Hope for HER2 low-expressing breast cancer

14 Apr 2008

Response to preventive HER2/neu peptide (E75) vaccine based on HER2/neu status

A HER2 peptide E75 vaccine reduced mortality in patients with HER2-positive breast cancer by half, according to Texas researchers.

In particular, patients with low-expressing HER2 tumors exhibited better response, not only immunologically, but clinically, with decreased breast cancer recurrence and no mortality following vaccination, report researchers from Brooke Army Medical Centre in San Antonio, Texas.

"The fact that HER2 low-expressors responded so favorably not only underscores the difference in mechanism between the vaccine vs. antibody therapy like trastuzumab, but also offers the hope of additional adjuvant therapy to the largest subset of breast cancer patients if proven in the upcoming phase III trial," said Linda C. Benavides, M.D., a resident in general surgery at Brooke Army Medical Centre.

HER2, a source of immunogenic peptides, is over-expressed in approximately 25 to 30 percent of patients with early stage breast cancer. The CVDP has conducted clinical trials with the HER2 E75-peptide vaccine in lymph node-positive and lymph node-negative patients with breast cancer who demonstrated varying levels of HER2 expression.

They conducted a subset analysis of 163 patients with breast cancer enrolled in the E75 vaccine trial to determine whether the level of HER2 expression affected vaccine response.

Of 163 patients assessed, 92 underwent vaccination. Within the vaccinated treatment arm, 29 (34 percent) were defined as HER2 over-expressors, and 56 (66 percent) were defined as low-expressors. The 71 patients in the control group included 22 (33 percent) over-expressors and 44 (67 percent) low-expressors. Patients over-expressing HER2 were similar with regard to prognostic and treatment factors, except that a statistically larger number of vaccinated over-expressors had hormone receptor-negative tumors (P = 0.02).

Following vaccination, immunologic responses were similar as measured by delayed-type hypersensitivity reaction; however, patients in the vaccination arm who were low-expressors of HER2 demonstrated an increased number of E75-specific CD8+ T cells when compared with the vaccinated over-expressors.

At a median follow-up of 30 months, disease recurrence rates were similar between HER2 over-expressors in both the vaccine and control groups, with recurrence rates of 18.2 percent and 13.8 percent, respectively.

Although these recurrence rates were comparable (P = 0.7), the researchers observed a greater than 50 percent reduction in mortality rate among patients whose disease recurred.

Interestingly, recurrence was more substantially reduced for vaccinated patients with low HER2 expression, Benavides says. Vaccinated low-expressors experienced 10.7 percent recurrence, compared with 18.2 percent for participants in the control group. Furthermore, the mortality rate among low-expressors with recurrent disease was 0 percent among vaccinated patients, versus 38 percent among the control group (P=0.08).

Taken together these findings may be significant for the greater than 50 percent of breast cancer patients whose tumors fall into the HER2 low-expressing category and who are not eligible for trastuzumab treatment, Benavides concludes.