Histological assessment of breast lesions identified exclusively by magnetic resonance.

Radiologic-pathologic correlation of lesions diagnosed by magnetic resonance (MR) is precluded by insufficient data on histological characteristics of lesions suspicious on MR but not visible on concurrent mammogram or ultrasound. The objective of this study was to describe histological features of breast lesions diagnosed exclusively by MR. The participants underwent MR-guided breast biopsy between 2007 and 2012 for a suspicious lesion not identified by mammography or ultrasound. Histology slides were interpreted retrospectively by a breast pathologist. Of 126 patients (126 lesions), 34 (27%) had new breast cancer, 51 (40.5%) previous breast cancer, and 41 (32.5%) dense breasts or a significant family history of breast cancer. MR identified 23 (18.3%) invasive cancers: 20 were Grade 1 and 17 were ductal. Of the 126 lesions, 16 (13%) were ductal carcinoma in situ (DCIS), four were atypical ductal hyperplasia and atypical lobular hyperplasia (3%), and 68 (54%) were benign. Fifteen biopsies (12%) had no significant pathology. Five DCIS lesions were upgraded to T1 invasive cancers. Approximately 30 per cent of suspicious lesions detected exclusively by MR are invasive or in situ cancers that are predominantly low grade. Further studies are needed to determine if malignant lesions can be prospectively distinguished by MR characteristics.

Patient age is related to decision-making, treatment selection, and perceived quality of life in breast cancer survivors.

BACKGROUND: Patients with breast cancer must choose among a variety of treatment options when first diagnosed. Patient age, independent of extent of disease, is also related to quality of life. This study examined the impact of patient age on treatment selected, factors influencing this selection, and perceived quality of life. METHODS: A 62-question survey evaluating breast cancer treatment and quality of life was mailed to breast cancer survivors. Responses were stratified by age (<50, 50-65, >65 years) and extent of disease. RESULTS: Of the 1,131 surveys mailed, 402 were included for analysis. There were 104, 179, and 119 women aged <50, 50-65, and >65 years, respectively. The median patient age was 58 years, and the average interval from diagnosis to survey participation was 31.5 months. CONCLUSIONS: Young women were more likely to have undergone aggressive therapies and had better physical functioning than old women. Old patients reported good quality of life and body image. Clinicians should consider patient age when discussing breast cancer treatment options.

Increased use of partial-breast irradiation has not improved radiotherapy utilization for early-stage breast cancer.

BACKGROUND: Radiotherapy (RT) reduces local recurrence after breast-conserving surgery (BCS) for breast cancer, but under-utilization of RT has been reported. Accelerated partial-breast irradiation (PBI) improves RT accessibility, but it is uncertain if this has improved RT utilization. METHODS: The Surveillance, Epidemiology and End Results registry was used to identify women who underwent BCS for stage 0 or 1 breast cancer from 2000 to 2009. Temporal trends in RT utilization and RT modality were determined. Chi-square analysis and multivariate logistic regression identified predictors of RT utilization and modality. RESULTS: Of 180,219 study patients, 131,343 (73 %) received RT; 123,703 (94 %) of RT recipients received whole-breast irradiation (WBI) and 6,251 (5 %) received PBI. PBI rates increased dramatically during the study period (0.32 % in 2000 vs. 6.5 % in 2009), but overall RT utilization remained relatively stable because of a decline in WBI (69.8 % in 2000 vs. 62.4 % in 2009). RT utilization was unchanged in rural counties, and declined for women <40 and ≥70 years of age, and for Native American, Asian and Hispanic patients. White and Black women used PBI most frequently (4 % each) and were the only race groups with improved RT utilization over time. Predictors of RT usage included age, race, marital status, tumor size, grade, hormone receptor status, lymph node evaluation, geographic region, metropolitan status, education, and employment status. CONCLUSIONS: Women who undergo RT are opting for PBI more frequently, but the increased use of this modality has not improved overall RT utilization for patients with early-stage breast cancer.

Microbial dysbiosis is associated with human breast cancer.

Breast cancer affects one in eight women in their lifetime. Though diet, age and genetic predisposition are established risk factors, the majority of breast cancers have unknown etiology. The human microbiota refers to the collection of microbes inhabiting the human body. Imbalance in microbial communities, or microbial dysbiosis, has been implicated in various human diseases including obesity, diabetes, and colon cancer. Therefore, we investigated the potential role of microbiota in breast cancer by next-generation sequencing using breast tumor tissue and paired normal adjacent tissue from the same patient. In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae is relatively enriched in paired normal tissue. The relative abundances of these two bacterial species were inversely correlated in paired normal breast tissue but not in tumor tissue, indicating that dysbiosis is associated with breast cancer. Furthermore, the total bacterial DNA load was reduced in tumor versus paired normal and healthy breast tissue as determined by quantitative PCR. Interestingly, bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer. Lastly, we observed lower basal levels of antibacterial response gene expression in tumor versus healthy breast tissue. Taken together, these data indicate that microbial DNA is present in the breast and that bacteria or their components may influence the local immune microenvironment. Our findings suggest a previously unrecognized link between dysbiosis and breast cancer which has potential diagnostic and therapeutic implications.

Improving size, lymph node metastatic rate, breast conservation, and mortality of invasive breast cancer in Rhode Island women, a well-screened population.

The beneficial impact of screening mammography on breast cancer outcome continues to be debated as demonstrated by guidelines published by the United States Preventive Services Task Force. A previous report from Rhode Island, which has a very high rate of mammographic screening, demonstrated significant improvements in invasive breast cancer presentation and mortality through 2001. This report updates data through 2008 to determine whether previous favorable trends continued. Rhode Island Cancer Registry data regarding invasive breast cancer presentation and mortality in 17,522 female residents diagnosed between 1987 and 2008, inclusive, were analyzed for demographic and pathological factors. Data were analyzed by four time periods: 1987-1992, 1993-1998, 1999-2003, and 2004-2008 and overall. Statistically significant improvements occurred over the four successive time periods, in mean cancer size (23.7, 20.9, 19.6, and 19.3 mm, p < 0.0001), pathologic grade (Grade I: 12, 15, 19, and 17 %; Grade III 57, 41, 36, and 35 %, p < 0.0001), breast conserving surgery (38, 56, 67, and 71 %, p < 0.0001) and mortality (37.3, 31.4, 25.1, and 22.6 per 100,000/year, p < 0.0001). The results showed that high screening rates favorably impacted presentation of and mortality from invasive breast cancer in Rhode Island. From 1987 to 2008, there has been a 39 % decline in breast cancer mortality considering 5 year periods (37.3 vs. 22.6 deaths per 100,000) and 41 % comparing the period from 1990 to 2008, which may exceed the goal of 50 % mortality reduction by 2015 established by the American Cancer Society.

Axillary ultrasound and fine-needle aspiration in the preoperative evaluation of the breast cancer patient: an algorithm based on tumor size and lymph node appearance.

OBJECTIVE: The objective of our study was to evaluate the utility of ultrasound-guided fine-needle aspiration (FNA) of the axillary lymph nodes in breast cancer patients depending on the size of the primary tumor and the appearance of the lymph nodes. SUBJECTS AND METHODS: Data were collected about tumor size, lymph node appearance, and the results of ultrasound-guided FNA and axillary surgery of 224 patients with breast cancer undergoing 226 ultrasound-guided FNA. Lymph nodes were classified as benign if the cortex was even and measured < 3 mm, indeterminate if the cortex was even but measured ≥ 3 mm or measured < 3 mm but was focally thickened, and suspicious if the cortex was focally thickened and measured ≥ 3 mm or the fatty hilum was absent. The results of ultrasound-guided FNAs were analyzed by the sonographic appearance of the axillary lymph nodes and by the size of the primary tumor. The sensitivity and specificity of ultrasound-guided FNA were calculated with axillary surgery as the reference standard. The sensitivity and specificity of axillary ultrasound to predict the ultrasound-guided FNA result were calculated. RESULTS: Of the 224 patients, 51 patients (23%) had a positive ultrasound-guided FNA result, which yields an overall sensitivity of 59% and specificity of 100%. The sensitivity of ultrasound-guided FNA was 29% in patients with primary tumors ≤ 1 cm, 50% in patients with tumors > 1 to ≤ 2 cm, 69% in patients with tumors > 2 to ≤ 5 cm, and 100% in patients with tumors > 5 cm. The sensitivity of ultrasound-guided FNA in patients with normal-appearing lymph nodes was 11%; indeterminate lymph nodes, 44%; and suspicious lymph nodes, 93%. Sonographic characterization of lymph nodes as suspicious or indeterminate was 94% sensitive and 72% specific in predicting positive findings at ultrasound-guided FNA. CONCLUSION: Ultrasound-guided FNA of the axillary lymph nodes is most useful in the preoperative assessment of patients with large tumors (> 2 cm) or lymph nodes that appear abnormal.

FePt nanoparticles as an Fe reservoir for controlled Fe release and tumor inhibition.

Chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) show the controlled release of Fe in low pH solution. The released Fe catalyzes H(2)O(2) decomposition into reactive oxygen species within cells, causing fast oxidation and deterioration of cellular membranes. Functionalized with luteinizing hormone-releasing hormone (LHRH) peptide via phospholipid, the fcc-FePt NPs can bind preferentially to the human ovarian cancer cell line (A2780) that overexpresses LHRH receptors and exhibit high toxicity to these tumor cells. In contrast, the fcc-FePt NPs pre-etched in the low pH (4.8) buffer solution show nonappreciable cytotoxicity. The work demonstrates that fcc-FePt NPs may function as a new type of agent for controlled cancer therapy.

MUC1 Knockdown With RNA Interference Inhibits Pancreatic Cancer Growth.

MUC1, a tumor associated glycoprotein over-expressed in 95% of pancreatic cancers, has been shown to be associated with a worse prognosis. The objective of this study was to determine the impact of loss of MUC1 expression on pancreatic tumor growth. PANC1 human pancreatic carcinoma cells with stable "knockdown" MUC1 expression were created using a MUC1 specific short interfering RNA (siRNA). PANC1 cells with "knockdown" MUC1 expression had decreased in vitro proliferation compared with PANC1 wild type and control cells. PANC1-MUC1siRNA cells grew significantly slower in severe combined immunodeficient (SCID) mice compared with wild type and negative controls. Our data suggested that decreasing MUC1 tumor expression by RNA interference may be a novel molecular approach for the treatment of pancreatic cancer.

MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent.

MUC1, a transmembrane glycoprotein, is abnormally over-expressed in most human adenocarcinomas. MUC1 association with cytoplasmic cell signal regulators and nuclear accumulation are important for its tumor related activities. Little is known about how MUC1 translocates from the cell membrane to the cytoplasm. In this study, live cell imaging was used to study MUC1 intracellular trafficking. The interaction between EGFR and MUC1 was mapped by FRET analysis and EGF stimulated MUC1 endocytosis was observed directly through live cell imaging. MUC1-CT endocytosis was clathrin and dynamin dependent. Rab5 over-expression resulted in decreased cell membrane localization of MUC1, with accumulation of MUC1 endocytic vesicles in the peri-nuclear region. Conversely, over-expression of a Rab5 dominant negative mutant (S34N) resulted in redistribution of MUC1 from the peri-nuclear region to the cytoplasm. Collectively, these results indicated that MUC1 intra-cellular trafficking occurs through a regulated process that was stimulated by direct EGFR and MUC1 interaction, mediated by clathrin coated pits that were dynamin dependent and regulated by Rab5.

Axillary lymph nodes: US-guided fine-needle aspiration for initial staging of breast cancer--correlation with primary tumor size.

PURPOSE: To retrospectively assess the sensitivity and specificity of ultrasonographic (US)-guided fine-needle aspiration (FNA) of axillary lymph nodes for preoperative staging of breast cancer across a range of primary tumor sizes, by using histologic findings as a reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study; informed consent was waived. US-guided FNA results in 74 patients with breast cancer (75 axillae) were compared with final pathologic results. Lymph nodes were classified as benign, indeterminate, or suspicious on the basis of US characteristics at retrospective review. US-guided FNA in the most suspicious node at US, or the largest node if all appeared benign, was performed. Final pathologic results (sentinel lymph node biopsy [SNB] or axillary lymph node dissection [ALND]) were compared with US and preoperative US-guided FNA results. Results were assessed according to tumor size. Sensitivity, specificity, and positive predictive value of US and US-guided FNA were calculated. RESULTS: Primary tumor sizes were 0.3-12 cm (mean, 3 cm). Patient age range was 31-81 years (mean age, 51 years). Sensitivity of US-guided FNA for predicting positive results at ALND or SNB was 71%-75%. Specificity was 100%. Sensitivity of US-guided FNA increased with primary tumor size. CONCLUSION: US-guided FNA of axillary lymph nodes in patients with newly diagnosed breast cancer had a sensitivity that increased with increasing size of the primary tumor.

Down-regulation of MUC1 in cancer cells inhibits cell migration by promoting E-cadherin/catenin complex formation.

MUC1, a tumor associated glycoprotein, is over-expressed in most cancers and can promote proliferation and metastasis. The objective of this research was to study the role of MUC1 in cancer metastasis and its potential mechanism. Pancreatic (PANC1) and breast (MCF-7) cancer cells with stable 'knockdown' of MUC1 expression were created using RNA interference. beta-Catenin and E-cadherin protein expression were upregulated in PANC1 and MCF-7 cells with decreased MUC1 expression. Downregulation of MUC1 expression also induced beta-catenin relocation from the nucleus to the cytoplasm, increased E-cadherin/beta-catenin complex formation and E-cadherin membrane localization in PANC1 cells. PANC1 cells with 'knockdown' MUC1 expression had decreased in vitro cell invasion. This study suggested that MUC1 may affect cancer cell migration by increasing E-cadherin/beta-catenin complex formation and restoring E-cadherin membrane localization.

A novel approach to T classification in tumor-node-metastasis staging of breast cancer.

BACKGROUND: The aim of this study was to examine the effect of measurement bias in breast cancer and to create a more rational T-size categorization in tumor-node-metastasis staging in response to smaller, screen-detected cancers and measurement bias. METHODS: From 1987 to 2003, 10,853 invasive nonmetastatic breast cancers enlisted in the Rhode Island Cancer Registry with a known dimension were reviewed. Data analyzed by proposed classifications included the rate of lymph node metastases and the mortality rate from breast cancer. RESULTS: The median diameter was 16 mm. Cancer measurements reflected the bias in pathologists' dimension recording, which is centered strongly about whole- and half-centimeter sizes. A new T classification is proposed with the following sizes and frequencies in the Rhode Island Cancer Registry: 1 to 2 mm = T1 mic (3% of registered cases); 3 to 7 mm = T1a (11%); 8 to 12 mm = T1b (23%); 13 to 17 mm = T1c (18%); 18 to 22 mm = T2a (17%); 23 to 27 mm = T2b (8%); 28 to 32 mm = T2c (8%); 33 to 42 mm = T3a (6%); 43 to 52 mm = T3b (3%), and greater than 52 mm = T3c (4%). The unadjusted odds ratio for the probability of node metastases was 1.43 (confidence interval, 1.40-1.46; P < .001) with each increase in proposed grouping. The range in the lymph node metastatic rate was 5.5% for tumors 1 to 2 mm to 64% for cancers greater than 52 mm. By Cox proportional hazard, the unadjusted hazard ratio for death from breast cancer for each increase in proposed grouping was 1.33 (confidence interval, 1.29-1.37; P < .001). The 10-year survival rate ranged from 98.3% for tumors 1 to 2 mm to 70.3% for cancers greater than 52 mm. CONCLUSIONS: A more rational T category for use in tumor-node-metastasis staging is presented to reflect the much smaller invasive breast cancers encountered by screening and to account for the dimension recording bias of pathologists. This new T category shows a clinically and statistically significant linear relationship for both incidence of lymph node metastases and hazard ratio of death.

Biology of ductal carcinoma in situ classification based on biologic potential.

Incidence of ductal carcinoma in situ (DCIS) has increased significantly during the last decade, comprising almost 20% of all breast cancers diagnosed today. DCIS is composed of malignant breast duct epithelial cells that have clonally proliferated and accumulated within the mammary duct lumen. It comprises a group of heterogeneous tumors with varying biologic behavior rendering its classification and management challenging. By definition, DCIS does not invade through the basement membrane; it is a preinvasive malignancy and systemic disease is nonexistent. The basis of treatment is to prevent progression into an invasive cancer such as ductal carcinoma. Most current DCIS classification schemes do not predict its potential to progress to invasive disease. In this review the natural history of DCIS, as it relates to its biologic potential to progress to invasive disease, is summarized, and a broad classification system that may provide a guideline for patient management is proposed.