Ovarian cancer patients survive longer with BRCA2 mutated in tumors
Women with high-grade ovarian cancer live longer and respond better to platinum-based chemotherapy when their tumors have BRCA2 genetic mutations, researchers at The University of Texas MD Anderson Cancer Center and the Institute for Systems Biology report in the Oct. 12 issue of the Journal of the American Medical Association.
"BRCA2-mutated tumors are more vulnerable to these DNA-damaging agents, which is really exciting because there are a number of drugs in clinical trials now that block DNA repair that might prove effective against these tumors in combinations," said senior author Wei Zhang, Ph.D., professor in MD Anderson's Department of Pathology.
BRCA2 and its cousin, BRCA1, are tumor-suppressing genes involved in DNA repair that, when mutated, raise a woman's risk for having breast or ovarian cancer.
"Uncovering the separate potential effects of BRCA1 and BRCA2 mutations takes us a step towards a more personalized approach to treating ovarian cancer, and perhaps other cancers," Zhang said. "This paper suggests those two genes, and the many others involved in DNA repair, are prime targets for further research."
Past studies of the possible clinical impact of BRCA1 and BRCA2 mutations tended to look at the two genes together and were limited by small sample sizes.
First author Da Yang, Ph.D., an Odyssey Fellow in MD Anderson's Department of Pathology, said their in-depth study was made possible by The Cancer Genome Atlas project. TCGA published a study of 489 cases of high-grade serous ovarian cancer, the most common form of the disease, that combined an exhaustive analysis of each tumor's genome with comprehensive clinical data on each patient.
"TCGA gave us enough analytical power to differentiate between BRCA1 and BRCA2 mutations and conduct a survival analysis," Yang said.
Improved overall survival
Of 316 cases, 29 tumors had BRCA2 mutations tumors and 37 had BRCA1 mutations. Tumors were similar in grade and stage. Findings include:
- 61 percent of patients with BRCA2 mutations survived for five years, compared with 25 percent of those with normal BRCA2 in their tumors.
- 44 percent of those with BRCA2 mutations lived three years after surgery and platinum treatment without disease progression, compared with 16 percent of those with normal BRCA2.
- BRCA1 mutations in tumors were not associated with survival.
- All of those with BRCA2 mutations responded to platinum chemotherapy, compared to 82 percent with the normal gene and 80 percent whose tumors had BRCA1 mutations.
- Their response to chemotherapy lasted 18 months, compared with 11.7 months for normal BRCA2 and 12.5 months for BRCA1 mutations.
- Tumors with BRCA2 variations also are hypermutants - they had more genetic mutations - with 84 mutations per tumor sample compared to 52 for normal BRCA2
BRCA2 is normally involved in the repair of double-strand DNA breaks. Cells with BRCA2 mutants are less capable of repair, allowing other genetic mutations to survive and grow, the type of genomic instability that cancer thrives upon.
However, cancer cells in turn rely on DNA repair to defend themselves against DNA-damaging drugs, such as platinum-based agents. So adding drugs that inhibit DNA repair could increase the effectiveness of chemotherapy, Zhang noted. PARP-inhibitors, a new class of drug in clinical trials, block DNA repair and may also be effective in treating BRCA2 mutated ovarian cancer.
Additional studies of the function of BRCA1 and BRCA2 mutations are needed to more fully understand and exploit their findings to treat cancer, Zhang and colleagues note.
Provided by University of Texas M. D. Anderson Cancer Center
- BRCA2 mutations associated with improved survival for ovarian cancer Apr 04, 2011 | not rated yet | 0
- BRCA2 genetic mutation associated with improved survival, chemotherapy response in ovarian cancer Oct 11, 2011 | not rated yet | 0
- Ashkenazi ovarian cancer patients with BRCA mutations live longer than those with normal gene Jan 02, 2008 | not rated yet | 0
- Olaparib shows promise in treating ovarian cancer, even without BRCA mutations Aug 21, 2011 | not rated yet | 0
- Standard chemo works better against metastatic BRCA1/2 breast cancer than against sporadic tumors Apr 17, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
20 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Cancer 8 hours ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
Cancer 9 hours ago | not rated yet | 0
A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...
Cancer 10 hours ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 11 hours ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 13 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
15 hours ago | 4.2 / 5 (5) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
13 hours ago | 4.9 / 5 (11) | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
15 hours ago | 4.6 / 5 (7) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
9 hours ago | 3.7 / 5 (3) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
10 hours ago | 5 / 5 (4) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
11 hours ago | 5 / 5 (1) | 0 |