Early Interval Breast Cancers May Have ‘Unique Biology’

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The timing of interval breast cancer (IBC) detection may predict breast cancer-specific mortality, say US researchers who found that patients diagnosed within a year of screening mammography had significantly worse survival than those with screening-detected disease. 

“The poor prognosis for women with IBCs diagnosed within 1 year after negative mammogram results might not be due to delayed diagnosis but rather to distinct biological characteristics associated with the cancer”, suggest Zhenzhen Zhang, from Oregon Health & Science University Knight Cancer Institute in Portland, and co-workers.

“For instance, increased lymph node involvement is often seen in IBCs and cannot be accounted for entirely by delayed diagnosis but rather may be due to a unique biology”, they write in JAMA Network Open.

The team analysed data from the Women’s Health Initiative study for 3019 women who completed their planned mammography schedule and were diagnosed with breast cancer.

This included 1050 cases of IBC and 1969 screening-detected breast cancers; almost a third (30.9%) of IBCs were detected within a year of the last mammogram with a negative result, while 69.1% were identified 1.0–2.5 years after the last negative mammogram.

IBC patients diagnosed within 1.0–2.5 years of a negative mammogram did not significantly differ from screening-detected patients in terms of prognostic factors or breast cancer-specific mortality, the authors say. 

By contrast, IBCs detected within a year of a negative mammogram were larger than screening-detected tumours (mean 1.97 vs 1.43 cm) and had a higher clinical stage, with a greater proportion including regional (28.4 vs 17.3%) or distant (3.7 vs 0.6%) disease. These IBCs were also more likely than screening-detected tumours to have lobular histology (13.0 vs 8.1%) and lymph node involvement (27.1 vs 17.0%). 

Initial analysis indicated that breast cancer-specific mortality was significantly greater for women with IBC within 1 year of a negative mammogram than those with screening-detected breast cancer, with a hazard ratio (HR) of 1.92. 

And this difference persisted in multivariable competing risk model analyses accounting for trial group, molecular subtype, waist-to-hip ratio, histology and either tumour size (HR=1.46) or lymph node involvement (HR=1.44). 

When both tumour size and lymph node status were adjusted for, however, there was no longer a significant difference in breast cancer-specific mortality between patients with IBC diagnosed within a year of a negative mammogram and those with screening-detected disease. 

Hypothesising that IBCs detected within a year of a negative mammogram may have “distinct tumor characteristics that identify them as at particularly high risk for metastasis”, Zhenzhen Zhang and co-authors believe their findings have “several clinical implications”.  

“Women who present with breast cancer symptoms at the time of negative screening mammogram results should either be recalled more frequently, have a shorter screening period, or undergo another imaging modality, such as ultrasonography or magnetic resonance imaging”, they suggest.

The investigators also postulate that “the combination of germline genomic testing with mammography may help distinguish indolent breast cancers from aggressive breast cancers detected by screening.”

The team concludes: “This study adds to a growing body of literature that argues for the development of novel approaches to detect life-threatening cancers currently missed by mammographic screening.” 

Reference 

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 Netw Open; 3: e207227. doi:10.1001/jamanetworkopen.2020.7227.