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The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.

ABSTRACT: BACKGROUND:Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic. METHODS:The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-?B localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05). RESULTS:For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-?B activation, and induced apoptosis. CONCLUSION:Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, V.

SUBMITTER: Lynn JV

PROVIDER: S-EPMC6538447 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.

Lynn Jeremy V JV Urlaub Kevin M KM Ranganathan Kavitha K Donneys Alexis A Nelson Noah S NS Subramanian Chitra C Cohen Mark S MS Buchman Steven R SR

Plastic and reconstructive surgery 20190601 6

<h4>Background</h4>Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the u ...[more]

PMID: 30907808

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Project description:BackgroundMastectomy currently constitutes a necessary surgical procedure in the oncologic setting and in the context of high risk. Prepectoral breast reconstruction (PBR) has been proposed as a surgical alternative to retropectoral techniques by providing less postoperative morbidity and a better cosmetic result. However, there is a lack of prospective studies that have evaluated its safety and patient-reported satisfaction.MethodsWe conducted a prospective cohort study to assess the safety, quality of life and cosmetic sequelae of PBR in women with breast cancer and high risk. The study's main objective is to assess the safety of PBR in terms of postsurgical complications and the feasibility of reconstruction (loss of implants). The secondary objectives are to evaluate oncologic safety (local relapses, residual glandular tissue) and to identify factors related to quality of life and cosmetic sequelae. The evaluation of residual tissue will be conducted by MRI 12 to 18 months after the surgery, and the quality-of-life assessment will be performed using the Breast-Q questionnaire. An initial patient evaluation will be conducted 12-18 months after the surgery, and a second evaluation will be performed at 5 years. The estimated sample size is 81 patients.DiscussionThe PreQ-20 study will analyze the impact of PBR on 3 separate measures: safety, quality of life and cosmetic sequelae. Unlike other studies that analyzed these three measures jointly for women with breast cancer and high risk, this study will individualize the results for these 2 patient groups. This differentiation is necessary from the methodological point of view, given that the 2 patient groups have separate clinical and emotional implications. The assessment of these groups will focus on the following aspects: postoperative complications, local relapses, evaluation of residual glandular tissue and incidence rate of primary tumors in the same, the cosmetic sequelae and the satisfaction and the quality-of-life assessment by the patients.Trial registrationClinicalTrials.gov: NCT04642508.

Project description:Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as "safe" included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years from tumor resection; (III) a minimum follow-up period of 3 years from lipofilling; (IV) presence of a control group; (V) controls matched for ER/PR/Her-2; (VI) a sub-group analysis focusing on ER/PR/Her-2; (VII) adequate powering. Nineteen studies met inclusion criteria. The range in time from breast conserving surgery to fat injection was 0-76 months. The average time to follow-up after lipofilling was 23 days-60 months. Two studies had a sufficient follow-up time from both primary resection and from lipofilling. Seventeen of the nineteen studies specified the interval between resection and lipofilling, but there is currently no consensus regarding how soon lipofilling can be performed following BCS. Eight studies performed a subgroup analysis in cases of recurrence and found recurrence after lipofilling was associated with number of positive axillary nodes, intraepithelial neoplasia, high grade histology, Luminal A subtype, age <50, Ki-67 expression, and lipofilling within 3 months of primary resection. Of the eleven studies that included a comparison group, one matched patient for Her-2 and there was a statistically significant difference in Her-2 positive cancers in the study arms of two articles. Several studies deemed lipofilling "safe," two showed association of lipofilling and local recurrence, and most studies concluded that further research was needed. Insufficient and contradictory data exists to demonstrate the safety of lipofilling after breast conserving surgery. A multicentered, well designed study is needed to verify the safety of this practice.

Dataset Information

The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.

Publications

The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.

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