Impact of Chemotherapy and Radiation Therapy on Inflammatory Response, Neovascularization, and Capsule Formation of Acellular Dermal Matrix in Breast Reconstruction: Analysis of the BREASTrial Biopsy Specimens.

BACKGROUND: The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a single-center, blinded, prospective, randomized, controlled trial established to compare outcomes using two popular types of acellular dermal matrices, AlloDerm and DermaMatrix, in tissue expander breast reconstruction. This study used the acellular dermal matrix biopsy specimens from the trial to evaluate how adjuvant therapy influences inflammation, neovascularization, and capsule formation of the acellular dermal matrix. METHODS: Punch biopsy specimens were taken at the time of expander exchange and were analyzed by a blinded pathologist. The inflammatory response was quantified by the number of fibroblasts, giant cells, and lymphocytes. Neovascularization and capsule formation were similarly quantified by the number of new capillaries and capsule presence and thickness, respectively. RESULTS: Histology specimens were collected from 109 patients (170 breasts). In the absence of adjuvant therapy, there was no significant difference between AlloDerm and DermaMatrix in terms of inflammation, neovascularization, or capsule thickness. Both acellular dermal matrices showed a significant decrease in inflammation and neovascularization with adjuvant therapy. When chemotherapy and radiation therapy were used, the decrease in inflammation was greatest for the group reconstructed with DermaMatrix (p < 0.039). CONCLUSIONS: Adjuvant therapy influences the inflammatory response, neovascularization, and capsule formation in both acellular dermal matrices. Adjuvant therapy has a protective effect on the inflammatory response toward both acellular dermal matrices in breast reconstruction. In the setting of chemotherapy and radiation therapy, DermaMatrix produced the greatest reduction in inflammation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Publisher Correction: Combating subclonal evolution of resistant cancer phenotypes.

The originally published version of this Article contained an error in Figure 4. In panel a, grey boxes surrounding the subclones associated with patients #2 and #4 obscured adjacent portions of the heatmap. This error has now been corrected in both the PDF and HTML versions of the Article.

Combating subclonal evolution of resistant cancer phenotypes.

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves.

The BREASTrial Stage II: ADM Breast Reconstruction Outcomes from Definitive Reconstruction to 3 Months Postoperative.

BACKGROUND: The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a prospective randomized trial comparing outcomes of tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The trial was divided into 3 outcome stages; this study reports stage II outcomes, which are those from the time of definitive reconstruction to 3 months postoperative. METHODS: A randomized trial was conducted to compare complication rates between AlloDerm and DermaMatrix groups. The impact of matrix type, age, obesity, radiation therapy, chemotherapy, and reconstruction type on complications was analyzed with regression models. RESULTS: Of the 128 patients (199 breasts) who were randomly assigned into the trial, 111 patients (173 breasts) were available for analysis in stage II. There was no difference in overall rates of complications (15.4% vs 18.3%, P = 0.8) or implant loss (2.2% vs 3.7%, P = 0.5) between the AlloDerm and DermaMatrix groups, respectively. Obesity was the only significant predictor of complications on regression analysis (odds ratio, 4.31, P = 0.007). Matrix type, age, radiation therapy, chemotherapy, or reconstruction type had no impact on the incidence/severity of complications. CONCLUSIONS: Acellular dermal matrix (ADM) will likely continue to have a role in breast reconstructive surgery; however, caution should be taken when using ADM because of relatively high complication rates, especially in obese patients. The particular ADM product should be selected based on individual surgeon preference, experience, and success rates. These data and forthcoming long-term outcomes from the Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial will enable surgeons to carefully weigh the risks and benefits of ADM use in breast reconstruction.

The breast reconstruction evaluation of acellular dermal matrix as a sling trial (BREASTrial): design and methods of a prospective randomized trial.

BACKGROUND: Recent literature has focused on the advantages and disadvantages of using acellular dermal matrix in breast reconstruction. Many of the reported data are from low level-of-evidence studies, leaving many questions incompletely answered. The present randomized trial provides high-level data on the incidence and severity of complications in acellular dermal matrix breast reconstruction between two commonly used types of acellular dermal matrix. METHODS: A prospective randomized trial was conducted to compare outcomes of immediate staged tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The impact of body mass index, smoking, diabetes, mastectomy type, radiation therapy, and chemotherapy on outcomes was analyzed. Acellular dermal matrix biointegration was analyzed clinically and histologically. Patient satisfaction was assessed by means of preoperative and postoperative surveys. Logistic regression models were used to identify predictors of complications. RESULTS: This article reports on the study design, surgical technique, patient characteristics, and preoperative survey results, with outcomes data in a separate report. After 2.5 years, we successfully enrolled and randomized 128 patients (199 breasts). The majority of patients were healthy nonsmokers, with 41 percent of patients receiving radiation therapy and 49 percent receiving chemotherapy. Half of the mastectomies were prophylactic, with nipple-sparing mastectomy common in both cancer and prophylactic cases. Preoperative survey results indicate that patients were satisfied with their premastectomy breast reconstruction education. CONCLUSION: Results from the Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial will assist plastic surgeons in making evidence-based decisions regarding acellular dermal matrix-assisted tissue expander breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The BREASTrial: stage I. Outcomes from the time of tissue expander and acellular dermal matrix placement to definitive reconstruction.

BACKGROUND: Use of acellular dermal matrix in tissue expander breast reconstruction has become a popular adjunct to the total submuscular technique. The question remains as to which matrix, if any, is ideal for breast reconstruction. METHODS: A randomized trial was conducted to analyze outcomes of immediate staged tissue expander breast reconstruction using either AlloDerm or DermaMatrix. The impact of obesity, radiation, and chemotherapy on complications and biointegration of matrix was investigated. The trial was divided into three stages, with stage I results reported here. RESULTS: One hundred twenty-eight patients (199 breasts) were randomized equally over 2.5 years. Most patients were white, healthy nonsmokers. The overall complication rate was 36.2 percent; half of the complications were minor. The AlloDerm and DermaMatrix groups had similar rates of complications (33.6 percent versus 38.8 percent; p = 0.52), consisting mostly of skin necrosis (17.8 percent versus 21.4 percent; p = 0.66) and infections (13.9 percent versus 16.3 percent; p = 0.29), both of which led to tissue expander losses (5 percent versus 11.2 percent; p = 0.11). The AlloDerm group required less time for completion of expansion (42 days versus 70 days; p < 0.001). Obesity was associated with poor matrix biointegration and a longer drain time, both of which were associated with higher complication rates. CONCLUSION: The Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial is the largest randomized trial to date in matrix breast reconstruction and emphasizes the importance of careful patient and allograft selection to minimize complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.