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The origin of breast cancer


doi: 10.1097/gme.0b013e31803816db
Personal Perspectives

Biological studies confirm that breast cancer is the result of an accumulation of a large number of individual genetic mutations that collectively alter elements of the complex internal signaling system of a cell. These aberrant genetic alterations, when assembled in a single breast cell, disrupt the control system to the extent that the cell functions autonomously in an erratic and irregular manner. Continual replication of a corrupted cell results in the formation of a colony of abnormal cells that may accumulate other aberrant mutations to eventually initiate cancer. What causes these mutations has been the topic of debate over a number of years, but because so many genetic alterations are involved, it is now conceded that one single factor could not possibly initiate all the changes. One plausible explanation involves a sequence of random, accidental, spontaneous mutations during normal stem cell replication. Some of these mutations may be an advantage to the host and their creation advances the functional ability of the breast, whereas abnormal mutations are usually deleted after activation of the complex apoptotic and inhibitory signaling system. When the defense system is corrupted, cells carrying the abnormal genes are able to avoid elimination, eventually passing abnormal mutations from one cell generation to the next. Accumulation of genetic abnormalities, over time, leads to development of a colony of cells that are pathologically abnormal. Biological studies confirm that cultured stem cells are capable of undergoing spontaneous mutations during mitosis, that sex hormones control the rate of mitosis, and that estrogen and progesterone therefore influence the rate that mutations occur. Accumulating the large number of mutations that eventually cause breast cancer can be achieved only if chromosomal abnormalities are carried from one generation of cells to the next to combine with genetic alterations generated spontaneously during stem cell mitosis.

Breast cancer occurs following the accumulation of a very large number of aberrant mutations which occur spontaneously as immature stem cells undergo rapid mitosis during breast development, or are passed from one cell generation to another as cells continue to divide. The role of sex hormones is to control the rate of mitosis, but neither estrogens nor progesterone appear to induce oncogenic mutations.

Received November 20, 2006; revised and accepted January 10, 2007.

Financial disclosure: None reported.

Address correspondence to: Barry G. Wren, AM, MD, MHPEd, FRANZCOG, FRCOG, Suite 506/180 Ocean St., Edgecliff, NSW, Australia 2027. E-mail:

©2007The North American Menopause Society