Menstrual cycle variation in mammographic breast density: so who cares?

So who cares? Is it really important that there is a 4% excess in the proportion of women with mammographically ‘‘extremely dense breasts’’ in the luteal phase of the menstrual cycle compared with the follicular phase? For that is what White et al. (1) have clearly shown in this issue of the Journal in a study based on an analysis of 2591 menstruating women who had screening mammograms in a health maintenance organization during the last 7 months of 1996. My opinion is that this excess is important. As White et al. (1) point out, increased mammographic density is associated with decreased mammographic sensitivity and decreased mammographic specificity. Both of these operating characteristics put younger women at a disadvantage compared with older women in terms of benefiting from the early detection of breast cancer. As for the small size of the effect (4% overall), it is often overlooked that a small effect on a large population can have an impact far greater than a large effect on a small population. When millions of women are being encouraged to seek mammographic screening in their forties, even a small effect may prove to be important. Women in their forties who undergo mammographic screening are facing high probabilities of false-positive screens, namely, a 30% cumulative risk after five mammograms and a 56% cumulative risk after 10 mammograms (2); however, they achieve only a rather small and delayed benefit in terms of a reduction in breast cancer mortality when they are screened in their forties (3,4). Women surely will welcome any opportunity to enhance mammography’s effectiveness. Follicular timing may appeal to them. White et al. (1) found that body mass index (BMI) had the strongest association with breast density overall. Fifty-three percent of women in the lowest BMI quartile had extremely dense breasts compared with 5% in the upper quartile. However, even after adjustment for BMI, menstrual cycle phase was associated with breast density. When women were stratified by BMI (above and below the median), the association of menstrual phase with density was stronger for women in the lower half (P<.01). The proportions of leaner women with extremely dense breasts in the luteal phase were 46% for week 3 and 45% for week 4, while in the follicular phase, the proportions were 40% for week 1 and 35% for week 2.