NEW YORK – A team from the California-based population genomics firm Helix, Renown Health, and the University of Nevada School of Medicine has demonstrated the potential for delayed mammography-based screening in women with lower-than-usual breast cancer risk based on pathogenic variant and polygenic risk score (PRS) data.
"[W]e are not using risk assessment tools effectively enough — whether they be family history-based or more direct genetic risk assessment," corresponding author Alexandre Bolze, a human genetic researcher and principal scientist at Helix, suggested in an email, noting that "the US needs to consider updating its risk assessment strategies for inherited diseases if we are to better control costs and importantly, better prevent advanced disease."
In a study published in JAMA Oncology on Thursday, Bolze and his colleagues retrospectively considered breast cancer incidence in relation to germline genetic features in nearly 25,600 female participants in the Healthy Nevada Project, looking at breast cancer rates in low-risk women who fell in the lowest risk category with a 313-variant breast cancer PRS and lacked pathogenic variants, likely pathogenic variants, or variants of uncertain significance in established risk genes such as BRCA1/2, PALB2, ATM, or CHEK2.
With pathogenic variant and PRS profiles gleaned from Helix's Exome+ clinical-grade exome sequencing and "microarray-equivalent" backbone sequencing, the team identified 410 high-risk participants and 22,843 participants who appeared to be at average risk of breast cancer.
The remaining 2,338 participants, who fell into the lowest 10 percent risk group with a breast cancer PRS, were classified as being at low risk for breast cancer, the researchers explained — a hypothesis backed up by available electronic health record data going back more than a decade.
"The findings of this retrospective case-control study underscore the value of genetics in individualizing the onset of breast cancer screening," the researchers wrote.
While breast cancer diagnoses came in at 0.69 percent by the age of 45 in the average-risk group, for example, the same breast cancer rate did not show up in the low-risk group until the age of 51. Likewise, 1.41 percent of average-risk participants had documented breast cancer diagnoses by age 50, while a similar diagnostic rate was not reached until age 58 in the low-risk group.
"These findings suggest that deferring mammogram screening by [five to 10] years for women at low risk of breast cancer aligns with new draft recommendations," the authors suggested, adding that "[i]mproving breast cancer risk stratification by implementing both high-risk and low-risk strategies in screening can refine preventive measures and optimize health care resource allocation."
In May of this year, the US Preventive Services Task Force proposed draft recommendations calling for mammogram-based screening every two years starting at the age of 40 in average-risk women.
Based on such findings, the team suggested that it might be possible to incorporate genetic information into breast cancer prevention efforts to dial down overscreening and related anxiety in the low-risk group and to enhance screening for those deemed at higher-than-usual risk genetically.
"[T]here needs to be efforts to increase screening (earlier and more often) for some individuals, as well as efforts to decrease screening for others," Bolze suggested. "This is important for logistics, and financial reasons, but also for personal reasons. No one wants to spend their life going to the health system getting screened for every common condition."
Though the authors conceded that it may be challenging for physicians to apply distinct, decreased screening strategies for individuals deemed to be at low risk of breast cancer based on genetics and other factors, they argued that "reliable risk assessment is essential to support informed decisions and build patient trust in both high-risk and low-risk scenarios."