Cancer Risk in a Large Inception Systemic Lupus Erythematosus Cohort: Effects of Demographic Characteristics, Smoking, and Medications

Abstract

ObjectiveTo assess cancer risk factors in incident systemic lupus erythematosus (SLE).MethodsClinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (overall risk and most common cancers) included demographic characteristics and time‐dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and the adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 score.ResultsAmong 1,668 patients (average 9 years follow‐up), 65 cancers occurred: 15 breast, 10 nonmelanoma skin, 7 lung, 6 hematologic, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 2 each gastric, head and neck, and thyroid, and 1 each rectal, sarcoma, thymoma, and uterine cancers. Half of the cancers (including all lung cancers) occurred in past/current smokers, versus one‐third of patients without cancer. Multivariate analyses indicated that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively associated and antimalarial drugs were negatively associated. Antimalarial drugs and higher disease activity were also negatively associated with nonmelanoma skin cancer risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with nonmelanoma skin cancer risk.ConclusionSmoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and nonmelanoma skin cancer. Antimalarials were negatively associated with breast cancer and nonmelanoma skin cancer risk. SLE activity was associated positively with hematologic cancer and negatively with nonmelanoma skin cancer. Since the absolute number of cancers was small, additional follow‐up will help consolidate these findings.

Cancer and Systemic Lupus Erythematosus

“…[96] The increased risk in non-melanoma skin cancer has been related to immunosuppressive therapies in inflammatory bowel disease [97,98], and one study has suggested an association with cyclophosphamide in SLE. [99] 6. DECREASED CANCER RISK IN SLE 6.1 Epidemiology SLE patients may have a decreased incidence rate of certain cancers compared to the general population.…”

“…[105,106] Emerging evidence suggests that antimalarials may indeed decrease risk of breast cancer in SLE. (Table 2) [99]. In addition, aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been linked with a decreased risk of some cancers in the general population.…”

Malignancy risk of non‐biologic immunosuppressive therapies: A review of the literature with evidence‐based treatment recommendations

“…Smoking as a risk factor for malignancy, specifically lung cancer, has also been reported in patients with SLE being treated with CYC. 52 A review of 143 patients with pemphigus and pemphigoid treated with oral CYC and prednisone detected bladder cancer in two patients over 4.8-9.7 year follow-up period. 53 Breast (2), skin (10) and laryngeal (1) cancers and leukaemia (2) were reported in others treated with CYC and prednisone.…”

“…[55][56][57] Patients with a positive smoking history are at even greater risk of developing malignancy. 52…”

Antimalarials may reduce cancer risk in patients with systemic lupus erythematosus: a systematic review and meta-analysis of prospective studies

“…Two thousand six hundred and eightynine articles were excluded after deleting duplication and screening titles and abstracts. After reviewing the full text of the remaining, 40 studies were excluded (lack of relevant data, n ¼ 6; review, case report, the meeting, case-control, n ¼ 15; not control, n ¼ 1; not related, n ¼ 16; duplicates, n ¼ 2), and eight studies were finally included [21,[24][25][26][27][28][29][30]. One study was also included after manually searching [22].…”