Phase Ia Clinical Trial on the Anti-Proliferative Effects of Boswellia serrata in Breast Cancer Patients

Boswellia serrata, commonly known as frankincense, is a natural resin extracted from the Boswellia tree, widely used for its medicinal properties. In preclinical studies, boswellic acids, the active components in frankincense, have shown anti-inflammatory and anti-tumor effects. These compounds have been reported to inhibit tumor proliferation, induce apoptosis, and suppress angiogenesis in various cancer cell lines, including those derived from breast, prostate, colon, and brain cancers. Despite its promising preclinical data, there have been limited studies investigating the efficacy of Boswellia serrata in human cancers.

This Phase Ia window of opportunity clinical trial was conducted to evaluate the biological effects and safety profile of oral Boswellia serrata in patients with invasive breast cancer. The trial aimed to assess changes in tumor cell proliferation and apoptosis before and after treatment with the extract, and to establish a foundation for future studies exploring its potential as a complementary therapy in breast cancer treatment.

Study Design and Methods: This open-label, single-center, single-arm, prospective Phase Ia trial involved 22 patients diagnosed with stages I-III invasive breast cancer. Participants were treated with Boswellia serrata at a dose of 2400 mg per day for a median of 11 days (ranging from 5 to 23 days) before their scheduled breast cancer surgery. The Boswellia serrata capsules (400 mg each) were administered orally, with patients instructed to take two capsules three times a day (morning, afternoon, and evening) with food.

The primary objective of the study was to determine whether Boswellia serrata could reduce breast tumor cell proliferation, as measured by Ki-67 immunohistochemistry (IHC), a well-known marker of cell proliferation. Tumor tissue samples from core biopsies taken before treatment and surgical excisions obtained after treatment were analyzed for changes in proliferation. A non-intervention control group consisting of untreated breast cancer patients was used to compare the results. Apoptosis was also assessed using the TUNEL assay, and the safety and tolerability of the drug were evaluated through patient-reported adverse events.

Results: Of the 22 enrolled patients, 20 received treatment, and 18 had sufficient tumor tissue for immunohistochemistry analysis. The median age of the participants was 60.1 years, with the majority being estrogen receptor (ER) or progesterone receptor (PR) positive, Her2-negative breast cancer patients. The primary outcome of the trial, changes in tumor proliferation, was measured by the percentage of Ki-67 positive cells in both the pre-treatment core biopsy and the post-treatment surgical excision samples.

The trial found a statistically significant reduction in tumor cell proliferation in patients treated with Boswellia serrata. Specifically, in the control group (n = 18), there was an increase in proliferation from core biopsy to surgical excision by 54.6 ± 21.4%. In contrast, patients treated with Boswellia serrata experienced a 13.8 ± 11.7% reduction in proliferation, a statistically significant difference (p = 0.008). This finding supports the hypothesis that Boswellia serrata exerts anti-proliferative effects in human breast cancer.

Interestingly, while Boswellia serrata reduced proliferation, it did not induce significant changes in apoptosis. The TUNEL assay, used to measure apoptosis, showed no meaningful difference between the control and treated groups (81.4 ± 57.3% vs. 73.0 ± 66.6%, p = 0.92). This suggests that Boswellia serrata’s anti-tumor effects are primarily driven by its ability to inhibit cell proliferation rather than promoting cell death via apoptosis.

In vitro experiments conducted as part of the study further confirmed the antiproliferative effects of Boswellia serrata on breast cancer cells. Both estrogen receptor-positive (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines demonstrated reduced proliferation when treated with Boswellia serrata in a dose-dependent manner. The extract inhibited cell proliferation at concentrations as low as 5 µM, with the half-maximal inhibitory concentration (IC50) values of 2.8 µM for MCF7 cells and 5.9 µM for MDA-MB-231 cells.

Safety and Tolerability: Boswellia serrata was well-tolerated by the study participants. The majority of reported adverse events were mild (Grade 1) and gastrointestinal in nature, such as nausea and indigestion. There was one Grade 3 adverse event (intraoperative hypotension), but it was deemed unrelated to the study drug. No serious adverse events directly attributable to Boswellia serrata were observed, supporting its safety profile in breast cancer patients.

The findings from this Phase Ia clinical trial provide the first evidence that Boswellia serrata has anti-proliferative effects in human breast cancer. The treatment resulted in a significant reduction in tumor cell proliferation without causing serious adverse effects. These results align with preclinical data demonstrating the anti-tumor properties of boswellic acids, and support further investigation of Boswellia serrata as a potential complementary therapy for breast cancer. 

References

Valente, Ingrid & Garcia, Denise & Abbott, Andrea & Spruill, Laura & Siegel, Julie & Forcucci, Jessica & Hanna, George & Mukherjee, Rupak & Hamann, Mark & Hilliard, Eleanor & Lockett, Mark & Cole, David & Klauber-DeMore, Nancy. (2024). The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer. Breast Cancer Research and Treatment. 204. 1-10. 10.1007/s10549-023-07215-4.