Abstract
Understanding metabolic and immune regulation inherent to patient populations is key to improving the radiation response for our patients. To date, radiation therapy regimens are prescribed based on tumor type and stage. Patient populations who are noted to have a poor response to radiation such as those of African American descent, those who have obesity or metabolic syndrome, or senior adult oncology patients, should be considered for concurrent therapies with radiation that will improve response. Here, we explore these populations of breast cancer patients, who frequently display radiation resistance and increased mortality rates, and identify the molecular underpinnings that are, in part, responsible for the radiation response and that result in an immune-suppressive tumor microenvironment. The resulting immune phenotype is discussed to understand how antitumor immunity could be improved. Correcting nutrient deficiencies observed in these populations should be considered as a means to improve the therapeutic index of radiation therapy.
Highlights
To date, radiation regimens for breast cancer are chosen and administered based on a patient’s tumor type and stage; typically, the only aspect of a radiation regimen that is changed is dosing, fractionation, overall treatment time, and volume of the breast and normal tissue treated
Since there is evidence that optimal local tumor control portends improved survival and fewer metastases, attention should turn toward differentiating which tumor types or patient characteristics might be associated with poor outcomes despite adequate radiation therapy (RT)
Chemotherapy and other systemic treatments have been tailored by genomic alterations for some women with breast cancer, successful modifications to radiation therapy regimens have been mostly limited to changes in the number of fractions or doses given
Summary
Radiation regimens for breast cancer are chosen and administered based on a patient’s tumor type and stage; typically, the only aspect of a radiation regimen that is changed is dosing, fractionation, overall treatment time, and volume of the breast and normal tissue treated. It has been established that certain patient characteristics or underlying tumor genetic milieu are associated with varying degrees of radiation sensitivity and these are not accounted for [3] Despite this finding, to date, there are scarce data for combining radiation with systemic therapies including chemotherapy or immunotherapy to improve the effect of radiation. Metabolic syndrome, advanced age, and diverse communities have increased with time and are known to have varying levels of radiation sensitivity [6–8] This is likely, in part, due to alteration of specific molecular pathways that are associated with a decrease in antitumor immunity, which can influence tumor biology and response to radiation. The future of radiation oncology, moving toward precision radiation, will need to account for molecular underpinnings specific to host populations and implement combination therapy strategies to even the playing field for all patients receiving radiation
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