Background: I-SPY 2 is an innovative collaboration to assess 8-12 investigational agents and numerous biomarkers in an adaptive, neoadjuvant clinical trial for patients with locally advanced breast cancer and a high likelihood of recurrence. The first site opened in March 2010, and the trial will eventually open in up to 20 sites and enroll 800 patients. It is well known that patients who have recently been diagnosed with breast cancer are often overwhelmed, frightened and cognitively impaired. Making treatment decisions and dealing with the strain of treatment are among the most traumatic events patients are likely to experience. Nevertheless, they are often significantly helped by peer support. Methods: The Breast Cancer Network of Strength (formerly Y-ME) provides 24x7 peer support for callers seeking information and/or support related to breast cancer. All peer counselors are trained and certified breast cancer survivors. I-SPY 2 partnered with this organization to leverage their services in the I-SPY 2 trial. In particular, ten experienced peer counselors received a day of training to prepare them to counsel I-SPY 2 patients. They learned about the details of the trial, support materials available to patients (i.e., I-SPY 2 brochure, DVD and website), and specific challenges patients going through the trial are likely to face. Training included extensive role play exercises. When patients agree to treatment within the I-SPY 2 trial, they are offered the option of peer counseling. If they so choose, a counselor will call five times during their six months of treatment. Calls will be scheduled to meet the needs of individual patients, but are expected to take place: 1) shortly after enrollment; 2) a week after the first chemotherapy treatment; 3) shortly after completion of pacitaxel and any investigational agent; 4) shortly before surgery; and 5) shortly after surgery. The goals of providing peer support to I-SPY2 participants are to: 1) provide participants with an opportunity to discuss their diagnosis,treatment, and trial issues to validate emotions and provide support for dealing with the rigors of receiving breast cancer treatment; 2) help patients understand and anticipate upcoming aspects of their treatment; and 3) encourage patients to comply with trial requirements and raise concerns with their health care providers. Discussion: The I-SPY 2 trial initially planned to offer patients who were deciding whether to participate in the trial the option of speaking to a peer counselor. However, one IRB objected to this use of peer counselors despite demonstration of peer counselors being helpful and not coercive. For example, when this service was provided in CALGB 49907, a majority of patients who used the service expressed appreciation of counseling, but only about 50% who spoke to counselors enrolled in the trial. In the current study, use of peer counselors will initially be restricted to enrolled patients. However, it is likely that it be expanded to patients contemplating participation at sites where IRBs agree. Future research will clarify which patients request counselors and why, how they view their experience, and to what extent peer counseling influences patient enrollment, compliance and trial completion.