TNF Inhibitors for RA: No Link to Breast Cancer

Larry Hand

August 17, 2014

Patients who have had breast cancer and who start tumor necrosis factor inhibitor (TNFi) treatment for rheumatoid arthritis (RA) more than 5 years after the cancer diagnosis may not be more subject to breast cancer recurrence than patients who do not start TNFi treatment, according to an article published online August 8 in the Annals of Rheumatic Disease.

"Breast cancer is perhaps the most significant malignancy in RA, since both diseases primarily affect women of older ages," first author Pauline Raaschou, MD, told Medscape Medical News. "Our findings are reassuring for both patients and clinicians, in the sense that they support the use of TNFi in patients with a history of breast cancer which is not particularly aggressive or very recent."

Dr. Raaschou, from the Clinical Epidemiology Unit at Karolinska Institutet, Stockholm, Sweden, and colleagues in the Anti-Rheumatic Therapy in Sweden Study Group used linked population-based databases to identify patients with RA with a history of breast cancer. They identified 143 female patients with a history of breast cancer who received TNFi treatment between 1999 and 2010 and matched them with patients selected from a cohort of patients with RA and a history of breast cancer who had not started TNFi treatment (n = 1598). They included 120 TNFi-treated and 120 biologics-naive individuals in their final analysis.

For the TNFi patients, who had more severe RA, the median time to starting RA treatment after cancer diagnosis was 9.4 years; the control patients had been matched for time since breast cancer diagnosis (± 3 years). Median follow-up came to 4.9 years for the TNFi group and 4.6 years for the biologics-naive group.

For the TNFi group, 9 patients developed a recurrence of breast cancer during a total of 592 person-years of follow-up compared with 9 patients in the biologics-naive group during 550 person years of follow-up.

The researchers calculated hazard ratios (HRs) for recurrence, using Cox regression analysis, adjusting for nodal status and type of surgery and chemotherapy for index cancer.

They found that the HR for TNFi-treated individuals compared with biologics-naive individuals was 0.8 (95% confidence interval [CI], 0.3 - 2.1). For TNFi patients who started treatment within 5 years of cancer diagnosis, the HR was 1.4 (95% CI, 0.3 - 2.4), and for those who started treatment 5 years after cancer diagnosis, the HR was 0.8 (95% CI, 0.3 - 2.4). None of the measures reached statistical significance.

"With an average follow-up of 5 years, we found no difference in the risk of breast cancer recurrence between TNFi-treated and matched biologics-naive patients with RA and a history of breast cancer," the researchers write.

Support Guidelines

"In essence, our results support most current clinical guidelines, which indicate that TNFi could be initiated if more than 5 years after solid cancer," Dr. Raaschou said. "It must be remembered that our study participants were selected in clinical practice to receive TNFi in spite of having a history of breast cancer. Through careful review of the medical history, we observed that the cancers among the patients later receiving TNFi tended to have a slightly better prognosis. It may be that the findings of our study do not apply to individuals with aggressive or very recent breast cancers. Thus, it is premature to suggest any major changes in current guidelines."

She noted, however, that she was surprised by "the often elaborate and very well informed discussion [related in the medical records], involving both patients and clinicians, about the pros and cons of initiating TNFi against a background of breast cancer."

Exciting, Needs Confirmation

"This is an excellent population-based study," Jonathan Kay, MD, director of clinical research in rheumatology and professor of medicine at the University of Massachusetts Medical School in Worcester, told Medscape Medical News. "This is somewhat reassuring, but it needs confirmation in other populations. It needs to be extended to other malignancies."

Such a study would be difficult in the United States, he said, because of privacy requirements and deidentification of health information. In contrast, the Swedish Cancer register has records on more than 95% of primary cancers, including diagnosis date, cancer morphology, and type of cancer, and reporting is mandatory for clinicians and pathologists, the study authors write.

Dr. Kay continued, "The results of this study suggest that one may be able to treat patients who have had breast cancer treated appropriately with a TNF inhibitor without significant risk of recurrence of that malignancy. As a result, patients with rheumatoid arthritis may be able to receive appropriate treatment for their joint disease, regardless of their history of breast cancer."

This research was supported by the Stockholm County Council, BTCure, the Swedish Cancer Society, Swedish Foundation for Strategic Research, Swedish Programme on Chronic Inflammation, and Swedish Research Council. For maintenance of the registry, the Swedish Society for Rheumatology has received funding from several pharmaceutical companies. One coauthor has reported receiving research funds from Pfizer and Astra-Zeneca and speaker's honoraria from Merck. The other authors have disclosed no relevant financial relationships. Dr. Kay reports that he has served as an advisor or consultant for Array BioPharma, Bristol-Myers Squibb Company, Centocor, Roche, UCB Pharma, Genentech, Pfizer, Eisai, and Covidien, as well as receiving a research funding from Roche and sanofi-aventis.

Ann Rheum Dis. Published online August 8, 2014. Abstract

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