The histopathological and molecular features of breast carcinoma with tumour budding-a systematic review and meta-analysis.

PURPOSE: Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. METHODS: A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS: Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). CONCLUSION: High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.

Association of clinical biomarkers and response to neoadjuvant therapy in breast cancer.

INTRODUCTION: Neoadjuvant therapy is an essential component of multimodality therapy for locally advanced breast adenocarcinoma (BC). Complete pathologic response (pCR) is a useful surrogate for long-term oncologic outcome. AIM: To assess the association between clinicopathologic, molecular and immunological markers and treatment response to neoadjuvant therapy in BC. METHODS: BC patients undergoing neoadjuvant therapy were identified from a prospectively maintained institutional database. Serum haematological/biochemical values, histopathologic, immunohistochemical data and TNM stage were obtained from electronic records. Patients were categorised into complete responders vs non-complete responders and responders vs non-responders. Statistical analysis was performed via SPSS. RESULTS: Overall, 299 BC patients were included. The average age was 49.8 ± 11.5 years. A pCR was evident in 22.6% (n = 69). pCR was associated with early T stage and non-luminal subtypes (HER2 enriched [HER2 +] and triple negative [TNBC]). The neutrophil-lymphocyte ratio (NLR) pre-operatively was lower in patients with a pCR (p = 0.02). The lymphocyte-CRP ratio (LCR) was also slightly reduced in responders (p = 0.049) at diagnosis. A pre-op NLR greater than 2 was not found to be a significant predictive factor (p = 0.071) on multivariable logistic regression analysis. T stage at diagnosis (p = 0.024), N stage (p = 0.001) and breast cancer subtype (p = 0.0001) were also determined to be significant predictive factors of complete response. CONCLUSION: pCR was more likely in patients with less advanced disease in BC. The presence of HER2 + or TNBC in BC also increases the likelihood of pCR. Neoadjuvant therapy stimulates the systemic inflammatory response; however, a reduced baseline NLR may be associated with increased pCR. Confirmation with larger datasets is required.

Thermal preconditioning prevents peritendinous adhesions and inflammation.

Adhesion formation is one of the foremost obstacles to a reliably good outcome in tendon and joint surgery. Thermal preconditioning has been found to reduce the inflammatory response through the induction of molecular chaperone expression, a recently described family of cytoprotective intracellular proteins. The authors analyzed the effect of thermal preconditioning on the inflammatory response to surgery, on tendon healing, and on the formation of peritendinous adhesions in 16 New Zealand White rabbits. Very significant decreases in adhesion formation and in the gliding and dimensions of tendons in animals that had thermal preconditioning were found. Tendons from these animals also showed a decreased level of adhesion formation and a significantly diminished inflammatory response on histologic examination with no biomechanically significant deleterious effect on the strength of tendon healing on testing load to failure. These findings are consistent with induction of heat shock proteins by hyperthermic pretreatment. Such prevention of peritendinous adhesions and the inflammatory response to injury and surgery without compromising healing are findings that have significant implications for tendon surgery and all surgery involving joints and soft tissues.