Trends in Lumpectomy and Oncoplastic Breast-Conserving Surgery in the US, 2011–2016

Background

Oncoplastic breast surgery aims to optimize efficacy of surgical resection and cosmesis to maximize patient satisfaction; however, despite the benefits, oncoplastic techniques have not been widely adopted in the US. This study examined trends in the incidence of lumpectomy (partial mastectomy) with or without oncoplastic techniques from 2011 to 2016.

Methods

This was a retrospective analysis of claims from the Optum Clinformatics database (January 2010–March 2017). Female patients with no history of breast surgery in the prior year were categorized into three independent cohorts: isolated lumpectomy (Lx), lumpectomy with tissue transfer (LxTT), or lumpectomy with mammaplasty and/or mastopexy (LxMM). Oncoplastic techniques (in cohorts two and three) were performed at either time of the initial lumpectomy or during 90-day follow-up.

Results

Overall, 19,253 patients met the inclusion criteria (91.1% Lx, 5.2% LxTT, and 3.7% LxMM). Significantly fewer patients with Lx had a family history of breast cancer compared with patients with oncoplastic techniques (26.4% vs. 33.7% and 37.9%, respectively; p?<?0.001). The incidence of Lx declined significantly from 2011 (92.9%) to 2016 (88.1%), while LxTT and LxMM increased from 4.2 to 7.2% and 2.8 to 4.7%, respectively (both p?<?0.001). The greatest utilization of oncoplastic techniques was observed in the Pacific census division (19.2%), while lowest utilization was in the East South Central division (3.2%; p?<?0.001).

Conclusions

While increased adoption of oncoplastic techniques was observed, the compound annual growth rate remained below 10% and varied significantly by region. Further adoption of oncoplastic techniques is necessary to improve cosmetic outcomes and patient satisfaction following breast-conserving surgery.

     

Influence of Age on the Clinical Outcome of Breast Cancer for Men and the Development of Second Primary Cancers

Background

Low incidence of breast cancer in men (BCM) (<?1% of all breast cancers) has led to a paucity of outcome data. This study evaluated the impact of age on BCM outcomes.

Methods

For this study, BCM patients treated between 2000 and 2011 were stratified by age (≤?65 or?>?65 years). Kaplan–Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk.

Results

The study identified 152 BCM patients with a median age of 64 years (range 19–96 years). The median body mass index (BMI) was 28 kg/m². Men age 65 years or younger (n?=?78, 51%) were more overweight/obese than men older than 65 years (n?=?74, 49%) (89% vs 74%, respectively; P?=?0.008). Both groups had similar nodal metastases rates (P?=?0.4), estrogen receptor positivity (P?=?1), and human epidermal growth factor receptor 2 (HER2)neu overexpression (P?=?0.6). Men 65 years of age or younger were more likely to receive chemotherapy (P?=?0.002). The median follow-up period was 5.8 years (range 0.1–14.4 years). The 5-year OS was 86% (95% confidence interval [CI] 80–93%), whereas the 5-year BCSS was 95% (95% CI 91–99%). The BCM patients 65 years of age and younger had better OS (P?=?0.003) but not BCSS (P?=?0.8). The 5-year cumulative incidence of SPC was 8.4% (95% CI 3.4–13.4%). The prior SPC rate was higher for men older than 65 years (n?=?20, 31%) than for those age 65 years or younger (n?=?7, 11%) (P?=?0.008). This did not account for differences in life years at risk. No difference was observed in SPC cumulative incidence stratified by age (P?=?0.3).

Conclusions

Men 65 years of age or younger received more chemotherapy and had improved OS, but not BCSS, compared with men older than 65 years. For all BCM, SPC is a risk, and appropriate screening may be warranted.

     

Failure of voriconazole therapy due to acquired azole resistance in Aspergillus fumigatus in a kidney transplant recipient with chronic necrotizing aspergillosis

Invasive aspergillosis (IA) affects the lungs and disseminates mostly in patients with neutropenia and/or patients who are receiving immunosuppressive and steroid therapies. Despite progress in the diagnosis of and therapy for IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for IA. Over recent years, triazole‐resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products, with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patients who are undergoing long‐term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. Herein we describe a kidney transplant recipient who failed to respond to voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in 8 months despite plasma concentrations within the recommended range of the drug, necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months.     

Characterization of regulatory T cells in obese omental adipose tissue in humans

Obesity‐associated visceral adipose tissue (AT) inflammation promotes insulin resistance and type 2 diabetes (T2D). In mice, lean visceral AT is populated with anti‐inflammatory cells, notably regulatory T cells (Tregs) expressing the IL‐33 receptor ST2. Conversely, obese AT contains fewer Tregs and more proinflammatory cells. In humans, however, there is limited evidence for a similar pattern of obesity‐associated immunomodulation. We used flow cytometry and mRNA quantification to characterize human omental AT in 29 obese subjects, 18 of whom had T2D. Patients with T2D had increased proportions of inflammatory cells, including M1 macrophages, with positive correlations to body mass index. In contrast, Treg frequencies negatively correlated to body mass index but were comparable between T2D and non‐T2D individuals. Compared to human thymic Tregs, omental AT Tregs expressed similar levels of FOXP3, CD25, IKZF2, and CTLA4, but higher levels of PPARG, CCR4, PRDM1, and CXCL2. ST2, however, was not detectable on omental AT Tregs from lean or obese subjects. This is the first comprehensive investigation into how omental AT immunity changes with obesity and T2D in humans, revealing important similarities and differences to paradigms in mice. These data increase our understanding of how pathways of immune regulation could be targeted to ameliorate AT inflammation in humans.     

Protection from EAE in DOCK8 mutant mice occurs despite increased Th17 cell frequencies in the periphery

Mutation of Dedicator of cytokinesis 8 (DOCK8) has previously been reported to provide resistance to the Th17 cell dependent EAE in mice. Contrary to expectation, we observed an elevation of Th17 cells in two different DOCK8 mutant mouse strains in the steady state. This was specific for Th17 cells with no change in Th1 or Th2 cell populations. In vitro Th cell differentiation assays revealed that the elevated Th17 cell population was not due to a T cell intrinsic differentiation bias. Challenging these mutant mice in the EAE model, we confirmed a resistance to this autoimmune disease with Th17 cells remaining elevated systemically while cellular infiltration in the CNS was reduced. Infiltrating T cells lost the bias toward Th17 cells indicating a relative reduction of Th17 cells in the CNS and a Th17 cell specific migration disadvantage. Adoptive transfers of Th1 and Th17 cells in EAE‐affected mice further supported the Th17 cell‐specific migration defect, however, DOCK8‐deficient Th17 cells expressed normal Th17 cell‐specific CCR6 levels and migrated toward chemokine gradients in transwell assays. This study shows that resistance to EAE in DOCK8 mutant mice is achieved despite a systemic Th17 bias.