A family history of breast cancer is often mentioned as a reason to start screening early, but when should that be? That's precisely the question German researchers sought to answer in their cohort study based on data from Sweden. They identified possible risk-based starting ages for breast cancer screening using population-based registers.
"The results suggest that current screening guidelines do not adequately provide evidence-based recommendation on starting age of screening for women with a family history of breast cancer. ... Screening women with a family history under the existing guidelines represents missed opportunities for early detection of early-onset breast cancer in women at increased risk owing to family history," wrote the group led by Trasias Mukama from the German Cancer Research Center in Heidelberg.
When to start
Screening can reduce breast cancer mortality by up to 20%, according to previous research. However, many national screening programs have adopted a one-size-fits-all approach, advising women ages 50 to 69 to obtain a biennial mammogram.
Even for women with a family history of breast cancer -- a known risk factor -- no clear-cut guidance exists. For instance, the American Cancer Society recommends that women with a family history of breast cancer start screening at age 40 or 10 years earlier than the youngest relative with a diagnosis.
This is largely based on expert opinion rather than empirical evidence, according to Mukama and colleagues.
"Although many risk-assessment models and tools have been developed, none of them provide the evidence-based risk-adapted starting age of screening for women with different constellations of family history," they wrote.
That's what the researchers sought to remedy with what could be the world's largest family-cancer dataset. All women born from 1932 onward and with at least one known first-degree relative were included in the study (n = 5,099,172). Data from January 1958 to December 2015 were collected.
The researchers found that 118,953 women (2.3%) received a diagnosis of primary invasive breast cancer. A total of 102,751 women (86.4%; mean age at diagnosis, 55.9) did not have a family history of breast cancer in their first- or second-degree relatives at the time of their diagnosis.
Mukama and colleagues used the data to develop what they called a risk-adapted starting age for breast cancer screening. The number varied by the number of first- and second-degree relatives with a breast cancer diagnosis and the age at diagnosis of the first-degree relatives.
For example, they found that a 40-year-old woman in the general population with no family history of cancer had a 1.1% 10-year cumulative risk of cancer. This rose to 1.8% for 45-year-old women and 2.2% for 50-year-old women, up to a lifetime risk of 9.4%.
They then calculated the cancer risk of women at similar ages based on how many relatives they had with cancer and worked backward to see at what age these women should start screening. For example, a woman with one second-degree relative with cancer would reach the same risk level as a 50-year-old woman at age 45, and she would reach the same risk level at age 41 if she had multiple second-degree relatives. If she had a single first-degree relative with cancer, she would reach the 2.2% cancer risk rate at age 50.
The researchers then provided risk-adapted starting ages that corresponded to ages provided in most breast screening guidelines: 40, 45, and 50 years.
|Risk-adapted starting ages for breast screening based on family history
||Age to begin screening
|No family history
|One 2nd-degree relative, no 1st-degree relative
|Two or more 2nd-degree relatives, no 1st-degree relative
|One 1st-degree relative, no 2nd-degree relatives
|One 1st-degree relative, one or more 2nd-degree relatives
|Two or more 1st-degree relatives, any number of 2nd-degree relatives
Mukama and colleagues were quick to caution that more studies are needed to investigate the effectiveness of less screening than is currently recommended for women with a low risk of breast cancer, as well as the cost-effectiveness of earlier initiation of screening for women with high risk owing to a family history of breast cancer.
"Nevertheless, it would be optimal if risk-adapted starting ages of screening for women with a family history were externally validated before implementation in clinical practice, although the current experts' opinion-based recommendations for screening relatives of patients with breast cancer are already in practice without validation," they noted.
In an editorial that accompanied the study, other researchers urged caution before adopting the risk-adapted strategy.
"Although we agree with Mukama et al in calling for a change in current screening guidelines to move toward improved strategies for risk-stratified breast cancer screening, we believe that more research is needed to ascertain the best approaches, particularly within the context of other existing and emerging risk prediction tools for breast cancer and its biologically heterogeneous subtypes," wrote Gretchen Gierach, PhD, from the U.S. National Cancer Institute in Bethesda, Maryland, U.S., and colleagues.
Using "family history alone would likely result in lower risk discrimination at the population level and produce less precise risk estimates," they added. "Thus, the trade-offs between simplicity and precision need to be balanced for specific implementation settings."
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