Breast tumors have their own specific microbiota, distinct from normal mammary gland tissue. Patients with breast cancer that present with locally advanced disease often undergo neoadjuvant chemotherapy to reduce tumor size prior to surgery to allow breast conservation or limit axillary lymph node dissection. The purpose of our study was to evaluate whether neoadjuvant chemotherapy modulates the tumor microbiome and the potential impact of microbes on breast cancer signaling. Using snap-frozen aseptically collected breast tumor tissue from women who underwent neoadjuvant chemotherapy (n ¼ 15) or women with no prior therapy at time of surgery (n ¼ 18), we performed 16S rRNA-sequencing to identify tumoral bacterial populations. We also stained breast tumor microarrays to confirm presence of identified microbiota. Using bacteria-conditioned media, we determined the effect of bacterial metabolites on breast cancer cell proliferation and doxorubicin therapy responsiveness. We show chemotherapy adminis-tration significantly increased breast tumor Pseudomonas spp. Primary breast tumors from patients who developed distant metastases displayed increased tumoral abundance of Brevundimonas and Staphylococcus. We confirmed presence of Pseudomonas in breast tumor tissue by IHC staining. Treatment of breast cancer cells with Pseudomonas aeruginosa conditioned media differentially effected proliferation in a dose-dependent manner and modulated doxorubicin-mediated cell death. Our results indicate chemotherapy shifts the breast tumor microbiome and specific microbes correlate with tumor recurrence. Further studies with a larger patient cohort may provide greater insights into the role of microbiota in therapeutic outcome and develop novel bacterial biomarkers that could predict distant metastases.Implications: Breast tumor microbiota are modified by therapy and affects molecular signaling.

Background Breast mound and nipple creation are the goals of the reconstructive process. Unlike in normal body mass index (BMI) women, breast reconstruction in the obese is associated with increased risk of perioperative complications. Our aim was to determine if reconstruction technique and the incidence of perioperative complications affect the achievement of reconstruction completion in the obese female. Methods Consecutive obese women (BMI ≥30) who underwent mastectomy and implant or autologous reconstruction were evaluated for the completion of breast reconstruction. Results Two hundred twenty-five women with 352 reconstructions were included. Seventy-four women underwent 111 autologous reconstructions and 151 women underwent 241 implant-based reconstructions. Chemotherapy, radiation, and delayed reconstruction timing was more common in the autologous patients. Major perioperative complications (requiring hospital readmission or unplanned surgery) occurred more frequently in the implant group (p ≤ 0.0001). Breast mounds were completed in >98% of autologous cases compared with 76% of implant cases (p ≤ 0.001). Nipple areolar complex (NAC) creation was completed in 57% of autologous patients and 33% of implant patients (p = 0.0009). The rate of successfully completing the breast mound and the NAC was higher in the autologous patient group (Mound odds ratio or OR 3.32, 95% confidence interval or CI 1.36–5.28 and NAC OR 2.7, 95% CI 1.50–4.69). Conclusion Occurrence of a major complication in the implant group decreased the rate of reconstruction completion. Obese women who undergo autologous breast reconstruction are more likely to achieve breast reconstruction completion when compared with obese women who undergo implant-based breast reconstruction.

Background: We aimed to identify degloving soft tissue injury (DSTI) patient characteristics, injury and reconstruction patterns, and factors affecting outcomes of DSTI injuries to propose a reconstructive protocol for these injuries. Methods: A retrospective analysis of consecutive patients with DSTIs of an extremity over a 22-year period has been done. Results: 188 patients with 201 extremity DSTIs were included. Mean patient age was 37 years, with follow-up of 19.6 months. In total, 96% of injuries were related to motor vehicles or machinery, and 74.6% of DSTIs had injuries to structures deep to skin/subcutis. The avulsed tissue was utilized in reconstruction in 71.6% of cases and 86.8% of these experienced some loss of the used avulsed tissues. Of the total cases, 82% employed skin grafting in reconstruction. Dermal regeneration templates were used in 32% of patients. An estimated 86.5% of patients had negative pressure wound therapy utilized. Of the injured patients, 21% required flap reconstruction and 22% required some form of amputation. Age, body mass index, and tobacco use did not increase perioperative complications or amputation. DSTIs with injury to structures deep to skin/subcutis were associated with negative pressure wound therapy use ( P = 0.02). DSTIs with underlying fractures required more procedures to reach reconstruction completion ( P = 0.008), had more minor ( P = 0.49) and major perioperative complications ( P = 0.001), longer time to heal ( P = 0.002), and increased need for amputation ( P = 0.02). Conclusions: Factors affecting the reconstructive management and outcome of DSTIs include injury to structures deep to the skin/subcutis. We categorized DSTIs based on the level of injury and proposed a systematic approach to extremity DSTIs which may be utilized by plastic surgeons and other surgical services to manage these complex injuries.

Background Superior aesthetic outcomes can be achieved with mastectomy techniques that maximize breast envelope preservation and maintain the nipple-areolar complex. This is the impetus for the popularization of the nipple-sparing mastectomy (NSM). Nipple-sparing mastectomy is a challenging procedure due to potential ischemia of the mastectomy flap (which includes the nipple-areolar complex) and the risk of incomplete oncologic resection. We review our experience with NSM, identify technique modifications used over time, and evaluate reconstructive outcomes of NSM and its modifications. Methods A retrospective review of consecutive patients with NSM and breast reconstruction over an 8-year period was completed. Results Fifty-five patients underwent 95 NSMs. Indications included invasive and in situ cancer, atypical ductal hyperplasia, and risk reduction. In the first 4 years of experience, the most frequently used NSM incision was radial (lateral) whereas use of a variety of incision patterns was noted in the second 4 years. Overall NSM and breast reconstruction complication rate for the entire study period was 50.9% and included a full-thickness mastectomy skin flap necrosis/nipple necrosis rate of 8.4%. In situ cancer of the nipple was identified in 3.2% of the patients, and 1 patient had locoregional recurrence. Overall complication rate was lower in the second 4 years of experience with NSM and reconstruction. One third of the patients underwent intraoperative fluorescent angiography (FA) to assess mastectomy skin perfusion before reconstruction start. Of the patients who had FA due to perfusion concerns, more than 70% of studies demonstrated poor perfusion and 83.3% of these patients had reconstruction delayed based on these results. Immediate, implant-based reconstruction was performed most commonly. An average of 2.66 procedures were required to achieve reconstruction completion, and 92.4% of the patients who sought reconstruction achieved completion. Conclusions At our institution, NSM use is increasing, NSM incision pattern types used are expanding, and complication rates are decreasing. Immediate, implant-based reconstruction is most commonly used in combination with NSM at our institution. Fluorescent angiography is used to assess mastectomy skin perfusion and likely limits mastectomy complication effects on reconstruction. Despite the occurrence of complications, most patients will complete the breast reconstruction process.

<p>Obesity influences breast tumor microbiota populations. Breast tumor 16S sequencing results were stratified based upon patient body mass index (BMI). Tumor bacterial populations from non-obese patients with a BMI of 20-27 (n=9) were compared with bacterial populations from obese patients with a BMI of 31-48 (n=8). A. Relative abundance of bacterial genera in different tumor samples is visualized by bar plots. Each bar represents a single tumor and each colored box a bacterial taxon. The height of a color box represents the relative abundance of that organism within the sample. ''Other'' represents lower abundance taxa. B. Phylum level distribution in tumors from obese and non-obese patients. Primary breast tumors from obese patients have decreased proportional abundance of Comamonadaceae (C) and Ruminococcaceae (D) family level taxa. E. Obese patients' breast tumors display elevated abundance of Enterobacteriaceae_unclassified. *p<0.05 and error bars show the min to max distribution.</p>

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Breast tumors were identified to have their own microbiota population distinct from mammary gland tissue. Breast cancer patients that present in the clinic with larger tumors often undergo neo-adjuvant chemotherapy to reduce tumor burden before surgery. The purpose of our study was to evaluate whether chemotherapy can modulate the tumor microbiome and the potential impact of microbes in the development of distant metastases. Using snap-frozen aseptically collected breast tumor tissue from women that underwent neo-adjuvant chemotherapy or women with no prior therapy at time of surgery, we performed 16S rRNA sequencing to identify tumoral bacterial populations. We also stained breast tumor microarrays (normal breast tissue, primary breast tumor, and lymph node metastases) to confirm presence of identified microbiota. Our data indicates that chemotherapy administration significantly increased breast tumor Pseudomonas and reduced the proportional abundance of Streptococcus. Primary breast tumors from patients that developed distant metastases later on in life (regardless of therapy) displayed increased tumoral abundance of Acinetobacter, Brevundimonas, and Staphylococcus. Stratifying patients based upon BMI indicates that obesity modulates breast tumor microbiota populations and needs to be considered in analyses. Furthermore, we confirm presence of Pseudomonas in breast tumor tissue by immunohistochemical staining. Our results indicate breast tumor microbiota populations can be modified by chemotherapy and specific microbes correlate with tumor recurrence. Further studies with a larger patient cohort may provide greater insights into the role of microbiota in therapeutic outcome and for the development of novel bacterial biomarkers that could predict distant metastases. Citation Format: Akiko Chiba, Alaa Bawaneh, Christine Velazquez, Edward Levine, Katherine L. Cook. Breast tumor microbiota populations are modulated by chemotherapy and may be indicative of outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2835.

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