Practice Update

JAMA Intern Med 2013 May 01;173(8)807-816, K Kerlikowske, W Zhu, RA Hubbard, B Geller, K Dittus, D Braithwaite, KJ Wernli, DL Miglioretti, ES O'Meara

TAKE-HOME MESSAGE

This large, prospective cohort study found that biennial screening mammography for most women aged 40 to 49 and 50 to 74 years, even among those with high breast density or receiving combination hormone therapy (risk factors for breast cancer), results in similar risks of presenting with advanced-stage disease as with annual screening mammography. Most women who undergo annual mammography are at high risk of false-positive results without benefit from the more frequent screening. However, a small proportion of women aged 40 to 49 with extremely dense breasts are more likely to present with advanced-stage disease if they undergo biennial vs annual screening; this benefit is counterbalanced by a higher risk of cumulative false-positive mammography results with annual screening.
Screen all women aged 50 to 74 biennially (regardless of breast density or hormone therapy use). When counseling women aged 40-49 about breast cancer screening, those with extremely high density breasts should be informed that annual mammography may minimize their risk of presenting with advanced-stage disease but the cumulative risk of false-positive results is high.

SUMMARY

PracticeUpdate Editorial Team

Updated US guidelines recommending that women aged 50 to 74 years undergo mammography biennially, instead of every 1 to 2 years as previously recommended, do not take into account women with additional breast cancer risk factors, such as increased breast density and postmenopausal use of hormonal therapy (HT). More frequent screening may be advantageous in these women, but few studies have reported outcomes when risk factors are combined with frequency of screening mammography.
This study evaluated women aged 40 to 74 years undergoing screening mammography in a community setting to determine whether the benefits (detection of early-stage disease) and harms (false-positive result or biopsy recommendation) differed by screening frequency according to age, breast density, and postmenopausal HT use. Breast Cancer Surveillance Consortium mammography registry data from 1994 through 2008 were used to identify women with and without breast cancer who had undergone annual, biennial, or triennial screening mammography. Analyses for benefit included 11,474 women with at least two screening examinations before diagnosis with breast cancer. Most of these women were aged ≥ 50 years, and > 50% had heterogeneously dense or extremely dense breasts. Analyses for harm included 922,624 women with no previous breast cancer and no cancer within 1 year of screening. Of these women aged 40 to 49 years, 55.1% had extremely dense breasts.
The risk of presenting with advanced-stage breast cancer was similar for most women aged 40 to 49 years and 50 to 74 years screened biennially compared with those screened annually, including those women with high breast density or who were receiving combination HT. Only women aged 40 to 49 years with extremely dense breasts were at increased risk of presenting with advanced-stage rather than early-stage disease when screened biennially vs annually (adjusted odds ratio [AOR] = 1.89; 95% CI, 1.06-3.39) and of presenting with a tumor size > 20 mm (AOR = 2.39; 95% CI, 1.37-4.18). Women aged 50 to 74 years with heterogeneously dense or extremely dense breasts who were receiving combination HT had an apparent, but nonstatistically significant, increased risk of advanced-stage disease (AOR = 1.56; 95% CI, 0.88-2.80) and tumor size > 20 mm (AOR = 1.59; 95% CI, 0.97-2.61) with biennial vs annual screening.
Annual screening was associated with a high probability of a false-positive mammography result in most women, with probability decreasing as the screening interval increased. Women aged 40 to 49 years were most likely to have at least one false-positive recall after 10 years of subsequent annual mammography, with cumulative probabilities of 68.9% and 65.5% in women with heterogeneously dense or extremely dense breasts, respectively. Likewise, women aged 50 to 74 years receiving combination HT and with heterogeneously dense or extremely dense breasts had similarly high cumulative probabilities of a false-positive result with annual screening (68.1% and 65.8%, respectively). Lowest cumulative probabilities were seen in women with fatty breasts across both age groups and regardless of combination HT use (30.3%–36.3%). Cumulative probabilities of at least one false-positive biopsy recommendation after 10 years were much lower than those of a false-positive recall, although of a similar pattern.
This study found that, with the exception of women aged 40 to 49 years with extremely dense breasts, biennial screening mammography was associated with a similar risk of presenting with advanced-stage disease compared with annual screening mammography, but overall the probability of a false-positive screening result was higher.

JAMA internal medicine