Book Review

Her-2: The making of Herceptin, a revolutionary treatment for breast cancer

N Engl J Med 1999; 340:486-487February 11, 1999

Article

Her-2: The making of Herceptin, a revolutionary treatment for breast cancer
By Robert Bazell. 214 pp. New York, Random House, 1998. $23.95. ISBN: 0-679-45702-X

This book describes the development of a new type of therapy for breast cancer, from the discovery of the molecular target to the completion of successful randomized, clinical trials and approval for use.

It is written as the story of the triumph of an inspired clinician against great opposition, which included his own colleagues, grant-awarding agencies, and pharmaceutical companies. There is no doubt that Dennis Slamon discovered the role of the erbB2 (her2) oncogene in breast and ovarian cancer and played a major part in preclinical studies that showed that inhibition of this molecular target was worthwhile. He was also a driving force in developing and conducting clinical trials that eventually led to the pivotal randomized trials that showed therapeutic activity. Having shared conference platforms with Slamon over the years, I think that Bazell's description of him is a caricature. Several other eminent oncologists are described in a similarly superficial style.

Bazell is a medical journalist, and where he describes factual matters such as the background of current radiotherapy and chemotherapy, his writing is clear, interesting, and accurate. The story is based heavily on detailed accounts of individual patients with breast cancer, their struggles with the disease, and their attempts to obtain the new therapy. It is interesting to learn how rapidly patients became aware of the potential value of the anti-erbB2 antibody, Herceptin, and how hard it was for many to be referred into trials by their oncologists. One major factor that emerges is the loss of professional fees when patients enter clinical trials.

The development of Herceptin had many vagaries, and Bazell tries to show how changes in management and staff at Genentech often disrupted the program. It was saved only by one or another person supporting it at the right time. If this is correct, it is a worrisome indication of how easily good scientific and clinical work can be discarded, thereby preventing development of a novel therapy. This story will be one of the most interesting sections of the book to the medical reader, because the scientific and medical aspects of breast cancer and its treatment are clearly aimed at the layperson or patient.

The development of Herceptin was unusual, because patient-advocate groups demanded access to the drug while it was still under investigation in a trial and in short supply. A lottery was set up for a certain number of patients who were not in trials to receive the drug each month as supplies became available. Bazell gives a good account of the power of such groups, which provide an important model for future trials of drugs with high activity and low toxicity in patients resistant to cytotoxic drugs.

The failure of Genentech to take advice from leading investigators almost caused the pivotal study to fail, but fortunately the situation was corrected. This near-tragedy highlights the need for broad-based studies and will interest workers in the pharmaceutical industry.

The book overemphasizes the ridicule that Slamon suffered. At the time Herceptin was being developed, larger companies were focusing on inhibition of the tyrosine kinase signaling pathway through a variety of means, including low-molecular-weight oral inhibitors of her2 and other steps downstream, such as ras. Also, John Mendelsohn, mentioned briefly in the book, had shown the role of another member of the erbB2 family, the epidermal growth factor receptor, in considerable detail. Thus, the academic medical and scientific community recognized and worked on many aspects of growth factor–receptor signaling as a target for therapy, but this fact is hardly recognized by Bazell in his attempt to develop the main theme of the story. I do not think medical practitioners will find this book useful, but they may like to know what their patients are reading, and the book has lessons for the pharmaceutical industry.

Adrian L. Harris, M.D.
University of Oxford, Oxford OX3 9DS, United Kingdom