Daniel F. Hayes, MD

The promise of pharmacogenetics is personalization of therapy for individuals through refinement of the risk/benefit profile of pharmaceuticals based on inherited gene mutations. Classic examples of the impact of pharmacogenetics in clinical practice include variants in dihydropyrimidine dehydrogenase and treatment with fluorouracil.

One of the primary challenges in the treatment of patients with early-stage breast cancer is determining which patients will benefit from adjuvant chemotherapy. Traditionally, treatment decisions have been made based on a combination of tumor characteristics and patient and physician perspectives regarding risks and benefits. Recent technologic advances, including the development of gene-expression arrays, have led to the identification of molecular signatures that provide prognostic information in addition to the basic clinicopathologic features of individual tumors. While these new methods allow for more refined determination of prognosis for an individual patient, few data are available to support use of these new technologies in the clinic for treatment decision-making. At present, data from a single retrospective study are available to support the use of one assay, the 21-gene recurrence score, for decision-making regarding adjuvant chemotherapy. Large, multinational clinical trials are currently ongoing to evaluate the use of two of the multiparameter assays, although it will be many years before oncologists can apply the results of these trials in the clinic.

For many people, a picture is much more instructive and memorable than text. The second edition of the Atlas of Breast Cancer is designed for such people. With 154 pages and 213 figures, it is a graphic overview of the pathophysiology, diagnosis, and treatment of breast cancer.

It has been roughly 20 years since chemotherapy dose escalation was proposed as a possible strategy for improving outcomes in patients with breast cancer.[1,2] This concept has sustained a series of remarkable rollercoaster-like controversies, with heated arguments at national meetings, substantial lay press coverage, patients suing their insurance companies seeking coverage, legislative fiats requiring third-party payment long before critical data were available, and a well-publicized episode of clinical scientific fraud that is nearly unprecedented in its audacity. How did we get here from there?

Although a substantial number of women will suffer and die from breast cancer during the upcoming years, we clearly have made stepwise progress in treating patients with this cancer over the last 3 decades. Each of these steps of progress has led to

It is ironic that the issue of aggressive local therapy for breast cancer has re-emerged as a controversial issue in the early 1990s, almost 100 years after Halsted proposed this theory in the early 1890s [1]. Since that time, both survival and quality of life seemed to have improved for patients with breast cancer, due to more sophisticated and effective treatments. Nonetheless, as Drs. Pierce and Lichter point out in their article, the precise balance between the benefits and risks of aggressive local therapy still remains to be defined.