Hydroxychloroquine Use and the Risk of Breast Cancer in Women With Systemic Lupus Erythematosus: A Systematic Review With No Eligible Studies.

Hydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and is frequently prescribed for long-term use, particularly in women. Although patients with SLE have been reported to have altered risks of malignancy, including breast cancer, the potential association between HCQ exposure and breast cancer incidence has not been clearly established. Given the widespread and prolonged use of HCQ, clarification of its long-term safety profile for cancer is clinically important. We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to evaluate the association between HCQ use and breast cancer risk in women with SLE. PubMed (MEDLINE), Embase, and Web of Science were searched from inception to December 29, 2025, without language restrictions. Eligible studies were required to include women with SLE, evaluate HCQ use as an independent exposure, report breast cancer incidence as an outcome, and provide extractable effect estimates. Two reviewers independently screened titles, abstracts, and full texts. The search identified 548 records; after removing 73 duplicates, 475 were screened, and 469 were excluded. Six full-text articles were assessed in detail, but none met the predefined inclusion criteria, most commonly due to a lack of independent assessment of HCQ exposure or the absence of breast cancer-specific outcome analyses. Consequently, no studies were included in the final review. Despite extensive epidemiological research on cancer risk in SLE, no studies have directly evaluated the association between HCQ use and breast cancer risk in women with SLE. From an epidemiological standpoint, the absence of eligible studies is not unexpected, given the relatively low incidence of breast cancer in SLE populations and the widespread use of HCQ as standard-of-care therapy. A broader analytic strategy - such as evaluating overall malignancy risk associated with HCQ exposure with site-specific cancers examined as secondary outcomes - may represent a more efficient approach for future studies. Nevertheless, the lack of breast cancer-specific analyses treating HCQ as an independent exposure highlights an important gap in the literature, particularly given the frequency with which this question arises in clinical counseling of women with SLE.