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1.
J Clin Oncol ; : JCO2001397, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897823
2.
J Natl Cancer Inst ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: covidwho-361366

RESUMO

Caring for older patients with breast cancer presents unique clinical considerations due to preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision-making for older patients is especially challenging and encourages us to re-focus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the 'new normal' for the approximately 30% of breast cancer patients age ≥70 years who are diagnosed in the U.S. annually and for the thousands of older patients living with recurrent and/or metastatic disease.

3.
Int J Radiat Oncol Biol Phys ; 108(1): 227-241, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417409

RESUMO

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.

5.
J Natl Cancer Inst ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449757

RESUMO

Caring for older patients with breast cancer presents unique clinical considerations due to preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision-making for older patients is especially challenging and encourages us to re-focus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the 'new normal' for the approximately 30% of breast cancer patients age ≥70 years who are diagnosed in the U.S. annually and for the thousands of older patients living with recurrent and/or metastatic disease.

6.
Clin Breast Cancer ; 20(3): 238-245, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32113750

RESUMO

BACKGROUND: The purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients had HR+/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes. RESULTS: Eight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase). CONCLUSIONS: RT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR+ MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR+ MBC.

8.
Breast J ; 26(3): 384-390, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31448540

RESUMO

Inflammatory breast cancer (IBC) exhibits dermal lymphatic involvement at presentation, and thus, the standard surgical approach is a nonskin-sparing modified radical mastectomy (MRM) without breast reconstruction (BR). In this study, we evaluated immediate and delayed BR receipt and its outcomes in IBC. Using an IRB-approved database, we retrospectively evaluated stage III IBC patients who received trimodality therapy (preoperative systemic therapy, followed by MRM and postmastectomy chest wall/regional nodal radiation). Patients with an insufficient response to preoperative systemic therapy and/or who required preoperative radiotherapy were excluded. BR receipt, timing, and morbidity were evaluated. Among 240 stage III IBC patients diagnosed between 1997 and 2016, 40 (17%) underwent BR. Thirteen (33%) had immediate, and 27 (67%) had delayed BR. Four patients had complications (1 [8%] immediate BR and 3 [11%] delayed BR); only 1 BR (delayed) was unsuccessful. From the MRM date, the median time to recurrence was 35 months (<1-212) and median overall survival was 87 months (<1-212). In this cohort of stage III IBC patients, only 11% pursued delayed BR following trimodality therapy, possibly attributable to the observed high recurrence rates hindering BR. Further studies addressing BR outcomes in IBC are needed for better counseling patients regarding their reconstructive options.

10.
Hematol Oncol Clin North Am ; 34(1): 1-12, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31739937

RESUMO

A series of landmark studies have increasingly emphasized the role of adjuvant radiotherapy for the definitive management of breast cancer. Although regional nodal irradiation, including the internal mammary nodes, was typically reserved for high-risk patients, there is now evidence of benefit to this approach even for those with a limited nodal disease burden. Similarly, low-risk disease has historically been treated with whole-breast tangents, although contemporary studies now support accelerated partial breast irradiation or the omission of radiotherapy in select cases. This article presents recent data informing these contemporary developments in the radiotherapeutic management of breast cancer.

11.
Breast Cancer Res Treat ; 178(3): 607-615, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31493031

RESUMO

PURPOSE: Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT). METHODS: We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events. RESULTS: At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05). CONCLUSIONS: With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento
12.
J Agric Food Chem ; 67(49): 13487-13495, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31347368

RESUMO

The occurrence in Riesling wine of the potent odorant 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN) is dependent upon vineyard and winemaking conditions, and TDN can have a prominent impact on the attributes of a wine after years in a bottle. As such, immediately assessing the impact of vineyard or winery treatments on future TDN formation requires forced creation of the aroma compound under non-wine-like conditions from other precursors. Here, we use a Box-Behnken approach and known TDN end points in commercial wines to optimize the conditions (pH, temperature, and time) of a "total TDN" hydrolytic assay for Riesling wine, which was intended to not interfere with yeast-derived formation pathways. The new assay (75 °C, pH 1.7, and 60 min) was used to determine the role of industry-relevant commercial yeasts as well as novel hybrid yeast strains on total TDN concentrations in young Riesling wines. While significant differences were observed between some yeasts, the impact of defoliation as a viticultural intervention outweighed yeast effects, suggesting that elevated TDN concentrations in wine are likely due to grape growing conditions and cannot be readily reduced or compensated for in the winery.


Assuntos
Naftalenos/análise , Naftalenos/metabolismo , Saccharomyces cerevisiae/metabolismo , Vinho/análise , Fermentação , Frutas/metabolismo , Frutas/microbiologia , Odorantes/análise , Vitis/metabolismo , Vitis/microbiologia
14.
Pract Radiat Oncol ; 9(5): 338-346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31063823

RESUMO

PURPOSE: Postmastectomy radiation therapy (PMRT) delivered to an immediate reconstruction increases the risk of surgical complications. Although acellular dermal matrix (ADM) has been used with immediate tissue expander (TE) reconstruction to improve cosmetic outcomes and minimize capsular contracture, there is a paucity of data on this approach in the setting of PMRT. METHODS AND MATERIALS: Thirty-two patients with stage I to III breast cancer were treated with mastectomy, immediate TE-ADM reconstruction, and PMRT between 2009 and 2012 in a prospective single-arm study. The primary objective was the "success" rate, determined by the number of patients at 2 years after PMRT having an intact final reconstruction, no major complications, and a cosmetic outcome rated by a physician as excellent or good. RESULTS: The median follow-up was 24 months. Final reconstruction status was known in 31 of 32 patients (96.9%; 1 patient left the country) and completed in 29 of 31 patients (93.5%; implant, n = 26; flap, n = 1; both, n = 2; none, n = 2). At 2 years, 6 patients were unevaluable (metastatic disease, n = 3; withdrawn consent, n = 1; left the country, n = 2). Of 26 evaluable patients, the success rate was 65.4% (17 of 26). Lack of success was the result of "fair" cosmesis (n = 2), infection (n = 2), severe capsular contracture (n = 1), major revision (n = 2), and no final reconstruction (n = 2). Most patients had good-to-excellent 2-year overall cosmesis based on patient perception (15; 62.5%) and physician evaluation (19; 79.2%). CONCLUSIONS: To the best of our knowledge, this is the first dedicated prospective trial evaluating long-term cosmetic and complication outcomes in patients treated with immediate TE-ADM reconstruction followed by PMRT. Most patients (65.4%) met the success criteria in this prospective single-arm series. The great majority (93.5%) achieved final reconstruction; most had good-to-excellent overall cosmetic outcomes (79.2%). The results with longer follow-up will be of interest, and further investigation of strategies to optimize reconstruction with PMRT are warranted.


Assuntos
Derme Acelular/metabolismo , Mastectomia/métodos , Radioterapia Adjuvante/efeitos adversos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Radioterapia Adjuvante/métodos , Dispositivos para Expansão de Tecidos , Adulto Jovem
15.
Breast Cancer Res Treat ; 176(2): 303-310, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004299

RESUMO

PURPOSE: Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T). METHODS: Patients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method. RESULTS: Of the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8). CONCLUSION: LRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy.


Assuntos
Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/epidemiologia , Paclitaxel/administração & dosagem , Receptor ErbB-2/metabolismo , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Metástase Linfática , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Estudos Prospectivos , Radioterapia Adjuvante , Receptor ErbB-2/antagonistas & inibidores , Análise de Sobrevida , Trastuzumab/farmacologia , Resultado do Tratamento
16.
Clin Breast Cancer ; 19(2): 146-155, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30584057

RESUMO

BACKGROUND: The aim of this study was to determine if, in inflammatory breast cancer (IBC), baseline metabolic activity (maximum standardized uptake value [SUVmax]) of primary tumor and involved regional lymph nodes (IRLN) are prognostic markers of response after neoadjuvant systemic therapy (NAS). PATIENTS AND METHODS: Baseline 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography scans were retrospectively reviewed among 61 women with IBC who received NAS, had mastectomy, and had available pathology reports. Primary tumor and IRLN SUVmax were compared between patients with a pathologic complete response (pCR) versus those with residual disease after NAS. A multivariate Cox model was fit to evaluate the effects of SUVmax on overall survival, adjusting for pCR and stratified by receptor status and disease stage. RESULTS: SUVmax in primary IBC tumors tended to increase with tumor grade (trend test P = .06) and was lower for stage III, non-triple-negative (TN) versus stage III, TN and stage IV, non-TN disease (P = .04). Neither primary tumor nor IRLN SUVmax was significantly different comparing pCR versus residual disease after NAS. Adjusting for pathology response in the overall survival model stratified by stage and receptor status, baseline SUVmax in primary IBC tumor was associated with an estimated hazard ratio of 1.10 (95% confidence interval, 0.97-1.25; P = .15) for patients with stage III, TN and stage IV, non-TN disease. This hazard ratio corresponded to a 1.74-fold risk of death with 1 standard deviation (SD = 5.9) increase in baseline SUVmax in primary IBC tumor. CONCLUSION: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography provides prognostic information for newly diagnosed IBC. Larger studies are needed to confirm these findings and assess how such early information could affect treatment choices for IBC in the neoadjuvant setting.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Neoplasias Inflamatórias Mamárias/diagnóstico por imagem , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Idoso , Axila , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Neoplasias Inflamatórias Mamárias/cirurgia , Excisão de Linfonodo , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Risco , Análise de Sobrevida , Resultado do Tratamento
18.
Front Microbiol ; 9: 1442, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034376

RESUMO

Wine yeast breeding programs utilizing interspecific hybridization deliver cost-effective tools to winemakers looking to differentiate their wines through the development of new wine styles. The addition of a non-Saccharomyces cerevisiae genome to a commercial wine yeast can generate novel phenotypes ranging from wine flavor and aroma diversity to improvements in targeted fermentation traits. In the current study we utilized a novel approach to screen isolates from an evolving population for increased fitness in a S. cerevisiae × S. uvarum interspecific hybrid previously generated to incorporate the targeted phenotype of lower volatile acidity production. Sequential grape-juice fermentations provided a selective environment from which to screen isolates. Chromosomal markers were used in a novel approach to identify isolates with potential increased fitness. A strain with increased fitness relative to its parents was isolated from an early timepoint in the evolving population, thereby minimizing the risk of introducing collateral mutations and potentially undesirable phenotypes. The evolved strain retained the desirable fermentation trait of reduced volatile acidity production, along with other winemaking traits of importance while exhibiting improved fermentation kinetics.

19.
Int J Radiat Oncol Biol Phys ; 101(2): 265-266, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726353

Assuntos
Pesquisa
20.
Pract Radiat Oncol ; 8(3): 145-152, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29545124

RESUMO

INTRODUCTION: The purpose of this guideline is to offer recommendations on fractionation for whole breast irradiation (WBI) with or without a tumor bed boost and guidance on treatment planning and delivery. METHODS AND MATERIALS: The American Society for Radiation Oncology (ASTRO) convened a task force to address 5 key questions focused on dose-fractionation for WBI, indications and dose-fractionation for tumor bed boost, and treatment planning techniques for WBI and tumor bed boost. Guideline recommendations were based on a systematic literature review and created using a predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength. RESULTS: For women with invasive breast cancer receiving WBI with or without inclusion of the low axilla, the preferred dose-fractionation scheme is hypofractionated WBI to a dose of 4000 cGy in 15 fractions or 4250 cGy in 16 fractions. The guideline discusses factors that might or should affect fractionation decisions. Use of boost should be based on shared decision-making that considers patient, tumor, and treatment factors, and the task force delineates specific subgroups in which it recommends or suggests use or omission of boost, along with dose recommendations. When planning, the volume of breast tissue receiving >105% of the prescription dose should be minimized and the tumor bed contoured with a goal of coverage with at least 95% of the prescription dose. Dose to the heart, contralateral breast, lung, and other normal tissues should be minimized. CONCLUSIONS: WBI represents a significant portion of radiation oncology practice, and these recommendations are intended to offer the groundwork for defining evidence-based practice for this common and important modality. This guideline also seeks to promote appropriately individualized, shared decision-making regarding WBI between physicians and patients.


Assuntos
Neoplasias da Mama/radioterapia , Radioterapia (Especialidade)/normas , Neoplasias da Mama/patologia , Feminino , Guias como Assunto , Humanos , Pessoa de Meia-Idade , Estados Unidos
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