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The study by Narumi-Harada et al1 is a secondary analysis of the Japan Strategic Anti-cancer Randomized Trial (J-START) cohort.2 J-START was the first randomized clinical trial powered to investigate the utility of supplemental ultrasonography for breast cancer screening, not only in terms of its diagnostic accuracy (ie, cancer detection rates and positive predictive values), but also to determine its oncologic efficacy. Oncologic efficacy of screening should ideally be evaluated by comparing mortality rates as an outcome. However, assessing mortality rates requires decades of follow-up, which means that the results of today’s screening studies would be available only in the far future, at a time when today’s technology will most likely be outdated anyway. Therefore, the efficacy of new screening methods is best evaluated by assessing the rate with which screening fails— that is, the interval cancer rate and/or the fraction of cancers that are detected when they are already at a locally advanced or metastatic stage as proxies for the actual end point, breast cancer–related mortality. The J-START study2 found that in Japanese women undergoing routine breast cancer screening, supplemental ultrasonography helped reduce interval cancer rates and the rate of late-stage disease and, thus, helped reduce breast cancer–related mortality. The secondary analysis1 was done to determine whether women’s breast density would modulate these results. Surprisingly, the authors found that the contribution of ultrasonography to early diagnosis of breast cancer in Japanese women did not depend on breast density.1 This is noteworthy because the current narrative regarding supplemental screening of breast cancer in Western countries says that it is needed only for women with dense breasts. The female breast is composed of fibroglandular and fat tissue in quite variable relative amounts; like many other biological features, the distribution of fibroglandular vs fat tissue components follows a bell-shaped curve. The more fibroglandular tissue a breast contains, the denser the tissue appears on the mammogram. This is because the fibroglandular tissue causes a strong attenuation of x-rays and, thus, appears white on mammograms, similar to breast cancer; a breast cancer may thus be hidden or masked by overprojecting fibroglandular tissue. Women’s individual breast density is determined mainly by genetic factors, with a modulating effect by endogenous or exogenous hormones. Accordingly, breast density may change over a woman’s lifetime; it is usually somewhat denser in young, premenopausal women and may become somewhat less dense after menopause. In addition to its masking effect, breast density has also been established as a factor independently associated with the risk of breast cancer development. The risk of breast cancer among women with extremely dense breasts is approximately double that among women with nondense breasts, and women with extremely dense breasts have a 4 to 6 times higher risk of breast cancer than do women with fatty breasts.3 In essence, women with dense breasts undergoing regular mammographic screening face an increased risk of a late diagnosis of breast cancer and, thus, of premature death from breast cancer. Therefore, in the US, women must be informed about their individual breast density and about the diagnostic and prognostic implications of it. Breast imaging societies recommend supplemental screening in these women to compensate for the weaknesses of mammography. Imaging methods + Related article