Developing an Effective Breast Cancer Vaccine

Hatem Soliman, MD

Disclosures

Cancer Control. 2010;17(3):183-190. 

In This Article

Appropriate Setting for Use

The issues surrounding the ideal setting for the use of breast cancer vaccines are complicated, not because of a lack of understanding of how immunotherapy works, but because of the various practical issues in demonstrating a clinical benefit in these different settings. The possible risk vs benefit of a particular proposed treatment may mandate that the initial trials be performed in metastatic patients with poorer prognosis. This would be the case particularly if a novel immunomodulating agent with an unknown or a significant toxicity profile is combined with a breast cancer vaccine for the first time. When compared to traditional cytotoxic agents, immunotherapy usually takes longer to exert its effect, responses are variable, and the immunotherapy probably works better in patients with a lower disease burden.[5,6] A lower disease burden gives the immune system time to mount a response before being overtaken, and it addresses the immunosuppressive environment seen in advanced cancer states. The well-established role of the graft-vs-leukemia effect after allogeneic stem cell transplantation provides ample evidence for this principle.[7]

While a cancer vaccine may be less effective in the metastatic setting, it may modulate the disease in a way that renders it more susceptible to subsequent chemotherapy and/or radiation treatments. This was observed in a phase II trial for small-cell lung cancer using a p53 dendritic cell (DC) vaccine in patients who completed initial chemotherapy.[8] While the response rate to the vaccine was typically low (5%), all patients were treated with paclitaxel in the second line. The response rate was 50%, much higher than the typical 10% rate observed in second-line treatment. In another study with CYP1B1 vaccine, Gribben et al[9] observed similar enhanced chemosensitivity to subsequent salvage chemotherapy in metastatic cancer patients who developed an immune response to the vaccine. It remains to be seen if this can be demonstrated in breast cancer patients undergoing similar treatment. Cancer vaccines tend to exhibit lower toxicity profiles than targeted/cytotoxic agents generate, making vaccines ideal maintenance treatments. These properties seem to indicate that the greatest promise of breast cancer vaccines would be in the adjuvant or minimal residual disease state.

Since adjuvant trials in breast cancer generally require large sample sizes and long follow-up for recurrence and survival, the initial funding of these studies may be cost-prohibitive. However, from a public health perspective, an effective adjuvant vaccine could help stem the larger societal costs of the expensive and toxic palliative treatments administered to patients with distant recurrences. Compared with hormone receptor-positive disease, certain subsets of breast cancer such as triple-negative disease may provide a population with shorter recurrence times and higher risk of recurrence.[10] Targeting a study population with sufficient risk of recurrence may maximize the odds that the vaccine will demonstrate a clinical benefit while potentially limiting the sample size required to do so. A possible consideration could be including enough eligible patients with a certain recurrence risk cutoff after standard adjuvant therapy (eg, > 20%) based on testing with Adjuvant! Online (http://www.adjuvantonline.com) or Oncotype DX (Genomic Health Inc, Redwood City, CA). If benefit is seen in patients with more aggressive disease expressing the immune target, it is likely that patients with more indolent disease expressing the same target would also benefit.

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