Scientists have discovered that low oxygen conditions, which often persist inside tumours, are sufficient to initiate a molecular chain of events that transforms breast cancer cells from being rigid and stationery to mobile and invasive.
Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine, said that high levels of RhoA and ROCK1 were known to worsen outcomes for breast cancer patients by endowing cancer cells with the ability to move, but the trigger for their production was a mystery.
He said that they now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions.
To move, cancer cells must make many changes to their internal structures, Semenza said.
Thin, parallel filaments form throughout the cells, allowing them to contract and cellular "hands" arise, allowing cells to "grab" external surfaces to pull themselves along. The proteins RhoA and ROCK1 are known to be central to the formation of these structures.
Moreover, the genes that code for RhoA and ROCK1 were known to be turned on at high levels in human cells from metastatic breast cancers.
In a few cases, those increased levels could be traced back to a genetic error in a protein that controls them, but not in most. This activity, said Semenza, led him and his team to search for another cause for their high levels.
The researchers found that women with high levels of RhoA or ROCK1, and especially those women with high levels of both, were much more likely to die of breast cancer than those with low levels.
The study is published in Proceedings of the National Academy of Sciences.
The way Angelina went public with her medical story on her own terms, in her own time - with a NY Times op-ed piece that caught the media fishbowl of Hollywood completely by surprise - reveals a woman who once seemed out of control to be one of Hollywood's most forceful and compassionate stars, using her fame with surgical precision to promote matters dear to her.
Oscar-winning actress Angelina Jolie disclosed that she had a preventive mastectomy after learning she had a gene mutation that significantly raised her risk of breast cancer. A look at the procedure:Q: What kind of surgery did Jolie have? A: Jolie had a preventive double mastectomy, meaning she chose to have both her breasts removed even though she had not been diagnosed with cancer.Q: Why did she have the operation?
A: Jolie says that she inherited a faulty version of the BRCA1 gene. Doctors told her she had an 87 percent chance of getting breast cancer and a 50 percent risk of ovarian cancer. She said the surgery reduced her risk of breast cancer to below 5 percent.Q: What did the procedure involve?
A: In double mastectomies, surgeons typically remove as much breast tissue as possible. In Jolie's case, the doctors preserved the skin covering her breasts, inserting "fillers" for the breast tissue to keep the skin elastic for reconstruction. According to Jolie, she had implants put in nine weeks later.Q: How many women have this faulty gene?
A: Only a small percentage of women inherit this same faulty gene, or a similar mutated version of a related gene, BRCA2. (The name stands for breast cancer susceptibility gene). These mutations are most commonly found in women of Eastern European Jewish descent. Q: How do these genes increase a woman's risk of breast or ovarian cancer?
A: The average woman has a 12 percent risk of developing breast cancer sometime during her life. In comparison, women who have inherited a faulty BRCA gene are about five times more likely to get breast cancer. In the U.S., about 5 to 10 percent of breast cancers are thought to be linked to harmful BRCA genes. Q: How can women find out if they have these gene mutations?
A: A genetic test using a blood test can detect these genes. Those at higher risk are those with close family members diagnosed with breast or ovarian cancer at an early age. Jolie says that her mother fought cancer for nearly a decade before dying at age 56. Genetic counseling is usually recommended to discuss the test and the results.Q. What does the test cost?
A. The test can cost several thousand dollars. According to Myriad Genetics, the sole provider of such tests in the U.S., 95 percent of patients have insurance that covers the test and the average out-of-pocket cost is $100. Myriad has a patient assistance program for those who aren't covered by insurance.Q: What other options might Jolie have had?
A: Doctors would likely have suggested earlier screening tests, including mammograms or MRIs, but those would only help them spot breast cancer earlier, not prevent it. They might also consider using breast cancer drugs preventively, though tests of long-term use are still ongoing. Not everyone opts for surgery. Q: How relevant is Jolie's decision to other women?
A: For most women, genetics will not play a big part in whether or not they get breast cancer. "The majority of women considering their breast cancer risk should focus on things like a healthy lifestyle, eating a balanced diet, keeping a healthy weight and not drinking too much alcohol," said Dr. Peter Johnson, chief clinician at Cancer Research U.K. But for women with a similar genetic risk to Jolie, it's possible her decision will prompt more procedures. "It's a very empowering message that women are not helpless when faced with a genetic cancer risk," Johnson said.
Picture for representational purpose only. 