentioned before, immunotherapy  has become a hot topic in breast cancer research. It garnered a lot of attention from researchers in April at the American Association for Cancer Research 2014 annual meeting (which I wrote about here). And the same was true for the ASCO 2014 Breast Cancer Symposium, held earlier this month in San Francisco. It was at the San Francisco meeting that I heard Elizabeth Mittendorf, a surgical oncologist at the University of Texas MD Anderson Cancer Center in Houston,  present findings from a phase II study  on a new type of breast cancer vaccine that appeared to help prevent recurrences in women with HER2+ breast cancer. The field of immunotherapy is focused on learning how to get the immune system—the body’s natural defense mechanism—to go after cancer cells. Typically, cancer cells are able to go about their business in a stealth fashion, turning off receptors that immune cells use to detect them. Researchers are trying to find a way to unblock and turn on T cells (a type of white blood cell that plays a central role in immune response) so that they can see and go after the cancer cells. Mittendorf is studying a number of different types of breast cancer vaccines.  The vaccine she discussed at the ASCO meeting is made up of a peptide derived from the HER2 protein called GP2. This peptide is exciting because it has the ability to get T cells to head out and kill HER2+ cancer cells.  It does this by attaching itself to a subset of a group of molecules called HLA, which are on the outer surface of cells. There are 3 major and 3 minor types of HLA proteins that each person may have. The immune system uses the HLAs to differentiate the person’s own cells from those of invaders such as bacteria and viruses. Cancer cells alter the HLA proteins in ways that protect them from the immune system. The vaccine attempts to reverse this for those cancers that overexpress the HER2 protein. Because the GP2 peptide is related to HER2 and can only attach to certain HLA molecules, the vaccine only has the potential to work in patients with HER+ tumors who have certain forms of HLA. This study looked at women who had the form called HLA-A2. Women who were interested in enrolling in the study had their blood tested to determine the type of HLA they had. Only those who tested positive for HLA-A2 and had HER2+ tumors could enroll. The patients had to be considered to be at high-risk for recurrence because this would allow the researchers to detect a benefit from the vaccine quickly. The researchers enrolled 190 women in the study; 89 received the vaccine along with granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein produced by T-cells, and 91 received GM-CSF alone. The women received one shot every month for six months followed by four booster shots given every six months. After about 34 months, 88 percent of the women who received the vaccine were disease-free compared to 81 percent of the women who had not received the vaccine. But when the researchers looked specifically at the women in the study who had tumors that tested 3 or higher on an IHC test which confirmed the HER2+ status and had received trastuzumab (Herceptin) prior to being vaccinated, they found that none of these women had had a recurrence. Mittendorf thinks this may be because Herceptin stimulates T-helper cells (cells that assist other white blood cells), it may get the immune system ready to take as much advantage as it can from the vaccine. The next step is to do a larger, phase III study to see if these results hold up. If they do, this vaccine may be one of the first to become available to HER2+ breast cancer patients. While this is exciting in and of itself, this study also has other implications. If this vaccine works in this setting, might it be possible to use it to get the immune system to prevent HER2+ DCIS from developing into cancer? Or might the vaccine even prevent women from ever getting a HER2+ breast tumor? Stay tuned, as this is only the beginning of many efforts to harness the immune system to treat and maybe prevent cancer.

 

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