D-Limonene, a bioactive compound found in citrus peels, shows potential anticancer activity and is better tolerated in breast cancer patients compared to its derivative perillyl alcohol.
For the methodology, the researchers conducted a comprehensive scoping review. They included peer-reviewed journal articles that reported on the effects of d-limonene and its derivatives on breast cancer in human subjects. They retrieved articles from academic databases including PubMed, EMBASE, CINAHL, Web of Science, and Cochrane reviews, and also through iterative review of bibliographies of relevant manuscripts. Titles and abstracts underwent a first round of screening against the inclusion criteria, followed by consensus meetings and full article review which resulted in the selection of a final set of studies. The results were reported in accordance with the PRISMA extension for scoping reviews.
In the discussion of the results, out of 367 records, five articles reporting on both phase 1 and phase 2 trials were included in the final review. Studies assessing the effect of d-limonene indicated it was well tolerated in participants and demonstrated that d-limonene concentrated in breast tissue could cause a reduction in tumor cyclin D1 expression, associated with halting tumor proliferation. Trials with perillyl alcohol, however, showed low tolerance and no effect on breast cancer. The analysis did not reveal a meaningful change in serum biomarkers linked with breast cancer, with the exception of an increase in insulin-like growth factor-1 levels, which is typically associated with higher cancer risk.