Date of Award

January 2022

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Michael Alperovich

Abstract

Background: Neoadjuvant chemotherapy (NACT) provides a survival advantage in breast cancer. Prior to mastectomy, NACT shrinks tumor size and improves pathological response in breast cancer. Evidence to date has evaluated the impact of chemotherapy on autologous breast reconstruction outcomes as a binary variable. In this study, we evaluate the effect of specific NACT regimens and dosage on the rate of post-operative complications after autologous breast reconstruction. We also evaluate the effect of NACT on circulating immune cells that orchestrate wound healing.Methods: Following IRB approval, patients who underwent NACT and microvascular breast reconstruction at Yale New Haven Hospital between 2013 and 2018 were identified. Demographic variables, oncologic history, chemotherapy regimens, and complication profiles were abstracted from the electronic medical record. Chemotherapy regimens were stratified by inclusion of anthracycline and order of taxane. Statistical analysis identified significantly varying factors between complication and no-complication cohorts. Chi-squared tests, Fischer exact tests, and t-tests were used for univariate analysis. Multivariate binary logistic regression was used to control for confounding variables. Results: 100 patients met inclusion criteria. In a multivariate regression model controlling for significant covariates like BMI and ASA, the administration of taxane-first in an anthracycline-containing chemotherapy regimen was associated with increased complications (OR = 3.521, p = 0.012). In particular, the administration of taxane-first was associated with a 2.5-fold increase in the incidence of fat necrosis (OR = 2.481, p = 0.040). Logistic regression model evaluating the effect of taxane-first regimen on complication rates, the AUC was estimated to be 0.760 (p < 0.0001), particularly fat necrosis 0.635 (p < 0.05). There was no correlation between anthracycline inclusion and postoperative outcomes. The dosage of chemotherapy, the number of days between NACT completion and surgery, and the number of circulating immune cells did not have a significant effect on postoperative outcomes. Conclusion: The administration of taxane first in an anthracycline-containing NACT regimen contributes to an increase in minor postoperative autologous breast reconstruction complications. particularly fat necrosis. Our report has the potential to inform the sequence of NACT administration but the benefits of taxane-first regimens in improving tumor outcome may outweigh increased post-reconstruction complication risk.

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This is an Open Access Thesis.

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