Jeffrey Peppercorn, MD, MPH

Oncologists would be well advised to consider their obligations to the patient, as well as other stakeholders, and be prepared to resolve potential conflicts that go beyond the focus of their clinical training.

This article will review and summarize the current data regarding the influence of the major cytochrome P450 2D6 (CYP2D6) genotypes and CYP2D6 inhibitors on tamoxifen metabolism and clinical efficacy. We will discuss the clinical relevance and limitations of this data and how to best incorporate our current understanding of CYP2D6 genotyping into our clinical practice and discussions with patients.

Breast cancer is the most common cancer in women, with over 180,000 new diagnoses of invasive disease annually in the United States, based on recent estimates.[1] Despite advances in therapy, over 40,000 women still die of breast cancer each year in the US.[1] While most women with breast cancer present with early-stage, potentially curable disease, young women face higher risks of recurrence and death compared to older women, which leads to challenges in selecting the optimal treatment strategy for these patients. The clinician is typically confronted with an otherwise healthy patient facing a life-threatening disease, and we are inclined to offer therapies with maximal benefit and minimal longterm toxicity, in the face of frequently inadequate or evolving data on how to achieve this.

As noted by Dr. Buzdar, breastcancer rarely affects men. Accordingto the most recent datafrom the National Cancer Institute’sSurveillance Epidemiology and EndResults program and the National Programof Cancer Registries, the incidenceof invasive breast cancer is 1.5cases per 100,000 men vs 134 casesper 100,000 women.[1] Breast cancerin women is a far greater public healthproblem and understandably has receivedthe lion’s share of researchfunding and public attention.