Friday, October 17, 2008

Neoplasms: Excerpt 7

Neoplasms: principles of development and diversity was published October 1, 2008. In the next few blogs, I will provide some short excerpts from the book.

Excerpt from Chapter 4 Section 4.6. Precancers

Precancers are neoplastic growths that precede the development of cancers. The precancers are extremely common lesions that can often be biopsied (excised as a tissue sample) and diagnosed by pathologists. In most cases, clear-cut morphological features distinguish precancers from cancers.

Suppose this were not the case. Suppose we lived in a world wherein precancers could not be distinguished from cancers, and suppose that we had no means by which we could study the biology of these important lesions. Even if we had no physical examples of precancers,we could infer the existence of these lesions from simple observations of tumor biology.

Here is an example. In the New York Times of December 15, 2006, there was a provocative article by Gina Kolata (70). Ms. Kolata wrote:

"Rates of the most common form of breast cancer dropped a startling 15 percent from August 2002 to December 2003, researchers reported yesterday. . . . The reason, they believe,may be because during that time, millions of women abandoned hormone treatment for the symptoms of menopause after a large national study concluded that the hormones slightly increased breast cancer risk."

Here is the problem with this news. The 15% drop in breast cancer rates occurred in the interval between August 2002 and December 2003, immediately after the large drop of hormone use among the population at risk for breast cancer. For most other diseases, this might lead you to suspect causality, but carcinogenesis is a multistep process that extends over many years. Based on our understanding of carcinogenesis, there is no reason to think that a decision to discontinue a drug could possibly result in a measurable drop in cancer incidence observed the following month!

It is commonly accepted that breast carcinogenesis takes about 15 years (from initiating event to tumor detection). Let us pretend that the 15-year number is good. Then if there is a large drop of cancers beginning in August 2002, would not it make sense to look for some change in carcinogen exposure that occurred starting in August 1987? The only way around this objection is to assume that the women who opted out of hormone treatment in August 2002 (and who may have accounted for the drop in breast cancer incidence starting the following month) harbored a lesion that was not quite cancer but that could develop into cancer. The “not quite cancerous” lesions are called precancers. The observations raise the question,“Has the reduction in hormone treatment in menopausal women resulted in a decrease in the progression of precancerous breast lesions?

Decades ago, epidemiologists closely studied the effects of smoking cessation on the incidence of lung cancer. The mathematical models for smoking-induced lung cancer did not fit the observed rates in lung cancer incidence in people who had ceased smoking. Epidemiologists inferred the there must be some phase of cancer development, independent of the continuing presence of the carcinogen, that transitions to cancer when smoking stops.

These lesions, that occur after initiation and that preceded the development of cancers are called precancers. Almost every cancer occurring in humans is preceded by an obligatory precancer. Understanding and controlling these lesions are among the most important goals in cancer research.

(to be continued)

The full table of contents is available. In the next few days, I will continue to discuss content from Neoplasms in my blogs.

-Jules Berman

Key words: tumors, tumour, neoplasms, neoplasia, carcinogenesis, tumor development, cancer research, neoplastic development, precancer preneoplasia, preneoplastic

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