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Breast cancer, a hormone‐dependent tumour, generally includes four molecular subtypes (luminal A, luminal B, HER2 enriched and triple‐negative) based on oestrogen receptor, progesterone receptor and human epidermal growth factor receptor‐2. Multiple hormones in the body regulate the development of breast cancer. Endocrine therapy is one of the primary treatments for hormone‐receptor‐positive breast cancer, but endocrine resistance is the primary clinical cause of treatment failure. Prolactin (PRL) is a protein hormone secreted by the pituitary gland, mainly promoting mammary gland growth, stimulating and maintaining lactation. Previous studies suggest that high PRL levels can increase the risk of invasive breast cancer in women. The expression levels of PRL and PRLR in breast cancer cells and breast cancer tissues are elevated in most ER+ and ER− tumours. PRL activates downstream signalling pathways and affects endocrine therapy resistance by combining with prolactin receptor (PRLR). In this review, we illustrated and summarized the correlations between endocrine therapy resistance in breast cancer and PRL, as well as the pathophysiological mechanisms and clinical practices. The study on PRL and its receptor would help explore reversing endocrine therapy‐resistance for breast cancer.

The morphology of nanomaterials combines the characteristics of their size, shape and spatial structure. Owing to the improved spatiotemporal control of the nanocarriers for anti-cancer drug delivery, the morphology adaptive nanomaterials have received tremendous attention in the field of nanomedicine, while they are able to respond through chemical or physical change. In this review, we summarize the recent advancements of morphology adaptive nanomaterials and their application in anti-cancer drug delivery system, wherein the size, shape and spatial structure of nanocarriers can be changed to adapt the complex living system, thus overcoming the pathological barriers in drug delivery. The overview of the recent examples shows that each step of delivery process can be improved by the morphology adaption, which represents the great potential for clinic translation of morphology adaptive nanomaterials.

Objective To develop a nomogram for predicting the possibility of four or more positive nodes in breast cancer patients with 1–3 positive sentinel lymph nodes (SLN). Materials and methods Retrospective analysis of data of patients from two institutions was conducted. The inclusion criteria were: invasive breast cancer; clinically node negative; received lumpectomy or mastectomy plus SLN biopsy followed by axillary lymph node dissection (ALND); and pathologically confirmed T1-2 tumor, with 1–3 positive SLNs. Patients from one institution formed the training group and patients from the other the validation group. Univariate and multivariate analyses were performed to identify the predictors of four or more positive nodes. These predictors were used to build the nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model. Results Of the 1480 patients (966 patients in the training group, 514 in the validation group), 306 (20.7%) had four or more positive nodes. Multivariate stepwise logistic regression showed number of positive (p, Highlights • Five predictors of four or more positive nodes in breast cancer patients were identified. • A nomogram was built using these five factors. • The nomogram was validated on an external cohort. • The proposed nomogram predicts four or more positive nodes with high accuracy. • The nomogram can help in decision making on use of regional nodal irradiation.

Triple-negative breast cancer (TNBC), a heterogeneous tumour that lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), is often characterized by aggressiveness and tends to recur or metastasize. TNBC lacks therapeutic targets compared with other subtypes and is not sensitive to endocrine therapy or targeted therapy except chemotherapy. Therefore, identifying the prognostic characteristics and valid therapeutic targets of TNBC could facilitate early personalized treatment. Due to the rapid development of various technologies, researchers are increasingly focusing on integrating 'big data' and biological systems, which is referred to as 'omics', as a means of resolving it. Transcriptomics and proteomics analyses play an essential role in exploring prospective biomarkers and potential therapeutic targets for triple-negative breast cancers, which provides a powerful engine for TNBC's therapeutic discovery when combined with complementary information. Here, we review the recent progress of TNBC research in transcriptomics and proteomics to identify possible therapeutic goals and improve the survival of patients with triple-negative breast cancer. Also, researchers may benefit from this article to catalyse further analysis and investigation to decipher the global picture of TNBC cancer.

Accurate testing of the status of human epidermal growth factor receptor type 2 (HER2) is a prerequisite for HER2-directed therapy. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) published joint guideline recommendations for HER2 testing in breast cancer in 2007 and it was updated in 2013. We compared the HER2 gene amplification status based on these two guidelines and analyzed the molecular characteristics of the equivocal cases. A total of 1894 patient samples were analyzed for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 FISH amplification was examined and re-assessed using 2013 guidelines. According to the 2013 ASCO/CAP recommendations, 763 (40.3%) cases were classified as HER2 positive compared with 729 (38.5%) cases defined by 2007 guidelines. There was a significant increase of 6.1% in the proportion of HER2 FISH equivocal cases that were interpreted using ASCO/CAP 2013 (7.3%) compared with 2007 (1.2%) guidelines (P

BACKGROUND This study was designed to introduce the key points about the transplantation of lower abdominal flap with vascularized lymph node and to evaluate the effect of breast restoration, breast reconstruction, and lymphatic transplantation to treat upper limb lymphedema after breast cancer surgery. MATERIALS AND METHODS The study was based on the retrospective study on 10 cases of postmastectomy lymphedema during January 2008 to March 2011. All patients, aged 36 to 50 years, have had one-side upper-limb lymphedema for 3 to 5 years. Six patients had accepted radiotherapy. Four patients had a diagnosis of severe lymphedema, and 2 patients had moderate lymphedema. The isotope radiography before the operation showed obstruction of lymphatic return, and the multidetector computed tomography that followed delivered a clear picture of the abdominal flap blood supply and the blood vessels in the breasts. During the operation, the scar contracture of the axilla was completely relaxed, and all patients accepted abdominal transplantation of lower abdominal flap with vascularized lymph node. After the operation, the elastic bandages were applied for one year as an adjuvant therapy. The follow-up visits were conducted 1, 3, 6, and 12 months after the surgery. The measurement indexes included mid-upper arm circumference, clinical symptoms, and lymphoscintigraphy. RESULTS All flaps worked well. One patient was found to have delayed wound healing; one patient saw no obvious improvement in lymphedema; 7 patients with lymphedema were relieved with apparent improvement in the affected limbs' mean perimeter and clinical symptoms; one patient recovered; and another patient was lost to follow-up. The mean reduction was 2.122±2.331 cm, and the reduction of the lymphedematous limb was statistically significant between the preoperative and 12-month postoperative groups (P

Convenient and fast testing using an immunochromatography test strip (ICTS) enables rapid yes/no decisions regarding a disease to be made. However, the fundamental limitations of an ICTS, such as a lack of quantitative and sensitive analysis, severely hampers its application in reliable medical testing for the early detection of cancer. Herein, we overcame these limitations by integrating an ICTS with quantum dot nanobeads (QD nanobeads), which were fabricated by encapsulating QDs within modified poly(tert-butyl acrylate-co-ethyl acrylate-co-methacrylic acid) and served as a robust signal-generating reagent for the ICTS. Prostate specific antigen (PSA) was used as a model analyte to demonstrate the performance of the QD nanobeads-based ICTS platform. Under optimized conditions, the concentration of PSA could be determined within 15 min with high sensitivity and specificity using only 40 μL of sample. The detection limit was enhanced by ∼12-fold compared with that of an ICTS that used QDs encapsulated by commercial 11-mercaptoundecanoic acid (QDs@MUA) as the signal-generating reagent. At the same time, the possible clinical utility of this approach was demonstrated by measurements recorded from PSA-positive patient specimens. Our data suggest that the QD nanobeads-based ICTS platform is not only rapid and low-cost but also highly sensitive and specific for use in quantitative point-of-care diagnostics; thus, it holds promise for becoming a part of routine medical testing for the early cancer of detection.

Quantum dot (QD) barcodes are becoming an urgent requirement for researchers and clinicians to obtain high-density information in multiplexed suspension (bead-based) assay. However, how to improve the stability of quantum dot barcodes is a longstanding issue. Here, we present a new self-healing encapsulation strategy to generate functionalized uniform quantum dots barcodes with high physical and chemical stability. This efficient and facile strategy could make porous polymer microspheres self-heal to encapsulate QDs via the thermal motion and interaction of the molecular chains. Consequently, the new strategy solved especially the QDs leakage problem and improved the chemical stability under different pH physiological conditions as well as the longtime storage stability. In the meantime, the encoding capacity and the spatial distribution uniformity of quantum dots could be also improved. Furthermore, immunofluorescence assays for alpha fetoprotein (AFP) detections indicated that carboxyl groups on the surface of QD-encoded microspheres could facilitate efficient attachment of biomacromolecules.

To analyze the relationship between the expression level of Ki67 and clinicopathological features in breast cancer.Data of 918 female patients with invasive ductal breast carcinoma treated in the Cancer Hospital, Chinese Academy of Medical Sciences from Jan. to Dec. 2010 were analyzed retrospectively. The correlation of Ki67 expression and other clinicopathological features in the breast cancer was analyzed.Among the 918 cases, the Ki67 index was 0.9% to 95% (mean value 27.8%). Taking the Ki67 index 14% as the boundary to divide the patients into two subgroups, 263 cases (28.6%) were ≤ 14%, and 655 cases (71.4%) were14%. There were significant differences between the Ki67 expression and age, tumor size, axillary lymph nodes status, histological grade and the expressions of C-erbB-2, estrogen receptor (ER) and progesterone receptor (PR) (P0.05 for all). All the Ki67 indexes of Ki67 expression in luminal B (30.44%), HER-2 overexpression (36.77%) and triple negative (47.40%) subtypes were significantly higher than that in the luminal A subtype (21.36%)(P0.01). The expression level of Ki67 in triple-negative subtype (47.40%) was significantly higher than that in the non-triple-negative subtype (24.79%)(P0.001).Ki67 index is significantly correlated with the age, tumor TNM stage, axillary lymph node status, histological grading, ER status, PR status and HER-2 status. A high expression level of Ki67 is a poor prognostic factor for breast cancer. The expression level of Ki67 should be detected routinely and it may become a useful prognostic marker in the treatment of breast cancer.

Luminal subtype breast cancer is defined as oestrogen receptor (ER)- and/or progesterone receptor (PR)- positive breast cancer. We detected the expression of ER-α, ER-Β1 and ER-Β2 in the tissue samples of invasive luminal subtype breast cancer patients, evaluated the correlations between these ER statuses and prognosis, and tried to clarify whether the status of ER-α isoforms provides clinically useful information further to what is already provided by the traditional ER-α/PR assay.The expression of ER-α, ER-Β1 and ER-Β2 in the paraffin-embedded sections of 162 invasive luminal subtype breast cancer patients was detected with an immunohistochemical staining method. With mid-long-term follow-up, the features of ER-α, ER-Β1 and ER-Β2 status and the correlations between clinical characteristics and the prognosis were analysed.ER-Β1-positive status was correlated with PR (rs=0.217, p0.01). The median follow-up time was 92 months (range, 4-98 months). Univariate analysis suggested that ER-Β1 status was significantly correlated to diseasefree survival (DFS) time (log rank=3.98, p=0.046), especially in patients with positive lymph nodes (log rank=6.20, p=0.013). In patients with smaller tumour size (=20 mm), negative ER-Β2 status was significantly correlated to overall survival time (log rank=3.87, p=0.049).In invasive luminal subtype breast cancers, ER-Β1 is correlated with good prognosis and could be regarded as one of the factors for evaluating DFS time, especially in lymph node-positive patients. There may be some interactions between ER-Β1 and PR. In clinical practice, besides routine detection of ER-α and PR in invasive luminal subtype breast cancers, immunohistochemical staining of ER-Β1 and ER-Β2 should be considered in order to achieve more useful information. Further studies are needed to confirm our findings.

e11538 Background: It is extremely important to identify proper cytotoxic agents for TNBC which had limited choices except chemotherapy. Capecitabine are well established as a major chemotherapeutic agent in metastatic setting. The efficacy of capecitabine-based chemotherapy has not been prospectively studied in TNBC and data remains scant. This study was designed to investigate the efficacy of capecitabine-based doublets in the treatment of metastatic TNBC. Methods: Eligible metastatic TNBC women with measurable diseases were recruited to receive either TX regimen (docetaxel 75mg/m2 iv d1 plus capecitabine 1000mg/m2 bid, d1-14,q3w) or NX regimen (vinorelbine 25mg/m2 iv d1, 8 plus capecitabine 1000mg/m2 bid, d1-14, q3w) at the discretion of physicians for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and secondary endpoints included progression free survival (PFS), overall survival (OS). Results: 45 mTNBC patients, 27 in TX and 18 in NX were recruited, mostly (73.3%) as 1st line and the remaining as the 2nd line. The total objective response rate was 20.0% and clinical benefit rate was 62.2%. After a median follow-up of 28 months, PFS was 5.2 months (95%CI, 4.1-6.3mons) and OS was 18.2months (95%CI, 8.7-27.7mons). Almost half of the patients (22/45) progressed during treatment or within one month of the treatment discontinuation. PFS was significantly longer if patients got CR/PR (9.6 vs 4.3mons, P=0.015). When comparing two doublets, the response rate was numerically but not statistically lower in TX group than in NX group (14.8% vs 27.8%, P=0.449). Similarly, no difference was found in either PFS (4.9 vs 5.2 mons, P=0.483) or OS (21.5 vs 18.3 mons, P=0.964) between two regimens. Conclusions: Although the overall survival seems to be reasonable, efficacy of capecitabine-contained TX or NX regimen was relatively poor in terms of tumor remission and progression free survival in mTNBC patients, suggesting capecitabine may have limited potency in this subtype. These two combinations may be considered to be acceptable but may not be recommended as prior choice for mTNBC patients.