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1.
J Vis Exp ; (168)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33616115

RESUMO

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are diagnosed with brain metastases each year. Significant progress has been made in improving survival outcomes for patients with primary breast cancer and systemic malignancies; however, the dismal prognosis for patients with clinical brain metastases highlights the urgent need to develop novel therapeutic agents and strategies against this deadly disease. The lack of suitable experimental models has been one of the major hurdles impeding advancement of our understanding of brain metastasis biology and treatment. Herein, we describe a xenograft mouse model of brain metastasis generated via tail-vein injection of an endogenously HER2-amplified cell line derived from inflammatory breast cancer (IBC), a rare and aggressive form of breast cancer. Cells were labeled with firefly luciferase and green fluorescence protein to monitor brain metastasis, and quantified metastatic burden by bioluminescence imaging, fluorescent stereomicroscopy, and histologic evaluation. Mice robustly and consistently develop brain metastases, allowing investigation of key mediators in the metastatic process and the development of preclinical testing of new treatment strategies.

2.
Transl Oncol ; 14(4): 101026, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33535154

RESUMO

Inflammatory breast cancer (IBC) is a highly aggressive breast cancer that metastasizes largely via tumor emboli, and has a 5-year survival rate of less than 30%. No unique genomic signature has yet been identified for IBC nor has any specific molecular therapeutic been developed to manage the disease. Thus, identifying gene expression signatures specific to IBC remains crucial. Here, we compare various gene lists that have been proposed as molecular footprints of IBC using different clinical samples as training and validation sets and using independent training algorithms, and determine their accuracy in identifying IBC samples in three independent datasets. We show that these gene lists have little to no mutual overlap, and have limited predictive accuracy in identifying IBC samples. Despite this inconsistency, single-sample gene set enrichment analysis (ssGSEA) of IBC samples correlate with their position on the epithelial-hybrid-mesenchymal spectrum. This positioning, together with ssGSEA scores, improves the accuracy of IBC identification across the three independent datasets. Finally, we observed that IBC samples robustly displayed a higher coefficient of variation in terms of EMT scores, as compared to non-IBC samples. Pending verification that this patient-to-patient variability extends to intratumor heterogeneity within a single patient, these results suggest that higher heterogeneity along the epithelial-hybrid-mesenchymal spectrum can be regarded to be a hallmark of IBC and a possibly useful biomarker.

3.
Commun Biol ; 4(1): 72, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452400

RESUMO

Inflammatory breast cancer (IBC) is a clinically distinct and highly aggressive form of breast cancer with rapid onset and a strong propensity to metastasize. The molecular mechanisms underlying the aggressiveness and metastatic propensity of IBC are largely unknown. Herein, we report that decorin (DCN), a small leucine-rich extracellular matrix proteoglycan, is downregulated in tumors from patients with IBC. Overexpression of DCN in IBC cells markedly decreased migration, invasion, and cancer stem cells in vitro and inhibited tumor growth and metastasis in IBC xenograft mouse models. Mechanistically, DCN functioned as a suppressor of invasion and tumor growth in IBC by destabilizing E-cadherin and inhibiting EGFR/ERK signaling. DCN physically binds E-cadherin in IBC cells and accelerates its degradation through an autophagy-linked lysosomal pathway. We established that DCN inhibits tumorigenesis and metastasis in IBC cells by negatively regulating the E-cadherin/EGFR/ERK axis. Our findings offer a potential therapeutic strategy for IBC, and provide a novel mechanism for IBC pathobiology.

4.
J Surg Oncol ; 123(4): 846-853, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33333583

RESUMO

BACKGROUND: This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). METHODS: A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. RESULTS: A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). CONCLUSIONS: The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

5.
Cancers (Basel) ; 12(11)2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33114311

RESUMO

The AJCC updated its breast cancer staging system to incorporate biological factors in the "prognostic stage". We undertook this study to validate the prognostic and anatomic stages for inflammatory breast cancer (IBC). We established two cohorts of IBC diagnosed without distant metastasis: (1) patients treated at The University of Texas MD Anderson Cancer Center between 1991 and 2017 (MDA cohort) and (2) patients registered in the national Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 (SEER cohort). For prognostic staging, estrogen receptor (ER)+/progesterone receptor (PR)+/ human epidermal growth factor receptor-2 (HER2)+/grade 1-2 was staged as IIIA; ER+/PR-/HER2-/grade 3, ER-/PR+/HER2-/grade 3, and triple-negative cancers as IIIC; and all others as IIIB. Endpoints were breast cancer-specific survival (BCSS), overall survival (OS), and disease-free survival (DFS). We studied 885 patients in the MDA cohort and 338 in the SEER cohort. In the MDA cohort, the prognostic stage showed significant predictive power for BCSS, OS, and DFS (all p < 0.0001), although the anatomic stage did not. In both cohorts, the Harrell concordance index (C index) was significantly higher in the prognostic stage than the anatomic stage for all endpoints. In conclusion, the prognostic stage provided more accurate prognostication for IBC than the anatomic stage. Our results show that the prognostic staging is applicable in IBC.

6.
Int J Radiat Oncol Biol Phys ; 108(2): 370-373, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32890515

RESUMO

PURPOSE: To evaluate burnout in an academic radiation oncology program after the workforce shifted to working from home all or part of the time to better understand the impact of remote work and if it is sustainable after the COVID-19 virus abates. METHODS AND MATERIALS: In May 2020, in the midst of work-safe policies in the state and stabilizing COVID-19 case numbers, the Qualtrics-based MiniZ burnout survey was amended to include questions related to COVID-19 and working from home and was emailed to all radiation oncology employees across 3 departments: radiation oncology, radiation physics, and experimental radiation oncology. Descriptive and χ2 statistics were calculated within Qualtrics using StatIQ to evaluate factors associated with burnout and positive work from home experience. RESULTS: Five hundred seventy-five employees completed the survey. Aggregating 3 responses that indicate having some degree of burnout, the rate of burnout across the cohort was 32%. For the same survey questions administered a year earlier, burnout rate was reported to be 40%. In the current survey, radiation oncology faculty and therapists had the highest reported burnout rates, at 47% and 44%, respectively (P = .031). The majority of employees working from home at least part of the time reported the experience was positive (74%, 323/436), and feeling positive about working from home was associated with reduced burnout (P = .030). Qualitative data review suggested the main drivers of unfavorable work-from-home responses were child/family care issues and information technology issues. CONCLUSIONS: Burnout was not increased during the emerging COVID-19 period compared with pre-COVID data. The shift to working from home was positive for most of the workforce and a potential benefit in reducing burnout for many staff groups. Maintaining work-from-home options post COVID-19 may help reduce burnout long term. It is important to personalize options for those unable to work effectively from home and to resolve information technology challenges to ensure functionality.


Assuntos
Esgotamento Profissional , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Radioterapia (Especialidade) , Trabalho/psicologia , Humanos , Pandemias
7.
Artigo em Inglês | MEDLINE | ID: mdl-32946965

RESUMO

PURPOSE: To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. RESULTS: Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). CONCLUSIONS: Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

8.
Adv Radiat Oncol ; 5(4): 567-572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32775771

RESUMO

During the coronavirus disease 2019 pandemic, minimizing exposure risk for patients with cancer and health care personnel was of utmost importance. Here, we present steps taken to date to flatten the curve at the radiation oncology division of a tertiary cancer center with the goal of mitigating risk of exposure among patients and staff, and optimizing resource utilization. Response to the coronavirus disease 2019 pandemic in this large tertiary referral center included volume reduction, personal protective equipment recommendations, flexible clinic visit interaction types dictated by need and risk reduction, and numerous social distancing strategies. We hope these outlined considerations can assist the wider radiation oncology community as we collectively face this ongoing challenge.

9.
Biotechnol Bioeng ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648934

RESUMO

Inflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor-stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three-dimensional, in vitro, vascularized, microfluidic IBC platform to quantify the spatial and temporal dynamics of tumor-vasculature and tumor-ECM interactions specific to IBC. Platforms consisting of collagen type 1 ECM with an endothelialized blood vessel were cultured with IBC cells, MDA-IBC3 (HER2+) or SUM149 (triple negative), and for comparison to non-IBC cells, MDA-MB-231 (triple negative). Acellular collagen platforms with endothelialized blood vessels served as controls. SUM149 and MDA-MB-231 platforms exhibited a significantly (p < .05) higher vessel permeability and decreased endothelial coverage of the vessel lumen compared to the control. Both IBC platforms, MDA-IBC3 and SUM149, expressed higher levels of vascular endothelial growth factor (p < .05) and increased collagen ECM porosity compared to non-IBCMDA-MB-231 (p < .05) and control (p < .01) platforms. Additionally, unique to the MDA-IBC3 platform, we observed progressive sprouting of the endothelium over time resulting in viable vessels with lumen. The newly sprouted vessels encircled clusters of MDA-IBC3 cells replicating a key feature of in vivo IBC. The IBC in vitro vascularized platforms introduced in this study model well-described in vivo and clinical IBC phenotypes and provide an adaptable, high throughput tool for systematically and quantitatively investigating tumor-stromal mechanisms and dynamics of tumor progression.

10.
Ann Surg Oncol ; 27(12): 4603-4612, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32710271

RESUMO

BACKGROUND: Modified radical mastectomy (MRM), which includes axillary dissection, is the standard of care for inflammatory breast cancer (IBC). While more limited axillary staging after neoadjuvant chemotherapy (NAC) in clinically node-positive non-IBC has been increasingly adopted, the impact of these techniques in IBC is not clear. To inform patient selection for further study of limited axillary surgery, we aimed to describe the frequency and factors associated with pathological node-negativity (ypN0) in IBC. METHODS: Patients with IBC who received NAC and MRM were identified from a prospective institutional database (2004-2019). Binary logistic regression analyses were conducted to identify factors associated with ypN0. RESULTS: Of 453 patients, 189 (41.7%) had a post-NAC clinical nodal stage (ycN stage) of N0 (ycN1: 150, 33.1%; ycN2: 4, 0.9%; ycN3: 47, 10.4%; unknown: 63, 13.9%); 156 (34%) were ypN0. On multivariable analysis, higher tumor grade was not associated with ypN0 (odds ratio [OR] 1.59, 95% confidence interval [CI] 0.90-2.81, p =0.11). Compared with hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-negative tumors (n =113, 24.9%), HR-positive/HER2-negative tumors (n =169, 37.3%) had a trend toward less ypN0 (OR 0.55, 95% CI 0.29-1.02, p =0.06); HR-positive/HER2-positive tumors (n =79, 17.4%) were similar to HR-negative/HER2-negative tumors (OR 0.72, 95% CI 0.35-1.48, p =0.37); and HR-negative/HER2-positive tumors (n =92, 20.3%) were associated with increased ypN0 (OR 4.82, 95% CI 2.41-9.63, p <0.001). As ycN stage increased, the likelihood of ypN0 decreased compared with ycN0 patients (ycN1/2: OR 0.54, 95% CI 0.32-0.89, p =0.02; ycN3: OR 0.29, 95% CI 0.13-0.67, p =0.004). CONCLUSIONS: One-third of patients with IBC who received NAC and MRM had pathologically negative nodes. Factors associated with ypN0 included ycN0 status and HR-negative/HER2-positive subtype. Large, prospective studies are needed to investigate the feasibility of alternative nodal evaluation strategies in IBC, with consideration to these subgroups.

11.
Toxicol Appl Pharmacol ; 401: 115092, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32512068

RESUMO

Inflammatory breast cancer (IBC) is a highly metastatic and lethal breast cancer. As many as 25-30% of IBCs are triple negative (TN) and associated with low survival rates and poor prognosis. We found that the microenvironment of IBC is characterized by high infiltration of tumor associated macrophages (TAMs) and by over-expression of the cysteine protease cathepsin B (CTSB). TAMs in IBC secrete high levels of the cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared to non-IBC patients. Herein, we tested the roles of IL-8 and MCP-1/CCL2 in modulating proteolytic activity and invasiveness of TN-non-IBC as compared to TN-IBC and addressed the underlying molecular mechanism(s) for both cytokines. Quantitative real time PCR results showed that IL-8 and MCP-1/CCL2 were significantly overexpressed in tissues of TN-IBCs. IL-8 and MCP-1/CCL2 induced CTSB expression and activity of the p-Src and p-Erk1/2 signaling pathways relevant for invasion and metastasis in TN-non-IBC, HCC70 cells and TN-IBC, SUM149 cells. Dasatinib, an inhibitor of p-Src, and U0126, an inhibitor of p-Erk1/2, down-regulated invasion and expression of CTSB by HCC70 and SUM149 cells, a mechanism that is reversed by IL-8 and MCP-1/CCL2. Our study shows that targeting the cytokines IL-8 and MCP-1/CCL2 and associated signaling molecules may represent a promising therapeutic strategy in TN-IBC patients.


Assuntos
Quimiocina CCL2/biossíntese , Genes src/fisiologia , Neoplasias Inflamatórias Mamárias/metabolismo , Interleucina-8/biossíntese , Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Feminino , Genes src/efeitos dos fármacos , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pessoa de Meia-Idade , Proteólise/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia
12.
BMC Cancer ; 20(1): 430, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32423453

RESUMO

BACKGROUND: The purpose of this study was to determine the prognostic role of hormone receptor (HR) on inflammatory breast cancer (IBC) to elucidate its aggressive biological behavior. METHODS: We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemical staining and determined the predictive and prognostic role of HR expression on 189 patients with HR+/HER2- IBC and 677 patients with HR+/HER2- stage III non-IBC. Furthermore, we performed gene expression (GE) analyses on 137 patients with HR+/HER2- IBC and 252 patients with HR+/HER2- non-IBC to detect genes that are specifically overexpressed in IBC. RESULTS: The expression of ER% was significantly associated with longer distant disease-free survival and overall survival. However, there was no significant relationship between ER% and neoadjuvant chemotherapy outcome. In the GE study, 84 genes were identified as significantly distinguishing HR+ IBC from non-IBC. Among the top 15 canonical pathways expressed in IBC, the ERK/MAPK, PDGF, insulin receptor, and IL-7 signaling pathways were associated with the ER signaling pathway. Upregulation of the MYC gene was observed in three of these four pathways. Furthermore, HR+/HER2- IBC had significantly higher MYC amplification, and the genetic alteration was associated with poor survival outcome. CONCLUSIONS: Higher ER expression was significantly associated with improved survival in both HR+/HER2- IBC and HR+/HER2- stage III non-IBC patients. HR+/HER2- IBC had several activated pathways with MYC upregulation, and the genetic alteration was associated with poor survival outcome. The results indicate that MYC may be a key gene for understanding the biology of HR+/HER2- IBC.

13.
Int J Radiat Oncol Biol Phys ; 108(3): 539-545, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32434040

RESUMO

PURPOSE: On June 13 to 14, 2019, the American Society for Radiation Oncology and the Radiological Society of North America convened a workshop on the treatment of oligometastatic disease in Washington, DC. The workshop was initiated for several reasons. First, oligometastatic disease is of increasing academic and community interest and has been identified by the American Society for Radiation Oncology membership as a top research priority. Second, emerging imaging and diagnostic technologies are more readily defining and detecting oligometastatic disease, making contemporary discussion of oligometastatic disease especially relevant. Third, radiosurgery and radiation in general are theorized to be ideal noninvasive therapy for the treatment of oligometastatic disease. Finally, innovations in targeted therapy and immune therapy have the potential to reverse widely disseminating disease into an oligometastatic state. METHODS AND MATERIALS: The workshop was organized into 2 keynote addresses, 6 scientific sessions, and 3 group discussions during an end-of-workshop breakout session. New scientific work was presented in the form of 4 oral presentations and a poster session. Workshop participants were charged with attempting to answer 3 critical questions: (1) Can we refine the clinical and biological definitions of oligometastatic disease; (2) how can we better treat oligometastatic disease; and (3) what clinical trials are needed? RESULTS: Here, we present the proceedings of the workshop. CONCLUSIONS: The clinical implications of improved treatment of oligometastatic disease are enormous and immediate. Radiation oncology and diagnostic radiology should rightly be at the forefront of the characterization and treatment of oligometastatic disease. Focused effort is required so that we can translate current efforts of large numbers of studies with few patients to larger studies of larger impact.

15.
Radiother Oncol ; 148: 157-166, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388150

RESUMO

BACKGROUND: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. CONCLUSION: While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.

16.
Oncologist ; 25(6): e990-e992, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32272505

RESUMO

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

17.
JAMA Oncol ; 6(4): 505-511, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917424

RESUMO

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain. Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone. Design, Setting, and Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019. Main Outcomes and Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models. Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051). Conclusions and Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.

20.
JAMA Oncol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750868

RESUMO

Importance: Mastectomy is standard for recurrence of breast cancer after breast conservation therapy with whole breast irradiation. The emergence of partial breast irradiation led to consideration of its application for reirradiation after a second lumpectomy for treatment of recurrence of breast cancer in the ipsilateral breast. Objectives: To assess the effectiveness and adverse effects of partial breast reirradiation after a second lumpectomy and whether the treatment is an acceptable alternative to mastectomy. Design, Setting, and Participants: The NRG Oncology/Radiation Therapy Oncology Group 1014 trial is a phase 2, single-arm, prospective clinical trial of 3-dimensional, conformal, external beam partial breast reirradiation after a second lumpectomy for recurrence of breast cancer in the ipsilateral breast after previous whole breast irradiation. The study opened on June 4, 2010, and closed June 18, 2013. Median follow-up was 5.5 years. This analysis used all data received at NRG Oncology through November 18, 2018. Eligible patients experienced a recurrence of breast tumor that was less than 3 cm and unifocal in the ipsilateral breast more than 1 year after breast-conserving therapy with whole breast irradiation and who had undergone excision with negative margins. Interventions: Adjuvant partial breast reirradiation, 1.5 Gy twice daily for 30 treatments during 15 days (45 Gy), using a 3-dimensional conformal technique. Main Outcomes and Measures: The main outcomes of the present study were the predefined secondary study objectives of recurrence of breast cancer in the ipsilateral breast, late adverse events (>1 year after treatment), mastectomy incidence, distant metastasis-free survival, overall survival, and circulating tumor cell incidence. Results: A total of 65 women were enrolled, with 58 evaluable for analysis (mean [SD] age, 65.12 [9.95] years; 48 [83%] white). Of the recurrences of breast cancer in the ipsilateral breast, 23 (40%) were noninvasive and 35 (60%) were invasive. In all 58 patients, 53 (91%) had tumors 2 cm or smaller. All tumors were clinically node negative. A total of 44 patients (76%) tested positive for estrogen receptor, 33 (57%) for progesterone receptor, and 10 (17%) for ERBB2 (formerly HER2 or HER2/neu) overexpression. Four patients had breast cancer recurrence, with a 5-year cumulative incidence of 5% (95% CI, 1%-13%). Seven patients underwent ipsilateral mastectomies for a 5-year cumulative incidence of 10% (95% CI, 4%-20%). Both distant metastasis-free survival and overall survival rates were 95% (95% CI, 85%-98%). Four patients (7%) had grade 3 and none had grade 4 or higher late treatment adverse events. Conclusions and Relevance: For patients experiencing recurrence of breast cancer in the ipsilateral breast after lumpectomy and whole breast irradiation, a second breast conservation was achievable in 90%, with a low risk of re-recurrence of cancer in the ipsilateral breast using adjuvant partial breast reirradiation. This finding suggests that this treatment approach is an effective alternative to mastectomy.

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