Saliva, Blood, Genetics: A New Era in Breast Cancer Screening

1) What is the "New Era"—From Uniformity to Personalization

Traditional breast cancer screening primarily operated uniformly based on "age." The announcement from Laval University (ULaval) is set to change this conventional wisdom. By calculating the Polygenic Risk Score (PRS) from DNA extracted from saliva, and integrating it with blood (circulating tumor DNA = ctDNA, etc.) and clinical and lifestyle factors, it estimates precise individual risk. This allows for setting the optimal point of "burden and effect" for each person, such as annual mammography + MRI from a young age for high-risk individuals and avoiding excessive screening for those with below-average risk. nouvelles.ulaval.ca+1

2) Key Technology: Polygenic Risk Score (PRS)

PRS is a risk indicator that adds up the small contributions of many common genetic polymorphisms (SNPs) related to cancer susceptibility. The ULaval article presents a PRS based on **"313 mutations" and explains its strength in reclassifying risk in cases where there is a family history but no clear high-risk genes (such as BRCA1/2). It suggests that out of 100 people previously considered moderate risk, actually **25 could be reclassified as low risk / 25 as high risk**, a clinically intuitive insight directly linked to revising screening strategies. nouvelles.ulaval.ca

3) Saliva × Blood Hybrid: Balancing Accessibility and Depth

• Saliva: Non-invasive and suitable for mass screening. Large-scale international studies and the PERSPECTIVE project have laid the foundation for calculating personalized scores using saliva DNA + questionnaires. CityNews Montreal+1

• Blood: As a liquid biopsy, it can analyze ctDNA, exosomes, circulating tumor cells, etc., and potentially be used continuously from pre-onset to post-treatment monitoring. At the screening stage, it contributes to detecting subtle changes in high-risk individuals and rationalizing follow-up. Wikipedia

4) Clinical Implementation Plan and Institutional Support Looking to 2026

ULaval is aiming for clinical implementation from 2026, with a research team in Quebec planning to test the detectability and clinical utility (rate of risk category change) of 313 mutations in 400 Quebec patients + 1,000 multi-ethnic Canadian women. On October 2, the Quebec National Assembly unanimously supported the transition to **"risk-based screening", and a petition with 42,000 signatures was submitted. The movement to institutionally support personalized screening is gaining momentum locally. nouvelles.ulaval.ca

5) Historical Accumulation: Risk Identification Research Led by ULaval

• 2019: Announcement that the saliva-based PR model demonstrated "unprecedented accuracy of lifetime risk." ulaval.ca+1

• 2023: Identification of new breast cancer susceptibility genes in an international collaborative study. This achievement fills the "genetic risk residuals" unexplained by existing BRCA, etc., directly linking to the refinement of PRS. pressroom.ulaval.ca

• 2025: Based on the outcomes of PERSPECTIVE, the social implementation of home kits for saliva + questionnaires and risk stratification tools is reported. CityNews Montreal+1

6) What is Happening Scientifically?—The Power of Bundling "Many Small Factors"

Rare but strong mutations like BRCA1/2 cannot explain the entire genetic risk of breast cancer. PRS, which bundles hundreds of mutations that are frequent but have small effects, is a technology that captures the "long tail."

Large-scale GWAS and international consortia from the late 2010s have rapidly advanced external validation in multi-ethnic cohorts, focusing on model transferability (application to non-European populations) as a major issue. ULaval's new plan also specifies performance verification in Asian and African women. nouvelles.ulaval.ca

7) Acceptability and Ethics for Recipients: The Key is "Understandable Options"

Surveys targeting Canadian women report that the majority are positive about providing personal information and saliva/blood samples, and the acceptability of risk stratification screening is generally high. However, there are some concerns about data use, genetic discrimination, and accountability, making transparent consent and genetic counseling indispensable. PMC+1

8) Implications for Japan: A "Gentle Upgrade" from Uniform Age

In Japan, mammography screening centered on those aged 40 and above is standard, but if risk stratification progresses, the following benefits can be expected.

• Strengthening Early Detection: Focus annual mammography + MRI from a young age on those truly at high risk.

• Reducing Overdiagnosis and Over-testing

  : Optimize screening intervals for low-risk individuals to reduce exposure, anxiety, and costs.

  Optimal Allocation of Medical Resources
: Prioritize allocation of imaging equipment and reading personnel to necessary groups.

• Home-based and Minimally Invasive: Reduce disparities in access by using saliva collection and home kits.

  For institutionalization, key factors include ①
external validation of PRS in the Japanese population
• , ②

  insurance coverage and cost-effectiveness, ③ explanatory support (genetic counseling), and ④ frameworks for data protection and discrimination prevention
  .

In

, trial pre-triage using

for those around 40 years old or with a family history.

1. For high-risk individuals, apply MRI combination and short-interval follow-up, and for

   low-risk individuals
, apply interval adjustments with informed consent.

2. Research use of

   blood biomarkers
(ctDNA and protein expression panels) to verify the usefulness of "detecting subtle changes."

3. Evaluate avoidance of overdiagnosis, QALY improvement, and optimization of equipment operating rates with health economic models

   , and move towards
phased introduction
4. .

10) Expectations and Limitations

: Approaching the ideal of screening that is *"faster, more accurate, and with less burden."*

• Limitations: There are many realistic challenges, such as

  ancestral population bias
of PRS,
• very early sensitivity

  of ctDNA, setting of pre-test probability, psychological impact, explanation of false positives and false negatives, and infrastructure differences between regions. A design focusing on multi-ethnic verification and **clinical utility (risk category change)** like ULaval is essential for implementation in Japan. nouvelles.ulaval.ca

Reference Article

Saliva, Blood, and Genetics: A New Era for Breast Cancer Screening - ULaval News