Breast cancer diagnosed in the year following a negative result after a mammogram, or interval breast cancer (IBC), has now been associated with an increase in mortality compared with screening-detected breast cancer, report JAMA Network Open study results published online June 30.
Previous research has shown a link between IBC and increased mortality, the authors of the present study noted, but it has not investigated whether there is an association between length of time after a screening that IBC was detected and mortality. IBC frequently is diagnosed at later stages compared with screening-detected cancers, and mortality is 2 to 3 times greater.
The authors took up their study to compare outcomes between women with mammography-detected breast cancer and women with IBC detected in 2 time periods:
- Within 1 year of a screening mammogram
- Between 1 and 2.5 years of a screening mammogram
Their secondary analysis used prospective cohort data from the Women’s Health Initiative on 3019 women with a mean (SD) age of 63.1 (6.8) years at enrollment, from 40 US clinical centers, and 68.5 (7.1) years when they received their diagnosis. The women all were participants in a hormone therapy trials, a dietary modification trial, or both. Mean time from enrollment to diagnosis was 5.5 (3.0) years (median, 5 years; range, 0-22 years).
All were followed for a median 19 years after recruitment from 1993 to 1998. Data were collected through March 31, 2018, and analyzed between October 25, 2018, and November 24, 2019. Variables included diagnosis date, mammogram date, and repeat mammogram recommended.
Results show that for the total 1050 cases of IBC diagnosed, most (69.1%; n = 726) occurred in between 1 and 2.5 years following a negative result for breast cancer on a mammogram. However, the cases of IBC diagnosed within 1 year had worse clinical outcomes because of these tumor characteristics that did breast cancers detected through screening:
- More lobular histologic characteristics: 13.0% vs 8.1
- More lymph node involvement: 27.1% vs 17.0%
- Larger tumors: 1.97 cm vs 1.43 cm
- Higher clinical stage: Regional: 28.4% vs 17.3% Distant: 3.7% vs 0.6%
Other results show higher HRs for IBC diagnosed within 1 year of a negative mammogram compared with screening-detected breast cancers (HR, 1.92; 95% CI, 1.39-2.65), even adjusting for trial group, molecular subtype, waist-to-hip ratio, histologic characteristics, and tumor size (HR, 1.46; 95% CI, 1.03-2.08) and lymph node involvement (HR, 1.44; 95% CI, 1.03-2.01).
Breaking some of these data down, women with IBC had both lower mean (SD) body mass index (BMI) and waist-to-hip ratio compared with women with screening-detected cancers:
- BMI: 28.6 (5.6) vs 29.5 (5.8) kg/m2
- Waist-to-hip ratio: 0.81 (0.08) vs 0.82 (0.08)
All diagnoses were confirmed using medical records and pathology reports, and results from the 2 to 3 mammograms that preceded the IBC or screening-detected breast cancer diagnosis were used to differentiate the 2 cancers. χ2 tests and t tests were used for categorical and continuous variables, respectively.
“Women with IBCs diagnosed within 1 year of negative mammogram results overall were associated with worse survival than women with breast cancers detected by screening,” the authors concluded. “These differences in survival may be due to a uniquely aggressive biology among IBC cases.”
To help ameliorate their findings, the authors suggest that women who have a negative mammogram yet symptoms of breast cancer undergo more frequent screenings, have shorter screening periods, or use mammography plus another screening method (eg, MRI, breast sonogram).
Irvin VL, Zhang Z, Simon MS, et al. Comparison of mortality among participants of Women’s Health Initiative trials with screening-detected breast cancers vs interval breast cancers. JAMA Network Open. Published online June 30, 2020. doi:10.1001/jamanetworkopen.2020.7227