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Importance: Surgery with complete tumor resection remains the main treatment option for patients with breast cancer. Yet, current technologies are limited in providing accurate assessment of breast tissue in vivo, warranting development of new technologies for surgical guidance. Objective: To evaluate the performance of the MasSpec Pen for accurate intraoperative assessment of breast tissues and surgical margins based on metabolic and lipid information. Design, Setting, and Participants: In this diagnostic study conducted between February 23, 2017, and August 19, 2021, the mass spectrometry-based device was used to analyze healthy breast and invasive ductal carcinoma (IDC) banked tissue samples from adult patients undergoing breast surgery for ductal carcinomas or nonmalignant conditions. Fresh-frozen tissue samples and touch imprints were analyzed in a laboratory. Intraoperative in vivo and ex vivo breast tissue analyses were performed by surgical staff in operating rooms (ORs) within 2 different hospitals at the Texas Medical Center. Molecular data were used to build statistical classifiers. Main Outcomes and Measures: Prediction results of tissue analyses from classification models were compared with gross assessment, frozen section analysis, and/or final postoperative pathology to assess accuracy. Results: All data acquired from the 143 banked tissue samples, including 79 healthy breast and 64 IDC tissues, were included in the statistical analysis. Data presented rich molecular profiles of healthy and IDC banked tissue samples, with significant changes in relative abundances observed for several metabolic species. Statistical classifiers yielded accuracies of 95.6%, 95.5%, and 90.6% for training, validation, and independent test sets, respectively. A total of 25 participants enrolled in the clinical, intraoperative study; all were female, and the median age was 58 years (IQR, 44-66 years). Intraoperative testing of the technology was successfully performed by surgical staff during 25 breast operations. Of 273 intraoperative analyses performed during 25 surgical cases, 147 analyses from 22 cases were subjected to statistical classification. Testing of the classifiers on 147 intraoperative mass spectra yielded 95.9% agreement with postoperative pathology results. Conclusions and Relevance: The findings of this diagnostic study suggest that the mass spectrometry-based system could be clinically valuable to surgeons and patients by enabling fast molecular-based intraoperative assessment of in vivo and ex vivo breast tissue samples and surgical margins.
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Neoplasias de la Mama , Adulto , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Márgenes de Escisión , Mama/cirugía , Mama/patología , Mastectomía , Espectrometría de MasasRESUMEN
Breast cancer is a highly heterogeneous group of diseases posing a significant challenge in biomarker-driven research and the development of effective targeted therapies. Especially the treatment of metastatic breast cancer poses even more challenges, as we still lose more than 42,000 women and men each year in the United States alone. New biological insight helps to improve breast cancer treatment through early detection, adaptation to chemotherapy resistance, and tailoring to find the right size of care. This review focuses on existing and new areas of predictive biomarkers under development to tailor the management of breast cancer and the application of integrative approaches that have resulted in the promising candidate biomarker discovery. Furthermore, we review new methods to detect metastatic progression using imaging, and blood-based assays. We hope to increase the attention and awareness of a new generation of therapeutic development strategies in metastatic breast cancer.
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BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER 2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.
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PURPOSE: Tubular carcinoma (TC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for TC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with TC remains unclear. MATERIALS AND METHODS: The National Cancer Database was queried (2004-2015) for patients with pN0M0 TC who underwent lumpectomy. Chi-square testing compared categorized variables between those who did and did not receive radiotherapy. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analysis identified variables prognostic for OS. Patients were divided into age cohorts ≤60 years and >60 years. Propensity score matching (PSM) was utilized to create similar cohorts. RESULTS: 9705 patients met selection criteria; 6182 (75.1%) received radiotherapy while 2045 (24.9%) did not. After PSM, radiotherapy (HR 0.582; 95% CI 0.494-0.686) and endocrine therapy (HR 0.737; 95% CI 0.623-0.872) were favorable prognostic factors on multivariate Cox regression analysis while age > 60 years (HR 5.131; 95% CI 3.753-7.016), Black race (HR 1.445; 95% CI 1.016-2.055), and Charlson-Deyo comorbidity score > 0 (HR 1.708; 95% CI 1.403-2.079) were unfavorable prognostic factors. After PSM, 5-year OS was 91.7% for those who received radiotherapy and 84.5% for those who did not; 10-year OS was 76.1% and 64.1%, respectively (p < 0.001). CONCLUSION: This is the largest study to date on TC and the prognostic impact of adjuvant radiotherapy. Postoperative radiotherapy is a favorable prognostic factor for OS in patients with pN0M0 TC, suggesting adjuvant radiotherapy should remain standard of care in these patients.
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Adenocarcinoma , Quimioterapia Adyuvante , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
BACKGROUND: Although randomized data support omitting adjuvant radiotherapy (RT) following breast conservation for T1-2N0 estrogen receptor positive breast cancer in ≥70-year-old women, there remains a knowledge gap regarding its omission for triple-negative BC (TNBC). METHODS AND MATERIALS: The National Cancer Database (NCDB) was queried for ≥70-year-old females with newly diagnosed T1-2N0M0 TNBC treated with breast conservation. Multivariable logistic regression ascertained factors associated with adjuvant RT administration. Overall survival (OS) between patients treated with or without adjuvant RT was estimated using the Kaplan-Meier method. Cox proportional hazards modeling determined variables associated with OS. RESULTS: Of 8526 patients, 6283 (74%) patients received adjuvant RT, and 2243 (26%) did not. RT was more frequently withheld in older patients, those with higher comorbidities, lower income, pT2 disease, following margin-positive resection, receipt of chemotherapy, and at academic centers (P < 0.05 for all). Median follow-up was 38.0 months. Five-year OS was greater in the adjuvant RT group (77.2% vs 55.3%, P < 0.001); these differences persisted when stratifying for age, T stage, and chemotherapy utilization (P < 0.001 for all). Omission of RT was also independently associated with poorer OS on multivariate analysis (P < 0.001). CONCLUSIONS: This investigation, the largest known such study to date, observed that omission of adjuvant RT for elderly women with T1-2N0 TNBC was associated with poorer OS; this was observed across a range of age groups, as well as following stratification by T stage and chemotherapy usage. Although these results do not imply causation, caution must be exercised when considering omission of adjuvant RT in node-negative TNBC patients.
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Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/radioterapia , Distribución por Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Bases de Datos Factuales , Estatus Económico/estadística & datos numéricos , Femenino , Humanos , Estimación de Kaplan-Meier , Mastectomía Segmentaria , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante/mortalidad , Estudios RetrospectivosRESUMEN
OBJECTIVES: Invasive papillary breast cancer (IPBCA) represents 0.5% of invasive BCA, and is thought to carry a favorable prognosis. This population-based study reports on prognostic factors, treatment, and outcomes of early-stage IPBCA to explore whether there is any evidence to support less aggressive treatment. MATERIALS AND METHODS: IPBCA cases from 1990 to 2009 of the recent Surveillance, Epidemiology, and End Results were analyzed. Inclusion criteria included patients with stage T1-2, N0 IPBCA. Univariate and multivariate analyses were performed using the variables of treatment, stage, race, hormone receptor status, grade (G1-3), and age. Treatment modalities included lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), and mastectomy alone (MA). RESULTS: Among 10,485 patients, median follow-up was 56 months. Five and 10-year overall survival (OS) were 93.1% and 76.8%, respectively. Patients treated with LRT had superior mean OS 16.8 versus 14.9 years for MA (P=0.0004) and 14.2 years for LA (P=0.0003). Improved OS also correlated with lower histologic grade (P<0.0001), lower T-stage (P<0.0001), and younger age (P<0.0001). Black patients had the worst OS (12.7 y, P<0.0001). CONCLUSIONS: LRT is associated with superior OS for early-stage invasive papillary BCA patients, when compared with LA or MA in this population-based study. The findings support the standard of care breast conservation approach for patients with invasive papillary BCA. Other prognostic factors associated with worse OS include increased age, higher T-stage, higher histologic grade, and black race.
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Neoplasias de la Mama/mortalidad , Carcinoma Papilar/mortalidad , Mastectomía Segmentaria/mortalidad , Mastectomía/mortalidad , Radioterapia/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Papilar/patología , Carcinoma Papilar/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Programa de VERF , Tasa de SupervivenciaRESUMEN
BACKGROUND: Granulomatous mastitis (GM) is a rare, chronic, inflammatory condition of the breast with unknown etiology that affects women of child-bearing age. It can be mistaken radiographically and clinically for breast cancer and due to its rarity can cause a delay in establishing a definitive diagnosis and subsequent initiation of treatment. Furthermore, GM has a progressive clinical course with multiple recurrences. To date, there is no universally accepted treatment for GM. The goal of this study is to review the experience with granulomatous mastitis at a large inner-city public hospital over a 10-y period. METHODS: A retrospective review of a prospectively maintained institutional database was queried for all patients with a histopathologic diagnosis of GM between July 1, 2000 and July 1, 2010. A separate database was created for these patients, and data was collected from electronic medical records and paper charts. Demographic, clinical, and outcomes data were analyzed using summary statistics. RESULTS: A total of 41 cases were identified. The median age at time of diagnosis was 34 y. Thirty-three (80%) patients were of Hispanic ethnicity. The most common physical findings were mass (n = 32, 78%), tenderness (n = 17, 41%), and erythema (n = 12, 29%). Three (7%) patients had a previous history of treatment for tuberculosis whereas 12 (29%) patients were human immunodeficiency virus-positive. Mammography and ultrasonography noted mass (n = 14, 34% and n = 15, 37%, respectively) as the most common radiographic finding. Core needle biopsy and incisional biopsy were used with equal frequency (n = 16, 37%) to establish a definitive pathologic diagnosis. The median number of days between onset of symptoms and definitive diagnosis was 73. Thirteen (32%) patients received antibiotics as initial treatment, whereas 23 (56%) underwent surgical procedures and 1 (2%) received steroid therapy. Steroids were used at any point in the clinical course of 7 (17%) patients, and none of these patients required definitive surgical treatment. CONCLUSIONS: GM affects women of childbearing age and typically presents as an inflamed breast mass with or without pain. The clinical features of GM among Hispanic patients are similar to those among other study populations in the reported literature. This disease is a diagnostic and therapeutic challenge and a high degree of clinical suspicion is warranted. Treatment with steroids may obviate the need for surgery in some patients. Reported recurrence rates for GM are high, and long-term follow-up is essential.
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Neoplasias de la Mama/diagnóstico , Mastitis Granulomatosa/diagnóstico , Hospitales de Condado , Hospitales Urbanos , Adulto , Antibacterianos/uso terapéutico , Biopsia , Mama/cirugía , Bases de Datos Factuales , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Mastitis Granulomatosa/tratamiento farmacológico , Mastitis Granulomatosa/cirugía , Humanos , Mamografía , Recurrencia , Estudios Retrospectivos , Esteroides/uso terapéutico , UltrasonografíaRESUMEN
BACKGROUND: Phyllodes tumors represent less than 1% of all breast neoplasms and can mimic fibroadenoma on core needle biopsy (CNB). The treatment of fibroepithelial (FE) neoplasms identified on CNB is controversial. We sought to identify factors that were associated with phyllodes tumors after CNB suggested FE neoplasm. MATERIALS AND METHODS: A retrospective database was queried for all patients diagnosed with FE neoplasm on CNB at Ben Taub General Hospital over a 10-y period. One hundred twenty-three patients were identified and demographic, clinical, and outcome data were analyzed. RESULTS: Of the 123 patients, 46 (37%) were found to have fibroadenomatous features and 59 (48%) were found to have FE features. All went on to have surgical excision. Forty (38%) contained phyllodes tumors, and 65 (62%) found no phyllodes tumor on final pathology. There were significant differences in the median size of the masses (4 cm versus 2.4 cm P < 0.002) and density of the masses (P < 0.001) between the group that contained phyllodes tumors and the group that did not on preoperative imaging. Further evaluation did not show any significant differences on preoperative imaging between benign and borderline/malignant phyllodes tumors. Hispanic ethnicity correlated with a higher chance of phyllodes tumor after CNB (P < 0.001). CONCLUSIONS: Women commonly present to clinics for evaluation of palpable breast masses. Based on the results of CNB, clinical decisions can be made to help direct treatment. If CNB identifies phyllodes tumor, surgical excision remains the standard of care; however, patients with suspicious FE neoplasms represent a treatment dilemma as many will prove to be benign. Preoperative size and the density of the mass on imaging and ethnicity were associated with phyllodes tumors on final pathology.
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Neoplasias de la Mama/patología , Fibroadenoma/patología , Neoplasias/patología , Tumor Filoide/patología , Adulto , Biopsia con Aguja Gruesa/métodos , Neoplasias de la Mama/cirugía , Bases de Datos Factuales , Diagnóstico Diferencial , Femenino , Fibroadenoma/cirugía , Humanos , Neoplasias/cirugía , Tumor Filoide/cirugía , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Estudios RetrospectivosRESUMEN
PURPOSE: To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). MATERIALS AND METHODS: Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 microg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. RESULTS: Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 microg. When indocyanine green dosages were 10 microg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 microg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. CONCLUSION: NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.