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1.
Chemistry ; 27(38): 9748-9752, 2021 Jul 07.
Article in English | MEDLINE | ID: mdl-33871915

ABSTRACT

A mild photocatalytic phenol oxygenation enabled by a continuous-flow photoreactor using visible light and pressurized air is described herein. Products for wide-ranging applications, including the synthesis of vitamins, were obtained in high yields by precisely controlling principal process parameters. The reactor design permits low organophotocatalyst loadings to generate singlet oxygen. It is anticipated that the efficient aerobic phenol oxygenation to benzoquinones and p-quinols contributes to sustainable synthesis.


Subject(s)
Light , Phenols , Benzoquinones , Phenol , Singlet Oxygen
2.
Breast J ; 25(1): 124-128, 2019 01.
Article in English | MEDLINE | ID: mdl-30525258

ABSTRACT

Accelerated partial breast irradiation (APBI), a radiation technique in which only the tumor bed is treated, has now become an acceptable radiation modality for selected early-stage breast cancer patients. Compared to conventional whole breast irradiation (WBI), APBI has some benefits with regard to the reduced total irradiated breast volume and the shorter treatment time. The role of APBI, which can be delivered using diverse techniques, has been evaluated in several prospective randomized phase III trials. These clinical trials demonstrate diverging outcomes relating to local recurrence, while establishing comparable effect in terms of survival between APBI with WBI. The aim of this study was to review the current status of APBI with a focus on clinical practice.


Subject(s)
Breast Neoplasms/radiotherapy , Radiotherapy/methods , Female , Humans , Meta-Analysis as Topic , Middle Aged , Neoplasm Recurrence, Local , Practice Patterns, Physicians' , Randomized Controlled Trials as Topic
3.
CA Cancer J Clin ; 60(6): 351-75, 2010.
Article in English | MEDLINE | ID: mdl-20959401

ABSTRACT

Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy.


Subject(s)
Inflammatory Breast Neoplasms/diagnosis , Inflammatory Breast Neoplasms/therapy , Biomarkers, Tumor/genetics , Body Mass Index , Chemotherapy, Adjuvant , Combined Modality Therapy/methods , Diagnosis, Differential , Disease Progression , Female , Humans , Incidence , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/genetics , Magnetic Resonance Imaging , Mammography , Neoplasm Staging , Obesity/complications , Positron-Emission Tomography , Prognosis , Radiotherapy, Adjuvant , Rare Diseases , Risk Assessment , Risk Factors , Survival Rate , Tomography, X-Ray Computed , Ultrasonography, Mammary , United States/epidemiology
4.
Breast J ; 23(1): 26-33, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27612282

ABSTRACT

Skin sparing mastectomy, a surgical procedure sparing a large portion of the overlying skin of the breast, and nipple-sparing mastectomy, sparing the whole nipple-areolar complex, are increasingly used, although their oncologic efficacy remains unclear. The aim of this study was to assess the radiation oncologists' opinions regarding the indications of radiation therapy (RT) after skin-sparing mastectomy and nipple-sparing mastectomy. Radiation oncology members of four national and international societies were invited to complete a questionnaire comprising of 22 questions to assess their opinions regarding RT indications in the context of skin-sparing and nipple-sparing mastectomy. A total of 298 radiation oncologists answered the questionnaire. 90.9% of respondents affirmed that breast cancer is one of their specializations. The majority declared that post-mastectomy RT is indicated for early-stage (stages I and II) breast cancer patients who present with risk factors for recurrence after skin-sparing or nipple-sparing mastectomy (87.2% and 80.2%, respectively). All suggested risk factors (tumor size, lymph node involvement, extracapsular extension, lymphovascular space invasion, positive surgical margins, triple negative tumor, multicentric tumor, and age) were considered as major elements (important or very important). There is no consensus regarding the necessity of evaluating residual breast tissue or the definition of residual breast tissue after mastectomy. All classic factors were considered as major elements, potentially influencing the decision to advice or not postoperative RT. Many uncertainties remain about the indications for RT after skin-sparing mastectomy or nipple-sparing mastectomy.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Mastectomy, Subcutaneous/methods , Practice Patterns, Physicians' , Radiation Oncologists , Breast Neoplasms/pathology , Europe , Female , Health Surveys , Humans , Male , Margins of Excision , Neoplasm Recurrence, Local/pathology , Nipples/surgery , North America , South America , Surveys and Questionnaires
6.
Breast Cancer Res ; 18(1): 97, 2016 09 29.
Article in English | MEDLINE | ID: mdl-27687248

ABSTRACT

BACKGROUND: Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness. METHOD: To elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo studies such as sphere-formation assays, Western blotting, flow cytometric apoptosis assays, and limited dilution xenotransplant models. Histological staining for Gal3 in tissue microarrays of breast cancer patients was performed to analyze the relationship of clinical outcome and Gal3 expression. RESULTS: Here, we show in a cohort of 87 node-positive breast cancer patients treated with doxorubicin-based chemotherapy that low Gal3 was associated with increased lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference in epithelial-like mammary spheres leads to EMT, increased sphere-formation ability, drug-resistance, and heightened aldefluor activity. Furthermore, Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic mouse models. CONCLUSIONS: Thus, in at least some breast cancers, loss of Gal3 might be associated with EMT and cancer stemness-associated traits, predicts poor response to chemotherapy, and poor prognosis.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/mortality , Galectin 3/genetics , Gene Expression , Neoplastic Stem Cells/metabolism , Adult , Aged , Aged, 80 and over , Animals , Biomarkers, Tumor , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Disease Models, Animal , Female , Galectin 3/metabolism , Gene Knockdown Techniques , Heterografts , Humans , Lymphatic Metastasis , Mice , Middle Aged , Neoplasm Staging , Phenotype , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Spheroids, Cellular , Tumor Cells, Cultured , Wnt Signaling Pathway , Young Adult
7.
Cancer ; 122(18): 2886-94, 2016 09 15.
Article in English | MEDLINE | ID: mdl-27305037

ABSTRACT

BACKGROUND: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.


Subject(s)
Breast Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Dose Fractionation, Radiation , Female , Humans , Longitudinal Studies , Middle Aged , Patient Reported Outcome Measures , Radiotherapy, Adjuvant
8.
Cancer ; 122(6): 917-28, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26716915

ABSTRACT

BACKGROUND: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC). METHODS: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment. RESULTS: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims. CONCLUSIONS: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC.


Subject(s)
Cardiovascular Diseases/mortality , Esophageal Neoplasms/radiotherapy , Lung Diseases/mortality , Organ Sparing Treatments/methods , Radiotherapy, Conformal/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Female , Humans , Imaging, Three-Dimensional , Lung Diseases/etiology , Male , Medicare , Odds Ratio , Propensity Score , Registries , Risk Assessment , SEER Program , Texas/epidemiology , Treatment Outcome , United States/epidemiology
9.
Ann Surg ; 263(2): 219-27, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25876011

ABSTRACT

OBJECTIVE: To evaluate complications after postmastectomy breast reconstruction, particularly in the setting of adjuvant radiotherapy. BACKGROUND: Most studies of complications after breast reconstruction have been conducted at centers of excellence; relatively little is known about complication rates in irradiated patients treated in the broader community. This information is relevant for decision making in patients with breast cancer. METHODS: Using the claims-based MarketScan database, we described complications in 14,894 women undergoing mastectomy for breast cancer from 1998 to 2007 and who underwent immediate autologous reconstruction (n = 2637), immediate implant-based reconstruction (n = 3007), or no reconstruction within the first 2 postoperative years (n = 9250). We used a generalized estimating equation to evaluate associations between complications and radiotherapy over time. RESULTS: Wound complications were diagnosed within the first 2 postoperative years in 2.3% of patients without reconstruction, 4.4% patients with implants, and 9.5% patients with autologous reconstruction (P < 0.001). Infection was diagnosed within the first 2 postoperative years in 12.7% of patients without reconstruction, 20.5% with implants, and 20.7% with autologous reconstruction (P < 0.001). A total of 5219 (35%) women received radiation. Radiation was not associated with infection in any surgical group within the first 6 months but was associated with an increased risk of infection in months 7 to 24 in all 3 groups (each P < 0.001). In months 7 to 24, radiation was associated with higher odds of implant removal in patients with implant reconstruction (odds ratio = 1.48; P < 0.001) and fat necrosis in those with autologous reconstruction (odds ratio = 1.55; P = 0.01). CONCLUSIONS: Complication risks after immediate breast reconstruction differ by approach. Radiation therapy seems to modestly increase certain risks, including infection and implant removal.


Subject(s)
Breast Neoplasms/surgery , Mammaplasty , Mastectomy , Postoperative Complications/etiology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/radiotherapy , Databases, Factual , Female , Follow-Up Studies , Humans , Logistic Models , Mammaplasty/methods , Middle Aged , Postoperative Complications/epidemiology , Radiotherapy, Adjuvant/adverse effects , Risk Factors , Treatment Outcome
10.
Ann Surg Oncol ; 23(8): 2385-90, 2016 08.
Article in English | MEDLINE | ID: mdl-26979306

ABSTRACT

PURPOSE: Value in healthcare-i.e., patient-centered outcomes achieved per healthcare dollar spent-can define quality and unify performance improvement goals with health outcomes of importance to patients across the entire cycle of care. We describe the process through which value-based measures for breast cancer patients and dynamic capture of these metrics via our new electronic health record (EHR) were developed at our institution. METHODS: Contemporary breast cancer literature on treatment options, expected outcomes, and potential complications was extensively reviewed. Patient perspective was obtained via focus groups. Multidisciplinary physician teams met to inform a 3-phase process of (1) concept development, (2) measure specification, and (3) implementation via EHR integration. RESULTS: Outcomes were divided into 3 tiers that reflect the entire cycle of care: (1) health status achieved, (2) process of recovery, and (3) sustainability of health. Within these tiers, 22 patient-centered outcomes were defined with inclusion/exclusion criteria and specifications for reporting. Patient data sources will include the Epic Systems EHR and validated patient-reported outcome questionnaires administered via our institution's patient portal. CONCLUSIONS: As healthcare costs continue to rise in the United States and around the world, a value-based approach with explicit, transparently reported patient outcomes will not only create opportunities for performance improvement but will also enable benchmarking across providers, healthcare systems, and even countries. Similar value-based breast cancer care frameworks are also being pursued internationally.


Subject(s)
Breast Neoplasms/therapy , Disease Management , Electronic Health Records , Outcome Assessment, Health Care , Value-Based Purchasing , Female , Focus Groups , Humans , Middle Aged , Quality of Health Care , Texas , United States
11.
Breast Cancer Res ; 17: 42, 2015 Mar 20.
Article in English | MEDLINE | ID: mdl-25887413

ABSTRACT

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d'orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth. METHODS: Hypothesizing the clinical presentation of IBC may be mediated in part by the microenvironment, we examined the effect of co-injection of IBC xenografts with mesenchymal stem/stromal cells (MSCs). RESULTS: MSCs co-injection significantly increased the clinical features of skin invasion and metastasis in the SUM149 xenograft model. Primary tumors co-injected with MSCs expressed higher phospho-epidermal growth factor receptor (p-EGFR) and promoted metastasis development after tumor resection, effects that were abrogated by treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. E-cadherin expression was maintained in primary tumor xenografts with MSCs co-injection compared to control and erlotinib treatment dramatically decreased this expression in control and MSCs co-injected tumors. Tumor samples from patients demonstrate correlation between stromal and tumor p-EGFR staining only in IBC tumors. CONCLUSIONS: Our findings demonstrate that the IBC clinical phenotype is promoted by signaling from the microenvironment perhaps in addition to tumor cell drivers.


Subject(s)
Inflammatory Breast Neoplasms/metabolism , Inflammatory Breast Neoplasms/pathology , Mesenchymal Stem Cells/metabolism , Phenotype , Animals , Antineoplastic Agents/pharmacology , Cadherins/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Disease Models, Animal , ErbB Receptors/metabolism , Erlotinib Hydrochloride/pharmacology , Female , Heterografts , Humans , Inflammatory Breast Neoplasms/genetics , Inflammatory Breast Neoplasms/mortality , Mice , Neoplasm Invasiveness , Neoplasm Metastasis , Signal Transduction/drug effects , Stromal Cells/metabolism , Tumor Burden/drug effects
12.
Cancer ; 121(24): 4324-32, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26348887

ABSTRACT

BACKGROUND: This study sought to determine outcomes for patients with metastatic breast cancer (MBC) with no evidence of disease (NED) after treatment and to identify factors predictive of outcomes once the status of NED was attained. METHODS: This study reviewed 570 patients with MBC who were consecutively treated between January 2003 and December 2005. Ninety patients (16%) attained NED, which was defined as a complete metabolic response on positron emission tomography or sclerotic healing of bone metastases on computed tomography or magnetic resonance imaging. The median follow-up for patients attaining NED was 100 months (range, 14-134 months). RESULTS: The 3- and 5-year overall survival (OS) rates were 44% and 24%, respectively, for the entire group and 96% and 78%, respectively, for those attaining NED. According to a landmark analysis, NED status was significantly associated with survival at 2 (P < .001; hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.16-0.34) and 3 years (P < .001; HR, 0.20; 95% CI, 0.14-0.30). From the time of NED, the median survival was 102 months (range, 14-134 months) with 5-year OS and progression-free survival (PFS) rates of 77% and 40%, respectively. According to a multivariate analysis, human epidermal growth factor receptor 2 positivity was significantly associated with OS in comparison with estrogen receptor positivity (P = .02; HR, 0.44; 95% CI, 0.21-0.90), and trastuzumab use was significantly associated with PFS (P = .007; HR, 0.48; 95% CI, 0.28-0.82). Thirty-one patients (34%) with NED remained in remission at the last follow-up. CONCLUSIONS: MBC patients who attain the status of NED have significantly prolonged survival with a durable response to therapy. Ultimately, this study provides essential outcome data for clinicians and patients living with MBC.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Bone Neoplasms/therapy , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/therapy , Carcinoma, Lobular/therapy , Liver Neoplasms/therapy , Lung Neoplasms/therapy , Trastuzumab/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/diagnosis , Carcinoma, Lobular/secondary , Cohort Studies , Disease-Free Survival , Female , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Magnetic Resonance Imaging , Middle Aged , Positron-Emission Tomography , Prognosis , Radiotherapy/methods , Remission Induction , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
13.
Breast Cancer Res Treat ; 152(2): 407-16, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26017070

ABSTRACT

Inflammatory breast cancer (IBC) is a rare and aggressive disease. Previous studies have shown that among patients with stage III breast cancer, IBC is associated with a worse prognosis than noninflammatory breast cancer (non-IBC). Whether this difference holds true among patients with stage IV breast cancer has not been studied. We tested the hypothesis that overall survival (OS) is worse in patients with IBC than in those with non-IBC among patients with distant metastasis at diagnosis (stage IV disease). We reviewed the records of 1504 consecutive patients with stage IV breast cancer (IBC: 206; non-IBC: 1298) treated at our institution from 1987 through 2012. Survival curves for IBC and non-IBC subcohorts were compared. The Cox proportional hazards model was used to determine predictors of OS. The median follow-up period was 4.7 years. IBC was associated with shorter median OS time than non-IBC (2.27 vs. 3.40 years; P = 0.0128, log-rank test). In a multicovariate Cox model that included 1389 patients, the diagnosis of IBC was a significant independent predictor of worse OS (hazard ratio = 1.431, P = 0.0011). Other significant predictors of worse OS included Black (vs. White) ethnicity, younger age at diagnosis, negative HER2 status, and visceral (vs. nonvisceral) site of metastasis. IBC is associated with shorter OS than non-IBC in patients with distant metastasis at diagnosis. The prognostic impact of IBC should be taken into consideration among patients with stage IV breast cancer.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Inflammatory Breast Neoplasms/mortality , Inflammatory Breast Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Female , Follow-Up Studies , Humans , Inflammatory Breast Neoplasms/epidemiology , Inflammatory Breast Neoplasms/therapy , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Proportional Hazards Models , Young Adult
14.
Mol Carcinog ; 54(4): 281-90, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24166930

ABSTRACT

Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤ 55. We found that carriers of the rs16430 0 bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR) = 1.37, 95% confidence interval (CI): 1.08-1.73; P = 0.010], compared with carriers of the 6 bp/6 bp genotype. This increased risk was more evident in older subjects (OR = 1.47, 95% CI = 1.06-2.03, P = 0.022), never smokers (OR = 1.67, 95% CI = 1.23-2.25, P < 0.001), never drinkers (OR = 1.44, 95% CI = 1.01-2.05, P = 0.043), and estrogen receptor-positive patients (OR = 1.46, 95% CI = 1.11-1.92, P = 0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0 bp allele had a decrease in both luciferase activity by ∼ 70% and mRNA levels by ∼ 50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561. Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤ 55 yr. Further validation in large population-based or cohort studies is needed.


Subject(s)
Breast Neoplasms/genetics , MicroRNAs/metabolism , Polymorphism, Single Nucleotide , Thymidylate Synthase/genetics , White People/genetics , 3' Untranslated Regions , Base Sequence , Binding Sites , Breast/metabolism , Breast Neoplasms/epidemiology , Female , Genetic Predisposition to Disease , Genetic Variation , Humans , Linkage Disequilibrium , MicroRNAs/chemistry , MicroRNAs/genetics , Middle Aged , Risk Factors , Sequence Alignment , Thymidylate Synthase/metabolism
15.
Ann Surg Oncol ; 22(5): 1434-40, 2015 May.
Article in English | MEDLINE | ID: mdl-25727554

ABSTRACT

Neoadjuvant chemotherapy is a standard treatment option for patients with locally advanced operable breast cancer and is increasingly used in early breast cancer. Initial randomized trials of neoadjuvant chemotherapy established equivalency to adjuvant chemotherapy in terms of survival, but they also demonstrated improved rates of breast conservation and the ability to modify the risk of locoregional recurrence after a favorable response to chemotherapy. High-quality nonrandomized data have helped to tailor radiotherapy treatment recommendations after neoadjuvant chemotherapy and breast-conserving surgery or mastectomy. Results from an ongoing phase 3 randomized trial (NSABP B-51/RTOG 1304) will help to clarify the value of locoregional radiotherapy for patients with clinical N1 disease that becomes node negative after neoadjuvant chemotherapy.


Subject(s)
Breast Neoplasms/therapy , Neoadjuvant Therapy , Radiotherapy, Adjuvant , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Clinical Trials as Topic , Combined Modality Therapy , Female , Humans , Mastectomy , Prognosis , Survival Rate
16.
AJR Am J Roentgenol ; 205(4): 905-11, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26397343

ABSTRACT

OBJECTIVE: The purpose of this study was to identify the prevalence of occult nodal metastases on routine ultrasound examination of internal mammary (IM) nodal basins in patients with breast cancer. MATERIALS AND METHODS: Patients with primary breast cancer (n = 595) underwent breast ultrasound evaluation between September 1, 2011, and April 1, 2012. For all patients, ultrasound examination included a survey of the axillary, infraclavicular, IM, and supraclavicular nodal basins. Patient demographics, breast cancer histopathologic type, and grade, size, location, and presence of metastatic nodes in regional nodal basins were recorded. Fisher exact test and Wilcoxon rank test were used for statistical analysis. RESULTS: Fifty-eight of 595 (10%) patients had positive IM ultrasound finding, with eight (1.3%) patients having isolated IM involvement. Patients with positive IM ultrasound findings were statistically significantly younger than those without such findings (median age, 42 vs 57 years; p < 0.0001). Of the 58 patients with positive IM ultrasound, 29 (50%) underwent ultrasound-guided needle biopsy, which confirmed malignancy in 26 of 29 (90%) patients. Nonlateral (p < 0.001) grade 3 (p < 0.001) tumors larger than 5 cm (p < 0.0006) with the estrogen receptor-negative HER2/neu-negative subtype (p < 0.001) associated with axillary, infraclavicular, or supraclavicular metastases (p < 0.001) were more likely to be associated with positive IM ultrasound findings. IM ultrasound resulted in an N status change for 46 of 595 (8%) patients and of the overall clinical stage for 38 (6.4%) patients. CONCLUSION: IM ultrasound and ultrasound-guided fine-needle aspiration biopsy are feasible, sensitive, and specific. Application of IM ultrasound and ultrasound-guided needle biopsy in a selected subpopulation of young patients with medial or central estrogen receptor-negative HER2/neu-negative breast cancer may result in a change in clinical stage and modify the treatment plan.


Subject(s)
Breast Neoplasms/diagnostic imaging , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Ultrasonography, Mammary , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Middle Aged , Neoplasm Staging , Retrospective Studies , Ultrasonography, Doppler
17.
Cancer ; 120(5): 702-10, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-24421077

ABSTRACT

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is a technologically advanced, and more expensive, method of delivering radiation therapy with a goal of minimizing toxicity. It has been widely adopted for head and neck cancers; however, its comparative impact on cancer control and survival remains unknown. The goal of this analysis was to compare the cause-specific survival (CSS) for patients with head and neck cancers treated with IMRT versus non-IMRT from 1999 to 2007. METHODS: CSS was determined using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and analyzed regarding treatment details, including the use of IMRT versus non-IMRT, using claims data. Hazard ratios (HRs) were estimated by the frailty model with a propensity score matching cohort and instrumental variable analysis. RESULTS: A total of 3172 patients were identified. With a median follow-up of 40 months, patients treated with IMRT had a statistically significant improvement in CSS compared with those treated with non-IMRT (84.1% versus 66.0%; P < .001). When each anatomic subsite was analyzed separately, all respective subgroups of patients treated with IMRT had better CSS than those treated with non-IMRT. In multivariable survival analyses, patients treated with IMRT were associated with better CSS (HR = 0.72, 95% confidence interval = 0.59 to 0.90 for propensity score matching; HR = 0.60, 95% confidence interval = 0.41 to 0.88 for instrumental variable analysis). CONCLUSIONS: Patients with head and neck cancers who were treated with IMRT experienced significant improvements in CSS compared with patients treated with non-IMRT techniques. This suggests there may be benefits to IMRT in cancer outcomes, in addition to toxicity reduction, for this patient population.


Subject(s)
Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Male , Medicare , Propensity Score , SEER Program , Treatment Outcome , United States/epidemiology
18.
Ethn Dis ; 24(4): 393-8, 2014.
Article in English | MEDLINE | ID: mdl-25417419

ABSTRACT

OBJECTIVE: We sought to compare hospice utilization for American Indian and White Medicare beneficiaries dying of cancer. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases to analyze claims for 181,316 White and 690 American Indian patients dying of breast, cervix, colorectal, kidney, lung, pancreas, prostate cancer, or stomach cancer from 2003 to 2009. RESULTS: A lower proportion of American Indians enrolled in hospice compared to White patients (54% vs 65%, respectively; P < .0001). While the proportion of White patients who used hospice services in the last 6 months of life increased from 61% in 2003 to 68% in 2009 (P < .0001), the proportion of American Indian patients using hospice care remained unchanged (P = .57) and remained below that of their White counterparts throughout the years of study. CONCLUSION: Continued efforts should be made to improve access to culturally relevant hospice care for American Indian patients with terminal cancer.


Subject(s)
Healthcare Disparities/ethnology , Hospice Care/statistics & numerical data , Indians, North American/statistics & numerical data , Medicare/statistics & numerical data , Neoplasms/ethnology , Terminally Ill/statistics & numerical data , Aged , Aged, 80 and over , Female , Hospices/statistics & numerical data , Humans , Male , Neoplasms/mortality , Neoplasms/therapy , SEER Program , United States , White People/statistics & numerical data
20.
Cancer ; 119(5): 1089-97, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23132206

ABSTRACT

BACKGROUND: Our goal was to investigate utilization trends for advanced radiation therapy (RT) technologies, such as intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS), in the last year of life among patients diagnosed with metastatic cancer. METHODS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked databases to analyze claims data in the last 12 months of life for 64,525 patients diagnosed with metastatic breast, colorectal, lung, pancreas, and prostate cancers from 2000 to 2007. Logistic regression modeling was conducted to analyze potential demographic, health services, and treatment-related variables' influences on receipt of advanced RT. RESULTS: Among the 19,161 (29.7%) patients who received radiation therapy, there was a significant decrease in the proportion of patients who received the simplest radiation technique (ie, 2D-radiation therapy) (P < .0001), and significant increases in the proportions of patients receiving more advanced radiation techniques (ie, IMRT, and SRS; P < .0001 for all curves); although the rates for use of IMRT and SRS in 2007 remained under 5%. On multivariate analyses, receipt of RT varied significantly by non-clinical characteristics such as race, marital status, neighborhood income, and SEER region. Patients who received hospice care in the last year of life were more likely to receive radiation therapy (OR = 1.35, 95% CI = 1.30-1.40) but less likely to be treated with IMRT (OR = 0.76, 95% CI = 0.62-0.92). CONCLUSIONS: Although the proportion of patients receiving RT in the last year of life for metastatic cancer did not change for most of the past decade, we observed significant trends toward more advanced radiation techniques.


Subject(s)
Neoplasm Metastasis/radiotherapy , Radiosurgery/statistics & numerical data , Radiotherapy, Intensity-Modulated/statistics & numerical data , Aged , Aged, 80 and over , Female , Hospice Care , Humans , Male , Radiosurgery/trends , Radiotherapy, Intensity-Modulated/trends , SEER Program , Socioeconomic Factors , Time Factors , United States/epidemiology
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