No rise in breast cancer recurrence found with TNF inhibitor use

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

[email protected]

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

[email protected]

Treatment with tumor necrosis factor inhibitors does not appear to increase the rate of breast cancer recurrence among patients with rheumatoid arthritis, according to findings from a Swedish case-control study.

The study’s results help to allay concerns about the potential for tumor necrosis factor (TNF) inhibitors to promote cancer recurrence, but it still leaves the agents’ possible effect on much more recently diagnosed cancer or cancers with poor prognosis unknown, said lead investigator Dr. Pauline Raaschou of the Karolinska Institute, Stockholm, and her colleagues in the ARTIS Study Group.

Although two previous studies have examined the risk of recurrence of any type of cancer in patients treated with a TNF inhibitor, it was unclear to the investigators how much the baseline risk of recurrence played a role and how much "channeling" of high-risk patients away from TNF inhibitors has potentially contributed to selection bias in such studies. Breast cancer seemed an ideal cancer type to study in this regard, the investigators said, because of women’s high lifetime risk and the dovetailing of peak age of onset of both breast cancer and RA at around age 60 years.

The researchers matched 120 patients who were treated with TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) to 120 patients who had never received treatment with a biologic. The patients had started TNF inhibitors or began follow-up a median of 9.4 years after their breast cancer diagnosis. The patients had a mean age of 66-67 years and their cancers were in remission at the start of follow-up (Ann. Rheum. Dis. 2014 Aug. 8 [doi:10.1136/annrheumdis-2014-205745]).

During 592 person-years of follow-up, nine patients treated with a TNF inhibitor developed a breast cancer recurrence for a crude incidence rate of 15/1,000 person-years, compared with nine of the biologic-naive patients during 550 person-years of follow-up for a rate of 16/1,000 person-years. This gave a hazard ratio of 0.8 with a 95% confidence interval of 0.3-2.1.

The risk did not change appreciably in different models that adjusted for small differences in prognostic factors for breast cancer recurrence and RA-related characteristics. There also were no differences in the risk of recurrence between individuals with a history of breast cancer within 5 years or later – a time frame in which many guidelines recommend using caution in starting TNF inhibitors – but only 15% of the patients started a TNF inhibitor within 5 years of their breast cancer, according to the investigators.

Dr. Raaschou and her associates noted that although their study is the largest on the topic to date, it still has limited power because at an alpha of .05, "a study of our design would require approximately 120 patients in each treatment group [i.e., our sample size] to have 80% power to detect a doubled risk, but 350 patients in each treatment group to detect a 50% increased risk."

This research was funded by a variety of Swedish medical societies, foundations, and programs. One author reported receiving research grants from Pfizer and AstraZeneca as part of a public-private research consortium and speaker’s honoraria from Merck. The Swedish Biologics Register, ARTIS, is maintained in part by funding from Abbott Laboratories, Bristol-Myers Squibb, Merck, Pfizer, Roche, SOBI, and UCB.

[email protected]