Abstract
The risk of extra-colonic cancer in IBD is unclear. While thiopurines and tumour necrosis factor-α antagonists (anti-TNFs) are associated with increased risk of skin cancer and lymphoma in IBD, there is scant data on breast cancer in IBD. We evaluated the prevalence of breast cancer in IBD and investigated the role of biologics, immunomodulators, and clinical characteristics of IBD in patients with IBD and breast cancer.
We queried a commercial database (Explorys Inc), an aggregate of Electronic Health Record data from 26 major integrated healthcare systems in the US from 1999 to 2019. We identified a cohort of eligible patients with a diagnosis of “Crohn’s disease” (CD) and “Ulcerative Colitis” (UC) between June 2014 and 2019, based on Systemized Nomenclature Of Medicine – Clinical Terms. We calculated the prevalence of “primary malignant neoplasm of breast” in IBD overall, and among different sub-groups and identified risk factors for breast cancer in IBD utilizing linear regression.
Of the 35,521,930 individuals in the database from October 2014–2019, we identified 165,750 and 140,640 individuals with a diagnosis of CD and UC with an overall prevalence rate of 0.47% and 0.4% respectively. Out of these, 3,160 individuals with CD and 3,340 individuals with UC had a co-diagnosis of breast cancer. The prevalence of breast cancer in individuals without IBD was 1.1%. Compared to individuals with breast cancer without IBD, the prevalence of breast cancer in CD was increased at 1.9% [OR: 1.79, 95% CI: 1.73–1.85, p<0.0001] and in UC was 2.3% [OR: 2.24, 95% CI: 2.17–2.32, p<0.0001].
Compared to individuals with IBD and no malignancy, individuals with IBD and breast cancer were predominantly females, elderly (>65yo), Caucasians, had history of tobacco use and appendectomy (Table 1). Anti-TNFs and vedolizumab were associated with increased risk of breast cancer in CD (ORs 1.82 and 1.38) but not in UC. Azathioprine was associated with increased risk of breast cancer in both CD and UC (ORs 1.9 and 1.29).
Demographic and clinical characteristics of individuals with Crohn’s disease (CD) and Ulcerative Colitis (UC) with breast cancer and individuals with IBD without breast cancer. P-values (Chi-square test) are <0.0001 for all comparisons unless otherwise indicated in table.
For UC, history of colectomy was associated with an increased risk of breast cancer with OR 1.51. For CD, history of total abdominal colectomy (TAC) with ileostomy or with ileoanal anastomosis, partial resection of the colon and small intestinal surgery were all associated increased risk of breast cancer. However, fistulizing disease, peri-anal disease, and incision and drainage of perineal or perirectal abscess were not associated with increased risk of breast cancer (Table 1).
We found a two-fold higher prevalence of breast cancer in patients with IBD compared to individuals without IBD. We identified tobacco use, appendectomy and surrogate markers of luminal inflammation (use of immunomodulators, biologic agents and history of intestinal surgery) to increase risk of breast cancer. Further prospective studies are needed to confirm these findings which have implications on agressive screening of breast cancer in females with IBD.
