Interval breast cancer is associated with other types of tumors

Abstract

Breast cancer (BC) patients diagnosed between two screenings (interval cancers) are more likely than screen-detected patients to carry rare deleterious mutations in cancer genes potentially leading to increased risk for other non-breast cancer (non-BC) tumors. In this study, we include 14,846 women diagnosed with BC of which 1,772 are interval and 13,074 screen-detected. Compared to women with screen-detected cancers, interval breast cancer patients are more likely to have a non-BC tumor before (Odds ratio (OR): 1.43 [1.19-1.70], P = 9.4 x 10^-5) and after (OR: 1.28 [1.14-1.44], P = 4.70 x 10^-5) breast cancer diagnosis, are more likely to report a family history of non-BC tumors and have a lower genetic risk score based on common variants for non-BC tumors. In conclusion, interval breast cancer is associated with other tumors and common cancer variants are unlikely to be responsible for this association. These findings could have implications for future screening and prevention programs.

Fig. 1

Prior and subsequent non-BC tumor diagnoses in IC compared with SDC. The effect size estimates of the association with interval breast cancer (IC) risk (black squares) compared with screen-detected breast cancer (SDC) as well as the 95% confidence intervals (CI, horizontal lines) for different prior and subsequent cancers are shown. The exact estimates derived from logistic regression models adjusted for age at diagnosis are given on the right-hand side of the plot with the accompanying 95% CI. a A prior non-BC tumor diagnosis (any type) as well as a prior lung, skin, non-melanoma skin, or colorectal cancer diagnosis was significantly associated with increased risk for IC compared with SDC. b A non-BC tumor diagnosis after breast cancer (any type) as well as a subsequent colorectal, skin, or non-melanoma skin cancer diagnosis was significantly more common in IC cases than in SDC cases. *P < 0.05; **P < 0.01; ***P < 0.001

Fig. 2

Cancer genetic risk scores in interval breast cancer risk. Cancer genetic risk scores (GRS) were computed in Caucasian patients from the LIBRO-1 (N = 1784), KARMA (N = 1690) and WHI (N = 1585) studies. The odds ratios of different cancer genetic risk scores (GRS) on interval breast cancer (IC) risk (black squares) compared with SDC as well as the 95% confidence intervals (CI, horizontal lines) were computed with logistic regression, adjusted for age at diagnosis, study and the first three principal components. The exact estimates are given on the right-hand side of the plot with the accompanying 95% CI. The breast cancer GRS, skin cancer GRS, non-melanoma skin cancer GRS as well as the combined all cancer GRS computed from the cancer risk increasing alleles of 304 variants (excluding any variants in known BC loci) was statistically significantly associated with a protective effect on IC risk compared with SDC. The other cancer-specific GRS were not significantly associated, although the majority of scores had a protective effect on IC. The GRS effect sizes are given per standard deviation of the score. *P < 0.05; **P < 0.01