Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Ampronix

Risk of Breast Cancer Later in Life for Girls Undergoing Radiotherapy Explained

By Medimaging International staff writers
Posted on 02 Oct 2013
Print article
Image: Computation model of the developing mammary gland beginning at three weeks of age (Photo courtesy of the US Department of Energy’s Lawrence Berkeley National Lab’s Life Sciences Division
Image: Computation model of the developing mammary gland beginning at three weeks of age (Photo courtesy of the US Department of Energy’s Lawrence Berkeley National Lab’s Life Sciences Division
Exposing young women and girls under the age of 20 to ionizing radiation can substantially raise the risk of their developing breast cancer later in life. Scientists may now have found the answer as to why this occurs. A collaborative study’s findings pointed to increased stem cell self-renewal and consequential mammary stem cell enrichment as the reason.

Breasts enriched with mammary stem cells as a result of ionizing irradiation during puberty show a later-in-life propensity for developing estrogen receptor (ER)-negative tumors. Estrogen receptors, i.e., proteins activated by the estrogen hormone, are vital for the normal development of the breast and other female sexual features during puberty.

“Our results are in agreement with epidemiology studies showing that radiation-induced human breast cancers are more likely to be ER-negative than are spontaneous breast cancers,” said Dr. Sylvain Costes, a biophysicist with US Department of Energy’s (DOE) Lawrence Berkeley National Lab’s Life Sciences Division (LBL; Berkeley, CA, USA). “This is important because ER-negative breast cancers are less differentiated, more aggressive, and often have a poor prognosis compared to the other breast cancer subtypes.”

Drs. Costes and Jonathan Tang, also with Berkeley Lab’s Life Sciences Division, were part of a collaboration led by Dr. Mary Helen Barcellos-Hoff, formerly with Berkeley Lab and now at the New York University School of Medicine (New York, NY, USA), that studied the so-called “window of susceptibility” known to exist between radiation treatments at puberty and breast cancer risk in later adulthood. The key to their success were two mammary lineage agent-based models (ABMs) they developed in which a system is modeled as a collection of autonomous decision-making units called agents. One ABM simulated the effects of radiation on the mammary gland during either the developmental stages or during adulthood. The other simulated the growth dynamics of human mammary epithelial cells in culture after irradiation.

“Our mammary gland ABM consisted of millions of agents, with each agent representing either a mammary stem cell, a progenitor cell or a differentiated cell in the breast,” stated Dr. Tang. “We ran thousands of simulations on Berkeley Lab’s Lawrencium supercomputer during which each agent continually assessed its situation and made decisions on the basis of a set of rules that correspond to known or hypothesized biological properties of mammary cells. The advantage of this approach is that it allows us to view the global consequences to the system that emerge over time from our assumptions about the individual agents. To our knowledge, our mammary gland model is the first multiscale model of the development of full glands starting from the onset of puberty all the way to adulthood.”

Epidemiologic research have shown that girls under 20 administered radiotherapy treatment for disorders such as Hodgkin’s lymphoma have about the same risk of developing breast cancer in their 40s as women who were born with a BRCA gene mutation. From their study, Drs. Costes, Tang, and their colleagues concluded that self-renewal of stem cells was the most likely responsible process.

“Stem cell self-renewal was the only mechanism in the mammary gland model that led to predictions that were consistent with data from both our in vivo mouse work and our in vitro experiments with MCF10A, a human mammary epithelial cell line,” Dr. Tang noted. “Additionally, our model predicts that this mechanism would only generate more stem cells during puberty while the gland is developing and considerable cell proliferation is taking place.”

The investigators are now looking for genetic or phenotypic biomarkers that would identify young girls who are at the greatest breast cancer risk from radiotherapy. The study’s findings from Dr. Barcellos-Hoff and her research group show that the ties between ionizing radiation and breast cancer extend beyond DNA damage and mutations.

“Essentially, exposure of the breast to ionizing radiation generates an overall biochemical signal that tells the system something bad happened,” Dr. Costes said. “If exposure takes place during puberty, this signal triggers a regenerative response leading to a larger pool of stem cells, thereby increasing the chance of developing aggressive ER-negative breast cancers later in life.”

The findings of this collaborative study have been published online August 23, 2013, in the journal Stem Cells.

Related Links:

Lawrence Berkeley US National Lab’s Life Sciences Division



Print article
Radcal

Channels

MRI

view channel
Image: The results of MRI scans are expected to inform future clinical guidelines for heart disease (Photo courtesy of the University of Leeds).

MRI Helps Identify High-Risk Heart Disease Patients

A new study concludes that magnetic resonance imaging (MRI) scans are the safest and most effective way to identify patients with suspected coronary heart disease (CHD). Researchers at the University... Read more

Nuclear medicine

view channel
Image: The images demonstrate that Ga-68 DOTATATE PET/CT anterior 3D MIP and axial fused images could visualize metastases and change the surgical plan for resection (Photo courtesy of Ronald C. Walker, MD / Journal of Nuclear Medicine).

Study Shows Safety and Efficacy of Imaging Technique for Neuroendocrine Tumors

The results of a new study have demonstrated the safety and efficacy of Ga-68 DOTATATE PET/CT scans, compared to In-111 pentetreotide scans, the current US imaging standard for the detection Neuroendocrine... Read more

General/Advanced Imaging

view channel
Image: Emory radiologists reduce Phantom Limb Pain (PLP) by applying a new non-invasive cryoablation procedure (Photo courtesy of Kevin Makowski, RBP).

Radiologists Demonstrate Minimally Invasive Procedure that can Freeze Phantom Limb Pain

Researchers have presented the results of a study investing the use of cryoablation to reduce Phantom Limb Pain (PLP) in patients with chronic pain in amputated limbs. The researchers showed that interventional... Read more

Imaging IT

view channel

Latest Release of Enterprise Imaging Platform Demonstrated at ACR 2016

A global enterprise diagnostic imaging and advanced visualization solutions provider has demonstrated the latest release of their Enterprise Imaging Platform that features thin-client, server-side processing, and simple diagnostic mobile access. The manufacturer made the announcement at the annual meeting of the American... Read more

Industry News

view channel

UK Health Service to Spend GBP 21.5 Million Upgrading Radiotherapy Resources

The UK’s National Health Service has agreed to acquire linear accelerators, and software from a human care company in a deal valued at GBP 21.5 million. The order includes linear accelerators (linacs), multileaf collimators, and a system for improving the speed and reducing the radiation dose of radiation therapy treatment.... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.