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RESEARCH ROUNDUP

Mastectomies Significantly Lower Risk of Breast Cancer

An international study led by researchers from the Abramson Cancer Center has found that a prophylactic double mastectomy--surgical removal of both breasts to prevent a cancer before it occurs--can lower the risk of developing breast cancer by 90% in women genetically pre-disposed to the disease. This is the first study to quantify the risk reduction for this procedure and its impact on hundreds of thousands of women in the U.S. who carry mutations in one or both of the two genes--BRCA1 and BRCA2--strongly linked to breast and ovarian cancer.  Their findings will appear in the March 15 edition of the Journal of Clinical Oncology.

"Women are still at risk for breast cancer after any kind of mastectomy as some breast tissue remains in the body after surgery," said lead author Dr. Timothy R. Rebbeck, associate professor of epidemiology at the School of Medicine and co-program leader of the Center's Cancer Epidemiology and Risk Reduction Program. "Now that we have quantified the benefit of a double mastectomy for reducing the chances of breast cancer, women in this high-risk group can make a better-informed decision about having breast surgery in addition to other forms of prevention, such as regular screening and/or other preventive surgeries, including ovary removal."

The PROSE study, (Prevention and Observation of Surgical Endpoints), followed 483 at-risk women from 11 sites in the U.S., Canada, the U.K. and the Netherlands for over six years. Most of the North American women chose not to have preventive, or prophylactic, double mastectomies. Women who chose to have prophylactic mastectomies were paired with women in a control group based on type of mutation, treatment center and year of birth within five years.  In addition, none of the participants had any previous or current diagnosis of cancer upon entering the study.

Breast cancer was diagnosed in two of 105 women (1.9%) who had double mastectomies. The occurrence of breast cancer was much greater in the control group, with 184 of 378 women (48.7%) developing breast cancer. 

Study results also confirmed a large risk reduction for breast cancer (95%) for women who also had their ovaries removed.

Funding for this study was provided through a research grant from the NIH, Penn's Abramson Cancer Center, the Breast Cancer Research Foundation, the Dana-Farber Women's Cancers Program, the US Department of Defense Breast Cancer Research Program, the Utah Cancer Registry, the Falk Medical Research Trust, the Utah State Department of Health, and the Nebraska State Cancer and Smoking-Related Diseases Research Program.

The Body's 911 Call: Why Blood Flow Stops Short

While it's common knowledge that high levels of LDL, also known as "bad" cholesterol, can lead to the restriction of blood vessels and a higher incidence of heart attack, stroke and diabetes, the exact method of "how" has remained a mystery. Now, researchers from Penn's School of Medicine have discovered the exact mechanism to explain why blood vessels are restricted in patients with cardiovascular diseases, thus preventing blood flow and causing disease symptoms. These finds were published in the February issue of Nature Structural and Molecular Biology.

"We all have oxygen-heavy toxins in our bodies," said Dr. Xiang Dong Tang, staff scientist in physiology. "When there are high levels of LDL or sugars in the blood, those toxins are generated in excess, and the body can't break them down as efficiently as a healthy body can. This kicks off a chain reaction that leaves blood vessels contracted. Now we know how that chain works, down to the amino acid residue that is targeted."

That amino acid is Cysteine at position 911 of a protein called the Maxi-K potassium channel, which is typically made of approximately 1,200 amino acids. The Maxi-K channel moves potassium ions out of blood vessel muscles and serves as a critical regulator for blood vessel tone. It works in one of two ways: either from an electric shock or an increase in calcium within the channel. When Cysteine911 is altered by an oxygen-heavy toxin, calcium doesn't enter the Maxi-K channel. If the Maxi-K channel is inhibited, then the vascular muscle isn't told to relax, thus restricting blood flow.

"We also found that the Maxi-K channel isn't permanently damaged when Cysteine911 is altered," said Dr. Toshinori Hoshi, associate professor of physiology and  co-author of the article. "In fact, with the right  chemical agent, it can be reversed." In initial laboratory tests, the researchers have found that a chemical, NS1619, can allow the damaged Maxi-K channel to continue to function. "This discovery could lead to the production of drugs that would reverse the negative effects on the Maxi-K channel. It would be an alternative method for treating cardiovascular diseases and even diseases relating to aging," said Dr. Hoshi.

Scientists also contributing to this research include Marcia L. Garcia from Merck Research Institution and Stefan H. Heinemann from Friedrich Schiller University. This research is funded by the NIH.

Cache of Seal Impressions Discovered in Western India

Excavating at the ancient town of Gilund in southern Rajasthan, India, one of the largest sites of the little-known Ahar-Banas culture, archaeologists led by teams from the University of Pennsylvania Museum and Deccan College, Pune, India have discovered a bin filled with more than 100 seal impressions dating to 2100-1700 B.C. The existence of the seals, and their particular styles, offer surprising new evidence for the apparent complexity of this non-literate, late and post-Indus Civilization-era culture, according to Dr. Gregory Possehl, curator-in-charge of UPM's Asian Section and excavation co-director. Dr. Possehl's collaborator, Dr. Vasant Shinde of Deccan College, and their teams made-up of professionals and students from around the world, have conducted excavations at Gilund over four seasons, beginning in 1999. The team is working to understand the social life, history and agricultural developments of these peoples, separated by about 200 miles of largely mountainous and desert-like regions from the powerful Indus Civilization that had its heyday 2500-1900 B.C. They came upon the bin with its seal impressions in the 2002-2003 season completed in February.

Clay, nature's soft and plentiful sealant, has been used by people for millennia to keep containers closed. Seals, on the other hand, frequently decorated with symbols to indicate a person or persons and used to make seal impressions that lay claim or suggest special rights to a container's contents, suggest a more stratified society. While no actual seals were discovered at Gilund, the unexpected collection of so many seal impressions strongly points to the presence of a populate of elite citizens who used stamps as identification of themselves and their elevated status--and who marked commodities that were stored in this building under their control. A large oval shaped bin about 5 feet deep and 2.5 feet in diameter at its midpoint, to keep the seal impressions in--and potentially keep others from duplicating specific impressions for their own use--further indicates the elitist nature of this warehouse.

The impression designs according to Dr. Possehl, offer additional evidence for a more worldly-wise culture than was formerly assumed to exist at Gilund. The impressions found in the bin were made from seals both round and rectilinear. The design motifs are generally quite simple, with wide-ranging parallels from Indus Civilization sites such as Chanhu-daro, Pirak, Kot Diji and Nindowari, 400 to 500 miles away. There are also distinct parallels with seals from another cultural group archaeologists call the Bactria-Margiana Archaeological Complex (BMAC), from as far away as Central Asia and northern Afghanistan, 1,000 miles to the northwest.

"Gilund is providing us with good evidence for a stratified society that had wide-ranging contacts between the peoples of western India, Pakistan, Afghanistan and Central Asia just at the end of the third millennium and the beginning of the second millennium," noted Dr. Possehl.

Generation Gap Explains Decline in Feminist Ranks

Despite gains brought about by the women's movement, young adults are far less likely than their middle-aged counterparts to call themselves feminists, according to a study conducted by Dr. Jason Schnittker, assistant professor of sociology at Penn, Dr. Jeremy Freese, assistant professor of sociology at the University of Wisconsin-Madison, and Dr. Brian Powell, professor of sociology at Indiana University.

Researchers examining the link between age and social attitudes about feminism found that support for abortion rights and gender equality in the workplace--a strong part of the feminist tradition--is virtually unrelated to whether young adults as well as senior citizens call themselves feminists.

"These results suggest that men and women whose political coming of age coincided with the feminist movement are more likely to think of themselves as feminists than their younger or older counterparts," said Dr. Schnittker, co-author of the report, Who Are Feminists and What Do They Believe: The Role of Generations. The report was published in the American Sociological Review.

Dr. Schnittker said that, while the feminist movement may not lose any of its hard-won accomplishments, the findings indicate that it may be increasingly difficult for contemporary feminists to present the united front once characteristic of feminism.  

"There appear to be many more conceptions of feminism these days than there were in earlier generations, allowing a variety of different people, with a variety of different ideologies, to self-identify as feminists. It's not just a story about some groups moving away from feminism, which most people have assumed, but about new groups and diverse ideological groups moving into it." The study also found that: