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The Effects of Estrogen, Tamoxifen, and Anastrazole on Skin Flap Viability: An in vivo rat model investigation of hormonal treatments used in breast cancer

Navid Pourtaheri MD PhD, Reza Lavasanijou MD, Derek Wang BS, Matthew Brown MD, Davood Varghai MD, Hooman Soltanian MD
Case Western Reserve University School of Medicine
2018-02-10

Presenter: Navid Pourtaheri, MD, PhD

Affidavit:
The bulk of this work submitted by Dr. Navid Pourtaheri represents his original work. There was some assistance in the conception of the study and data collection provided by the study co-authors.

Director Name: Anand R. Kumar

Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Breast (Aesthetic and Recon.)

Purpose:
Tissue necrosis is common in mastectomy flaps. Aromatase inhibitors like Anastrozole and selective estrogen receptor modulators like Tamoxifen are commonly used to treat estrogen-receptor positive breast cancer. A protective effect of estrogen on skin healing has been described, yet the role of estrogen, tamoxifen, and Anastrozole in skin flap necrosis has not been elucidated.

Materials and Methods:
Fourty adult rats (~0.25kg Sprague-Dawley albino) divided into five groups of eight were studied: 1) negative control, un-treated; 2) control, ovariectomized (OVX); 3) OVX given estrogen (OVVX+E); 4) OVX given estrogen+tamoxifen (OVX+E+T); 5) OVX given Anastrozole (OVX+A). Ovariectomy was performed to minimize estrogen variation between subjects. After two-weeks on their regiment, all subjects underwent surgery to raise a 2.5x9cm dorsal skin flap (McFarlane) sewn back into place. Subjects were monitored for one week and sacrificed. Skin flaps were photographed in-situ and harvested. Blinded analyses was performed by four reviewers grossly and histologically/immunohistochemically. ANOVA comparison was performed.

Results:
Median percent areas of flap necrosis were similar (all p>0.05): 50.2±7.2 (negative control), 47.0±9.8 (OVX), 47.1±12.1 (OVX+E), 45.0±13.4 (OVX+E+T), 42.6±6.4 (OVX+A). Median percentages of necrotic tissue contraction were similar: 0.8±9.8 (negative control), 10.5±6.8 (OVX), 4.5±10.6 (OVX+E), 5.7±3.8 (OVX+E+T), 5.6±14.0 (OVX+A). Median percentages of overall flap contraction were similar: 12.2±6.8 (negative control), 19.5±7.6 (OVX), 17.9±16.9 (OVX+E), 9.3±6.7 (OVX+E+T), 22.0±11.2 (OVX+A). No appreciable trends in neovascularization, inflammation, or collagen deposition were noted between groups.

Conclusions:
Compared to surgical technique (skin flap dimensions and thickness), estrogen and its modulating drugs play a diminutive role in causing tissue necrosis.

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