Researchers conducting a large national registry study recommended changes to current breast cancer screening guidelines that would make family history a more important consideration in setting ages to begin regular mammography.
Elham Kharazmi, MD, PhD, of the National Center for Tumor Diseases in Heidelberg, Germany, and colleagues looked at data from large Swedish data sets on 5,099,172 women born there from 1932 onward with at least one known first-degree relative. Of these women in the latest dataset from 2017, 2.3% were diagnosed with primary invasive breast cancer, the majority of whom (86.4%) had no family history of the disease.
As described in the team’s nationwide cohort study online in JAMA Oncology, the risk-adapted starting age of screening was defined as the age by which women with a family history of breast cancer attained a 10-year cumulative risk that was similar to the average risk for women at the recommended age of screening initiation in the general population — in this case a cumulative risk of 2.2%.
The age at which this risk was achieved varied by the number of relatives affected. For example, when screening initiation was recommended at age 50 for the general population, those women with one affected first-degree relative had a similar risk (2.2%) at age 40. Those women with multiple affected first-degree relatives alone or with additional affected second-degree relatives attained a similar risk at age 35.
Age at diagnosis of the first-degree relative was also found to modify the age at which women with a family history should initiate screening. When screening is recommended to begin at age 40 for the general population, women with one first-degree relative reached the same risk at age 30 overall, the analysis showed. This changed to age 32 for women whose relative was diagnosed with breast cancer from ages 40 to 44, and increased to age 36 for women with a relative diagnosed after age 50.
“We have identified the equivalent ages at which women with different constellations of family history of breast cancer attained 10-year cumulative risk similar to that of women with average risk at the age at which initiating screening is suggested, hence providing evidence-based risk-adapted starting ages of screening for women with family history,” Kharazmi and colleagues wrote. “We believe this information is clinically useful for counseling women with particular constellations of family history, including family history in extended relatives or for whom current guidelines advise individualized decision making.”
Only primary invasive breast cancers were considered in the study. In the general population, the risk for developing breast cancer in the next 10 years was 1.1% at age 40, 1.8% at age 45, and 2.2% at age 50. Lifetime risk for breast cancer was 9.4% among women with no family history compared with 11% to 23% among those with a family history.
Cautions from Accompanying Editorial
However, the integration of these findings into the current, and ever-evolving landscape of personalized breast cancer screening presents some challenges, according to Gretchen L. Gierach, PhD, MPH, of the National Cancer Institute in Bethesda, Maryland, and colleagues writing in an accompanying editorial.
“Identification of a subset of the population who may need to initiate screening earlier must be balanced with potential costs of false-positive results, particularly given that the number of additional cases that would be detectable by screening would still be relatively low in younger women,” the editorialists wrote. “Population-wide, risk-stratified screening programs have the potential to improve the cost-effectiveness of mammographic screening and to reduce potential harms from over-diagnosis and false-positive findings, but such programs might require reducing screening for those at low risk and increasing screening for those at high risk.”
Additionally, risk scores that incorporate polygenic risk are also starting to be used to establish starting age of screening based on genetic risk, Gierach and colleagues noted.
“Because approximately 85% of women in the Swedish cohort do not have a family history of breast cancer and estimates based only on family history would not apply to them, incorporating additional information from common variants and classical risk factors is important to estimate the risk-adapted starting age of screening,” the editorialists said.
They, as well as the study researchers, also pointed out that the performance of screening mammography, the focus of the study, tends to be lower in younger women, who often have denser breasts. In these cases, other screening modalities, such as breast tomosynthesis and ultrasonography, may be needed for routine screening.
“Although we agree with [Kharazmi’s group] 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,” Gierach and co-authors wrote.
Kharazmi reported support from a research grant from the German Academic Exchange Service, and a co-author noted support from the China Scholarship Council.
Both the researchers and the editorialists reported having no conflicts of interest.
Source Reference: Mukama T, et al “Risk-adapted starting age of screening for relatives of patients with breast cancer” JAMA Oncol 2019; doi:10.1001/jamaoncol.2019.3876.
Source Reference: Gierach GL, et al “Toward risk-stratified breast cancer screening: consideration for changes in screening guidelines” JAMA Oncol 2019; doi:10.1001/jamaoncol.2019.3820.