Women with the gene that causes breast cancer are developing the disease almost eight years earlier than their mothers or aunts who also had the disease, a new study suggests.
The findings, published Sept. 12 in CANCER, a peer-reviewed journal of the American Cancer Society, could change the way women are screened for breast cancer in the future, according to the study's authors. "There is a trend overall that the age of onset for breast cancer is getting younger," said Dr. Banu Arun, senior author of the study.
Researchers from the MD Anderson Cancer Center at the University of Texas followed 132 women who tested positive for either the BRCA 1 or BRCA 2 gene, and found 106 had a female family member in the previous generation with either breast or ovarian cancer.
Women can be tested for the BRCA genes, known as tumour suppressors, mutations of which have been linked to a significantly increased hereditary risk of developing breast and ovarian cancer.
In comparing the women's ages at diagnosis, researchers found the daughters were diagnosed almost eight years earlier than women in the previous generation.
Arun, a medical oncologist and professor, said she was not surprised to see the study's findings.
"In our practice, we have somehow seen that trend that with each subsequent generation we are seeing younger onset of breast cancer," said Arun.
The study's authors believe the trend of women being diagnosed with breast cancer earlier than their mothers could be explained by a phenomenon known as anticipation.
Anticipation occurs in genetic diseases like Huntington's, in which the disease occurs at younger ages or with increased severity from generation to generation as a result of the DNA instability.
Their findings showed the median age of diagnosis was 42 for the second generation, compared to a median age of 48 in the first generation. Using a mathematical model to account for anticipation, the researchers found the average difference in age of breast cancer onset between generations was 7.9 years.
However, Arun said the findings reveal there may be a combination of other factors involved in the earlier onset of breast cancer, like hormones, diet, lifestyle and environmental factors, which the study did not investigate.
"I think it's a combination of factors — it's a mixed picture," she said.
The researchers noted better screening methods and increased awareness of breast cancer could also have had an effect on the study's results, said Arun.
"The individuals in the second generation, because they already had a first-degree relative with breast cancer, they started their screening earlier anyway," she said. "With better and earlier screening, it may be that we are diagnosing them sooner."
The research confirms that women with BRCA mutations should continue to be screened using mammograms and MRI, and should consider preventive prophylactic surgeries — in other words, removing breast tissue and ovaries to reduce the risk of developing cancer.
However, women with a close relative with the BRCA gene should perhaps be screened at an even earlier age, said Arun.
"The current guidelines, without having a lot of data, is to start screening five to 10 years earlier than their youngest affected family member," said Arun.
Although he agreed the age of onset for breast cancer seems to be getting younger compared to past generations, Dr. Steven Narod, co-discoverer of the BRCA 1 and BRCA 2 gene, claimed there are several flaws in the research that affect the study's conclusion.
One problem, he said, is the researchers assumed the mothers and aunts of women who tested positive for the BRCA genetic mutation also carried the same gene mutation.
"Suppose 10 per cent of them didn't have a mutation, then generation one represents a mix of sporadic and hereditary cases, while generation two is made up of 100 per cent hereditary cases, which are by definition younger," said Narod.
Narod said the earlier onset of breast cancer diagnosis between generations of women with the BRCA gene is more likely a result of the cohort effect, not genetic anticipation.
"The concept of anticipation is that the mutation becomes more expressed as generations go on," he said, whereas the cohort effect states the probability of getting a disease depends on the year of birth.
In his own research, Narod said his team recently uncovered a particular BRCA mutation, which they believe arose at least 70 generations ago.
"If the mutation arose 70 generations ago, and each generation it became younger and younger — how could it jump 10 years in one generation?" he asked. "That means it should have jumped 700 years since it came along."
However, Arun said there are modifying factors in our present-day world that affect women's risk of developing breast or ovarian cancer. For example, some women have a higher risk of developing breast cancer if they take estrogen replacement therapy, she said.
"But several hundred years ago, women were not taking estrogen," she explained. "There are all kinds of environmental factors that are different in this century than in any other time."
As this study followed only 132 women, the authors said they hope to expand their future research to include more breast cancer patients and look at other cancer-causing factors.