Factors Contributing to Mammography Failure in Women Aged 40-49 Years

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Abstract
Background: Younger women (40–49 years) have lower mammographic sensitivity (i.e., greater proportion of cancers detected after a negative mammogram) than older women (≥50 years). We explored the effect of tumor growth rate, breast density, mammographic image quality, and breast cancer risk factors on mammographic sensitivity in younger and older women. Methods: We studied 576 women (n = 73 aged 40–49 years and n = 503 aged 50 years or older) who were diagnosed with invasive breast cancer between 1988 and 1993. Interval cancers were defined as those diagnosed within 12 or 24 months after a negative screening mammogram and before a subsequent mammogram. Tumor growth rate was assessed by mitotic figure count and Ki-67 positivity. The main outcome measures were percentage of women with interval cancer (1 –mammographic sensitivity) by age, odds ratio (OR) of interval cancer by age, and excess odds (i.e., the percentage of the odds ratio for age that was explained by individual covariates). Results: Interval cancers occurred in 27.7% of younger women and 13.9% of older women within 12 months (OR = 2.36, 95% confidence interval [CI] = 1.14 to 4.77) and in 52.1% of younger women and 24.7% of older women within 24 months (OR = 3.58, 95% CI = 2.15 to 5.97). Greater breast density explained 67.6% of the decreased mammographic sensitivity in younger women at 12 months, whereas rapid tumor growth explained 30.6% and breast density explained 37.6% of the decreased sensitivity in younger women at 24 months. Conclusions: Breast density largely explained decreased mammographic sensitivity at 12 months, whereas rapid tumor growth contributed to decreased mammographic sensitivity at 24 months. A 12-month versus a 24-month mammography screening interval may therefore reduce the adverse impact of faster growing tumors on mammographic sensitivity in younger women.