Locally advanced breast cancers are more likely to present as Interval Cancers: results from the I-SPY 1 TRIAL (CALGB 150007/150012, ACRIN 6657, InterSPORE Trial)

Abstract

Interval cancers (ICs), defined as cancers detected between regular screening mammograms, have been shown to be of higher grade, larger size, and associated with lower survival, compared with screen-detected cancers (SDCs) and comprise 17% of cancers from population-based screening programs. We sought to determine the frequency of ICs in a study of locally advanced breast cancers, the I-SPY 1 TRIAL. Screening was defined as having a mammogram with 2 years, and the proportion of ICs at 1 and 2 years was calculated for screened patients. Differences in clinical characteristics for ICs versus SDCs and screened versus non-screened cancers were assessed. For the 219 evaluable women, mean tumor size was 6.8 cm. Overall, 80% of women were over 40 and eligible for screening; however, only 31% were getting screened. Among women screened, 85% were ICs, with 68% diagnosed within 1 year of a previously normal mammogram. ICs were of higher grade (49% vs. 10%) than SDCs. Among non-screened women, 28% (43/152) were younger than the recommended screening age of 40. Of the entire cohort, 12% of cancers were mammographically occult (MO); the frequency of MO cancers did not differ between screened (11%) and non-screened (15%). ICs were common in the I-SPY 1 TRIAL suggesting the potential need for new approaches beyond traditional screening to reduce mortality in women who present with larger palpable cancers.

Figures

Fig. 1

Tumor growth rates and periodic screening. Growth rates for three tumor types are illustrated in years. Shown is the progression of cancer, beginning as an early cancer (microscopic disease), as a localized tumor that is mostly likely to be cured, as regional disease that is less likely curable, and as distant, metastatic disease resulting in death. Tumor type A is a slow-growing cancer that may never be detected in a patient’s lifetime. Type B tumors are detectable by screening and will be cured by early detection. Type C tumors grow very rapidly, becoming clinically apparent during the interval between annual screening mammography. Type C tumors do not benefit from current screening approaches

Fig. 2

Distribution of I-SPY 1 patients. The I-SPY 1 cohort consisted of 221 patients. Two patients were excluded. Screened patients had documented screening mammograms within 2 years. Non-screened patients were either younger than 40 years old or were without a screening mammogram within the last 2 years. IC interval cancer, SDC screen-detected cancer

Fig. 3

Tumor grade of ICs versus SDCs. At clinical presentation, ICs were more likely to be higher grade: grade 1 (7%), grade 2 (44%), grade 3 (49%). SDCs were grade 1 (10%), grade 2 (80%), and grade 3 (10%). IC interval cancer, SDC screen-detected cancer