Background:Large cohort studies have consistently reported decreased occurrence of breast cancer among women with RA. However, both the reasons behind this decreased risk and if it is present already before RA diagnosis, is unclear. The occurrence of RA following breast cancer is clinically and etiologically important also for other reasons. Long-term adjuvant anti-hormonal treatment with tamoxifen or aromatase inhibitors has become mainstay for estrogen receptor positive breast cancer, but are often associated with arthralgia as a side effect. Some studies have suggested that these therapies not only induce arthralgia, but also inflammatory arthritis.Objectives:To examine the risk of incident breast cancer in women with RA, and the risk of RA in women with a history of breast cancer, taking anti-hormonal treatment for breast cancer into account.Methods:Using nationwide Swedish registers, women with new-onset RA diagnosed 2006-2016 were identified. Each RA patient was matched on age, sex, and place of residence to 5 randomly selected control subjects from the general population. Through register linkages, we collected information on breast cancer, breast cancer risk factors (age at childbirth, number of children, hormone replacement therapy), and socio-economy. The relative risk of breast cancer after RA was assessed using Cox regression, and the relative risk of RA in women with a history of breast was assessed using conditional logistic regression.Results:The risk of incident breast cancer in women with RA was reduced and the association was not attenuated by adjustment for breast cancer risk factors (HR=0.80, 95%CI 0.68-0.93)(Table 1). The risk was similar among seronegative RA, (HR=0.77, 95%CI 0.58-1.02), and seropositive RA, (HR=0.81, 95%CI, 0.67-0.98), and for all age groups. We noted reduced risks for all TNM stages, and for both pre- and postmenopausal breast cancer (assessed with age cutoff 50 years). The risk of RA in women with a history of breast cancer was similarly reduced (OR=0.87, 95%CI, 0.79-0.95). Odds ratios (OR) stratified by serostatus and age at RA diagnosis yielded similar results. There was no clear trend in the level of risk reduction when examining the risk by menopausal status, or cancer stage at breast cancer diagnosis. Women with breast cancer treated with tamoxifen (OR=0.86, 95%CI 0.62-1.20), or aromatase inhibitors (OR=0.97, 95%CI 0.69-1.37), did not have an increased risk of RA compared to women with breast cancer treated differently.Table 1.Risk of breast cancer in women with RA, overall and by serostatus (events and hazard ratios), and risk of RA in women with a history of breast cancer, overall and by serostatus (events and odds ratios)No. of breast cancers, patients with RANo. of breast cancers, comparators/controlsRR (95% CI)Risk of breast cancer in women with RA19011910.80 (0.68-0.93)Seronegative RA553460.77 (0.58-1.02)Seropositive RA1247720.81 (0.67-0.98)Risk of RA in women with breast cancer55531930.87 (0.79-0.95)Seronegative RA1579210.85 (0.71-1.01)Seropositive RA36720880.88 (0.78-0.98)Conclusion:There is a decreased risk of breast cancer in patients with RA, and a similar decrease in risk of breast cancer before RA diagnosis. We did not find evidence to support that the decreased risk of breast cancer was due to known risk determinants. Furthermore, adjuvant anti-hormonal therapy as used in secondary breast cancer pharmacoprevention did not seem to increase the risk of RA.Disclosure of Interests:Hjalmar WADSTRÖM: None declared, Andreas Pettersson: None declared, Karin Ekström Smedby: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma
Risk of breast cancer before and after rheumatoid arthritis, and the impact of hormonal factors
