Abstract Introduction: Black women have higher mortality from breast cancer (BrCa) than other populations. While several factors contribute to this disparity, insulin-like growth factor 1 receptor (IGF-1R), is notably overexpressed in tumors originating in Black women compared to White women, which is associated with tumor progression and resistance to radiation therapy (RT). Caloric restriction (CR) is noted to reduce the expression of members of the IGF-1R pathway. We hypothesize that CR increases the efficacy of RT, in Black women, by downregulating the IGF-1R pathway to decrease tumor growth. Methods: To understand the feasibility of implementing CR in Black women with BrCa, patients received a CR diet during adjuvant breast RT on an IRB approved investigator-initiated clinical trial and pre- and post- measures were evaluated. BrCa cell lines originating from Black (MD-MBA-468 and MD-MBA-157) or White patients (MDA-MB-231 and MDA-MB-436) were exposed to RT in the presence and absence of CR medium, IGF-1 to upregulate the pathway, and PPP, an IGF-1R inhibitor to evaluate the role of dietary interventions and IGF-1R pathway modulation in altering the RT response. Finally, human BrCa tissue was collected and ex vivo explants were used to evaluate the role of diet to augment the RT response. Results: In the pilot clinical trial, 32 patients were enrolled, 50% of whom were Black (16B/16W). Black patients had more adverse baseline physiologic parameters and corresponding higher insulin and systemic inflammation as measured by ESR, IFNγ, Il-1β, and TNFα at baseline. Adherence to CR was 87.3% for the Black patients who had an average weight loss of 7.33 lbs, and decreased insulin and cholesterol levels after CR+RT. In intro, in Black originating cells, cell viability experiments showed that CR+RT decreased cell viability by 53% & 46% while RT alone reduced viability by 32 & 41%. In White originating cells, CR+RT decreased cell viability by 52% and 53% while RT alone reduced viability by 42% and 26%. IGF-1R inhibition with PPP caused a more significant decrease in viability when given with RT than CR+RT did. The opposite effect was noted when IGF-1 was added to the cell lines and that increase was prevented by treatment with IGF-1+RT+CR. This was confirmed in vivo. Explants revealed CR helped decrease proliferation and increase apoptosis for all cancer patients. Conclusion: Taken together, these data demonstrate that Black patients can adhere to dietary interventions during RT therapy for breast cancer which may help achieve better tumor control via downregulation of the IGF-1R pathway which is often notably upregulated in this population. This benefit is widely applicable with equivalent efficacy between patients of both races and all breast cancer subtypes. Future studies should investigate the role of downregulating IGF-1R via dietary interventions to narrow disparities in breast cancer outcomes in our black patient population. Citation Format: Noelle B. Francois, Anuradha A. Shastri, Siani Harding, Tiziana DeAngelis, Adeseye Adekeye, Nicole Simone. Calorie restriction to augment radiation response in models of Black women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 707.
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May 1, 2024
Jomar Frengen + 6
Open Access