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BACKGROUND: Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. METHODS: Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson's correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. RESULTS: EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = - 0.18), PR (r = - 0.25), and AR (r = - 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). CONCLUSION: These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Receptores Androgénicos/genética , Progesterona , Receptores de Estrógenos/metabolismo , Antígeno Ki-67/genética , Pronóstico , Estrógenos , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Biomarcadores de Tumor/metabolismo , Receptor ErbB-2 , Proteínas de HomeodominioRESUMEN
PURPOSE: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor-positive (HR+) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance. EXPERIMENTAL DESIGN: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test. RESULTS: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69-1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N+ subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14-0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (-1.2% absolute benefit; HR, 1.11; 95% CI, 0.76-1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N+/HER2- subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15-0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849). CONCLUSIONS: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR+ N+ patients with HER2- disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes.
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Neoplasias de la Mama , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: Young age at breast cancer diagnosis correlates with unfavorable clinicopathologic features and worse outcomes compared with older women. Understanding biological differences between breast tumors in young versus older women may lead to better therapeutic approaches for younger patients. EXPERIMENTAL DESIGN: We identified 100 patients ≤35 years old at nonmetastatic breast cancer diagnosis who participated in the prospective Young Women's Breast Cancer Study cohort. Tumors were assigned a surrogate intrinsic subtype based on receptor status and grade. Whole-exome sequencing of tumor and germline samples was performed. Genomic alterations were compared with older women (≥45 years old) in The Cancer Genome Atlas, according to intrinsic subtype. RESULTS: Ninety-three tumors from 92 patients were successfully sequenced. Median age was 32.5 years; 52.7% of tumors were hormone receptor-positive/HER2-negative, 28.0% HER2-positive, and 16.1% triple-negative. Comparison of young to older women (median age 61 years) with luminal A tumors (N = 28 young women) revealed three significant differences: PIK3CA alterations were more common in older patients, whereas GATA3 and ARID1A alterations were more common in young patients. No significant genomic differences were found comparing age groups in other intrinsic subtypes. Twenty-two patients (23.9%) in the Young Women's Study cohort carried a pathogenic germline variant, most commonly (13 patients, 14.1%) in BRCA1/2. CONCLUSIONS: Somatic alterations in three genes (PIK3CA, GATA3, and ARID1A) occur at different frequencies in young versus older women with luminal A breast cancer. Additional investigation of these genes and associated pathways could delineate biological susceptibilities and improve treatment options for young patients with breast cancer. See related commentary by Yehia and Eng, p. 2209.
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Neoplasias de la Mama , Adulto , Anciano , Neoplasias de la Mama/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , Femenino , Genómica , Células Germinativas/metabolismo , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Breast cancer in young women is more likely to have higher risk features and be associated with germline BRCA1/BRCA2 mutations. We present the clinicopathologic features of breast cancers in a prospective cohort of young women, and associations between surrogate molecular subtype and BRCA1/BRCA2 mutation status. METHODS: Histopathological features, biomarker status, tumour stage and BRCA status were collected. Invasive tumours were categorised as luminal A-like (ER + and/or PR + , HER2-, grade 1/2), luminal B-like (ER + and/or PR + , HER2 + , or ER + and/or PR + , HER2-, and grade 3), HER2-enriched (ER/PR-, HER2 + ) or triple-negative. RESULTS: In all, 57.3% (654/1143) of invasive tumours were high grade. In total, 32.9% were luminal A-like, 42.4% luminal B-like, 8.3% HER2-enriched, and 16.4% triple-negative. Among different age groups, there were no differences in molecular phenotype, stage, grade or histopathology. 11% (131) of tumours were from BRCA mutation carriers; 64.1% BRCA1 (63.1% triple-negative), and 35.9% BRCA2 (55.3% luminal B-like). DISCUSSION: The opportunity to provide comparisons across young age groups, BRCA mutation status, surrogate molecular phenotype, and the identification of more aggressive hormone receptor-positive phenotypes in this population provides direction for future work to further understand and improve disparate outcomes for young women with luminal B-like cancers, particularly BRCA2-associated cancers, with potential implications for tailored prevention and treatment.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/patología , Receptor alfa de Estrógeno/metabolismo , Mutación , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Adolescente , Adulto , Factores de Edad , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Clasificación del Tumor , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Altered mechanical properties of the tumor matrix have emerged as both the cause and consequence of breast carcinogenesis. Increased tumor stiffness has traditionally provided a viable metric to screen for malignancies via palpation or imaging. Previous studies have demonstrated that the microscale mechanical properties of the cell substrate influence tumor proliferation and invasive migration in vitro. Nevertheless, the association of the mechanical microenvironment with clinical hallmarks of aggressiveness in human breast tumors, including histopathological subtype, grade, receptor expression status, and lymph node involvement is poorly understood. This is largely due to the lack of tools for mapping tumor viscoelastic properties in clinical specimens with high spatial resolution over a large field of view (FoV). Here we introduce laser Speckle rHEologicAl micRoscopy (SHEAR) that for the first time enables mapping the magnitude viscoelastic or shear modulus, |G*(x,y,ω)|, over a range of frequencies (ω = 1-250 rad/second) in excised tumors within minutes with a spatial resolution of approximately 50 µm, over multiple cm2 FoV. Application of SHEAR in a cohort of 251 breast cancer specimens from 148 patients demonstrated that |G*(x,y,ω)| (ω = 2π rad/second) closely corresponds with histological features of the tumor, and that the spatial gradient of the shear modulus, |∇|G*(x,y,ω)||, is elevated at the tumor invasive front. Multivariate analyses established that the metrics, (|G* |) and (|∇|G* ||), measured by SHEAR are associated with prognosis. These findings implicate the viscoelastic properties of the tumor microenvironment in breast cancer prognosis and likely pave the path for identifying new modifiable targets for treatment. SIGNIFICANCE: Laser speckle rheological microscopy establishes the links between microscale heterogeneities of viscoelasticity and histopathological subtype, tumor grade, receptor expression, as well as lymph node status in breast carcinoma.
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Fenómenos Mecánicos , Microscopía Confocal , Neoplasias/patología , Reología , Microambiente Tumoral , Algoritmos , Biomarcadores de Tumor , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Teóricos , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias/diagnóstico por imagen , Neoplasias/etiologíaRESUMEN
Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in brain. We determine that this phenotype is an adaptation to decreased lipid availability in brain relative to other tissues, resulting in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
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Neoplasias Encefálicas , Neoplasias de la Mama , Neoplasias Encefálicas/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Ácido Graso Sintasas/genética , Ácidos Grasos/uso terapéutico , Femenino , Humanos , Microambiente TumoralRESUMEN
PURPOSE: Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20-40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. METHODS: We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. RESULTS: Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81-5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. CONCLUSIONS: Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.
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Neoplasias de la Mama , Mastectomía Segmentaria , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Neoplasia Residual , Péptido Hidrolasas , Estudios Prospectivos , ReoperaciónRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0216997.].
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The article Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery, written by Barbara L. Smith et al., was originally published electronically on the publisher's internet portal on January 2, 2020, without open access.
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BACKGROUND: Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20-40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. METHODS: Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology. RESULTS: In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal. CONCLUSIONS: The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.
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Neoplasias de la Mama/cirugía , Cuidados Intraoperatorios , Mastectomía Segmentaria/métodos , Recurrencia Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Péptido Hidrolasas/metabolismo , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Diagnóstico por Imagen , Estudios de Factibilidad , Femenino , Colorantes Fluorescentes/química , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/cirugía , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: We aimed to assess the risk of malignancy (ROM) and predictive values in prior breast cytology studies as a basis for the new International Academy of Cytology (IAC) Yokohama system for reporting breast fine-needle aspiration biopsy (FNAB) cytology, which classifies cytologic diagnoses into 5 categories: (1) insufficient material, (2) benign, (3) atypical, (4) suspicious of malignancy, and (5) malignant. STUDY DESIGN: Publications between January 1, 1997, and December 31, 2017, that studied the performance characteristics of FNAB from palpable and nonpalpable breast masses were identified through the PubMed database. Data for number of total cases and cases within each diagnostic category, if available, were collected. Performance characteristics, including absolute sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM for each category were recorded or, when possible, calculated. RESULTS: The literature review resulted in a case cohort of 33,341 breast FNABs, drawn from 27 studies. Pooling these cases together, the ROM for insufficient material, benign, atypical, suspicious, and malignant were 30.3, 4.7, 51.5, 85.4, and 98.7%, respectively. The complete sensitivity and specificity were 96.3 and 98.8%, correspondingly. The PPV and NPV were 98.7 and 95.3%, correspondingly. The false-negative and false-positive rates were 3.7 and 1.0%, respectively. CONCLUSIONS: This meta-analysis demonstrates that the diagnostic categories of the new IAC Yokohama System each carry an implied ROM, which increases from the benign to malignant categories. This study also shows the high sensitivity and specificity of FNAB for breast lesions.
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Neoplasias de la Mama/diagnóstico , Citodiagnóstico/normas , Patología Clínica/normas , Guías de Práctica Clínica como Asunto/normas , Medición de Riesgo/métodos , Biopsia con Aguja Fina , Neoplasias de la Mama/cirugía , Femenino , Humanos , Valor Predictivo de las Pruebas , Sociedades MédicasRESUMEN
PURPOSE: Genome-wide-association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with an increased risk of breast cancer. Most of these studies were conducted primarily in postmenopausal breast cancer patients. Therefore, we set out to assess whether or not these breast cancer variants are also associated with an elevated risk of breast cancer in young premenopausal patients. METHODS: In 451 women of European ancestry who had prospectively enrolled in a longitudinal cohort study for women diagnosed with breast cancer at or under age 40, we genotyped 44 SNPs that were previously associated with breast cancer risk. A control group was comprised of 1142 postmenopausal healthy women from the Nurses' Health Study (NHS). We assessed if the frequencies of the adequately genotyped SNPs differed significantly (p≤0.05) between the cohort of young breast cancer patients and postmenopausal controls, and then we corrected for multiple testing. RESULTS: Genotyping of the controls or cases was inadequate for comparisons between the groups for seven of the 44 SNPs. 9 of the remaining 37 were associated with breast cancer risk in young women with a p-value <0.05: rs10510102, rs1219648, rs13387042, rs1876206, rs2936870, rs2981579, rs3734805, rs3803662 and rs4973768. The directions of these associations were consistent with those in postmenopausal women. However, after correction for multiple testing (Benjamini Hochberg) none of the results remained statistically significant. CONCLUSION: After correction for multiple testing, none of the alleles for postmenopausal breast cancer were clearly associated with risk of premenopausal breast cancer in this relatively small study.
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Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Adulto , Alelos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Receptores de Estrógenos/genética , Factores de RiesgoRESUMEN
The International Academy of Cytology (IAC) gathered together a group of cytopathologists expert in breast cytology who, working with clinicians expert in breast diagnostics and management, have developed the IAC Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy (FNAB) Cytology. The project was initiated with the first cytopathology group meeting in Yokohama at the 2016 International Congress of Cytology. This IAC Yokohama System defines five categories for reporting breast cytology, each with a clear descriptive term for the category, a definition, a risk of malignancy (ROM) and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category will be presented more fully in a subsequent atlas. The System emphasizes that the crucial requirements for diagnostic breast FNAB cytology are a high standard for the performance of the FNAB and for the making of direct smears, and well-trained experienced cytopathologists to interpret the material. The performance indicators of breast FNAB, including specificity and sensitivity, negative predictive value, positive predictive value and ROM stated in this article have been derived from the recent literature. The current practice of breast FNAB has evolved with the increasing use of ultrasound guidance and rapid on-site evaluation. Two recent publications have shown a range of ROM for the insufficient/inadequate category of 2.6-4.8%, benign 1.4-2.3%, atypical 13-15.7%, suspicious of malignancy 84.6-97.1%, and malignant 99.0-100%. The management algorithm in the System provides options because there are variations in the management of breast lesions using FNAB and core-needle biopsy in those countries utilizing the "triple test" of clinical, imaging, and FNAB assessment, and also variations in the availability of CNB and imaging in low- and middle-income countries. The System will stimulate further discussion and research, particularly in the cytological diagnostic features of specific lesions within each category and in management recommendations. This will lead to continuing improvements in the care of patients with breast lesions and possible modifications to the IAC Yokohama System.
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Neoplasias de la Mama/diagnóstico , Citodiagnóstico/normas , Guías de Práctica Clínica como Asunto/normas , Garantía de la Calidad de Atención de Salud , Biopsia con Aguja Fina , Neoplasias de la Mama/cirugía , Femenino , Humanos , Sociedades MédicasRESUMEN
OBJECTIVE: Differentiation between gynecomastia, a common cause of male breast enlargement, and breast cancer is crucial for appropriate management. Fine-needle aspiration biopsy has been shown to be sensitive and specific in assessing female breast lesions, comparable to core needle biopsy. Few such studies have been conducted in men. We assessed its diagnostic value in a male patient cohort. STUDY DESIGN: Men who underwent fine-needle aspiration (FNA) for palpable breast lesions at Massachusetts General Hospital from January 2007 to December 2016 were evaluated. Clinical data, radiographic findings, and cytologic diagnoses of 74 breast FNA from 71 men were reviewed. Breast aspirates were classified as nondiagnostic, benign, atypical, suspicious for malignancy, or malignant. Histology was obtained in 37 cases, and clinical and radiological data were used as follow-up in 37 patients. RESULTS: Most FNA biopsies (73%) were performed by cytopathologists, and 93.2% of the breast FNA in men were adequate; 58% showed benign processes, mostly gynecomastia (n = 22), and 28.4% (n = 21) were malignant, most often ductal carcinoma. No false-positive cytologies were obtained, and there was 1 false-negative cytology. In our study, FNA of palpable male breast lesions was 95.8% sensitive and 100% specific. CONCLUSIONS: FNA allows sensitive, specific, and safe evaluation and diagnosis of palpable male breast lesions.
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Neoplasias de la Mama Masculina/diagnóstico , Citodiagnóstico/normas , Patología Clínica/normas , Guías de Práctica Clínica como Asunto/normas , Biopsia con Aguja Fina , Neoplasias de la Mama Masculina/clasificación , Neoplasias de la Mama Masculina/cirugía , Humanos , Masculino , Valor Predictivo de las PruebasRESUMEN
Breast MRI is the most sensitive imaging modality for assessment of the nipple-areola complex (NAC), which is important both in cancer staging and in high-risk screening. However, the normal appearance of the nipple at MRI is not well defined because of a paucity of scientific literature on this topic. Hence, there is a lack of descriptive terminology and diagnostic criteria, which may account for the wide variability in interpretation among radiologists when assessing the NAC on MR images. In light of the current shift toward possible expanded use of abbreviated (ie, fast) breast MRI for screening in women at average risk for cancer in particular, and because an increasing number of women now undergo nipple-sparing mastectomy for therapeutic and/or prophylactic indications, careful assessment of the NAC at MRI is essential. In this article, the normal pattern of nipple enhancement at MRI is defined on the basis of findings observed in healthy individuals, normal nipple enhancement at MRI is correlated with the structural anatomy of the nipple at histopathologic analysis, and artifacts and pitfalls related to MRI of the NAC are reviewed. Understanding the normal range of nipple morphology and enhancement at MRI is important, as it enables radiologists to better differentiate between normal and abnormal nipple findings with increased diagnostic confidence. ©RSNA, 2018 See discussion on this article by Cohen and Holbrook .
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Neoplasias de la Mama/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Imagen por Resonancia Magnética/métodos , Pezones/diagnóstico por imagen , Adulto , Anciano , Mama/anatomía & histología , Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía Segmentaria , Persona de Mediana Edad , Estadificación de Neoplasias , Pezones/anatomía & histología , Pezones/patología , Estudios Retrospectivos , Sensibilidad y EspecificidadAsunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Carcinoma Lobular/secundario , Receptor alfa de Estrógeno/genética , Mutación , Anciano , Dolor de Espalda/etiología , Neoplasias Óseas/complicaciones , Neoplasias de la Mama/genética , Carcinoma Lobular/genética , Receptores ErbB/análisis , Femenino , Humanos , Dolor Pélvico/etiología , Receptores de Esteroides/análisisRESUMEN
PURPOSE: Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. METHODS: We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis. RESULTS: In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. CONCLUSIONS: Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/análisis , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
PURPOSE: Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. METHODS: Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology. RESULTS: Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015. CONCLUSION: The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.