Guidelines and Care: What Comes Next?

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Clifford A. Hudis, MD, FACP

[T]he guideline provides…clinicians with a starting point for decision-making and also covers the vast majority of initial treatment decisions. It is a framework for wise clinicians to begin their thought processes for individual patients and also enables the conduct of ‘next step’ clinical trials by identifying gaps in our knowledge.

—Clifford A. Hudis, MD, FACP

The goal of clinical, translational, and basic research is, in the end, the betterment of life on earth. Advances in basic and clinical science ultimately should lead to information that, in turn, enables clinicians to make better treatment decisions for individual patients in order to improve their lives. However, there are barriers to success that we have to overcome.

For example, not all treatments are available in all locales, and a critical issue is simply the dissemination of knowledge and results. Relatedly, many skilled clinicians lack the time to carefully consider and weigh every available clinical trial result, instead depending on experts to interpret and contextualize the results of studies. This is, of course, a never-ending process.

The ASCO Clinical Practice Guidelines Process

The ASCO Clinical Practice Guidelines process addresses the issue of knowledge dissemination. An international expert panel reviews the relevant available evidence (consisting of phase I to phase III clinical trials as well as historical practice patterns), weighs the evidence, and through a rigorous and transparent process attempts to arrive at the best answers to common clinical challenges. In many cases there really are no “best” answers, and sometimes there is no real evidence at all. But, with regard to breast cancer, one of most prevalent and frequent life-threatening malignancies in the world, we actually do have significant amounts of high-quality data to consider.

In the current example—the guideline on chemotherapy and targeted therapy in advanced HER2-negative or HER2 status–unknown breast cancer—the expert panel had 79 studies and 20 systematic reviews or meta-analyses to consider, as well as 29 studies specific to second-line treatment or beyond.1 These data were published since 1993 and represent the standard-setting or practice-changing studies conducted in the modern era of breast cancer therapy. Because an earlier panel focused on HER2-positive disease, this effort addressed the remainder of metastatic breast cancer, both hormone-sensitive and -insensitive HER2-“negative” (really “normal”) disease. Reflecting the era in which it was generated, the evidence also included trials in which HER2 status was not known.

The results are presented in an easy-to-read tabular fashion in the Journal of Clinical Oncology1 and are further summarized here in The ASCO Post. For readers who need more, the source documents are described in the Journal of Clinical Oncology paper with detailed references.

From a practical perspective, the guidelines mirror those of other groups, such as the International Consensus Conference for Advanced Breast Cancer and the National Comprehensive Cancer Network, as well as some of the recommendations ASCO recently made to the Choosing Wisely Campaign.2-4 It should be reassuring that independent groups of experts have, more or less, come to similar conclusions regarding the management of advanced or metastatic breast cancer. At the same time, the complementarity of the approaches is helpful in this area of practice, since each of these efforts provides a different perspective on some of the treatment issues yet arrives at more or less identical conclusions.

Why the Need for Guidelines?

Some clinicians have asked why we need guidelines—sometimes because they come from an era where individual physicians were thought to be capable of making the best possible treatment decisions for individual patients, and sometimes because they believe that somatic mutation and other molecular analysis will replace broader clinical guidelines on the way to increasingly individualized treatment.

To the first group of skeptics, we could point out that there will always be a need for clinical judgment and thoughtfulness in the application of any guideline. Patients, as we are all taught, don’t necessarily “read the textbook,” and breast cancer in particular has notable clinical variations that are not always reflected in clinical trial experience. That said, the guideline provides all clinicians with a starting point for decision-making and also likely covers the vast majority of initial treatment decisions. It is a framework for wise clinicians to begin their thought processes for individual patients and also enables the conduct of “next step” clinical trials by identifying gaps in our knowledge. For example, the current guideline can’t address the role of surgical resection of oligo-progression (that is, disease progression in the face of effective therapy that is limited to just one site).

To the more modern skeptics who believe that sequencing contains the answers to treatment, we can note that this may be increasingly true in some situations in the near future, but even then the proliferation of targets and effective drugs will increase the need for guidelines to assist busy clinicians!

Across all of modern society, it is generally the case that the standardization of practices improves quality and lowers cost by limiting unnecessary variation. In medicine, we have a special obligation to temper that truth with the fact that individual patients require individualized care and thought. The purpose of this guideline is to facilitate that discussion, and I believe it will help considerably. At the same time, we look forward to the next step in our use of science and bioinformatics to help improve the care given to individual patients by skilled and thoughtful physicians: CancerLinQ. ■

Disclosure: Dr. Hudis reported no potential conflicts of interest.


1. Partridge AH, Rumble B, Carey LA, et al: Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2–negative (or unknown) advanced breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. September 2, 2014 (early release online).

2. Cardoso F, Costa A, Norton L, et al: ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Ann Oncol. September 18, 2014 (early release online).

3. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer, version 3.2014. Available at Accessed September 20, 2014.

4. Schnipper LE, Lyman GH, Blayney D, et al: American Society of Clinical Oncology 2013 top five list in oncology. J Clin Oncol 31:4362-4370, 2013.


Dr. Hudis is Chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center; Professor of Medicine, Weill Cornell Medical College;, and Immediate Past-President, American Society of Clinical Oncology.

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