Sentinel Lymph Node Identification in Post Neoadjuvant Chemotherapy Breast Cancer Patients Undergoing Surgical Excision Using Lymphosonography.

OBJECTIVES: This study evaluated the efficacy of lymphosonography in the identification of sentinel lymph nodes (SLNs) in post neoadjuvant chemotherapy patients with breast cancer scheduled to undergo surgical excision. METHODS: Seventy-nine subjects scheduled for breast cancer surgery with SLN excision completed this IRB-approved study, out of which 18 (23%) underwent neoadjuvant chemotherapy before surgery. Subjects underwent percutaneous Sonazoid (GE Healthcare) injections around the tumor area for a total of 1.0 mL. Lymphosonography was performed using CPS on an S3000 HELX scanner (Siemens Healthineers) with a linear probe. Subjects received blue dye and radioactive tracer as part of their standard of care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and Sonazoid. The results were compared between methods and pathology findings. RESULTS: Seventy-two SLNs were surgically excised from 18 subjects, 29 were positive for blue dye, 63 were positive for radioactive tracer and 57 were positive for Sonazoid. Comparison with blue dye showed that both radioactive tracer and lymphosonography achieved an accuracy of 53% (P > .50). Comparison with radioactive tracer showed that blue dye had an accuracy of 53%, while lymphosonography achieved an accuracy of 67% (P < .01). Of the 72 SLNs, 15 were determined malignant by pathology; the detection rate was 47% for blue dye (7/15), 67% for radioactive tracer (10/15) and 100% for lymphosonography (15/15) (P < .001). CONCLUSIONS: Lymphosonography achieved similar accuracy as radioactive tracer and higher accuracy than blue dye for identifying SLNs. The 15 SLNs positive for malignancy were all identified by lymphosonography.

Pediatric and Adolescent Breast Conditions: A Review.

Breast conditions in pediatric and adolescent patients vary from benign congenital changes to pathological findings. Although most breast conditions are benign, there are rare cases of malignancy that are important to identify during development. As such, it is critical to understand the classification and management of the different pediatric and adolescent breast conditions that might present to clinicians who care for pediatric and adolescent patients. In this review, congenital, benign, and malignant pediatric/adolescent breast conditions are discussed.

Sentinel Lymph Node Identification in Patients With Breast Cancer Using Lymphosonography.

The objective of the work described here was to evaluate the efficacy of lymphosonography in identifying sentinel lymph nodes (SLNs) in patients with breast cancer undergoing surgical excision. Of the 86 individuals enrolled, 79 completed this institutional review board-approved study. Participants received subcutaneous 1.0-mL injections of ultrasound contrast agent (UCA) around the tumor. An ultrasound scanner with contrast-enhanced ultrasound (CEUS) capabilities was used to identify SLNs. Participants were administered with blue dye and radioactive tracer to guide SLN excision as standard-of-care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and UCA, and sent for pathology. Two hundred fifty-two SLNs were excised; 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Comparison with blue dye revealed accuracies of 96.2% for radioactive tracer and 99.4% for lymphosonography (p > 0.15). Relative to radioactive tracer, blue dye had an accuracy of 68.5%, and lymphosonography achieved 86.5% (p < 0.0001). Of 252 SLNs excised, 34 were determined to be malignant by pathology; 18 were positive for blue dye (detection rate = 53%), 23 for radioactive tracer (detection rate = 68%) and 34 for UCA (detection rate = 100%) (p < 0.0001). Lymphosonography was similar in accuracy to radioactive tracer and higher in accuracy than blue dye in identifying SLNs. All 34 malignant SLNs were identified by lymphosonography.

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials.

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources.

Contrast-enhanced Spectral Mammography: Technique, Indications, and Clinical Applications.

RATIONALE AND OBJECTIVES: Contrast-enhanced spectral mammography (CESM) combines the benefits of full field digital mammography with the concept of tumor angiogenesis. Technique and practical applications of CESM are discussed. MATERIALS AND METHODS: An overview of the technique is followed by a demonstration of practical applications of CESM in our practice. RESULTS: We have successfully implemented CESM into our practice as a screening, diagnostic, staging, and treatment response tool. CONCLUSION: It is important to understand the technique of CESM and how to incorporate it into practice.

Attitudes and Decisional Conflict Regarding Breast Reconstruction Among Breast Cancer Patients.

BACKGROUND: The decision to undergo breast reconstruction (BR) surgery after mastectomy is made during stressful circumstances. Many women do not feel well prepared to make this decision. OBJECTIVE: Using the Ottawa Decision Support Framework, this study aims to describe women's reasons to choose or not choose BR, BR knowledge, decisional preparedness, and decisional conflict about BR. Possible demographic, medical, BR knowledge, and attitudinal correlates of decisional conflict about BR were also evaluated. METHODS: Participants were 55 women with early-stage breast cancer drawn from the baseline data of a pilot randomized trial evaluating the efficacy of a BR decision support aid for breast cancer patients considering BR. RESULTS: The most highly ranked reasons to choose BR were the desire for breasts to be equal in size, the desire to wake up from surgery with a breast in place, and perceived bother of a scar with no breast. The most highly ranked reasons not to choose BR were related to the surgical risks and complications. Regression analyses indicated that decisional conflict was associated with higher number of reasons not to choose BR and lower levels of decisional preparedness. CONCLUSIONS: The results suggest that breast cancer patients considering BR may benefit from decisional support. IMPLICATIONS FOR CLINICAL PRACTICE: Healthcare professionals may facilitate decision making by focusing on reasons for each patient's uncertainty and unaddressed concerns. All patients, even those who have consulted with a plastic surgeon and remain uncertain about their decision, may benefit from decision support from a health professional.

Acceptability and pilot efficacy trial of a web-based breast reconstruction decision support aid for women considering mastectomy.

OBJECTIVE: The study aim was to test the acceptability and preliminary efficacy of a novel interactive web-based breast reconstruction decision support aid (BRAID) for newly diagnosed breast cancer patients considering mastectomy. METHODS: Fifty-five women considering mastectomy were randomly assigned to receive the BRAID versus the Cancer Support Community's Frankly Speaking About Cancer: Breast Reconstruction pamphlet. Participants completed measures of breast reconstruction (BR) knowledge, preparation to make a decision, decisional conflict, anxiety, and BR intentions before randomization and 2 weeks later. RESULTS: In terms of acceptability, enrollment into the study was satisfactory, but the rate of return for follow-up surveys was lower among BRAID participants than pamphlet participants. Both interventions were evaluated favorably in terms of their value in facilitating the BR decision, and the majority of participants completing the follow-up reported viewing the materials. In terms of preliminary efficacy, both interventions resulted in significant increases in BR knowledge and completeness and satisfaction with preparation to make a BR decision, and both interventions resulted in a significant reduction in decision conflict. However, there were no differences between interventions. CONCLUSION: A widely available free pamphlet and a web-based customized decision aid were highly utilized. The pamphlet was as effective in educating women about BR and prepared women equally as well to make the BR decision as compared with a more costly, customized web-based decision support aid. Copyright © 2015 John Wiley & Sons, Ltd.

Impact of Oncotype DX on treatment decisions in ER-positive, node-negative breast cancer with histologic correlation.

Oncotype DX, a gene-expression profiling assay, provides stratification of patients with estrogen-receptor positive, lymph-node-negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen-receptor positive, node-negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen-receptor positive, lymph-node-negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.

Prolactin inhibits BCL6 expression in breast cancer through a Stat5a-dependent mechanism.

BCL6 is a transcriptional repressor that recognizes DNA target sequences similar to those recognized by signal transducer and activator of transcriptions 5 (Stat5). BCL6 disrupts differentiation of breast epithelia, is downregulated during lactation, and is upregulated in poorly differentiated breast cancer. In contrast, Stat5a mediates prolactin-induced differentiation of mammary epithelia, and loss of Stat5 signaling in human breast cancer is associated with undifferentiated histology and poor prognosis. Here, we identify the mammary cell growth factor prolactin as a potent suppressor of BCL6 protein expression in human breast cancer through a mechanism that requires Stat5a, but not prolactin-activated Stat5b, MEK-ERK, or PI3K-AKT pathways. Prolactin rapidly suppressed BCL6 mRNA in T47D, MCF7, ZR75.1, and SKBr3 breast cancer cell lines, followed by prolonged reduction of BCL6 protein levels within 3 hours. Prolactin suppression of BCL6 was enhanced by overexpression of Stat5a but not Stat5b, was mimicked by constitutively active Stat5a, but did not require the transactivation domain of Stat5a. Stat5 chromatin immunoprecipitation demonstrated physical interaction with a BCL6 gene regulatory region, and BCL6 transcript repression required histone deacetylase activity based on sensitivity to trichostatin A. Functionally, BCL6 overexpression disrupted prolactin induction of Stat5 reporter genes. Prolactin suppression of BCL6 was extended to xenotransplant tumors in nude mice in vivo and to freshly isolated human breast cancer explants ex vivo. Quantitative immunohistochemistry revealed elevated BCL6 in high-grade and metastatic breast cancer compared with ductal carcinoma in situ and nonmalignant breast, and cellular BCL6 protein levels correlated negatively with nuclear Stat5a (r = -0.52; P < 0.001) but not with Stat5b. Loss of prolactin-Stat5a signaling and concomitant upregulation of BCL6 may represent a regulatory switch facilitating undifferentiated histology and poor prognosis of breast cancer.

Timing of sentinel lymph node biopsy and reconstruction for patients undergoing mastectomy.

Options for immediate breast reconstruction after mastectomy are directly affected by nodal status. Historically, axillary dissection has been performed simultaneously with mastectomy. The advent of sentinel lymph node biopsy (SLNB) drastically changed the trends in breast cancer surgery. SLNB is often performed at the time of mastectomy and may negate the need for a formal axillary dissection. The algorithm presented here outlines an approach where SLNB is performed as a separate outpatient operation several days prior to mastectomy when immediate reconstruction is planned. While this approach requires a separate procedure, SLNB can be performed with minimal morbidity with monitored anesthesia care and local anesthesia. The significance of this algorithm is that it allows time for complete pathologic evaluation prior to definitive surgery, eliminating the dependency on frozen section diagnosis. This method also decreases the possibility of irradiating a fresh autologous flap if radiation therapy is deemed necessary after further pathology review of the sentinel node specimen. We endorse SLNB as a separate outpatient procedure prior to definitive surgery with reconstruction, particularly latissimus dorsi myocutaneous flap. This method involves a close team approach between the breast and plastic surgeons.

Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database.

BACKGROUND: Breast carcinomas in African-American patients appear to be more aggressive than in Caucasian patients due to multifactorial differences. METHODS: The authors compiled pathology data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database regarding stage, histologic grade, and estrogen receptor (ER) expression in breast carcinomas diagnosed in 197,274 African-American and Caucasian patients between 1990 and 2000, and the same information, along with nuclear grade, Ki-67, c-erb-B2, and p53 expression, in 2230 African-American and Caucasian patients diagnosed at Thomas Jefferson University Hospital between 1995 and 2002. Immunohistochemical markers were assayed in paraffin-embedded, formalin-fixed tissue stained with hematoxylin and eosin using antibodies to these proteins, with differences in expression analyzed by the chisquare test. RESULTS: In both databases, more African-American patients presented with advanced stage tumors and higher histologic (P < .001) and nuclear grade (P < .001) than Caucasian patients. African-American patients had less ER positivity (51.9% vs 63.1%; P < .001) but significantly higher Ki-67 (42.4% vs 28.7%; P < .001) and p53 expression (19.4% vs 13.1%; P < .05) than Caucasian patients with all stages of disease. In addition, the basal or "triple-negative" breast cancer phenotype was more common in African-American patients than in Caucasian patients (20.8% vs 10.4%; P < .0001), and was associated with higher histologic and nuclear grade (P < .0001). CONCLUSIONS: African-American patients with breast carcinomas are more likely than Caucasian patients to present with tumors that are of a later stage and higher grade, with higher Ki-67 expression and more ER negativity, thereby highlighting a greater need for early screening among African-American women. Molecular studies that may explain these differences, and correlations with survival, have been proposed to identify therapeutic targets.

Diagnosis, treatment, and management of breast cancer in previously augmented women.

Augmentation mammaplasty is rapidly becoming one of the most frequently performed cosmetic surgeries. However, as the augmented patient population ages, major concerns associated with the screening, diagnosis and treatment of breast cancer are being realized. Although current evidence convincingly indicates that breast implants do not play a role in inducing localized or systemic disease, particularly breast cancer, recent studies have shown implants not only reduce the sensitivity of mammography, but interfere with mammographic detection, possibly leading to delayed breast cancer diagnosis. In addition, the risk for local recurrence, as well as unfavorable cosmetic results, breast fibrosis, and capsular contracture following radiation therapy as part of breast-conserving therapy in previously augmented patients are of great concern. Given the overall lack of treatment consensus, paucity of literature, and increasing number of augmented breast cancer patients, we provide a retrospective review of the diagnosis, treatment, and follow-up of 12 augmented patients from 1998 to 2004 who developed breast cancer. Eight of 12 augmented patients presented with a palpable mass on physical examination, which prompted further mammographic evaluation. Abnormalities in the remaining four individuals were detected on routine mammographic screening. Pathology staging results were available for all 12 patients. Breast-conserving therapy was used to treat six patients and adequate negative pathologic margins were obtained in all patients. The remaining six patients were treated with mastectomy due to multifocal disease, inadequate margins, or proximity to the implant capsule. Thus far, one patient has had local recurrence and one patient has had distant recurrence after initial surgery. No evidence of local or systemic recurrence, infection, contracture, poor cosmetic outcome, or other complications has been detected in the remaining 10 patients as of the most recent follow-up. Based on this small cohort of augmented women, the presence of implants led to an increased proportion of palpable tumors, in spite of routine screening mammography. Consistent with other studies, although our results suggest a tendency toward delayed diagnosis in augmented women relative to age-matched controls, this did not appear to influence the overall prognosis.