Thursday 23 January 2020

Does Breast Implant–Associated ALCL Begin as a Lymphoproliferative Disorder?



by Kadin, Marshall E.; Adams, William P. Jr.; Inghirami, Giorgio; Di Napoli, Arianna 

Plastic and Reconstructive Surgery: January 2020 - Volume 145 - Issue 1 - p 30e-38e

Summary: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has been included as a provisional entity in the revised version of the World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissue. To increase opportunities to intervene with early diagnosis, treatment, and possible prevention, it is important to consider that BIA-ALCL may evolve from a preexisting lymphoproliferative disorder characterized by (1) an indolent localized (in situ) disease in approximately 80 percent of reported cases; (2) a requirement for external cytokine stimulation for cell survival; (3) CD30+ cells in some clinically benign seromas/capsules; (4) undetected T-cell clonality in some cases; (5) JAK/STAT mutations in only a minority of cases; and (6) cure by capsulectomy and implant removal in most cases. BIA-ALCL resembles CD30+ cutaneous lymphoproliferative disorder: ALK−, CD30+ anaplastic cells with an aberrant T-cell phenotype; overexpression of oncogenes (JUNB, SATB1, pSTAT3, SOCS3) in lymphomatoid papulosis; frequent apoptosis; complete spontaneous regression in lymphomatoid papulosis; and partial spontaneous regression in cutaneous ALCL. Unlike CD30+ cutaneous lymphoproliferative disorder, BIA-ALCL cannot be readily observed over time to study the different steps in progression to ALCL. BIA-ALCL also shares features of lymphomas of mucosa-associated lymphoid tissue, which are clinically indolent, initially localized, antigen driven, and caused by Gram-negative bacteria. Further studies of cytokines, clonality, mutations, and other biomarkers are needed to identify possible premalignant steps in the evolution of benign late seromas to BIA-ALCL.

Outcomes of DIEP Flap and Fluorescent Angiography: A Randomized Controlled Clinical Trial



by Varela, Ramon; Casado-Sanchez, Cesar; Zarbakhsh, Shirin; Diez, Jesus; Hernandez-Godoy, Juan; Landin, Luis

Plastic and Reconstructive Surgery: January 2020 - Volume 145 - Issue 1 - p 1-10

Background: Breast reconstruction with the deep inferior epigastric perforator (DIEP) flap can be associated with complications such as fat necrosis. The authors’ objective was to assess the safety and efficacy of fluorescent angiography with indocyanine green to reduce fat necrosis. Methods: The authors designed a parallel, randomized, controlled clinical trial for unilateral breast reconstruction. The poorly vascularized tissues of the DIEP flap were removed based on a clinical evaluation in group 1 and based on angiographic criteria in group 2. The authors recorded the flap dimensions, perfusion in terms of fluorescence intensity, complications, reoperations, and BREAST-Q questionnaire scores for both groups. Results: The study included a total of 51 patients. The flaps showed no size differences after the tissue was excised. The flaps of group 2 presented higher perfusion rates (p = 0.001). The incidence of fat necrosis was 59.3 percent in group 1 and 8.3 percent in group 2 (p = 0.001). Four cases of partial necrosis were recorded in group 1 (18.2 percent) compared with none in group 2 (0 percent) (p = 0.131). Four patients underwent reoperation in group 1 (14.8 percent) compared with none in group 2 (0 percent) (p = 0.113). The patients in group 2 reported higher scores in all domains of the BREAST-Q. Conclusions: Fluorescent angiography with indocyanine green significantly reduced the incidence of fat necrosis without diminishing the flaps’ dimensions. The perfusion rates were significantly higher and the patients reported significantly greater satisfaction and quality of life. Fluorescent angiography with indocyanine green may be considered a safe and effective tool to enhance the outcomes of breast reconstruction with the DIEP flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial


by Robert Coleman, Dianne M Finkelstein, Carlos Barrios, Miguel Martin, Hiroji Iwata, Roberto Hegg, John Glaspy, Alvaro Montaño Periañez, Katia Tonkin, Ines Deleu, Joohyuk Sohn, John Crown, Suzette Delaloge, Tian Dai, Ying Zhou, Danielle Jandial, Arlene Chan

The Lancet Oncology ARTICLES| VOLUME 21, ISSUE 1, P60-72, JANUARY 01, 2020

Background
Denosumab is a fully human monoclonal antibody that binds to, and inhibits, the receptor activator of RANKL (TNFSF11) and might affect breast cancer biology, as shown by preclinical evidence. We aimed to assess whether denosumab combined with standard-of-care adjuvant or neoadjuvant systemic therapy and locoregional treatments would increase bone metastasis-free survival in women with breast cancer.
Method
In this international, double-blind, randomised, placebo-controlled, phase 3 study (D-CARE), patients were recruited from 389 centres in 39 countries. We enrolled women (aged ≥ 18 years) with histologically confirmed stage II or III breast cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1. On eligibility confirmation, investigators at each site telephoned an interactive voice response system to centrally randomly assign patients (1:1) based on a fixed stratified permuted block randomisation list (block size 4) to receive either denosumab (120 mg) or matching placebo subcutaneously every 3–4 weeks, starting with neoadjuvant or adjuvant chemotherapy, for about 6 months and then every 12 weeks for a total duration of 5 years. Stratification factors were breast cancer therapy, lymph node status, hormone receptor and HER2 status, age, and geographical region. The primary endpoint was the composite endpoint of bone metastasis-free survival. This trial is registered with ClinicalTrials.govNCT01077154.
Findings
Between June 2, 2010, and Aug 24, 2012, 4509 women were randomly assigned to receive denosumab (n=2256) or placebo (n=2253) and included in the intention-to-treat analysis. The primary analysis of the study was done when all patients had the opportunity to complete 5 years of follow-up with an analysis data cutoff date of Aug 31, 2017. The primary endpoint of bone metastasis-free survival was not significantly different between the groups (median not reached in either group; hazard ratio 0·97, 95% CI 0·82–1·14; p=0·70). The most common grade 3 or worse treatment-emergent adverse events, reported in patients who had at least one dose of the investigational product (2241 patients with denosumab vs 2218 patients with placebo), were neutropenia (340 [15%] vs 328 [15%]), febrile neutropenia (112 [5%] vs 142 [6%]), and leucopenia (62 [3%] vs 61 [3%]). Positively adjudicated osteonecrosis of the jaw occurred in 122 (5%) of 2241 patients treated with denosumab versus four (<1 152="" 2218="" 82="" acute="" and="" consciousness.="" deaths="" depressed="" due="" group="" hypocalcaemia="" in="" leukaemia="" level="" myeloid="" o:p="" occurred="" of="" patients="" placebo="" the="" to="" treated="" treatment-emergent="" treatment-related="" two="" versus="" with="">
Interpretation
Despite preclinical evidence suggesting RANKL inhibition might delay bone metastasis or disease recurrence in patients with early-stage breast cancer, in this study, denosumab did not improve disease-related outcomes for women with high-risk early breast cancer.
Funding
Amgen.

[Articles] Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial



by Peter Schmid, Hope S Rugo, Sylvia Adams, Andreas Schneeweiss, Carlos H Barrios, Hiroji Iwata, Véronique Diéras, Volkmar Henschel, Luciana Molinero, Stephen Y Chui, Vidya Maiya, Amreen Husain, Eric P Winer, Sherene Loi, Leisha A Emens, IMpassion130 Investigators

The Lancet Oncology: ARTICLES| VOLUME 21, ISSUE 1, P44-59, JANUARY 01, 2020

Consistent with the first interim analysis, this second interim overall survival analysis of IMpassion130 indicates no significant difference in overall survival between the treatment groups in the intention-to-treat population but suggests a clinically meaningful overall survival benefit with atezolizumab plus nab-paclitaxel in patients with PD-L1 immune cell-positive disease. However, this positive result could not be formally tested due to the prespecified statistical testing hierarchy. For patients with PD-L1 immune cell-positive metastatic triple-negative breast cancer, atezolizumab plus nab-paclitaxel is an important therapeutic option in a disease with high unmet need.

Breast Implant Illness: Are Social Media and the Internet Worrying Patients Sick?



by Adidharma, Widya; Latack, Kyle R.; Colohan, Shannon M.; Morrison, Shane D.; Cederna, Paul S. 

Plastic and Reconstructive Surgery: January 2020 - Volume 145 - Issue 1 - p 225e-227e

Physicians are seeing an increase in breast implant illness, a phrase describing ill-defined symptoms attributed to breast implants.1,2 Because of extensive media attention on breast implant-related issues, it is understandable why patients may confuse breast implant illness with other breast implant-related diagnoses, including breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a type of non-Hodgkin lymphoma.3,4 Given the increasing role of online media in disseminating medical information, understanding information regarding breast implant illness on such platforms and how it impacts patients’ understanding of breast implant illness may inform physicians how to more effectively communicate with their patients.3 In this study, we assessed Google Trends and Twitter content to identify catalysts to the increased incidence of breast implant illness…

A Nipple-Areola Stencil for Three-Dimensional Tattooing: Nipple by Number



by Azouz, Solomon; Swanson, Marco; Omarkhil, Mirwais; Rebecca, Alanna 

Plastic and Reconstructive Surgery: January 2020 - Volume 145 - Issue 1 - p 38-42

Summary: Medical tattooing is a critical reconstructive component in women following mastectomy. Recently, novel three-dimensional tattooing techniques mimicking depth by using light and shadow principles have allowed for aesthetically superior results. However, results are variable between providers, and professionals skilled in tattooing are often inaccessible to patients. To assess the need and obtain more background information regarding current practices, the authors recorded survey results from 753 plastic and reconstructive surgery offices. Results showed that 23 percent of facilities that offer reconstruction do not perform or refer for nipple-areola complex tattooing, leaving the patients to seek the service on their own. In this article, the authors present the nipple-by-number device, a three-dimensionally–printed stencil to ensure an accurate, consistent, and personalized aesthetic result during three-dimensional nipple-areola complex tattooing. The nipple-by-number device permits the plastic surgeon or supervised treating specialist to inexpensively, efficiently, and expeditiously perform the three-dimensional nipple-areola complex tattooing in their office. Furthermore, the device gives the patients the option of having their premorbid nipple-areola complex anatomy restored through preoperative photographs or choosing a different nipple-areola complex from a catalogue of designs. The device can be applied on any reconstructed breast mound whether or not a nipple projection procedure has been performed.