Risk of Breast Cancer After Negative Screening Mammography

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Anne Marie McCarthy, PhD

Anne Marie McCarthy, PhD

A study reported in JAMA Oncology by Anne Marie McCarthy, PhD, of the Division of General Internal Medicine, Massachusetts General Hospital, and colleagues identified the risk of interval breast cancer after negative screening mammography, including the risk of poor-prognosis breast cancer.

The study involved mammography data from the Population-Based Research Optimizing Screening Through Personalized Regimens (PROSPR) consortium. The study population included women aged ≥ 40 years with no prior diagnosis of breast cancer who had screening mammography between 2011 and 2014.

Cancer diagnoses within 1 year after screening were obtained from state registries. Poor-prognosis breast cancer was defined as distant metastases, positive regional lymph nodes, estrogen receptor–positive and/or progesterone receptor–positive and HER2-negative invasive cancer ≥ 2 cm in diameter, triple-negative invasive cancer ≥ 1 cm in diameter, or HER2-positive invasive cancer ≥ 1 cm in diameter.

Interval Cancers

Among 306,028 women included in the analysis, screening mammography was negative in 272,881. Among them, 160 interval breast cancers were identified, including 90 with a good prognosis (3.3/10,000) and 70 with a poor prognosis (2.6/10,10,000).

Cases with poor-prognosis disease accounted for 43.8% of diagnoses among women with negative screening mammography vs 26.9% among those with positive screening mammography (P < .001). Among all women with negative mammography, those with dense breasts vs nondense breasts were at greater risk of an interval cancer diagnosis of any prognosis (odds ratio [OR] = 2.07, P = .02). Neither age nor family history was significantly associated with cancer diagnosis after negative screening mammography. Among women with a diagnosis of cancer after negative mammography, younger age was associated with an increased risk of poor-prognosis cancer (OR = 3.52, P = .048 for age 40–49 vs 70–89; P for trend = .005). Neither breast density nor family history was associated with a poor prognosis.

Breast density was not associated with cancer diagnosis after positive screening mammography. Age (OR = 0.22, P < .001, for age 40–49 vs 70–89) and family history (OR = 1.29, P < .001, for positive vs negative family history) were associated with the likelihood of a breast cancer diagnosis. None of these factors was associated with risk for poor-prognosis cancer.

The investigators concluded, “Although the rate of breast cancer after negative mammography results is small, the likelihood that such cases will be associated with a poor prognosis highlights the need to improve early detection for these women. Although breast density is predictive of interval cancer overall, it is less predictive of whether that interval cancer will have a poor prognosis. Younger age is predictive of interval breast cancer with a poor prognosis…. [B]reast density has received much attention as the primary factor identifying a need for supplemental screening, but considering both breast density and age may be more effective in identifying women who are at risk for breast cancer with a poor prognosis.” ■

McCarthy AM, et al: JAMA Oncol 4:998-1001, 2018.




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