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    1 Comment for this article
    Observations on Observational study limitations
    Robert Rosenberg MD FACR, David Seidenwurm MD FACR | Professor Emeritus University of New Mexico, Diagnostic Imaging Sutter Health Sacramento CA
    Miglioretti et al (ref 1) report an observational study of annual mammography versus biennial mammography. The paper does not recognize that there are many reasons for variation in intervals of screening related to behavioral, demographic and medical factors that may influence the comparison. One such omission is the use of breast imaging between screening studies, another is the timeliness of women to return for health care due to symptoms. Women with more frequent studies in the follow up period would have lower stage cancers than those with fewer studies. These represent uncorrected confounders.

    The similar sensitivity of mammography in the
    two groups - ~76% and 72%, is an indication of an observational study problem. Typically, there is a greater sensitivity difference between annual and biennial screening because many more interval cancers occur in the second year compared to the first year. An earlier report from the Breast Cancer Surveillance Consortium using slightly different methods showed greater differences between annual and biennial screening – 74% vs 62% (Ref 2) as does a report from the UK (Fig 1 of Ref 3).

    Several possible explanations exist for the discrepancy:

    1) missing interval cancers in the biennial screening group due to delayed care or more patients lost to follow up,

    2) less than 2 year follow up in the biennial group due to early screening in the second year (by definition - early screens truncate follow up and cancers are not interval cancers), and 3) other differences in the health care use or access of the two groups.

    Available metrics to assess these potential confounders that are included in the Consortium data include comparison of use of diagnostic and breast imaging between screening examinations, and comparison of the total cancers including interval and screen detected cancers in the two populations over a two-year period of time.

    Therefore, this paper likely systematically underestimates the differences of annual vs. biennial screening.

    1) Miglioretti DL, Zhu W, Kerlikowske K, Breast Tumor Prognostic Characteristics and Biennial vs Annual Mammography, Age, and Menopausal Status. JAMA Oncol. 2015;1(8):1069-1077. doi:10.1001/jamaoncol.2015.3084.

    2) Bennett RL, Sellars SJ, Moss SM. Interval cancers in the NHS breast cancer screening programme in England, Wales and Northern Ireland. British Journal of Cancer (2011) 104, 571 – 577.

    3) White, E, Miglioretti, DL, Yankaskas, BC, et al. Biennial versus annual mammography and the risk of late-stage breast cancer. JNCI; DEC 15 2004; v.96, no.24, p.1832-183.
    Original Investigation
    November 2015

    Breast Tumor Prognostic Characteristics and Biennial vs Annual Mammography, Age, and Menopausal Status

    Author Affiliations
    • 1Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, Davis
    • 2Group Health Research Institute, Group Health Cooperative, Seattle, Washington
    • 3Departments of Medicine and Epidemiology and Biostatistics, University of California–San Francisco, San Francisco,
    • 4General Internal Medicine Section, Department of Veterans Affairs, University of California–San Francisco, San Francisco
    • 5Department of Surgery, Office of Health Promotion Research, University of Vermont College of Medicine, Burlington
    • 6University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington
    • 7Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
    • 8Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
    • 9Department of Radiology, The University of North Carolina, Chapel Hill
    • 10Cancer Control Science Department, American Cancer Society, Atlanta, Georgia
    JAMA Oncol. 2015;1(8):1069-1077. doi:10.1001/jamaoncol.2015.3084

    Importance  Screening mammography intervals remain under debate in the United States.

    Objective  To compare the proportion of breast cancers with less vs more favorable prognostic characteristics in women screening annually vs biennially by age, menopausal status, and postmenopausal hormone therapy (HT) use.

    Design, Setting, and Participants  This was a study of a prospective cohort from 1996 to 2012 at Breast Cancer Surveillance Consortium facilities. A total of 15 440 women ages 40 to 85 years with breast cancer diagnosed within 1 year of an annual or within 2 years of a biennial screening mammogram.

    Exposures  We updated previous analyses by using narrower intervals for defining annual (11-14 months) and biennial (23-26 months) screening.

    Main Outcomes and Measures  We defined less favorable prognostic characteristics as tumors that were stage IIB or higher, size greater than 15 mm, positive nodes, and any 1 or more of these characteristics. We used log-binomial regression to model the proportion of breast cancers with less favorable characteristics following a biennial vs annual screen by 10-year age groups and by menopausal status and current postmenopausal HT use.

    Results  Among 15 440 women with breast cancer, most were 50 years or older (13 182 [85.4%]), white (12 063 [78.1%]), and postmenopausal (9823 [63.6%]). Among 2027 premenopausal women (13.1%), biennial screeners had higher proportions of tumors that were stage IIB or higher (relative risk [RR], 1.28 [95% CI, 1.01-1.63]; P = .04), size greater than 15 mm (RR, 1.21 [95% CI, 1.07-1.37]; P = .002), and with any less favorable prognostic characteristic (RR, 1.11 [95% CI, 1.00-1.22]; P = .047) compared with annual screeners. Among women currently taking postmenopausal HT, biennial screeners tended to have tumors with less favorable prognostic characteristics compared with annual screeners; however, 95% CIs were wide, and differences were not statistically significant (for stage 2B+, RR, 1.14 [95% CI, 0.89-1.47], P = .29; size >15 mm, RR, 1.13 [95% CI, 0.98-1.31], P = .09; node positive, RR, 1.18 [95% CI, 0.98-1.42], P = .09; any less favorable characteristic, RR, 1.12 [95% CI, 1.00-1.25], P = .053). The proportions of tumors with less favorable prognostic characteristics were not significantly larger for biennial vs annual screeners among postmenopausal women not taking HT (eg, any characteristic: RR, 1.03 [95% CI, 0.95-1.12]; P = .45), postmenopausal HT users after subdividing by type of hormone use (eg, any characteristic: estrogen + progestogen users, RR, 1.16 [95% CI, 0.91-1.47]; P = .22; estrogen-only users, RR, 1.14 [95% CI, 0.94-1.37]; P = .18), or any 10-year age group (eg, any characteristic: ages 40-49 years, RR, .1.04 [95% CI, 0.94-1.14]; P = .48; ages 50-59 years, RR, 1.03 [95% CI, 0.94-1.12]; P = .58; ages 60-69 years, RR, 1.07 [95% CI, 0.97-1.19]; P = .18; ages 70-85 years, RR, 1.05 [95% CI, 0.94-1.18]; P = .35).

    Conclusions and Relevance  Premenopausal women diagnosed as having breast cancer following biennial vs annual screening mammography are more likely to have tumors with less favorable prognostic characteristics. Postmenopausal women not using HT who are diagnosed as having breast cancer following a biennial or annual screen have similar proportions of tumors with less favorable prognostic characteristics.