The Molecular Basis Of Breast Cancer Prevention And Treatment

The incidence of breast cancer is still rising, and the disease remains largely incurable once it becomes malignant. It is the most prevalent cancer in Europe and USA, with 41,000 new cases each year in the UK [1]. Fortunately we are beginning to gain insights into the origins of breast cancer, and now know that many of the key risk factors are related to life-styles associated with the hectic, consumer-based trends of Western cultures. For example, we consume more calories, eat fewer nutritive foods, and do less exercise than our forebears, leading to early menarche, obesity, and ingestion of fewer naturally occurring compounds that quench free radicals and reduce oxidative stress on DNA. Moreover, many women have their first full-term pregnancies when they are older. Paradoxically this knowledge is a reason to be optimistic about the future, because the implication is that breast cancer is a disease that is largely preventable; it is not common in some Far Eastern countries although women from those societies become prone if they migrate to the West. If we can identify how these risk factors impact on breast development and in particular understand the molecular changes within breast epithelium that lead to genomic alterations, then we have a chance to establish preventative strategies to ameliorate the disease.

JosÐ"© and Irma Russos' new book on the Molecular Basis of Breast Cancer: Prevention and Treatment tackles the problem by following a logical path of first introducing the disease from the epidemiological point of view, before discussing how the breast develops and becomes altered in cancer, and how we might seek to understand it through both in vivo and culture models. The book ends with two chapters on possible modalities for how the disease might be inhibited in the first place. Some of these are very interesting, and I particularly liked the chapters on Epidemiological considerations; the first half of the one on The (human) breast as a developing organ, where relatively few studies have been published in comparison to the mouse; and the chapter on Preventive strategies, which delves into the structure and activities of many naturally-occurring chemopreventives as well as anti-inflammatories, anti-estrogens, and other compounds that are likely to have properties to protect against the onset of cancer.

The central idea in the book comes from the observation that early pregnancy protects against breast cancer, and posits that a treatment to artificially induce differentiation within mammary epithelial cells could represent a radical new approach to prevent much of the disease. The epidemiological data from which this hypothesis arises is supported strongly by experimental observations that a state of pregnancy induced naturally, or by estrogen/progesterone treatment, or by human chorionic gonadotropin (hCG, a hormone that stimulates ovaries to produce higher levels of estrogen and progesterone) has a dramatic inhibitory effect on carcinogen-induced mammary cancer. The authors argue a case for ectopic administration of hCG as a possible preventative strategy. However, although this might be a neat strategy for eliminating tumours in rats, it is rather premature to consider it as preventative in humans. The likely targets for neoplastic genomic modifications are breast stem cells and we have no idea how hCG might affect the behaviour of these cells. A succession of breast cancer prevention trials began in 1985, and it would have been good to see a discussion of these. There is no mention, for example, of the STAR trial, which is one of the largest breast cancer preventive studies ever, examining the comparative effectiveness of tamoxifen and raloxifene. In a book where 'prevention' of breast cancer features in the title, one might have expected a broad debate on all the existing strategies, exploring the way that they work as well.

There are several other aspects of the book that are also rather problematic. First, with reams of new data in the literature and the resultant emergence of novel concepts, I would expect a long textbook (448 pages) on the basis of breast cancer to include a wide-ranging and in-depth look at its molecular control. We know that cancer is largely due to genomic instability that arises within populations of (as yet undefined) stem cells, and involves the escape of protective apoptosis and immune surveillance mechanisms, deregulated proliferation, and inappropriate sampling of the environment so that tumour cells ignore normal positional cues and thereby migrate to and survive at distant metastatic sites. However, the contemporary ideas on many key topics, including mechanisms of genomic instability and telomere rescue, apoptosis avoidance, cell cycle regulation in cancer,