Book Review

Breast Cancer: Molecular genetics, pathogenesis, and therapeutics

N Engl J Med 1999; 341:1244October 14, 1999

Article

Breast Cancer: Molecular genetics, pathogenesis, and therapeutics
(Contemporary Cancer Research.) Edited by Anne M. Bowcock. 582 pp., illustrated. Totowa, N.J., Humana Press, 1999. $145. ISBN: 0-89603-650-3

A century ago, William Halsted introduced the radical mastectomy as a treatment for breast cancer and with it transformed breast cancer from an incurable disease to one whose course physicians could hope to alter. With the addition of radiation therapy and chemotherapy to the less disfiguring modified radical mastectomy in the mid-1970s, the treatment of breast cancer became genuinely multimodal, if nonspecific. The addition of hormonal therapies, the refinement of chemotherapeutic regimens, and the important shift toward breast-conserving surgery that followed similarly served to increase the sophistication with which this disease is approached.

Despite these advances, breast cancer has exacted a steadily increasing human cost, with incidence climbing inexorably at a rate of 1 percent per year and mortality remaining relatively unchanged for the better part of a century. With more than 180,000 women given the diagnosis each year, breast cancer is by far the most prevalent cancer among women in the United States and is second only to lung cancer as a cause of death from cancer. Moreover, far from being a disease restricted to the elderly, breast cancer is the most common cause of death from cancer among women who are 25 to 54 years of age, a fact of some note given that cancer is the leading cause of death among women 35 to 54 years of age and the leading cause of death from disease among women 25 to 34 years of age. By any measure — physical, social, economic, or emotional — the toll taken by this disease is staggering.

Despite the high prevalence and acute public awareness of this disease, the number of investigators and the resources committed to studying breast cancer have remained puzzlingly low. That is, they were low until recent massive increases in funding for breast-cancer research, spurred by advocacy groups and by the National Cancer Institute, were implemented early in this decade. The availability of money, particularly during a time of scarce resources in biomedical research, and the intense public interest in breast cancer triggered an enormous influx of investigators, energy, and ideas into this field. Consequently, during the past decade our understanding of the basis of this disease has evolved from isolated islands of information to a more coherent and connected conceptual landscape integrating multiple aspects of physiology, epidemiology, molecular biology, and genetics. Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics presents the fruits of the recent surge in breast-cancer research.

This book is not intended to cover all topics related to breast cancer, but rather to provide an introduction to current thinking in breast-cancer genetics — ideas on which future advances in breast-cancer research and treatment are likely to be based. The book has four sections, which deal with the causes of breast cancer, the biology of tumor progression and metastasis, diagnostics, and therapeutics. Research scientists will particularly appreciate the section on etiology, with its outstanding chapters on genetic alterations in breast cancer, hereditary breast-cancer genes, estrogen receptors, and essentially every important family of growth factors known to be involved in the pathogenesis of the disease. Similarly, the second section contains several excellent chapters on the part played by molecules such as nm23, integrins, matrix metalloproteinases, and the urokinase plasminogen activation system on breast-cancer progression and metastasis. Finally, clinicians as well as scientists will appreciate the forward-looking chapters on current and future innovations in breast-cancer therapeutics as well as those on environmental risk factors such as tobacco smoke, phytoestrogens, pesticides, and pollutants.

Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics successfully steers between the impossibility of a comprehensive book on all aspects of breast cancer and the undesirability of a quasi-random selection of isolated topics. The chapters are clearly written, succinct, and eminently readable for the physician as well as the molecular biologist. Although sparsely illustrated, the book is well referenced and summarizes a wealth of data in a straightforward and digestible manner. Although the chapters are written by acknowledged leaders in each of the disciplines covered, the treatment of topics is balanced and thorough rather than self-referential.

A hundred years have passed since Halsted. We now stand poised at the edge of a new era in breast-cancer treatment, largely as a result of the advances in breast-cancer research made possible by the enormous resources marshaled over the past decade. The future is bright. Applications now on the horizon include the determination of breast-cancer risk in women in the general population, prevention programs based on inherited susceptibility to endogenous or environmental agents, the tailoring of therapeutic regimens to individual tumors on the basis of their genetic profile, the development of novel therapeutic approaches based on molecular insights, and the definition of populations at risk. Ultimately, the important, if primitive, surgical advances pioneered by Halsted at the close of the 19th century will give rise at the beginning of the next millennium to therapeutic approaches that are more refined and more specific — directed against molecular targets identified as a result of the current explosion in breast-cancer research. For the research scientist, epidemiologist, and clinician, this book will serve as an interesting and useful guide to the coming era.

Lewis A. Chodosh, M.D., Ph.D.
University of Pennsylvania School of Medicine, Philadelphia, PA 19104