Cancer (document en anglais)

Irradiation of juvenile, but not adult, mammary gland increases stem cell self-renewal and estrogen receptor negative tumors

Breast cancer is by far the most frequent cancer among women in the world. This malignant tumor of the mammary gland, which represents 16% of all female cancer, can also affect men but is rare (two hundred times less common than in women). There are several types

of breast cancer depending on where cancerous cells grow: they can either be confined within the breast tissue or be present in the tissue that surrounds the mammary glands. Numerous factors increase the risk of developing breast cancer such as family history,

age -increased incidence after 30 years-, obesity, dietary factors -alcohol for example- and radiations.

Some studies have shown that ionizing radiation could raise the risk of developing breast

cancer: indeed, young adults given radiotherapy treatment for disorders such as Hodgkin's disease -a cancer of the lymphatic system- had an increased risk of developing breast cancer later in life. Moreover, compared to spontaneous breast cancers, radiation-induced breast cancers are more likely to be “Estrogen-Receptor (ER) negative” type meaning that they

are less differentiated, more aggressive and often have a poor prognosis.

If the reason why ionizing radiation raised the risk of developing breast cancer was until

now unknown, scientists may now know why. Indeed, a collaborative study in which researchers from Berkeley Lab played a crucial role, points out the link between the exposure of young women under 20 years of age to ionizing radiation and the significant increase in

the risk of developing a breast cancer in later adulthood. Sylvain Costes and Jonathan

Tang developed a computational model of the mammary gland called the ABM (Agent-Based Model). It is “the first multi-scale model of the development of full glands from the

onset of puberty all the way to adulthood”. They used the MCF10A human mammary epithelial cell line to test self-renewal versus dedifferentiation. Their experimentations showed that radiation exposure and treatment with Transforming Growth Factor β (TGF β) are necessary to increase self-renewal of MCF10A cells but not dedifferentiation, indicating that these are independent processes.

From their studies, Costes, Tang and their collaboration partners show that ionizing radiation lead to an increase in self-renewing stem cells and, consequently, to the apparition of a larger number of stem cells in the mammary gland.

This enrichment shows a predisposition to develop the “ER negative” tumors with cells deficient in estrogen receptor, which is essential for normal breast development and also for the appearance of other female sexual characteristics.

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