By Sophie Bainbridge
SAN DIEGO -- April 14, 2008 -- A preventive HER2/neu peptide (E75) vaccine is showing great promise in the prevention of breast cancer recurrence and reducing mortality when recurrences do occur in women with HER2/neu-positive breast cancer, researchers reported here at the American Association for Cancer Research (AACR) Annual Meeting 2008.
Breast cancer patients who received the E75 vaccine experienced a boost in their immunity, with a rise in T-lymphocytes, and this translated into decreased breast cancer recurrence and a 50% reduction in mortality at 30 months, said Linda C. Benavides, MD, Resident in General Surgery, Brooke Army Medical Center, San Antonio, Texas.
In particular, women with low-expressing HER2/neu tumours who were vaccinated had better immunological and clinical responses, with decreased breast cancer recurrence and zero mortality. This result "surprised, delighted, and excited" the researchers, Dr. Benavides said on April 14.
"The fact that HER2 low-expressors responded so favourably not only underscores the difference in mechanism between the vaccine versus antibody therapy like trastuzumab, but it also offers the hope of additional adjuvant therapy to the largest subset of breast cancer patients if proven in the upcoming phase 3 trial," she said in a press briefing.
HER2/neu is a source of immunogenic peptides and is overexpressed in 30% of patients with early-stage breast cancer. Dr. Benavides and her colleagues tested the vaccine, a 9-amino-acid protein, to determine its efficacy in boosting immunity and in reducing recurrence and mortality rates in 163 node-negative and node-positive patients demonstrating all levels of HER2/neu expression.
Of the 94 women that received the vaccine, 30 women were HER2/neu overexpressors and 64 were low-expressors. HER2/neu overexpressors were determined to express more than 2.0 HER2/neu tumours on fluorescent in situ hybridisation (FISH) and more than 3 HER2/neu tumours on immunohistochemistry (IHC). HER2/neu low-expressors included patients with IHC results showing no tumours to 2 HER2/neu-positive tumours.
The remaining 71 patients served as unvaccinated controls. Of these, 22 were overexpressors of HER2/neu and 49 were low-expressors.
The women were vaccinated once a month over 6 months, and were given boosters every 6 months.
All patients showed an immunological response to the vaccine, as measured by delayed-type hypersensitivity reactions. However, vaccinated overexpressor patients showed a decreased number of E75-specific CD8+ T cells compared with their low-expressor counterparts.
At a median follow-up of 30 months, disease recurrence rates were similar between vaccinated and nonvaccinated overexpressors (18% and 14%, respectively; P = .7). However, mortality rates were better in the vaccinated overexpressors than nonvaccinated overexpressors (25% vs 50%, P=NS), Dr. Benavides said.
Importantly, recurrence of breast cancer was substantially lower among the vaccinated patients with low HER2/neu expression, who experienced an 11% recurrence rate compared with 18% for controls.
The mortality rate among low-expressors with recurrent disease was 0% among vaccinated patients versus 38% among the control group (P = .08).
Dr. Benavides said that these findings are very encouraging for the more than 50% of breast cancer patients whose tumours fall into the HER2/neu low-expressing category and who are not eligible for trastuzumab treatment.
"It would be wonderful to be able to offer these patients adjuvant treatment, which is something they have not had previously."
[Presentation title: Response to a Preventive HER2/Neu Peptide (E75) Vaccine Based on HER2/neu Status. Abstract 2545]
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