Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications.

Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the recent research explosion on cell-to-cell communication via exosomes and other extracellular vesicles has rekindled interest in microRNA-based clinical applications. microRNAs appear to be a preferential and important cargo of exosomes in mediating biological effects in recipient cells. This review highlights recent studies on the biology of exosomal microRNAs (exo-miRNAs) and discusses potential clinical applications. From a diagnostic perspective, circulating exo-miRNAs may represent breast cancer cell content and/or tumor microenvironmental reactions to cancer cell growth. Thus, serum or plasma analysis of exo-miRNAs could be useful for early disease detection or for monitoring treatment response and disease progression. From a therapeutic perspective, exo-miRNAs derived from different cell types have been implicated in supporting or restraining tumor growth, conferring drug resistance, and preparing the metastatic niche. Strategies to interfere with the loading or delivery of tumor-promoting exo-miRNAs or to replenish tumor-suppressive miRNAs via exosomal delivery are under investigation. These recent studies provide new hope and opportunities, but study design limitations and technical challenges will need to be overcome before seriously considering clinical application of exo-miRNAs.

Pseudoangiomatous Stromal Hyperplasia on Core Needle Biopsy Does Not Require Surgical Excision.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign localized fibrotic lesion. Historically, PASH has been difficult to differentiate from angiosarcoma. This difficulty has led to recommendations of surgical excision. We sought to identify the incidence of upgraded pathology to atypia or malignancy on surgical excisional biopsy after identification of PASH on core needle biopsy (CNB). A 5-year retrospective review at a single institution was conducted including all cases of PASH confirmed on CNB. The data set was divided into patients who underwent excisional biopsy and those followed only by imaging. Primary end points included the incidence of subsequent malignancy or high-risk pathology on histologic analysis or the presentation of suspicious imaging. Thirty-seven patients were reviewed, 19 (51.4%) underwent surgical excision and 18 (48.6%) were followed with imaging alone. A palpable mass was noted in 36.8 per cent of patients in the excisional group versus 5.6 per cent in the imaging group (P = 0.02). The median follow-up for the excisional and imaging groups were 43 and 35 months, respectively (P = 0.85). The 95 per cent confidence interval for the presence of malignancy was 0 to 9.4 per cent. Although further characterization of PASH is needed, our data support using CNB with follow-up imaging as a safe alternative to excisional biopsy in the absence of symptoms or other clinical factors. However, further research in this area is needed.

Screening mammography in men with BRCA mutations: is there a role?

Male breast cancer is rare, with an estimated incidence of 1.08 per 100,000 men, and a death rate less than one third of that. However, the incidence of breast cancer in men with the BRCA2 mutation is significantly higher, 7.1% before age 70 (Evans et al., J Med Genet. 2010; 47:710). Due to the low incidence of male breast carcinoma, and even lower incidence of male BRCA2 positive breast cancers, clear screening guidelines for patients at risk for male for breast cancer have not been established. We report a case of male breast carcinoma in a patient with the BRCA2 mutation detected by screening mammography, and review the literature regarding screening mammography in men.

MRI versus breast-specific gamma imaging (BSGI) in newly diagnosed ductal cell carcinoma-in-situ: a prospective head-to-head trial.

BACKGROUND: Mammography remains the standard imaging technique for the diagnosis of ductal carcinoma-in-situ (DCIS). Functional breast imaging, including breast magnetic resonance imaging (MRI), has known limitations in evaluating DCIS. To date, there are limited data on the utility of breast-specific gamma imaging (BSGI) in DCIS. We sought to prospectively compare the sensitivity of BSGI to MRI in newly diagnosed DCIS patients. METHODS: Patients with newly diagnosed DCIS from June 1, 2009, through May 31, 2010, underwent a protocol with both breast MRI and BSGI. Each imaging study was read by a separate dedicated breast radiologist. Patients were excluded if excisional biopsy was performed for diagnosis, if their MRI was performed at an outside facility, or if final pathology revealed invasive carcinoma. RESULTS: There were 18 patients enrolled onto the study that had both MRI and BSGI for newly diagnosed DCIS. The sensitivity for MRI was 94% and for BSGI was 89% (P > 0.5, NS). There was one index tumor not seen on either MRI or BSGI, and one index tumor seen on MRI but not visualized on BSGI. DISCUSSION: Although BSGI has previously been shown to be as sensitive as MRI for detecting known invasive breast carcinoma, this study shows that BSGI is equally as sensitive as MRI at detecting newly diagnosed DCIS. As a result of the limited number of patients enrolled onto the study, larger prospective studies need to be performed to determine the true sensitivity and specificity of BSGI.

First three sentinel lymph nodes accurately stage the axilla in breast cancer.

Sentinel lymph node (SLN) biopsy is the preferred method of assessing lymph nodes in breast cancer. Recent literature suggests increasing morbidity with increased number of SLN removed. However, controversy exists regarding the number of SLN that should be removed. A retrospective review of patients undergoing SLN biopsy for breast cancer from 2003 to 2005 was performed. Data analyzed included the number of SLNs, nodes per specimen, and pathology. The order of SLN removal was documented and the first positive lymph node noted. Three hundred fifty-three patients underwent successful SLN biopsy. On average, only one surgical SLN was identified. However, the average number of pathologically identified SLN was 1.3. Nodal disease was identified in 79 patients (22.4%). The first SLN was positive in 70 of those patients (88.6%). Six additional patients were diagnosed by the second SLN (76 of 79 [96.2%]), and all 79 patients were identified within the first three nodes. All patients with nodal disease were identified within three SLNs. These data support the concept that surgeons do not need to remove all identifiable sentinel nodes. Moreover, surgeons could consider limiting the number of excised SLNs to three.

Effect of Center of Excellence requirement by Centers for Medicare and Medicaid Services on practice trends.

BACKGROUND: To report the effect of the American Society of Bariatric Surgery or American College of Surgeons-designated Centers of Excellence designation in Michigan on our practice trends and patient populations. As of February 2006, weight loss surgery for Medicare beneficiaries are reimbursed when procedures are performed at American Society of Bariatric Surgery or American College of Surgeons-designated Centers of Excellence. METHODS: Patients who underwent laparoscopic Roux-en-Y gastric bypass surgery by an individual surgeon from June 1 to October 31 in 2004, 2005, and 2006 were stratified according to use of private third-party insurance versus Medicare (MC) insurance. The demographic data, body mass index, numbers of medications and co-morbidities, operative time, lengths of stay, morbidity, and mortality were analyzed. Significance was assessed at P <.05. RESULTS: From June 1 to October 31 in 2004, 2005, and 2006, 255 patients with MC or private third-party insurance underwent laparoscopic Roux-en-Y gastric bypass surgery, with the percentage of MC patients increasing from 15.3% and 10.2% in 2004 and 2005 to 30.9% in 2006. The MC patients were older (56.1 +/- 1.3 yr versus 44.1 +/- 0.7 yr; mean +/- standard error of mean), had more co-morbidities (5.1 +/- 0.2 versus 3.5 +/- 0.1), required more medications (10.3 +/- 0.6 versus 5.6 +/- 0.3), had undergone more previous operations (2.1 +/- 0.2 versus 1.3 +/- 0.1), and had longer operative times (148 +/- 11.1 versus 121 +/- 3.1 min) than the private third-party insurance patients; the differences were all significant. The differences in gender, body mass index, and length of stay were not significantly different. CONCLUSION: The Centers for Medicare and Medicaid Services requirements for Centers of Excellence designation resulted in a significant increase in the Medicare case load within our institution. This population tended to be older and more complex, with longer operative times. The changes present new challenges in patient care, including the coordination of care for the multiple co-morbidities of older obese patients with a multispecialty care team.