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Summary
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A first-degree breast cancer family history and polygenic risk score (PRS) can guide earlier screening for women aged 30-50. This approach increases life-years gained and breast cancer deaths averted but also leads to more false positives and overdiagnoses.

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Area of Science:

  • Oncology
  • Genetics
  • Preventive Medicine

Background:

  • Assessing the clinical utility of first-degree breast cancer family history and polygenic risk scores (PRS) for screening decisions in women aged 30-50 years.
  • Evaluating risk stratification models for personalized breast cancer screening.

Purpose of the Study:

  • To determine if family history and PRS can inform breast cancer screening strategies in women aged 30-50.
  • To compare the benefits and harms of tailored screening versus established guidelines.

Main Methods:

  • Utilized two established breast cancer models to simulate digital mammography screening strategies.
  • Defined risk groups by family history and PRS (313 single nucleotide polymorphisms).
  • Varied screening initiation ages (30-50) and intervals (annual to triennial), comparing outcomes to existing guidelines.

Main Results:

  • Family history-informed screening initiated at age 40 (vs. 50) increased life-years gained by 36% and averted 20% more breast cancer deaths, with higher false positives (63%) and overdiagnoses (21%).
  • PRS-tailored screening showed smaller gains (20% life-years, 11% deaths averted) with lower increases in harms (10% overdiagnoses, 26% false positives).
  • Combined family history and PRS yielded the greatest benefits: 29% increase in life-years gained and 18% more breast cancer deaths averted.

Conclusions:

  • Breast cancer family history and PRS can guide earlier screening decisions for at-risk women under 50.
  • Increased overdiagnoses and false positives are anticipated with these personalized screening approaches.
  • Risk stratification using both family history and PRS offers the most significant improvements in screening outcomes.