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Why Has Breast Cancer Screening Failed to Decrease the Incidence of de Novo Stage IV Disease?

Danielle R Heller1, Alexander S Chiu2, Kaitlin Farrell3

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Stage IV breast cancer (BC) presents with more aggressive biology than early-stage BC, explaining why screening mammography has not reduced late-stage diagnoses. Aggressive tumors are linked to higher odds of Stage IV BC.

Keywords:
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Area of Science:

  • Oncology
  • Cancer Biology
  • Epidemiology

Background:

  • Despite decades of screening mammography, the incidence of Stage IV breast cancer (BC) has not declined.
  • Previous research suggests many BCs are small due to favorable biology, not early detection.
  • This study investigates the biological differences between Stage IV BC and small, screen-detected BCs.

Purpose of the Study:

  • To compare the biological characteristics of Stage IV breast cancer with those of small, early-stage breast cancers.
  • To determine if biological differences explain the lack of decrease in Stage IV BC incidence despite screening efforts.

Main Methods:

  • Utilized SEER*Stat to analyze trends in localized, regional, and distant female BC incidence.
  • Queried the National Cancer Database (NCDB) for invasive cancers (2010-2015), comparing patient and disease variables across stages.
  • Classified tumors into indolent, intermediate, and aggressive biological subtypes based on ER, PR, Her2, grade, and lymphovascular invasion.

Main Results:

  • Confirmed an increase in distant BC incidence from 1973-2015 (APC = 0.46).
  • Stage IV BC is more prevalent in younger, Black, uninsured women with lower socioeconomic status and larger, aggressive tumors.
  • Stage IV disease comprised 37.6% aggressive and 6.0% indolent tumors, contrasting with sub-centimeter Stage I disease (5.1% aggressive, 40.6% indolent; p < 0.001).
  • Aggressive tumors were associated with over a threefold increased odds of Stage IV presentation (OR 3.2).

Conclusions:

  • Stage I and Stage IV breast cancers are biologically distinct populations.
  • These biological differences likely account for the persistent incidence of Stage IV breast cancer, irrespective of screening mammography.