The Molecular Basis Of Breast Cancer Prevention And TreatmentEssay Preview: The Molecular Basis Of Breast Cancer Prevention And TreatmentReport this essayThe 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.
JosД© 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,
, in vitro therapies, and tumor progression as part of the “lancet” have the potential to help resolve the problems in so defining a book from one that covers a wider area, without including any of those relevant to understanding this area in separate sections. There is no such one in the book, but there are a couple of references for that (i.e., at the top of the chapter and at chapter 3):
There is no evidence to support the notion that “socially inherited mutations” of the HER2a receptor, which is necessary for breast cancer survival to occur, are responsible for most of the observed and observed genetic changes that have been associated with the formation of breast cancer.
There is, however, some evidence that such mutations can have profound effects on the development of normal and abnormal breast cell lines and can also alter host health and survival. For example, human breast cell lines may be exposed to mutations in the HER2a response (and not all breast cell lines survive), but this is considered a general issue, which will be discussed in future chapters. Additionally, a single event may explain the vast variation in immune responses in the present study. Thus, this does not make the specific study important – all the evidence is there for heterogeneity, and the differences between authors mean that this specific study will not make for a reliable study on the origins of the diseases. Nevertheless, many of the comments above and on previous publications in this journal point towards an obvious advantage of a multi-layered and complex analysis of this topic rather than simply an analysis of only one paper’s literature alone.
Furthermore, many of the references for the authors also include an analysis of the different types of gene expression and the changes that occur over time in certain regions in the genome, which is in many ways an intriguing way of looking at the gene regulation of cancer, but which is just another way of getting a look at variation in immune system activity.
It is important to note at the outset that the general pattern of gene expression in human breast cancers is extremely heterogeneous, with some cancers more closely linked to their origin, while others have a particularly significant influence. In particular, a large body of evidence for the direct role of genes implicated in human breast cancers and the many different types and mechanisms they take part in is provided in the supplementary figure for the text. I will try not to over-state the significance of these figures. There are many more such references I will not consider here:
References for the authors include:
The gene expression and tumor growth in this study are described in more detail in a peer-reviewed paper in the journal Cell Expression and Disease, available in the Supplement. There are, of course, hundreds of different mutations that occur within a particular cell line. They are not solely responsible for causing mutations in the cell wall. The mutation in the human HER2b gene is common among all common cancer cells and is an example of a gene that is involved in certain cancer progression and survival.
Here is what the paper says about human breast cancer:
The gene expression and tumor growth in this study are described in more detail in a peer-reviewed paper in the journal Cell Expression and Disease, available in the Supplement. There are, of course, hundreds of different mutations that occur within a particular cell line. They are not solely responsible for creating mutations in the cell wall. The mutation in the human HER2b gene is common among all common cancer cells and is an