Primary acinic cell carcinoma of the breast: A case report and literature review.

Acinic cell carcinoma (ACCA), a type of malignant epithelial neoplasm, tends to occur in the parotid gland, and is occasionally found within the breast. Published literature regarding primary ACCA of the breast is scarce, and the number of reports may be fewer than 100. At present, full clinical details have not been published. As an extremely rare disorder, ACCA cannot be definitively diagnosed depending on microscopic structure alone and often requires the assistance of immunohistochemistry. Currently, universal therapies are not available. Here, we present a 47-year-old patient with a history of a palpable mass in the outer upper quadrant of the left breast for more than 2 years, which had obviously increased in size in the last half year. This patient was definitively diagnosed with primary ACCA of the breast. Neoadjuvant chemotherapy was performed preoperatively, and drug sensitivity tests based on primary tumor cells were conducted after surgery and successfully screened chemotherapy schemes for the patient's greater benefit. The whole treatment course followed the guidelines for invasive breast cancer. The patient was free of symptoms for 14 months after surgery. Long-term follow-up is in progress. Altogether, to further broaden the understanding of primary ACCA of the breast, we detail the diagnosis and treatment of one patient and review the relevant literature.

Characteristics of breast cancer in Central China, literature review and comparison with USA.

INTRODUCTION: This work was to analyze characteristics of breast cancer (BC) in Central China, summarize main characteristics in China and compare with USA. METHODS: BC main characteristics from four hospitals in Central China from 2002 to 2012 were collected and analyzed. All the single and large-scale clinical reports covering at least ten years were selected and summarized to calculate the BC characteristics of China. BC Characteristics in USA were selected based on the database from Surveillance, Epidemiology, and End Results (SEER) Program. RESULTS: Age distribution in Central China was normal with one age peak at 45-49 years, displaying differences from USA and Chinese American with two age peaks. BC characteristics in Central China displayed distinct features from USA and Chinese American, including significant younger onset age, lower proportion of patients with stage I, lymph node negative, small tumor size and ER positive. A total ten long-term and large-scale clinical reports were selected for BC characteristics of Mainland China analysis. A total of 53,571 BC patients were enrolled from 1995 to 2012. The main characteristics of BC in Mainland China were similar as that in Central China, but were significant different from developed regions of China (Hong Kong and Taiwan), USA and Chinese American. CONCLUSIONS: BC characteristics in Central China displayed representative patterns of Mainland China, while showed distinct patterns from Chinese patients in other developed areas and USA.

Fourier transform infrared spectroscopy for the distinction of MCF-7 cells treated with different concentrations of 5-fluorouracil.

BACKGROUND: In order to provide personalized treatment to patients with breast cancer, an accurate, reliable and cost-efficient analytical technique is needed for drug screening and evaluation of tumor response to chemotherapy. METHODS: Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used as a tool to assess cancer cell response to chemotherapy. MCF-7 cells (human breast adenocarcinoma cell line) were treated with different concentrations of 5-fluorouracil (5-FU). The inhibition of cell proliferation was monitored by MTT, and apoptosis rates were determined by flow cytometry. Finally, spectra of the cell populations were acquired by ATR-FTIR. RESULTS: The cell response to 5-FU was detectable at different concentrations by ATR-FTIR. First, a band observed at 1741 cm(-1), representing membrane phospholipids, was enhanced with increasing 5-FU concentrations. In addition, the MCF-7 cell spectrum shifted progressively from 1153 to 1170 cm(-1) with increasing drug doses. Finally, the normalized band intensity of 1741 cm(-1)/Amide I was highly correlated with the percentage of apoptotic cells as assessed by partial correlation analysis. CONCLUSIONS: These findings suggest that the effects of different concentrations of drugs can be monitored by ATR-FTIR, which may help evaluate the response to chemotherapy and improve treatment strategies.

Quick-response magnetic nanospheres for rapid, efficient capture and sensitive detection of circulating tumor cells.

The study on circulating tumor cells (CTCs) has great significance for cancer prognosis, treatment monitoring, and metastasis diagnosis, in which isolation and enrichment of CTCs are key steps due to their extremely low concentration in peripheral blood. Herein, magnetic nanospheres (MNs) were fabricated by a convenient and highly controllable layer-by-layer assembly method. The MNs were nanosized with fast magnetic response, and nearly all of the MNs could be captured by 1 min attraction with a commercial magnetic scaffold. In addition, the MNs were very stable without aggregation or precipitation in whole blood and could be re-collected nearly at 100% in a monodisperse state. Modified with anti-epithelial-cell-adhesion-molecule (EpCAM) antibody, the obtained immunomagnetic nanospheres (IMNs) successfully captured extremely rare tumor cells in whole blood with an efficiency of more than 94% via only a 5 min incubation. Moreover, the isolated cells remained viable at 90.5 ± 1.2%, and they could be directly used for culture, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry (ICC) identification. ICC identification and enumeration of the tumor cells in the same blood samples showed high sensitivity and good reproducibility. Furthermore, the IMNs were successfully applied to the isolation and detection of CTCs in cancer patient peripheral blood samples, and even one CTC in the whole blood sample was able to be detected, which suggested they would be a promising tool for CTC enrichment and detection.

Lymph node ratio is more predictive than traditional lymph node stratification in lymph node positive invasive breast cancer.

OBJECTIVE: To evaluate the relationships between lymph node ratio (LNR, the ratio of positive lymph nodes in excised axillary lymph nodes) and disease-free survival (DFS) by comparing with traditional absolute positive lymph node number (pN classification) for prediction of breast cancer (BC) progrnosis. METHODS AND PATIENTS: We retrospectively reviewed patients who received comprehensive therapy in Department of Breast Surgery, Hubei Cancer Hospital, China from Jan 2002 to Dec 2006 (Group A), and Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, China from Jun 2008 to May 2012 (Group B). Patients were allocated to low-risk (≤0.20), intermediate-risk (> 0.20 but ≤ 0.65), high-risk (>0.65) groups by LNR. The primary endpoint was 5-DFS. RESULTS: A total of 294 patients were included in our study. LNR was verified as a negative prognostic factor for DFS (P= 0.002 in Group A, P< 0.0001 in Group B). Then we found the effects of pN and LNR delamination on disease-free survival (DFS) had statistical significance (P=0.012 for pN and P=0.031 for LNR stratification in Group A, both of them P<0.001 in Group B). Compared to pN staging, LNR staging displayed superior performance in prognosis, the adjusted hazard ratio of recurrence being 2.07 (95%CI, 1.07 to 4.0) for intermediate risk group (P=0.030) and 2.44 (95%CI, 1.21 to 4.92) for high risk group (P=0.013) in Group A. CONCLUSIONS: LNR stratification proved an adverse prognostic factor of DFS in lymph nodes positive invasive BC using cut-off values 0.20 and 0.65, and was more predictive than traditional pN classification for 5-DFS.

Quantum dot-based quantitative immunofluorescence detection and spectrum analysis of epidermal growth factor receptor in breast cancer tissue arrays.

BACKGROUND: The epidermal growth factor receptor (EGFR) is a promising therapeutic target in cancer, but its clinical value in breast cancer remains controversial. Our previous studies have found that quantitative analysis of biomarkers with quantum dot-based nanotechnology had better detection performance than conventional immunohistochemistry. The present study was undertaken to investigate the prognostic value of EGFR in breast cancer using quantum dot-based quantitative spectral analysis. METHODS: EGFR expression in 65 breast cancer specimens was detected by immunohistochemistry and quantum dot-immunohistochemistry, and comparisons were made between the two methods. EGFR expression in tissue microarrays of 240 breast cancer patients was then detected by quantum dot-immunohistochemistry and spectral analysis. The prognostic value of EGFR immunofluorescence area (EGFR area) for five-year recurrence-free survival was investigated. RESULTS: The same antigen localization, high correlation of staining rates (r = 0.914), and high agreement of measurement (κ = 0.848) of EGFR expression in breast cancer were found by quantum dot-immunohistochemistry and immunohistochemistry. The EGFR area showed significant differences by tumor grade, lymph node status, HER2 status, and hormone receptor status (all P < 0.05). Patients in the large EGFR area (≥ 30.51) group had a significantly higher five-year recurrence rate (47.2% versus 27.4%, P = 0.002) and worse five-year recurrence-free survival (log-rank test, P = 0.0015) than those in the small EGFR area (<30.51) group. In the subgroups, EGFR area was an independent prognosticator in the HER2-positive and lymph node-positive subgroups. CONCLUSION: Quantum dot-based quantitative detection demonstrates the prognostic value of EGFR area in the HER2-positive and lymph node-positive subgroups of invasive breast cancer.

Quantum dots-based molecular classification of breast cancer by quantitative spectroanalysis of hormone receptors and HER2.

The emerging molecular breast cancer (BC) classification based on key molecules, including hormone receptors (HRs), and human epidermal growth factor receptor 2 (HER2) has been playing an important part of clinical practice guideline. The current molecular classification mainly based on their fingerprints, however, could not provide enough essential information for treatment decision making. The molecular information on both patterns and quantities could be more helpful to heterogeneities understanding for BC personalized medicine. Here we conduct quantitative determination of HRs and HER2 by quantum dots (QDs)-based quantitative spectral analysis, which had excellent consistence with traditional method. Moreover, we establish a new molecular classification system of BC by integrating the quantitative information of HER2 and HRs, which could better reveal BC heterogeneity and identify 5 molecular subtypes with different 5-year prognosis. Furthermore, the emerging 5 molecular subtypes based on simple quantitative molecules information could be as informative as multi-genes analysis in routine practice, and might help formulate a more personalized comprehensive therapy strategy and prognosis prediction.

The quantitative detection of total HER2 load by quantum dots and the identification of a new subtype of breast cancer with different 5-year prognosis.

Accurate classification is fundamental for breast cancer (BC) personalized care. Current BC classification based on the either traditional morphological staging or molecular signatures seems inefficient to reveal the"true"behaviors of invasive BC evolution. An appropriate approach combining the macro- and micro-pathologic information might be more useful academically as well as clinically. Here we explore a holistic approach by integrating a key molecular prognostic indicator of BC, HER2, with quantitative determination using quantum dots (QDs)--based nanotechnology and spectral analysis, and a key macropathologic indicator, tumor size, resulting a new indicator, total HER2 load. This indicator might better reveal BC heterogeneity and new subtypes of BC with different 5-year disease-free survival compared with current methods, which could be helpful in formulating a more personalized targeted therapy for BC. Furthermore, this mode integrating macro- and micro-pathological indicators might help gain new insights into invasive BC biological behaviors.

Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2.

Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis. Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (scFvs) that bind to human FGF-2. After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor. This 1A2 scFv was then cloned into the pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8x10(-9)M to rhFGF-2. In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells. More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells. For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity. It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival.

[Treatment of bone loss associated with breast cancer: a review].

The widespread use of adjuvant systemic therapy, to some extent, contributes to the steady fall in the mortality of early breast cancer patients over recent years. However, some of the treatments have adverse effects on the bone metabolism with increased bone loss which may result in osteoporosis and associated fractures. Most of the effects on the bone are mediated by endocrine changes, either induction of an early menopause by chemotherapy and ovarian ablation, or further suppression of postmenopausal circulating estrogens by aromatase inhibitors. Chemotherapy may also have direct effects on bone cell function. Bone health of breast cancer patients is a highly topical issue with increasing data supporting the use of aromatase inhibitors in recent years.