Featured Research

from universities, journals, and other organizations

Higher estrogen production in the breast could confer greater cancer risk than thought

Date:
August 14, 2011
Source:
Georgetown University Medical Center
Summary:
Could some women who naturally produce excess aromatase in their breasts have an increased risk of developing breast cancer? Investigators say their mice study shows that overproduction of aromatase, which converts testosterone into estrogen, in breast tissue is even more important in pushing breast cancer development than excess production of the estrogen receptor that the hormone uses to activate mammary cells.

Could some women who naturally produce excess aromatase in their breasts have an increased risk of developing breast cancer? Results of a new animal study suggests that may be the case, say researchers at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center.

Related Articles


In the issue of August 15 Cancer Research, the investigators say their mice study shows that overproduction of aromatase, which converts testosterone into estrogen, in breast tissue is even more important in pushing breast cancer development than excess production of the estrogen receptor that the hormone uses to activate mammary cells. In addition, the researchers found that aromatase over-expressing mice also expressed more estrogen receptors on the breast cells.

While current breast cancer therapies target both of those processes -- inhibition of aromatase and inactivation of the estrogen receptor -- the researchers say this study suggests that aromatase inhibitors may prove to be a more potent choice for cancer prevention in postmenopausal women. Tamoxifen and other drugs that block the estrogen receptor have long been used to prevent breast cancer and deter recurrence, while aromatase inhibitors are only now being studied as a protectant.

"We know that estrogen is the fuel that most breast tumors use to grow, and this study shows us that making more estrogen in the breast, right next to cells that can use the hormone as fuel, appears to be a key trigger of early breast cancer," says the study's senior investigator, Priscilla Furth, M.D., professor of oncology and medicine at Georgetown Lombardi.

The study also reached another important conclusion, says Edgar Díaz-Cruz, Ph.D., a postdoctoral researcher working in the Furth laboratory and first author of the study.

"This study appears to help inform a longstanding controversy about whether it is systemic estrogen or estrogen produced in the breast that is the primary risk factor for breast cancer," he says. "With our animal models, we've demonstrated that local production of estrogen in mammary tissue is potent enough to spur development of breast cancer, and does not require estrogen from the ovaries or produced from fat tissue, as had been hypothesized."

Their study set out to achieve two goals: to look at whether production of estrogen or production of estrogen receptors in the breast was more potent in breast cancer development, and to find more answers to the controversy alluded to by Díaz-Cruz.

To address these issues, the researchers developed the first "conditional" mouse model of aromatase production in mammary tissue. That means they inserted a gene into mice that expresses human aromatase in the animal's mammary tissue -- a gene the researchers can turn on or off.

They compared this new mouse model to one they had developed several years ago -- a conditional mouse model in which a gene that produces estrogen receptors (ER) could also be turned on and off.

While they study found that both mouse models experienced the earliest stages of tumor formation, known as preneoplasia, the aromatase over-expressing mice model exhibited both increased preneoplasia and outright development of cancer. These mice also expressed proteins that are tightly linked to cancer, Furth says.

The researchers also found, to their surprise, that aromatase over-expressing mice expressed more estrogen receptors than did the ER-conditional mice. "Increased aromatase produced both more estrogen and the receptors that the hormone needs to enter breast cells," says Díaz-Cruz. "This is obviously a greater risk for development of breast cancer than just over-expression of estrogen receptors."

"In our conditional mice, aromatase provides a double whammy -- more estrogen and more estrogen receptors," Furth notes.

These mice also over-expressed progesterone receptors, downstream targets of estrogen receptors that can be cancer-promoting in some settings, as shown in this study in the context of aromatase over-expression.

Furth notes that the amount of aromatase and estrogen receptors produced in these mice is high, but not higher than would be expressed in a woman with breast cancer. "These were not super large amounts. Comparable levels can be measured in women."

Finally, they tested the effect of local versus systemic estrogen on development of preneoplasia. The researchers made three comparisons: between mice in which the ER was over-expressed; mice that had excess estrogen due to aromatase; and mice that were given more estrogen systemically. "If we give extra systemic estrogen, we don't see any increased risk of breast cancer, but the risk increases with extra expression of ER, and is higher still with local production of aromatase," says Díaz-Cruz. "That suggests that estrogen production in the breast is an important risk factor for development of breast cancer."

What these results suggest for women is that if females vary in the amount of aromatase they naturally produce, as some studies suggest, then women with higher aromatase levels may be more susceptible to breast cancer, Furth says.

"Some day we may have a test available that can determine individual aromatase levels in postmenopausal women so that a preventive aromatase inhibitor can be prescribed to women at higher risk for breast cancer," she says.

The research was funded by the National Cancer Institute and a Susan G. Komen for the Cure Postdoctoral Fellowship grant awarded to Díaz-Cruz.

Co-authors include G. Ian Gallicano, Ph.D., director of the Transgenic Core Facility at GUMC, and Yasuro Sugimoto Ph.D. and Robert W. Brueggemeier Ph.D. from the College of Pharmacy at The Ohio State University.


Story Source:

The above story is based on materials provided by Georgetown University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. E. S. Diaz-Cruz, Y. Sugimoto, G. I. Gallicano, R. W. Brueggemeier, P. A. Furth. Comparison of Increased Aromatase versus ER  in the Generation of Mammary Hyperplasia and Cancer. Cancer Research, 2011; 71 (16): 5477 DOI: 10.1158/0008-5472.CAN-10-4652

Cite This Page:

Georgetown University Medical Center. "Higher estrogen production in the breast could confer greater cancer risk than thought." ScienceDaily. ScienceDaily, 14 August 2011. <www.sciencedaily.com/releases/2011/08/110812124842.htm>.
Georgetown University Medical Center. (2011, August 14). Higher estrogen production in the breast could confer greater cancer risk than thought. ScienceDaily. Retrieved March 28, 2015 from www.sciencedaily.com/releases/2011/08/110812124842.htm
Georgetown University Medical Center. "Higher estrogen production in the breast could confer greater cancer risk than thought." ScienceDaily. www.sciencedaily.com/releases/2011/08/110812124842.htm (accessed March 28, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, March 28, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
WH Plan to Fight Antibiotic-Resistant Germs

WH Plan to Fight Antibiotic-Resistant Germs

AP (Mar. 27, 2015) — The White House on Friday announced a five-year plan to fight the threat posed by antibiotic-resistant bacteria amid fears that once-treatable germs could become deadly. (March 27) Video provided by AP
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) — In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins