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Systemic Inflammation After Radiation Predicts Locoregional Recurrence, Progression, and Mortality in Stage II-III Triple-Negative Breast Cancer.

ABSTRACT:

Purpose

Patients with triple-negative breast cancer experience high rates of recurrence after radiation, which may be facilitated by the recruitment of circulating tumor cells to proinflammatory microenvironments in the absence of lymphocytes. We hypothesized that patients with lymphopenia and elevated inflammatory hematologic markers after radiation therapy would have an increased risk of locoregional failure.

Methods and materials

With approval, we retrospectively studied a cohort of women treated with adjuvant radiation therapy for stage II-III triple-negative breast cancer. We analyzed the relationship between post-radiation therapy neutrophil:lymphocyte ratio (NLR) and locoregional recurrence by using Cox regression.

Results

One-hundred thirty patients met inclusion criteria, and median follow-up time was 7.6 years. Patients with an NLR ≥3 had a higher rate of locoregional failure (P = .04) and lower overall survival (P = .04). After adjusting for stage (hazard ratio [HR], 5.5; P < .0001) and neoadjuvant chemotherapy (HR, 2.5; P = .0162), NLR was highly predictive of locoregional failure (HR, 1.4; P = .0009). NLR was also highly predictive of overall survival (HR, 1.3; P = .0007) after adjustment for stage and neoadjuvant chemotherapy.

Conclusions

Innate peripheral inflammation after radiation therapy for triple-negative breast cancer in an immunocompromised setting may be a novel prognostic biomarker for locoregional recurrence, progression, and survival. This finding supports preclinical studies of post-radiation therapy inflammation-mediated tumor progression. Further studies are needed to confirm this finding and develop treatment strategies.

SUBMITTER: Sherry AD

PROVIDER: S-EPMC7473500 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy.This was an institutional review board-approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservation or mastectomy), and adjuvant radiation therapy between 1997 and 2015. Medical records were reviewed for clinical stage, tumor grade and subtype, neoadjuvant chemotherapy regimen, type of surgery, pathologic stage, use of radiation therapy, date and location of recurrence, and date of death. Molecular subtypes were defined using immunohistochemistry and histologic grade. ypT0 and ypN0 were defined as no residual invasive disease in breast or nodes, respectively. LRR was defined as any failure within the breast, chest wall, or regional lymph nodes. Statistical analysis was performed; LRR and DFS rates over 30 months were determined from Kaplan-Meier plots.Ninety-four patients with TNBC were analyzed, of whom 72 received radiation therapy. This subgroup was isolated for further investigation. Median follow-up was 32.5 months in this group. The pathologic complete response (pCR) rate was 36%, and presence or absence of disease in breast and/or nodes was significantly predictive of LRR. In TNBC patients who received radiation therapy, 30-month LRR was 22% in 41 patients with ypT+ versus 0% in 31 patients with ypT0 (P = .003), 23% in 31 patients with ypN+ versus 5% in 41 patients with ypN0 (P = .016), and 20% in 46 patients with residual disease in breast or nodes versus 0% in 26 patients with pCR (P = .015). The difference in the rate of LRR between those who underwent lumpectomy versus mastectomy did not reach significance (8% vs 17%, respectively). Furthermore, patients with residual disease had a higher rate of DFS events (hazard ratio, 3.58; 95% confidence interval, 1.37-9.41; P = .006). The difference in DFS was not significantly associated with the type of surgery received.Patients with TNBC treated with neoadjuvant chemotherapy who have residual disease in the breast or lymph nodes at the time of surgery have significantly higher rates of locoregional failure and lower DFS compared with those with a pCR despite the use of adjuvant radiation therapy. Strategies to intensify therapy for patients with residual disease warrant further investigation.