Study reveals inverse association between breast cancer, arthritis

Women with rheumatoid arthritis (RA) have a reduced risk of breast cancer; similarly, women with breast cancer have a reduced risk of RA, reveals a Swedish study. Moreover, adjuvant antihormonal therapy for breast cancer prevention does not appear to increase the risk of RA.

“In this large population-based study, we made a series of important observations … [In a] cohort of patients followed from RA diagnosis, there was a decreased risk of breast cancer … independent of RA serostatus, [which] remained after adjusting for breast cancer risk factors*,” said the researchers. These associations were observed at 5 years (hazard ratios [HRs], 0.80, 0.77, and 0.81 for overall, seronegative and seropositive, respectively). [Ann Rheum Dis 2020;79:581-586]

“Furthermore, the risk of future RA in women with a history of breast cancer was reduced,” they added, an effect that was observed at index date (odds ratio [OR], 0.87).

Studies have shown arthralgia and inflammatory arthritis as typical side effects of antihormonal therapy. [J Rheumatol 2015;42:55-59; RMD Open 2017;3:e000523] However, the current findings showed otherwise, given the reductions in RA risk in breast cancer patients on tamoxifen, aromatase inhibitors (AIs), or both (ORs, 0.86, 0.97, and 0.68, respectively) vs those who have never received antihormonal treatments.

Looking into the cumulative exposure however, there was a trend towards a higher RA risk among women receiving AI at the beginning of treatment (<6 months; OR, 1.58). Nonetheless, this dropped with longer exposure time (>24 months; OR, 0.57), suggesting that antihormonal therapy did not seem to be a risk factor for RA development, they said.

Shared contributing factors

A total of 15,921 women with RA (mean age at index date 59 years) were identified and matched with 79,441 women from a general cohort. At index date, 555 women with RA had a history of breast cancer. At a mean follow up of 5 years, breast cancer was identified in 190 women with RA.

“[Taken together,] the relative risk of RA in women with a history of breast cancer was similar to the relative risk of breast cancer in women with a history of RA … [T]his would argue against the hypothesis that the decreased risk of breast cancer in patients with RA is due to the RA disease or its treatment,” explained the researchers.

“Rather, our data suggest that RA and breast cancer share genetic or environmental factors acting earlier in life. In this regard, it is interesting that the breast cancer ORs and HRs were similar for seropositive and seronegative RA,” they continued.

Despite the large sample, long follow up, and registers with high internal validity and coverage, the team was not able to establish the origins of the link between the two conditions. The adjustments for risk factors did little to influence the findings, noted the researchers. “Whether this is due to residual confounding or a true absence of confounding is difficult to ascertain, but we did observe that these factors were indeed risk factors for breast cancer in our study population.”

The lack of data on other potential confounders (menarche, menopause, breastfeeding, body mass index, smoking, alcohol consumption) should also be taken into context, they added.

“[Nonetheless,] we believe that our nationwide study with a clearly defined population, which could account for person-time at risk, age, and several other potential confounders, and the use of an appropriate comparator group, provides a reliable estimate … Our findings suggest that other factors, independent of RA, drive the inverse association between the two diseases,” they said.