By Daniel F. Hayes, MD, FASCO
University of Michigan Comprehensive Cancer Center

Thirty-four years ago, as a second-year medical oncology fellow at the Sidney Farber Cancer Institute (now the Dana-Farber Cancer Institute), I was told to take a few months and decide what I’d like to do with the rest of my life. Having completed this anxiety-provoking task on my own, I was called into the office of the legendary Emil (Tom) Frei III, MD (1924-2013), and was told he had arranged for me to work with Donald W. Kufe, MD, in the Laboratory of Molecular Pharmacology at the Sidney Farber Cancer Center.

My first reaction was that if Dr. Frei had my career already planned, why hadn’t he told me months ago and saved me the ulcers associated with looking around (this was before proton pump inhibitors, of course)! My second thought was that in my entire academic career, I had only received two C’s—one in conversational French (most deservedly so) and one in pharmacology (mostly because I thought it was boring).

This was going to be a long year.

However, Dr. Kufe had no intention of turning me into a pharmacologist. Rather, he had generated several monoclonal antibodies directed against a breast cancer metastasis. My job was to screen them to find a circulating antigen that might be a useful blood test for breast cancer. After a crash course in immunologic methodology— and thanks to the help of colleagues in the laboratory—I found a very high molecular-weight circulating antigen in several patients’ blood specimens. This antigen was soon shown to be the product of the MUC1 gene, and became the analyte within the CA15-3 assay, which is now widely used to monitor patients with metastatic breast cancer.

What does this have to do with the collaboration between ASCO and the College of American Pathologists (CAP)? I had been taught the scientific method during my medical school laboratory experience, including the importance of a pre-existing hypothesis and proper experimental design. Further, as a clinical fellow, I had been taught the scientific methodology of clinical research, which was equally rigorous in regards to hypothesis, experimental design, understanding pre-ordained endpoints, and—for the first time in my life—the absolute requirement of collaboration with highly trained biostatisticians.

As I entered the world of tumor marker research, I assumed there must be an equally rigorous set of rules for this area of research that bridged the lab and the clinic, now designated “translational research.” However, I could not find them.

To address this gap, in 1995, ASCO decided to get into the guidelines business, wisely deciding that if we don’t tell ourselves what to do, someone else will. ASCO decided that its first two guidelines would focus on the use of colony-stimulating growth factors and tumor biomarkers. A group of us with interest in tumor biomarkers in breast and colorectal cancers met and created the first ASCO guidelines, which have now been serially updated, and expanded to selected other malignancies.¹ We also generated a white paper, published in the Journal of the National Cancer Institute, which established a framework for tumor biomarker development and evaluation.²

The Beginning Of The ASCO-CAP Collaboration

At roughly the same time, the College of American Pathologists (CAP) was also thinking about guidelines. Led by a remarkably energetic pathologist from Utah, Elizabeth (Liz) H. Hammond, MD, CAP was also addressing breast cancer markers, in particular estrogen receptors (ER) and HER2. Dr. Hammond invited me to present my nascent ideas about tumor biomarkers in general, including two sound bites that have gained some traction: “A Bad Tumor Marker Is as Bad as a Bad Drug” and “Luck Is Not a Good Strategy in Golf or Science.”

Over time, Dr. Hammond and I began to realize it made no sense for ASCO and CAP to be generating separate guidelines for the same disease and biomarkers.

Fast forward to the 2005 ASCO Annual Meeting and the unbelievable results of adjuvant trastuzumab. Who can forget the proclamation by George W. Sledge, Jr., MD, FASCO, in his discussion after the presentation of the combined NSABP/NCCTG and the HERA trials: “Nothing short of amazing.”

Within a week I received an email from Antonio C. Wolff, MD, FACP, FASCO, then Chair of the parent ASCO Clinical Practice Guidelines Committee, in which he expressed concern over the increasingly complex situation regarding HER2 testing. I forwarded the email to Dr. Hammond, who forwarded it to the sitting president of CAP. Thanks to the visionary leadership of both organizations, the first ASCO/CAP joint workshop and Expert Panel Meeting on tumor marker guidelines was held at ASCO headquarters in Alexandria, VA, a few months after that historic set of presentations at the ASCO Annual Meeting.

Joining Efforts For International Cancer Care

At the workshop, we heard story after story of the disturbing inter-laboratory variability of HER2 evaluation, and began discussing what we could do to improve this unacceptable situation, with a variety of concrete recommendations. At the end of the day, I noted to Antonio and Liz, “This was a single day that would change the practice of oncology”—not something one often gets to do in one’s career!

The rest is history. The joint ASCO/CAP Panel came up with a set of guidelines that spanned pre-analytical, analytical, statistical, and clinical guidelines that were simultaneously published in the Journal of Clinical Oncology and the Archives of Pathology and Laboratory Medicine (an unprecedented circumstance). CAP developed a national proficiency testing program for HER2 testing. And we’ve witnessed a remarkable improvement in the consistency of HER2 testing both in North America and around the world.^3,4 The ASCO/ CAP collaboration has been extended to address ER and progesterone receptor testing, and now into other diseases and other markers with considerable impact.

What’s next? Both ASCO and CAP have major footprints in the area of international medicine (ASCO through its portfolio of international programs, including International Cancer Corps, Cancer Control in Primary Care Courses, and International Clinical Trials Workshops).

In summer 2015, ASCO and CAP held a workshop at ASCO headquarters to address how we might jointly enhance pathology services in low-income nations. The workshop was attended by myself, ASCO and CAP leadership, leaders in international medicine from both ASCO and CAP, and, most importantly, a medical oncologist and a pathologist from each of four pilot lowincome countries: Vietnam, Uganda, Honduras, and Haiti.

During the workshop, we learned that the major cancer-related killer in many low-income countries is not lung, breast, or colorectal cancers, but cervical cancer. How sad: a disease that is currently absolutely treatable for cure if detected early and, parenthetically, which should be preventable with widespread vaccination programs in the next 2 to 3 decades. However, the ability to perform careful PAP smear histology is limited in many such countries, leading to unnecessary morbidity and mortality.

We can, and will, positively affect this situation. ASCO and CAP will partner to provide training for both doctors and support staff, such as histo-technologists, over the next few years. Our collaboration with CAP is but one example of how ASCO can, and does, make a difference—a big one—for hundreds of thousands, and even millions, of patients around the world.

References

1. Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. J Clin Oncol. 1996;14:2843-77.

2. Hayes DF, Bast RC, Desch CE, et al. J Natl Cancer Inst. 1996;88:1456-66.

3. Wolff AC, Hammond ME, Schwartz JN, et al. J Clin Oncol. 2007;25:118-45.

4. Wolff AC, Hammond ME, Schwartz JN, et al. Arch Pathol Lab Med. 2007;131:18-43.