Searching for an Ideal Preclinical Model to Analyze Oncologic Safety of Breast Lipofilling: Preliminary Results

Abstract

INTRODUCTION: Preclinical studies aiming to evaluate the microenvironment of breast cancer (BC) are very important for analysis of risk and the behavior of this disease to treatments proposed in humans, such as breast lipofilling. Laboratorial studies used so far for this purpose present serious methodologic problems. They are based on models that use cancer-induced carcinogens that have a residual systemic effect or through the use of nonluminal human BC implanted in immunosuppressed murine hosts. This article, although, presents preliminary results of a big project aiming to develop a preclinical studies capable of assessing risks. The primary objective here was to analyze the effectiveness of cafeteria diet (CD)—a known risk factor for BC in humans—to stimulate the mammary gland and the time required for this to trigger some effect over the murine breast tissue. METHODS: Eighteen Sprague-Dawley rats with 28 days of life were randomly divided into 4 groups: 2 controls (C1 and C2), where rats were fed with standard diet, and 2 groups that received CD (D1 and D2). CD was introduced at rats’ age of 6 weeks, what is similar to the human age (HA) of 7 years old. The following variables were collected and analyzed: weight, naso-anal length, Lee index—what is similar to the human body mass index, fasting glycemia, perigonadal fat pad weight, and groin fat pad volume. Six thoracic breasts, adipose tissue of omentum and subcutaneous of each rat were harvested for analysis. These samples were studied through histologic analysis with hematoxylin/eosin staining. Statistical analyses were performed on SPSS software using paired t tests, analysis of variance (analysis of variance, 1 way) for ordinal variables, and McNemar’s test for categorical variables. RESULTS: Ten rats (C1 e D1) were analyzed with 17 weeks old (HA = 20 years old) and 8 (C2 e D2) with 26 weeks old (HA = 32 years old). The mean weight in C1 was 250.14 g and in D1 was 332.65 g (P = 0.01); in C2, it was 263.09 g and in D2, 426.76 g (P < 0.001). The mean Lee index was, respectively, 303.37, 313.43, 298.12, 332.63 in groups C1, D1, C2 e D2 (P = 0.45 between C1 and D1; P = 0.002 between C2 and D2). The mean fasting glycemia value was 76.06 mg/dl (P = 0.26); the mean perigonadal fat pad weight was 8.21 g (P < 0.001 between control and CD groups in both times). The mean groin fat pad volume was 5.08 ml, with significant difference between C1 and D1 (P = 0.007) and C2 and D2 (P = 0.001). Regarding the mammary microenvironment, it was observed 20% of duct ectasia in D1 versus 8% in C1 (P < 0.001) within 11 weeks under CD. One adenofibroma was observed in D2 at 12th week after CD onset and other at the 13th. CONCLUSION: This study showed that the CD was an effective method to induce changes in the breast microenvironment even in young rats without compromising the glycemic status (which might be a bias). These data suggest that CD can be an effective inducer for tumorigenesis in older rats. These preliminary results can lead to the development of future preclinical models for the assessment of BC risk.