Impact of menstrual phase on false-negative mammograms in the Canadian National Breast Screening Study

The efficacy of breast carcinoma screening should be enhanced if false-negative mammography were reduced. Prospectively collected data from the Canadian National Breast Screening Study were used to examine whether menstrual cycle phase was associated with false-negative outcomes for mammographic screening.

Of 8887 women ages 40-44 years at the onset of screening, randomized to receive annual mammography and clinical breast examination, reporting menstruation no more than 28 days prior to their screening examination, and with a valid radiologic report, 1898 had never used oral contraceptives or replacement estrogen with or without progesterone. The remainder were past (6573) and current (416) estrogen users. Similar selection criteria were applied at subsequent screens. The distribution of false-negative and false-positive mammography in relation to true-negative and true-positive mammography was examined with respect to the follicular (Days 1 to 14) and luteal (Days 15-28) menstrual phases.

Comparing luteal with follicular mammograms in 6989 patients who ever used estrogen, the unadjusted odds ratio (2-sided P-values) for false-negatives versus true-negatives was 2.16 (0.05) and the adjusted odds ratio was 1.47 (0.05). In 1898 never-users, parallel odds ratios for luteal false-negatives were 0.55 (1.0) and 0.74 (1.0), respectively.

These results suggest that menstruating women who have used hormones may have an increased risk of false-negative results for screening mammograms performed in the luteal phase of the menstrual cycle. An increased risk of false-negative mammography might adversely affect screening efficacy. The impact of menstrual phase on mammographic interpretation, especially for women who ever used hormones, requires further investigation.