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1.
Ann Surg ; 277(3): e617-e623, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33938495

RESUMO

OBJECTIVE: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes. SUMMARY OF BACKGROUND DATA: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery. METHODS: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and QOL and decision satisfaction. RESULTS: Of 288 women (mean age 56 years, 58% non-Hispanic White), 50 had CPM, 75 had unilateral mastectomy, and 163 had BCS. Mean pain severity scores were higher at one (2.78 vs 1.9, P = 0.016) and 6 months (2.79 vs 1.96, P = 0.031) postsurgery in women who had CPM versus those who did not, but there was no difference at 12 and 18 months. Comparing mastectomy versus BCS, pain severity was higher at 1 and 12 months. There was a significant interaction between pain severity and time point for CPM ( P = 0.006), but not mastectomy status ( P = 0.069). Regardless of surgery type, Black women had higher pain severity ( P = 0.004) than White women. Higher pain interference was associated with lower QOL ( P < 0.001) and lower decision satisfaction ( P = 0.034). CONCLUSIONS: Providers should counsel women considering mastectomy about the potential for greater acute pain and its impact on overall well-being. Racial/ethnic disparities in pain exist and influence pain management in breast surgical patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Mastectomia , Dor
2.
Ann Surg Oncol ; 29(6): 3822-3828, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35233742

RESUMO

BACKGROUND: Nonpalpable breast lesions require precise preoperative localization to facilitate negative margins with breast-conserving therapy. The traditional use of wires has several challenges including patient discomfort, wire migration, and coordination of schedules between radiology and the operating room. Radioactive seed localization overcomes some of these challenges, but radiation safety requirements have limited adoption of this technology. The authors examined their institutional experience with Magseed as an alternative technology for localization and compared outcomes with those of wire and radioactive seed localization. METHODS: An institutional review board (IRB)-approved retrospective study was performed to evaluate patients who underwent excisional biopsy or segmental mastectomy after wire-guided localization (WGL), radioactive seed localization (RSL), or Magseed localization (ML). The clinical and pathologic factors of the three groups were assessed with a negative margin rate as the primary outcome measure. RESULTS: Of the 1835 patients in the study, 825 underwent WGL, 449 underwent RSL, and 561 underwent ML. For the patients with either multiple lesions or a large lesion that required bracketing, multiple localization devices were placed in 31% of the WGL patients, 28% of the RSL patients, and 23% of the ML patients (p = 0.006). Negative margins were achieved in 91% of the WGL patients, 89% of the RSL patients, and 89% of the ML patients (p = 0.4). CONCLUSION: Localization of non-palpable breast lesions using Magseed is a safe and effective alternative to WGL and RSL that overcomes radiation safety limitations and increases radiology and surgery scheduling efficiency.


Assuntos
Neoplasias da Mama , Radioisótopos do Iodo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Fenômenos Magnéticos , Margens de Excisão , Mastectomia , Mastectomia Segmentar , Estudos Retrospectivos
4.
J Surg Oncol ; 123(5): 1206-1214, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33577715

RESUMO

PURPOSE: To evaluate the acceptability and impact of 3D-printed breast models (3D-BMs) on treatment-related decisional conflict (DC) of breast cancer patients. METHODS: Patients with breast cancer were accrued in a prospective institutional review board-approved trial. All patients underwent contrast-enhanced breast magnetic resonance imaging (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre- and post-3D-BM review. 3D-BM acceptability was assessed post-3D-BM review. RESULTS: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in two patients with bilateral breast cancer. The mean patient age was 48.8 years (28-72). The tumor stage was Tis (7), 1 (8), 2 (8), and 3 (4). The nodal staging was 0 (19), 1 (7), and 3 (1). Tumors were unifocal (15), multifocal (8), or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to seven patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25), and impartial to surgical options (17/24). There was a significant reduction in the overall DC post-3D-BM review, indicating patients became more assured of their treatment choice (p = 0.002). Reduction post-3D-BM review was also observed in the uncertainty (p = 0.012), feeling informed about options (p = 0.005), clarity about values (p = 0.032), and effective (p = 0.002) Decisional Conflict Scale subscales. CONCLUSIONS: 3D-BMs are an acceptable tool to decrease DC in breast cancer patients.


Assuntos
Neoplasias da Mama/cirurgia , Técnicas de Apoio para a Decisão , Conhecimentos, Atitudes e Prática em Saúde , Imageamento por Ressonância Magnética/métodos , Mastectomia/estatística & dados numéricos , Participação do Paciente , Impressão Tridimensional/instrumentação , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/psicologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/psicologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/psicologia , Carcinoma Lobular/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Mastectomia/psicologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
5.
J Surg Oncol ; 120(6): 897-902, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31441070

RESUMO

A patient-specific 3-dimensional printed model (3DPM) of a woman with breast cancer was created. Mastectomy was favored as BCS would necessitate significant breast size alteration due to the extent of disease. After review of the 3D printed model, the patient and surgeon agreed on breast-conserving surgery. Use of patient-specific 3DPM in the setting of breast cancer may aid patient decision making and surgical planning, leading to enhanced surgical and oncological outcomes.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Impressão Tridimensional/instrumentação , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
6.
Ann Surg Oncol ; 26(10): 3071-3079, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342361

RESUMO

BACKGROUND: Patients with epidermal growth factor receptor 2-positive (HER2+) breast cancer and pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) may be candidates for nonoperative clinical trials if residual invasive and in situ disease are eradicated. METHODS: This study analyzed 280 patients with clinical T1-2N0-1 HER2+ breast cancer who underwent NST followed by surgical resection to determine key characteristics of patients with pCR in the breast and lymph nodes compared with those with residual disease. RESULTS: Of the 280 patients, 102 (36.4%) had pCR in the breast and lymph nodes after NST, and 50 patients (17.9%) had residual ductal carcinoma in situ (DCIS) in the breast only. For 129 patients (46.1%), DCIS was present on the pretreatment biopsy, and NST failed to eradicate the DCIS component in 64.3%. Patients with residual disease were more likely to have hormone receptor-positive (HR+) tumors than those with negative tumors (73.4% vs. 50.8%; p < 0.0001). Radiologic response (odds ratio [OR], 5.62; p = 0.002) and HR+ status (OR, 2.56; p < 0.0001) were predictive of residual disease. Combined imaging methods after NST had a sensitivity of 97.1% and a negative predictive value of 70.6% for detection of residual disease. Patients with invasive disease and DCIS shown on the pretreatment core biopsy were less likely than those without DCIS to achieve pCR in the breast (31% vs. 43%; p = 0.038). CONCLUSION: The study results delineate and identify unique characteristics associated with HER2+ breast cancers that are important in selecting patients for inclusion in clinical trials assessing nonoperative management after NST, and the low negative predictive value of imaging mandates image-guided biopsy for selection.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Linfonodos/patologia , Terapia Neoadjuvante/métodos , Neoplasia Residual/patologia , Seleção de Pacientes , Receptor ErbB-2/metabolismo , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Seguimentos , Humanos , Biópsia Guiada por Imagem/métodos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/metabolismo , Prognóstico , Estudos Prospectivos
8.
Ann Surg Oncol ; 26(6): 1720-1728, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30877499

RESUMO

BACKGROUND: Intraoperative margin assessment for breast cancer patients undergoing segmental mastectomy (SM) enables identification of positive margins, with immediate excision of additional tissue to obtain negative margins. OBJECTIVE: The aim of this study was to determine the ability of digital breast tomosynthesis (DBT) to detect positive margins compared with an institution's standard extensive processing (SEP). METHODS: SM specimens underwent intraoperative SEP with two-dimensional (2D) imaging of the intact and sliced specimen, with review by a breast radiologist and gross assessment by a breast pathologist. Findings guided the surgeon to excise additional tissue. DBT images of intact specimens were prospectively obtained and retrospectively reviewed by a breast radiologist. A positive margin was defined as tumor at ink. RESULTS: Ninety-eight patients underwent 99 SMs. With SEP, 14 (14%) SM specimens had 19 positive margins. SEP did not detect 3 of the 19 positive margins, for a sensitivity of 84%, specificity of 78%, positive predictive value (PPV) of 11%, and negative predictive value (NPV) of 99%. Moreover, DBT did not detect 5 of the 19 positive margins, for a sensitivity of 74% (p > 0.05), specificity of 91% (p < 0.05), PPV of 21.5%, and NPV of 99%. With SEP guidance to excise additional tissue, six cases had final positive margins, with SEP not identifying three of these cases and DBT not identifying two. Pathology from the second surgery of these patients showed either no additional malignancy or only focal ductal carcinoma in situ. CONCLUSIONS: DBT is an accurate method for detecting positive margins in breast cancer patients undergoing SM, performing similar to institutional labor-intensive, intraoperative standard processing.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Cuidados Intraoperatórios , Mamografia/métodos , Margens de Excisão , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
9.
Pract Radiat Oncol ; 9(1): e4-e13, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30125673

RESUMO

PURPOSE: This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy. METHODS AND MATERIALS: A total of 281 patients with pTis, pT1N0, or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled from December 2008 through August 2014. APBI was delivered using 3-dimensional CRT (n = 29) or with SAVI (n = 176), Contura (n = 56), or MammoSite (n = 20) brachytherapy catheters. Patients were evaluated at protocol-specified intervals, at which time the radiation oncologist scored cosmetic outcome, toxicities, and recurrence status using a standardized template. RESULTS: The median follow-up time is 41 months. Grade 1 seroma and fibrosis were more common with brachytherapy than with 3-dimensional CRT (50.4% vs 3.4% for seroma; P < .0001 and 66.3% vs 44.8% for fibrosis; P = .02), but grade 1 edema was more common with 3-dimensional CRT than with brachytherapy (17.2% vs 5.6%; P = .04). Grade 2 to 3 pain was more common with 3-dimensional CRT (17.2% vs 5.2%; P = .03). Actuarial 5-year rates of fair or poor radiation oncologist-reported cosmetic outcome were 9% for 3-dimensional CRT and 24% for brachytherapy (P = .13). Brachytherapy was significantly associated with inferior cosmesis on mixed model analysis (P = .003). Significant predictors of reduced risk of adverse cosmetic outcome after brachytherapy were D0.1cc (skin) ≤102%, minimum skin distance >5.1 mm, dose homogeneity index >0.54, and volume of nonconformance ≤0.89 cc. The 5-year ipsilateral breast recurrence was 4.3% for brachytherapy and 4.2% for 3-dimensional CRT APBI patients (P = .95). CONCLUSIONS: Brachytherapy APBI is associated with higher rates of grade 1 fibrosis and seroma than 3-dimensional CRT but lower rates of grade 1 edema and grade 2 to 3 pain than 3-dimensional CRT. Rates of radiation oncologist-reported fair or poor cosmetic outcomes are higher with brachytherapy. We identified dosimetric parameters that predict reduced risk of adverse cosmetic outcome after brachytherapy-based APBI. Ipsilateral breast recurrence was equivalent for brachytherapy and 3-dimensional CRT.


Assuntos
Braquiterapia/efeitos adversos , Neoplasias da Mama/radioterapia , Cosméticos , Recidiva Local de Neoplasia/diagnóstico , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Edema/etiologia , Feminino , Fibrose/etiologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Dor/etiologia , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Seroma/etiologia
10.
Ann Surg ; 269(1): 150-157, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28742682

RESUMO

OBJECTIVE: To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. BACKGROUND: Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins <2 mm. METHODS: One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). RESULTS: A univariate analysis revealed that age <40 years (n = 89; P = 0.02), no RT (n = 298; P = 0.01), and negative margin width <2 mm (n = 120; P = 0.005) were associated with LRR. The association between margin width and LRR differed by adjuvant RT status (interaction P = 0.02). There was no statistical significant difference in LRR between patients with <2 mm and ≥2 mm negative margins who underwent RT (10-yr LRR rate, 4.8% vs 3.3%, respectively; hazard ratio, 0.8; 95% CI, 0.2-3.2; P = 0.72). For patients who did not undergo RT, those with margins <2 mm were significantly more likely to develop a LRR than were those with margins ≥2 mm (10-yr LRR rate, 30.9% vs 5.4%, respectively; hazard ratio, 5.5; 95% CI, 1.8-16.8, P = 0.003). CONCLUSIONS: Routine additional surgery may not be justified for patients with negative margins <2 mm who undergo RT but should be performed in patients who forego RT.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Margens de Excisão , Mastectomia Segmentar/métodos , Estadiamento de Neoplasias , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Cancer ; 125(3): 365-373, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30359480

RESUMO

BACKGROUND: Clips are often placed to mark axillary nodes with biopsy-confirmed metastases in patients with breast cancer. The evaluation of clipped nodes after chemotherapy can identify patients who have eradication of nodal disease. The goal of this study was to determine whether preoperative fine-needle aspiration (FNA) of clipped nodes after neoadjuvant chemotherapy (NAC) could predict the presence of residual disease. METHODS: This prospective registry study enrolled 50 patients with a clip placed to mark nodes with biopsy-confirmed metastases who had completed NAC. Participants underwent FNA of the clipped node before seed-localized lymph node excision. FNA pathology was compared with surgical pathology. RESULTS: There were 36 patients (72%) with residual disease on surgical pathology: 3 (8%) had a nondiagnostic aspirate, carcinoma was seen in 14 (39%), and 19 (53%) had a false-negative result. The sensitivity of FNA was 42.4%, its specificity was 100%, and its negative predictive value was 40.6%. In a univariate analysis, the odds of a true-positive result increased significantly with the mean initial size of the clipped node (odds ratio [OR], 4.3; P = .004) and the size of the metastatic focus after NAC (OR, 1.3; P = 0.003), whereas normalization of nodes after chemotherapy (OR, 0.1) and a lack of response on ultrasound (OR, 0.11) were associated with a false-negative result (P = .01). CONCLUSIONS: FNA of marked nodes after chemotherapy has a high false-negative rate. This highlights the need for surgical staging of the axilla after NAC to assess the response.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Monitoramento de Medicamentos/métodos , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Adulto , Axila , Biópsia por Agulha Fina/instrumentação , Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/patologia , Estudos de Viabilidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Biópsia de Linfonodo Sentinela/instrumentação , Biópsia de Linfonodo Sentinela/métodos , Instrumentos Cirúrgicos , Resultado do Tratamento , Ultrassonografia
12.
J Clin Oncol ; 36(25): 2630-2638, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30044695

RESUMO

Purpose The incidence of contralateral prophylactic mastectomy (CPM) has continued to increase. We prospectively examined psychosocial outcomes before and up to 18 months after surgery in women who did or did not have CPM. Methods Women with unilateral, nonhereditary breast cancer completed questionnaires before and 1, 6, 12, and 18 months after surgery. Primary psychosocial measures were cancer worry and cancer-specific distress. Secondary measures were body image, quality of life (QOL), decisional satisfaction, and decisional regret. Results A total of 288 women (mean age, 56 years; 58% non-Hispanic white) provided questionnaire data, of whom 50 underwent CPM. Before surgery, women who subsequently received CPM had higher cancer distress ( P = .04), cancer worry ( P < .001), and body image concerns ( P < .001) than women who did not have CPM. In a multivariable repeated measures model adjusted for time, age, race/ethnicity, and stage, CPM was associated with more body image distress ( P < .001) and poorer QOL ( P = .02). There was a significant interaction between time point and CPM group for cancer worry ( Pinteraction < .001), suggesting that CPM patients had higher presurgery cancer worry, but their postsurgery worry decreased over time and was similar to the worry of patients who did not have CPM. QOL was similar between CPM groups before surgery but declined 1 month after surgery and remained lower than patients who did not have CPM after surgery ( Pinteraction = .05). Conclusion These results may facilitate informed discussions between women and their physicians regarding CPM. Fear and worry may be foremost concerns at the time surgical decisions are made, when women may not anticipate the adverse future effect of CPM on body image and QOL.


Assuntos
Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/psicologia , Mastectomia Profilática/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem Corporal/psicologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida/psicologia
13.
Ann Surg ; 267(5): 946-951, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28549010

RESUMO

OBJECTIVE: To determine the accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) in assessing the presence of residual cancer in the breast after neoadjuvant systemic therapy (NST). SUMMARY BACKGROUND DATA: Pathologic complete response (pCR) rates after NST have improved dramatically, suggesting that surgery might be avoided in some patients. Safe avoidance of surgery would require accurate confirmation of no residual invasive/in situ carcinoma. METHODS: Forty patients with T1-3N0-3 triple-negative or HER2-positive cancer receiving NST were enrolled in this single-center prospective trial. Patients underwent ultrasound-guided or mammography-guided FNA and VACB of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting residual breast disease after NST. RESULTS: Median initial clinical tumor size was 3.3 cm (range, 1.2-7.0 cm); 16 patients (40%) had biopsy-proven nodal metastases. After NST, median clinical tumor size was 1.1 cm (range, 0-4.2 cm). Nineteen patients (47.5%) had a breast pCR and were concordant with pathologic nodal status in 97.5%. Combined FNA/VACB demonstrated an accuracy of 98% (95% CI, 87%-100%), false-negative rate of 5% (95% CI, 0%-24%), and negative predictive value of 95% (95% CI, 75%-100%) in predicting residual breast cancer. VACB alone was more accurate than FNA alone (P = 0.011). CONCLUSIONS: After NST, image-guided FNA/VACB can accurately identify patients with a breast pCR. Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Biópsia Guiada por Imagem/métodos , Mastectomia/métodos , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Axila , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/secundário , Quimioterapia Adjuvante , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Metástase Linfática , Mamografia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Reprodutibilidade dos Testes
14.
Clin Cancer Res ; 23(21): 6468-6477, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29093017

RESUMO

Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed. Phenotypic profiling was performed by determining efficacy of a panel of standard and investigational agents.Results: Twenty-six PDXs were developed from 25 patients. Twenty-two were generated from residual disease following neoadjuvant chemotherapy, and 24 were from triple-negative breast cancer (TNBC). These PDXs harbored a heterogeneous set of genomic alterations and represented all TNBC molecular subtypes. On RPPA, PDXs varied in extent of PI3K and MAPK activation. PDXs also varied in their sensitivity to chemotherapeutic agents. PI3K, mTOR, and MEK inhibitors repressed growth but did not cause tumor regression. The PARP inhibitor talazoparib caused dramatic regression in five of 12 PDXs. Notably, four of five talazoparib-sensitive models did not harbor germline BRCA1/2 mutations, but several had somatic alterations in homologous repair pathways, including ATM deletion and BRCA2 alterations.Conclusions: PDXs capture the molecular and phenotypic heterogeneity of TNBC. Here we show that PARP inhibition can have activity beyond germline BRCA1/2 altered tumors, causing regression in a variety of molecular subtypes. These models represent an opportunity for the discovery of rational combinations with targeted therapies and predictive biomarkers. Clin Cancer Res; 23(21); 6468-77. ©2017 AACR.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Ftalazinas/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Acrilonitrila/administração & dosagem , Acrilonitrila/análogos & derivados , Compostos de Anilina/administração & dosagem , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mutação em Linhagem Germinativa , Humanos , Camundongos , Inibidores de Fosfoinositídeo-3 Quinase , Ftalazinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
JAMA Surg ; 152(7): 665-670, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28423171

RESUMO

Importance: A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. Objective: To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design. Design, Setting, and Participants: This prospective cohort study at a single-institution academic national comprehensive cancer center included 527 consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. Main Outcomes and Measures: Patients who achieved a breast pCR were compared with patients who did not based on subtype, initial ultrasonographic findings, and documented pathologic nodal status. Incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pCR and compared using relative risk ratios with 95% CIs. Results: The analysis included 527 patients (median age, 51 [range, 23-84] years). Among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence of residual nodal disease (P < .01). Patients without a breast pCR had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P < .001) compared with those with a breast pCR. Conclusions and Relevance: Breast pCR is highly correlated with nodal status after NCT, and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a breast pCR.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Excisão de Linfonodo , Linfonodos/fisiologia , Receptor ErbB-2/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Axila , Biópsia por Agulha Fina , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/patologia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Seleção de Pacientes , Estudos Prospectivos , Medição de Risco , Ultrassonografia , Adulto Jovem
16.
Ann Surg Oncol ; 24(1): 64-69, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27557827

RESUMO

Axillary ultrasound is increasingly utilized for nodal staging preoperatively in patients presenting with invasive breast cancer to provide guidance for preoperative chemotherapy or proceeding directly to surgery. Improvements in ultrasound technology make it possible to assess the nodal burden in order to identify those patients not eligible for ACOSOG Z0011 management. However, its ability to detect metastasis is variable and dependent on operator's skills, size of metastatic deposit, and primary tumor histology subtype. Therefore, sentinel lymph node biopsy is still performed with a normal axillary ultrasound. Current debate questions whether there is a benefit to diagnosing metastasis with ultrasound-guided needle biopsy as this may lead to more axillary node dissections in an era of its decreasing role. In node-positive patients, axillary ultrasound has been preliminarily shown to be helpful in assessing nodal response after preoperative chemotherapy and improve the accuracy of sentinel node dissection which may spare future patients' axillary node dissection. Improvements in axillary ultrasound and other imaging modalities along with predictive models based on tumor biology may make axillary surgery a procedure of the past for many breast cancer patients.


Assuntos
Axila/diagnóstico por imagem , Axila/patologia , Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Ultrassonografia/métodos , Biópsia por Agulha , Ensaios Clínicos como Assunto , Feminino , Humanos , Biópsia Guiada por Imagem , Excisão de Linfonodo , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Biópsia de Linfonodo Sentinela , Ultrassonografia de Intervenção , Procedimentos Desnecessários
17.
Ann Surg Oncol ; 24(3): 652-659, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27822630

RESUMO

PURPOSE: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have low regional recurrence rates when treated with breast-conserving surgery and radiation therapy (XRT) and many avoid a completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment. METHODS: An institutional database was utilized to identify patients treated with a TM for invasive breast cancer and who had a positive SLN from 1994 to 2010. Clinicopathologic factors were analyzed. Regional recurrence rate, recurrence-free survival (RFS), and overall survival (OS) were determined. RESULTS: A total of 525 patients with invasive breast cancer and a positive SLN were treated with TM, including 58 patients who did not have CLND or XRT and 12 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The incidence of regional recurrence was not significantly different for patients who received no further axillary treatment compared to those who underwent CLND without XRT or those treated with XRT without CLND (10 years rate: 3.8 vs. 1.6 and 0 % respectively). RFS and OS were not significantly different among patients who received no further axillary treatment compared to those who underwent CLND, XRT, or both. CONCLUSIONS: In select patients with early-stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo , Mastectomia Simples , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Radioterapia Adjuvante , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela , Taxa de Sobrevida , Carga Tumoral
18.
Am J Surg Pathol ; 40(10): 1375-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27627744

RESUMO

Radioactive seed localization is a new procedure for localizing breast lesions that has several advantages over the standard wire-localization procedure. It is reported to be safe for both patients and medical personnel. Although it is theoretically possible to transect the titanium-encapsulated seed while processing the breast specimen in the pathology laboratory, the likelihood of such an event is thought to be exceedingly low. In fact, there are no previous reports of such an event in the literature to date. We recently encountered 2 cases in which a radioactive seed was inadvertently transected while slicing a breast specimen at the grossing bench. In this report, we describe each case and offer recommendations for minimizing radioactive exposure to personnel and for preventing radioactive contamination of laboratory equipment.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Marcadores Fiduciais/efeitos adversos , Radioisótopos do Iodo/efeitos adversos , Exposição Ocupacional , Exposição à Radiação , Compostos Radiofarmacêuticos/efeitos adversos , Adulto , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Exposição Ocupacional/prevenção & controle , Patologia Cirúrgica , Exposição à Radiação/prevenção & controle
20.
AJR Am J Roentgenol ; 206(5): 1112-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27007608

RESUMO

OBJECTIVE: The objective of this study was to compare the potential influence of imaging variables on surgical margins after preoperative radioactive seed localization (RSL) and wire localization (WL) techniques. MATERIALS AND METHODS: A total of 565 women with 660 breast lesions underwent RSL or WL between May 16, 2012, and May 30, 2013. Patient age, lesion type (mass, calcifications, mass with associated calcifications, other), lesion size, number of seeds or wires used, surgical margin status (close positive or negative margins), and reexcision and mastectomy rates were recorded. RESULTS: Of 660 lesions, 127 (19%) underwent RSL and 533 (81%) underwent WL preoperatively. Mean lesion size was 1.8 cm in the RSL group and 1.8 cm in the WL group (p = 0.35). No difference in lesion type was identified in the RSL and WL groups (p = 0.63). RSL with a single seed was used in 105 of 127 (83%) RSLs compared with WL with a single wire in 349 of 533 (65%) WLs (p = 0.0003). The number of cases with a close positive margin was similar for RSLs (26/127, 20%) and WLs (104/533, 20%) (p = 0.81). There was no difference between the RSL group and the WL group in close positive margin status (20% each, p = 0.81), reexcision rates (20% vs 16%, respectively; p = 0.36), or mastectomy rates (6% each, p = 0.96). Lesions containing calcifications were more likely to require more than one wire (odds ratio [OR], 4.44; 95% CI, 2.8-7.0) or more than one seed (OR, 7.03; 95% CI, 1.6-30.0) when compared with masses alone (p < 0.0001). Increasing lesion size and the presence of calcifications were significant predictors of positive margins, whereas the use of more than one wire or seed was not (OR, 0.9; 95% CI, 0.5-1.5) (p = 0.75). CONCLUSION: Close positive margin, reexcision, and mastectomy rates remained similar in the WL group and RSL group. The presence of calcifications and increasing lesion size increased the odds of a close positive margin in both the WL and RSL groups, whereas the use of one versus more than one seed or wire did not.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Marcadores Fiduciais , Mamografia/métodos , Mastectomia Segmentar/métodos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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