Skin Microbiome, Inflammation, and Skin Toxicities in Women With Breast Cancer Receiving Moderately Hypofractionated Radiation Therapy.

Abstract

Up to 95% of women during and after radiation therapy (RT) for breast cancer have reported cutaneous toxicity. However, the biologic link between skin microbiome and skin toxicities from RT remains largely unknown. This study aimed to assess the associations of skin microbiome with clinician- and patient-reported skin toxicities and inflammatory markers in women with breast cancer receiving RT. A prospective, longitudinal study was conducted at a single institution. Thirty-two women with breast cancer undergoing moderately hypofractionated RT for 3 to 4 weeks after breast conserving surgery were enrolled and 30 of them were analyzed. A total of 240 swabs for skin microbiome and 120 plasma samples were collected pre-RT baseline (T₁), week-1 of RT (T₂), week-3 of RT (T₃), and 3 months post-RT (T₄), from the cancer-affected and contralateral healthy breasts. Skin microbiome specimens were processed using 16S V1-V3 sequencing. Differences in skin microbiome of the treated breasts during RT (T₂ and T₃) were observed compared with the skin microbiome of pre-RT baseline breasts (T₁) and contralateral, healthy breasts, with the affected breasts having an increased abundance of pathogenetic Finegoldia (P = .001), Dermacoccus (P = .01), and Variovorax (P = .003) during RT. Longitudinal analysis showed that decreased Variovorax but increased Staphylococcus were associated with increased clinician-reported grade 2 pruritus (P = .002) and dermatitis (P = .012), and increased patient-reported moderate or severe darkened skin (P = .002) and itchy skin (P = .012). Additionally, the plasma interferon gamma was associated with changes in skin microbiome in women with breast cancer undergoing RT. This study shows changes in the skin microbiome during well-tolerated moderately hypofractionated breast RT. The skin microbiome return toward baseline appears to associate with improvement of clinician- and patient-reported skin toxicities post-treatment. Although there were few high-grade toxicities observed among frequently prescribed courses of hypofractionated whole breast RT, changes in skin microbiome may be of interest as further targets of symptomatic relief or intervention as ultrahypofractionated courses become more common.