Our instinctive response to a challenge says a lot about us. In that light, the decision to partner with the American Society of Clinical Oncology (ASCO) to write guidelines for laboratory testing for HER2 positivity speaks well for the College. The guidelines (currently in press, to be simultaneously posted later this month on the Web sites of the Archives
of Pathology & Laboratory Medicine and Journal of Clinical Oncology, then to appear in print simultaneously later this year) will ensure reliable laboratory test results when we assess breast-cancer patient eligibility for treatment with trastuzumab (Herceptin).
HER2 is a protein that is overexpressed in about 20 percent of breast cancers; tumors that overexpress HER2 grow faster and are more likely to recur. An article relating results of a multicenter, international, randomized clinical trial using trastuzumab in early HER2-positive disease was published in the New England Journal of Medicine on
Oct. 20, 2005. An editorial that accompanied the results called them “simply
It had been known for a long time that trastuzumab was a useful tool against HER2-positive metastatic breast cancer, with a robust response rate of 30 percent. But this new research showed that when patients with early HER2-positive breast cancer were treated with trastuzumab, the response rate was about 50 percent. It was heady, groundbreaking stuff.
Oncologists were extremely excited about it, but their enthusiasm was tempered by worries about inconsistencies in laboratory test results. In earlier trials involving metastatic cancer, institutional readings for HER2 had been falsely positive about 25 percent of the time when compared with the central review of those samples.
Trastuzumab is a powerful drug with significant cardiotoxicity. It is also expensive. There was talk about restricting HER2 testing to a small group of laboratories that had shown reliable results. That was the chatter around this time last fall, when CAP Education Committee chair M. Elizabeth H. Hammond, MD, got a call from Daniel F. Hayes, MD, who is responsible for ASCO activities with respect to breast cancer. Dr. Hayes asked if the College would be willing to form an ASCO/CAP panel to develop guidelines for laboratory testing for HER2 positivity.
Knowing the stakes for breast cancer patients, we quickly agreed and began to recruit experts from our scientific committees and the international community. Our president-elect, Jared Schwartz, MD, PhD, would co-chair for the CAP along with Dr. Hammond. Dr. Hayes recruited Antonio C. Wolff, MD, who chairs the ASCO group with responsibility for guidelines development, to join him as an ASCO co-chair.
The panel consisted of 24 experts from around the world, in addition to invited reviewers and contributors. CAP consultants included members of the Council on Scientific Affairs, Council on Accreditation, Checklist Committee, and the scientific resource committees in immunohistochemistry, cytogenetics, molecular pathology, and surgical pathology. Council on Scientific Affairs chair Thomas M. Wheeler, MD, coordinated their responses. The hours were long, the scrutiny was intense, and panel members made up the rules of collaboration as they went along. Yet it was, by all accounts, an extremely satisfying experience. The process that evolved was thoughtful and sound; the product that resulted is precise and explicit.
A year later, I was a member of the standing-room-only
crowd at CAP ’06 that heard Dr. Wolff give a tremendous oncologist’s perspective on the new guidelines. The following evening, I was part of another standing-room-only crowd that heard Dr. Hammond’s
walk-through describing not only the content of the guidelines but
also the plans to implement their goals through proficiency testing,
laboratory accreditation, and a variety of educational tools.
This is the first time the College has worked closely with a clinical organization on joint guidelines to improve laboratory testing. The experience was entirely new, the barriers were considerable, and the stakes were high. The results are a credit to both groups. We knew going in that patients with false-positive results could suffer serious side effects from a drug that could not work for them, and that patients with false-negative results would not have access to dramatically useful therapies. We had more than enough reason to put aside any theoretical differences, and no difficulty in doing so.
Targeted therapies are the direction of the
future. Testing for HER2 is only the first of many such new and highly
complex challenges in this new era. We will have to use all of the
skills we have, and if we don’t have the necessary skills we will have
to learn them. The College will see to it that pathologists have what
they need to ensure quality analytical and interpretive work in their
I think the pathologists at CAP ’06 who crowded in to hear Drs. Wolff and Hammond knew that they were part of an important moment for the College and for pathology. That was the mood in the room each time (when he reached the podium, Dr. Wolff joked that he “felt like a rock star”).
The ASCO-CAP collaboration is a model for future partnerships with clinical colleagues. These partnerships create opportunities to bring science from bench to bedside in record time. And they underscore the importance of continuous quality improvement in the laboratory as science leaps forward to create new therapies that would have been almost inconceivable 25 years ago.
Dr. Sodeman welcomes communication from CAP members. Send your letters to him at firstname.lastname@example.org.