Study unpicks gene changes behind breast cancer
Scientists have mapped the complete genetic codes of 21 breast cancers and created a catalogue of the mutations that accumulate in breast cells, raising hopes that the disease may be able to be spotted earlier and treated more effectively in future.
The research, the first of its kind, untangles the genetic history of how cancer evolves, allowing scientists to identify mutational patterns that fuel the growth of breast tumors, and start to work out the processes behind them.
“These findings have implications for our understanding of how breast cancers develop over the decades before diagnosis in adults and might help to find possible targets for improved diagnosis or therapeutic intervention in the future,” said Mike Stratton, who led the research team.
Breast cancer kills more than 450,000 women a year worldwide and is the most common cancer among women, accounting for 16 percent of all cases, according to the World Health Organization (WHO).
A study last year by the Institute for Health Metrics and Evaluation in the United States found that global breast cancer cases have more than doubled in just three decades, from 641,000 cases in 1980 to 1.6 million cases in 2010 - a pace that far exceeds global population growth.
U.S. Breast Cancer Statistics
- About 1 in 8 U.S. women (just under 12%) will develop invasive breast cancer over the course of her lifetime.
- In 2011, an estimated 230,480 new cases of invasive breast cancer were expected to be diagnosed in women in the U.S., along with 57,650 new cases of non-invasive (in situ) breast cancer.
- About 2,140 new cases of invasive breast cancer were expected to be diagnosed in men in 2011. A man’s lifetime risk of breast cancer is about 1 in 1,000.
- From 1999 to 2005, breast cancer incidence rates in the U.S. decreased by about 2% per year. The decrease was seen only in women aged 50 and older. One theory is that this decrease was partially due to the reduced use of hormone replacement therapy (HRT) by women after the results of a large study called the Women’s Health Initiative were published in 2002. These results suggested a connection between HRT and increased breast cancer risk.
- About 39,520 women in the U.S. were expected to die in 2011 from breast cancer, though death rates have been decreasing since 1990 - especially in women under 50. These decreases are thought to be the result of treatment advances, earlier detection through screening, and increased awareness.
- For women in the U.S., breast cancer death rates are higher than those for any other cancer, besides lung cancer.
“This is the first time we’ve been able to delve fully into breast cancer genomes in such a thorough way,” said Peter Campbell, head of cancer genetics and genomics at the Wellcome Trust Sanger Institute in Cambridge, where the studies were led.
The work had given scientists “a full panoramic view of the cancer genome” and helped them identify “mutational patterns rather than individual mutations in specific genes”, he added.
DNA MUTATIONS
“We’ve known for many years now that all cancers are due to abnormalities of DNA…that occur in every single cell of the body over the course of a lifetime,” said Stratton.
“But although we’ve known that, it’s remarkable how rudimentary our knowledge is about what the processes are that cause these abnormalities, these mutations in our DNA.”
Stratton’s team sequenced the genomes of the 21 breast cancers and catalogued all the mutations. They found five major processes that cause one letter of code to be changed to another letter. Genetic code comes in four DNA letters, A,C,G and T.
U.S. Breast Cancer Statistics
- Besides skin cancer, breast cancer is the most commonly diagnosed cancer among American women. Just under 30% of cancers in women are breast cancers.
- White women are slightly more likely to develop breast cancer than African-American women. However, in women under 45, breast cancer is more common in African-American women than white women. Overall, African-American women are more llkely to die of breast cancer. Asian, Hispanic, and Native-American women have a lower risk of developing and dying from breast cancer.
- In 2011, there were more than 2.6 million breast cancer survivors in the US.
- A woman’s risk of breast cancer approximately doubles if she has a first-degree relative (mother, sister, daughter) who has been diagnosed with breast cancer. About 15% of women who get breast cancer have a family member diagnosed with it.
- About 5-10% of breast cancers can be linked to gene mutations (abnormal changes) inherited from one’s mother or father. Mutations of the BRCA1 and BRCA2 genes are the most common. Women with these mutations have up to an 80% risk of developing breast cancer during their lifetime, and they are more likely to be diagnosed at a younger age (before menopause). An increased ovarian cancer risk is also associated with these genetic mutations.
- In men, about 1 in 10 breast cancers are believed to be due to BRCA2 mutations, and even fewer cases to BRCA1 mutations.
- About 85% of breast cancers occur in women who have no family history of breast cancer. These occur due to genetic mutations that happen as a result of the aging process and life in general, rather than inherited mutations.
- The most significant risk factors for breast cancer are gender (being a woman) and age (growing older).
Stratton said one of the most exciting findings was that one of these processes is characterized by small pockets of massively mutated regions of the genome.
This sudden “storm” of mutations is often seen in breast cancers, he explained in an audio briefing.