Risk Factors and Tumor Characteristics of Interval Cancers by Mammographic Density

Abstract

Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.

The epidemiology, radiology and biological characteristics of interval breast cancers in population mammography screening

“…10, 11, 14, 39, 45, 51 The detailed findings, summarised in our results, are complex but reveal some common findings. Mammographic density was consistently associated with occult BCs (followed by true interval BCs) rather than missed interval cases, 10, 14 highlighting a likely masking effect.…”

“…Missed cases had larger mean invasive tumour size than true intervals (28.5 vs. 24 mm, p  = 0.003).Interval BCs in year 2 of inter-screen interval for digital mammography were more frequently receptor triple negative than those occurring year 2 following film-screen mammography ( p  = 0.02).Meshkat 47 Interval vs. screen-detected BCs, screening unit for the Irish breast screening program (2010–13)Interval BCs had higher tumour grade ( p  < 0.05) and higher stage (proportion stage 1 vs. 2; p  < 0.001) than screen-detected BCs. Invasive lobular was more frequent among interval than screen-detected BCs (21% vs. 11%, p  < 0.05).Interval BCs less likely to be ER positive (76% vs. 81%, p  < 0.05) and more likely to overexpress HER2 (20% vs. 10%, p  < 0.05) than screen-detected BCs.Holm 45 Interval vs. screen-detected BC among women diagnosed with invasive BC (2001–08), Stockholm, Sweden, by breast density.Interval BCs in non-dense breasts (<20% density) were more likely to harbour lymph node metastases (OR 3.55) than screen-detected BC in non-dense breasts.Interval BCs in non-dense breasts more likely to be ER negative (OR 4.05), PR negative (OR 2.63), HER2 positive (OR 5.17), and triple negative (OR 5.33) than screen-detected BC.Domingo 14 Study of 2245 invasive BCs (948 were interval BCs) diagnosed 2000–09 in participants in population breast screening in Spain: compares interval and screen-detected BC, as well as categories of interval BCs, by densityMean tumour size significantly larger for all radiological categories of interval BCs (range from 19.3 mm for occult cases to 25.3 mm for true interval cases) than mean tumour size for screen-detected BC (15.7 mm) [ p  < 0.001 comparison across all groups]. Proportion with lymph node metastases higher for all categories of interval BCs (range from 38% for occult cases to 50% for true interval and minimal-sign cases) than screen-detected BC (30%), [ p  < 0.001 comparing all groups].…”

“…11, 45 Holm et al 45 showed that interval BCs occurring in non-dense breasts (defined by<20% density) had poorer prognostic features than screen-detected BC (Table 3), whereas interval BCs in dense breasts (≥50% density) were phenotypically more similar to screen-detected cancers. Eriksson et al 51 compared survival in interval and screen-detected BC allowing for mammographic density in women aged 50 years and older; they showed that hazard rates for BC-specific survival were significantly higher for interval than for screen-detected cancers, independent of density.…”

Breast Cancer Screening for Women at Average Risk

“…In 2014, there were an estimated 3,088,180 female survivors of invasive breast cancer 40 years of age and older, approximately 4% of the total population; 14 a 2005 prevalence estimate of those having received a diagnosis of in-situ breast cancer was 570,403, expected to increase to over 1 million by 2016; 15 0.2 to 0.3 percent of the general population and 2 percent of Ashkenazi Jewish women are estimated to be carriers of the BRCA1 or BRCA2 mutation, 16 and overall 5.8% of mammography screening age women may be either known or suspected mutation carriers based on having approximately a 20% or greater lifetime risk of breast cancer based on assessment of family history with specialty software; 17 and in 2010 it was estimated that there were 50,000 to 55,000 women in the U.S. who had been treated with moderate to high-dose chest radiation for pediatric and young adult cancers. 18 There also are women outside of these risk categories who are still at higher than average risk of breast cancer and for whom mammography alone may be less effective, including women with significant family histories but who do not have a high probability of being carriers of identified mutations, 19 women with a prior diagnosis of benign proliferative breast disease, 20 and women with significant mammographic breast density. 21 .…”

Breast Cancer With a Poor Prognosis Diagnosed After Screening Mammography With Negative Results

“…1 These interval cancers (cases of cancer diagnosed during the interval between examinations) include both cancers that were present during screening mammography but were missed on examination and rapidly growing cancers that present symptomatically and tend to have a poorer prognosis than cancers detectedduringscreening. 1–3 Identifyingwomenwhoareathigh risk of breast cancer with a poor prognosis despite regular screening mammography could enable targeted supplemental screening for women for whom screening mammography may not be sufficient. This study describes the incidence of and risk factors associated with breast cancer with a poor prognosis after screening mammography with negative findings.…”