Tumour exosome integrins determine organotropic metastasis.

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6ß4 and α6ß1 were associated with lung metastasis, while exosomal integrin αvß5 was linked to liver metastasis. Targeting the integrins α6ß4 and αvß5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Advocating Nonsurgical Management of Patients With Small, Incidental Radial Scars at the Time of Needle Core Biopsy: A Study of 77 Cases.

CONTEXT: Radial scars are benign sclerosing lesions that are routinely excised when diagnosed in a needle core biopsy. Optimal management for patients with incidental and small (≤5 mm) radial scars is uncertain. OBJECTIVE: To assess pathologic upgrade of radial scars diagnosed in needle core biopsy samples and identify a subset of patients who could benefit from conservative management. DESIGN: Patients with a diagnosis of radial scar in a needle core biopsy who underwent excision of the biopsied area were identified. Radial scars greater than 5 mm in size and those with coexisting atypia, carcinoma, and papillary lesions were excluded. After histologic-radiographic correlation, rates of pathologic upgrade were assessed. RESULTS: Seventy-seven radial scars diagnosed in 66 patients were included. Overall, 9 of 77 (12%) showed upgrade to a high-risk lesion (6 lobular carcinoma in situ, 2 atypical ductal hyperplasia, 1 atypical lobular hyperplasia), while none (0%) showed upgrade to invasive carcinoma or ductal carcinoma in situ. One of 22 incidental radial scars (4.5%) showed upgrade on excision versus 6 of 36 (16.7%) for radial scars considered to be the radiographic target (P = .23). Older age was associated with upgrade (P < .001). CONCLUSIONS: No incidental or small (≤5 mm) radial scars excised revealed invasive carcinoma or ductal carcinoma in situ on excision. Provided there is good pathologic-radiologic concordance, it appears reasonable for these patients to be managed conservatively.

A Comparative Retrospective Analysis of Complications After Oncoplastic Breast Reduction and Breast Reduction for Benign Macromastia: Are These Procedures Equally Safe?

INTRODUCTION: Oncoplastic breast reduction has been shown to be an effective approach to breast conservation surgery in women with macromastia. Clear surgical margins can be achieved while simultaneously improving symptomatic macromastia and enhancing aesthetic outcomes. Little has been written about postoperative complications after this procedure, beyond the risk of locoregional recurrence. This study aimed to compare the complication profile for oncoplastic breast reduction versus reduction for benign macromastia. METHODS: A retrospective review of our experience with oncoplastic breast reduction was performed. This represented a consecutive series of 118 patients undergoing bilateral breast reduction during the 7-year study period from March 2005 to March 2012. There were 64 patients identified who underwent oncoplastic breast reduction. Patients were determined to be a good candidate for breast conservation therapy if it was felt that clear surgical margins could be obtained without mastectomy. Postoperative complications (within 6 weeks of surgery) were compared to a control group of 56 patients undergoing reduction for benign macromastia. The associations between complications and potential risk factors were analyzed using logistic regression. RESULTS: Patients undergoing oncoplastic breast reduction and reduction for benign macromastia had some key differences. In general, macromastia patients were younger (mean age, 42.3 vs 57.5 years; P < 0.001) and had lower body mass index (mean, 26.1 vs 30.6 kg/m2; P < 0.001) compared to those patients having oncoplastic reduction. Within the oncoplastic reduction group, 14 (21.9%) patients had a total of 16 complications; among the benign macromastia group, 9 (16.1%) patients had a total of 10 complications (P = 0.420). On univariate analysis, oncoplastic reduction was not predictive of having a perioperative complication (odds ratio, 1.462; 95% confidence interval, 0.579-3.696; P = 0.422). Body mass index was found to be predictive of having a complication after reduction for either indication (odds ratio, 1.108; 95% confidence interval, 1.018-1.206; P = 0.017). Within the oncoplastic reduction cohort at an average follow-up of 34.6 months (range, 0.3-90.3 months), 5 (7.9%) patients developed locoregional recurrence and 2 patients developed distant metastasis. CONCLUSIONS: Compared with reduction mammoplasty for benign macromastia, a widely accepted procedure, patients undergoing oncoplastic breast reduction were equally likely to have a postoperative complication. Elevated body mass index was shown to be a statistically significant predictor of having a complication after reduction for either indication. Overall complication rates were acceptably low for both procedures.

The effect of metformin on breast cancer outcomes in patients with type 2 diabetes.

Observational data suggest that metformin use decreases breast cancer (BC) incidence in women with diabetes; the impact of metformin on BC outcomes in this population is less clear. The purpose of this analysis was to explore whether metformin use influences BC outcomes in women with type 2 diabetes. Prospective institutional databases were reviewed to identify patients with diabetes who received chemotherapy for stages I-III BC from 2000 to 2005. Patients diagnosed with diabetes before or within 6 months of BC diagnosis were included. Males and those with type I, gestational, or steroid-induced diabetes were excluded. Patients were stratified based on metformin use, at baseline, defined as use at time of BC diagnosis or at diabetes diagnosis if within 6 months of BC diagnosis. Kaplan-Meier methods were used to estimate rates of recurrence-free survival (RFS), overall survival (OS), and contralateral breast cancer (CBC). We identified 313 patients with diabetes who received chemotherapy for BC, 141 (45%) fulfilled inclusion criteria and 76 (54%) used metformin at baseline. There were no differences in clinical presentation or tumor characteristics between metformin users and nonusers. At a median follow-up of 87 months (range, 6.9-140.4 months), there was no difference in RFS (P = 0.61), OS (P = 0.462), or CBC (P = 0.156) based on metformin use. Five-year RFS was 90.4% (95% CI, 84-97) in metformin users and 85.4% (95% CI, 78-94) in nonusers. In this cohort of patients with type 2 diabetes receiving systemic chemotherapy for invasive BC, the use of metformin was not associated with improved outcomes.

Long-term patient-reported satisfaction after contralateral prophylactic mastectomy and implant reconstruction.

PURPOSE: To determine whether satisfaction and health-related quality of life (HR-QoL) differ between women who do and do not undergo contralateral prophylactic mastectomy (CPM) in the setting of implant reconstruction using the BREAST-Q, a validated patient-reported outcome instrument. METHODS: From 2000 to 2007, a total of 3,874 patients with stage 0 to III unilateral breast cancer (BC) had mastectomy; 688 (18 %) pursued CPM within 1 year. Patients who completed the BREAST-Q reconstruction module as part of BREAST-Q validation studies or routine clinical care formed our study cohort. Comparisons were made between CPM and no-CPM patients using univariate analysis and multivariate models (MVA). RESULTS: Of 294 patients with BREAST-Q data, 112 (38 %) had CPM. Median time from mastectomy to BREAST-Q was 52 months. CPM patients were younger (mean 47 vs. 50 years), more likely to be White (98 vs. 86 %), married (84 vs. 71 %), have a family history of BC (60 vs. 44 %), and to choose silicone implants (67 vs. 48 %). There were no differences in tumor or treatment characteristics between groups at the time of BREAST-Q. Patients with CPM had a higher mean score for Satisfaction with Breasts (64.4 vs. 54.9; p < 0.001) and Satisfaction with Outcome (74.8 vs. 67.7; p = 0.007); other HR-QoL domains did not differ. On MVA, CPM and the absence of lymphedema were significant predictors of Satisfaction with Breasts (CPM p = 0.005, lymphedema p = 0.039). CPM was not associated with improved Satisfaction with Outcome. CONCLUSIONS: This study suggests that in the setting of implant reconstruction, CPM has a positive correlation with patient satisfaction with their breasts, but not with improvements in other HR-QoL domains.

A prospective analysis of the association between indwelling surgical drains and surgical site infection in plastic surgery.

INTRODUCTION: Many surgeons fear that closed-suction drains serve as a portal for bacterial entry into surgical spaces. Despite a lack of supporting evidence, postoperative antibiotics are often prolonged while drains remain in place. METHODS: Medical records of all patients who underwent intraoperative Jackson-Pratt drain placement and sterile removal over a 12-month period were prospectively analyzed. RESULTS: Fifty-four patients with 101 drains were included. Drains were in place for 5 to 43 days [mean (SD), 13.5 (6.3) days]. Sixty-three percent of drains had positive cultures. All patients received perioperative antibiotics. Thirty-nine patients received postoperative antibiotics [mean (SD), 13.8 (13.8) days]. There were 2 cases of cellulitis. One patient required reoperation. CONCLUSIONS: Sixty-six drains (65.3%) were placed in the presence of prosthetic material. Although nearly two thirds of drains were colonized with bacteria, our wound infection rate was extremely low (5.6%). Thus, closed-suction drains may be left in place for an extended period without increasing the risk of infection, even in the presence of prosthetic material.