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| 1 | Chinese guidelines for diagnosis and treatment of breast cancer2018(English version)显示文摘Breast cancer is the most common malignancy in women and is a major threat to women's health. Currently, with comprehensive treatment modalities, the outcomes of breast cancer are among the best of solid tumors. A set of Chinese guidelines and recommendations are developed to standardize the clinical practice, to ensure the quality and safety of medical service, and to ultimately improve the survival of breast cancer patients. | National Health Commission of the People's Republic of China | 2019 | Chinese Journal of Cancer Research2019，31，2： | 50 |
| 2 | Magnetic resonance imaging in breast cancer:A literature review and future perspectives显示文摘Early detection and diagnosis of breast cancer are essential for successful treatment. Currently mammography and ultrasound are the basic imaging techniques for the detection and localization of breast tumors. The low sensitivity and specificity of these imaging tools resulted in a demand for new imaging modalities and breast magnetic resonance imaging(MRI) has become increasingly important in the detection and delineation of breast cancer in daily practice. However, the clinical benefits of the use of pre-operative MRI in women with newly diagnosed breast cancer is still a matter of debate. The main additional diagnostic value of MRI relies on specific situations such as detecting multifocal, multicentric or contralateral disease unrecognized on conventional assessment(particularly in patients diagnosed with invasive lobular carcinoma), assessing the response to neoadjuvant chemotherapy, detection of cancer in dense breast tissue, recognition of an occult primary breast cancer in patients presenting with cancer metastasis in axillary lymph nodes, among others. Nevertheless, the development of new MRI technolo-gies such as diffusion-weighted imaging, proton spectroscopy and higher field strength 7.0 T imaging offer a new perspective in providing additional information in breast abnormalities. We conducted an expert literature review on the value of breast MRI in diagnosing and staging breast cancer, as well as the future potentials of new MRI technologies. | Gisela LG Menezes Floor M Knuttel Bertine L Stehouwer Ruud M Pijnappel Maurice AAJ van den Bosch | 2014 | World Journal of Clinical Oncology2014，5，2： | 25 |
| 3 | Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice显示文摘Objective: To study the inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Methods: Female mice were selected as experimental animals, and breast cancer tumor-bearing mouse models were established and then divided into group A, B, C and D that respectively received saline, recombinant human endostatin, ginsenosides Rg3 and recombinant human endostatin combined with Rg3 intervention; 7 d, 14 d and 21 d after intervention, tumor tissue volume was measured; 21 d after intervention, mice were killed, tumor tissue was collected, and m RNA contents of angiogenesis molecules, invasion molecules, autophagy marker molecules and autophagy signaling pathway molecules were detected. Results: At 7 d, 14 d and 21 d after intervention, tumor tissue volume of group B, C and D was lower than that of group A, and tumor tissue volume of group D was lower than that of group B and C; m RNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, m TOR, PI3 K, Akt, JNK and Beclin-1 in tumor tissue of group B, C and D were significantly lower than those of group A, and LC3-II/LC3-I was significantly higher than that of group A; m RNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, m TOR, PI3 K, Akt, JNK and Beclin-1 in tumor tissue of group D were significantly lower than those of group B and C, and LC3-II/LC3-I was higher than that of group B and C. Conclusions: Endostar combined with ginsenoside Rg3 has stronger inhibiting effect on breast cancer tumor growth in tumor-bearing mice than single drug, and it can inhibit angiogenesis and cell invasion, and enhance cell autophagy. | Yun Zhang Qing-Zhan Liu Su-Ping Xing Jin-Ling Zhang | 2016 | Asian Pacific Journal of Tropical Medicine2016，9，2： | 24 |
| 4 | Theranostic nanoparticles with tumor-specific enzyme-triggered size reduction and drug release to perform photothermal therapy for breast cancer treatment显示文摘Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency,nanoparticles need to change size so as to fully utilize the enhanced permeability and retention(EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin(BSA) protected gold nanocluster(Au NC@CBSA,21.06 nm) to both load indocyanine green(ICG) and act as imaging probe to realize theranostic. Then Au NC@CBSA-ICG was fabricated with negatively charged hyaluronic acid(HA) to form Au NC@CBSAICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed Au NC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter in vitro or in vivo, Au NC@CBSAICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated Au NC@CBSA-ICG@HA was potential for breast cancer therapy. | Rui Liu Chuan Hu Yuanyuan Yang Jingqing Zhang Huile Gao | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 24 |
| 5 | Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999-2017显示文摘Objective: Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics,management and outcomes of young breast cancer patients over time.Methods: Females under 40 years of age diagnosed with breast cancer during the periods 1999-2017 and1999-2015 were identified in the Fudan University Shanghai Cancer Center(FUSCC) and the population-based Surveillance, Epidemiology, and End Results(SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.Results: The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ(DCIS)(from 8.8% to 16.9%;P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort(from 35.3% to 41.9%;P=0.008), whereas it decreased in SEER cohort(from 42.4% to 33.0%;P<0.0001). The percentage of estrogen receptor(ER)-positive cancers was consistently increased in both the invasive ductal carcinoma(IDC) and DCIS patients in the two cohorts. Breastconserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period.Conclusions: With the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial deescalation in surgical therapies in young breast cancer patients. | Rong Guo Jing Si Jingyan Xue Yonghui Su Miao Mo Benlong Yang Qi Zhang Weiru Chi Yayun Chi Jiong Wu | 2019 | Chinese Journal of Cancer Research2019，31，4： | 24 |
| 6 | Contrast-enhanced ultrasound:The evolving applications显示文摘Contrast-enhanced ultrasound(CEUS)is a major breakthrough for ultrasound imaging in recent years.By using a microbubble contrast agent and contrast-specific imaging software,CEUS is able to depict the microand macro-circulation of the targeted organ,which in turn leads to improved performance in diagnosis.Due to the special dual blood supply system in the liver,CEUS is particularly suitable for liver imaging.It is evident that CEUS facilitates improvement for characterization of focal liver lesions(FLLs),detection of liver malignancy,guidance for interventional procedures,and evaluation of treatment response after local therapies.CEUS has been demonstrated to be equal to contrast-enhanced computed tomography or magnetic resonance imaging for the characterization of FLLs.In addition,the applicability of CEUS has expanded to non-liver structures such as gallbladder,bile duct,pancreas,kidney,spleen,breast,thyroid,and prostate.The usefulness of CEUS in these applications is confirmed by extensive literature production.Novel applications include detecting bleeding sites and hematomas in patients with abdominal trauma,guiding percutaneous injection therapy and therefore achieving the goal of using interventional ultrasonography in managing splenic trauma,assessing the activity of Crohn’s disease,and detecting suspected endoleaks after endovascular abdominal aneurysm repair.Contrast-enhanced intraoperative ultrasound(US)and intracavitary use of CEUS have been developed and clinically studied.The potential use of CEUS involves sentinel lymph node detection,drug or gene delivery,and molecular imaging.In conclusion,the advent of CEUS has greatly enhanced the usefulness of US and even changed the status of US in clinical practice.The application of CEUS in the clinic is continuously evolving and it is expected that its use will be expanded further in the future. | Hui-Xiong Xu | 2009 | World Journal of Radiology2009，1，1： | 23 |
| 7 | The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility显示文摘Objective: To examine the effect of pSer9-GSK-3β on breast cancer and to determine whether the underlying metabolic and immunological mechanism is associated with ROS/eIF2B and natural killer(NK) cells.Methods: We employed TWS119 to inactivate GSK-3β by phosphorylating Ser9 and explored its effect on breast cancer and NK cells. The expression of GSK-3β, natural killer group 2 member D(NKG2D) ligands, eIF2B was quantified by PCR and Western blot. We measured intracellular reactive oxygen species(ROS) and mitochondrial ROS using DCFH-DA and MitoSOX^(TM) probe,respectively, and conducted quantitative analysis of cellular respiration on 4T1 cells with mitochondrial respiratory chain complex Ⅰ/Ⅲ kits.Results: Our investigation revealed that TWS119 downregulated NKG2D ligands(H60 a and Rae1), suppressed the cytotoxicity of NK cells, and promoted the migration of 4T1 murine breast cancer cells. Nevertheless, LY290042, which attenuates p-GSK-3β formation by inhibiting the PI3K/Akt pathway, reversed these effects. We also found that higher expression of p Ser9-GSK-3β induced higher levels of ROS, and observed that abnormality of mitochondrial respiratory chain complex Ⅰ/Ⅲ function induced the dysfunction of GSK-3β-induced electron transport chain, naturally disturbing the ROS level. In addition, the expression of NOX3 and NOX4 was significantly up-regulated, which affected the generation of ROS and associated with the metastasis of breast cancer. Furthermore, we found that the expression of pSer535-eIF2B promoted the expression of NKG2D ligands(Mult-1 and Rae1) following by expression of pSer9-GSK-3β and generation of ROS.Conclusions: The PI3K/Akt/GSK-3β/ROS/eIF2B pathway could regulate NK cell activity and sensitivity of tumor cells to NK cells,which resulted in breast cancer growth and lung metastasis. Thus, GSK-3β is a promising target of anti-tumor therapy. | Fengjiao Jin Zhaozhen Wu Xiao Hu Jiahui Zhang Zihe Gao Xiao Han Junfang Qin Chen Li Yue Wang | 2019 | Cancer Biology & Medicine2019，16，1： | 20 |
| 8 | The influence of stage at diagnosis and molecular subtype on breast cancer patient survival: a hospital.based multi.center study显示文摘Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To estimate the survival differences among patients with different stages and various subtypes of breast cancer, we conducted a hospital-based multi-center study on breast cancer in Beijing, China.Methods: All resident patients diagnosed with primary, invasive breast cancer between January 1,2006 and December 31,2010 from four selected hospitals in Beijing were included and followed up until December 31,2015. Hospitalbased data of stage at diagnosis, hormone receptor status, and selected clinical characteristics, including body mass index(BMI), menopausal status, histological grade, and histological type, were collected from the medical records of the study subjects. Overall survival(OS) and cancer-specific survival(CSS) were estimated. Cox proportional hazards models were employed to evaluate the associations of stage at diagnosis and molecular subtype with patient survival.Results: The 5-year OS and CSS rates for all patients were 89.4% and 90.3%. Survival varied by stage and molecular subtype. The 5-year OS rates for patients with stage I, Ⅱ, Ⅲ, and IV diseases were 96.5%, 91.6%, 74.8%, and 40.7%,respectively, and the corresponding estimates of 5-year CSS rates were 97.1%, 92.6%, 75.6%, and 42.7%, respectively.The 5-year OS rates for patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast cancer were92.6%, 88.4%, 83.6%, and 82.9%, respectively, and the corresponding estimates of 5-year CSS rates were 93.2%, 89.1 %,85.4%, and 83.5%, respectively. Multivariate analysis showed that stage at diagnosis and molecular subtype were important prognostic factors for breast cancer.Conclusions: Survival of breast cancer patients varied significantly by stage and molecular subtype. Cancer screening is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes. | Tingting Zuo Hongmei Zeng Huichao Li Shuo Liu Lei Yang Changfa Xia Rongshou Zheng Fei Ma Lifang Liu Ning Wang Lixue Xuan Wanqing Chen | 2017 | Chinese Journal of Cancer2017，36，11： | 18 |
| 9 | Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets显示文摘Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases. | Nadia Rucci Patrizia Sanità Simona Delle Monache Edoardo Alesse Adriano Angelucci | 2014 | World Journal of Clinical Oncology2014，5，3： | 18 |
| 10 | Systemic treatment strategies for triple-negative breast cancer显示文摘Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success. | Budhi Singh Yadav Suresh C Sharma Priyanka Chanana Swaty Jhamb | 2014 | World Journal of Clinical Oncology2014，5，2： | 18 |
| 11 | Comprehensive metabolomics expands precision medicine for triple-negative breast cancer显示文摘Metabolic reprogramming is a hallmark of cancer.However,systematic characterizations of metabolites in triple-negative breast cancer(TNBC)are still lacking.Our study profiled the polar metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC.Combining with previously established transcriptomic and genomic data of the same cohort,we conducted a comprehensive analysis linking TNBC metabolome to genomics.Our study classified TNBCs into three distinct metabolomic subgroups:C1,characterized by the enrichment of ceramides and fatty acids;C2,featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer;and C3,having the lowest level of metabolic dysregulation.Based on this newly developed metabolomic dataset,we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets.The transcriptomic luminal androgen receptor(LAR)subtype overlapped with metabolomic C1 subtype.Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate(S1P),an intermediate of the ceramide pathway,is a promising therapy for LAR tumors.Moreover,the transcriptomic basal-like immune-suppressed(BLIS)subtype contained two prognostic metabolomic subgroups(C2 and C3),which could be distinguished through machine-learning methods.We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors.Together,our study reveals the clinical significance of TNBC metabolomics,which can not only optimize the transcriptomic subtyping system,but also suggest novel therapeutic targets.This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC. | Yi Xiao Ding Ma Yun-Song Yang Fan Yang Jia-Han Ding Yue Gong Lin Jiang Li-Ping Ge Song-Yang Wu Qiang Yu Qing Zhang François Bertucci Qiuzhuang Sun Xin Hu Da-Qiang Li Zhi-Ming Shao Yi-Zhou Jiang | 2022 | Cell Research2022，32，5： | 18 |
| 12 | Granulomatous lobular mastitis secondary to Mycobacterium fortuitum显示文摘Granulomatous lobular mastitis is a rare inflammatory disease of the breast of unknown etiology. Most present as breast masses in women of child-bearing age. A 29-year-old female presented with a swollen, firm and tender right breast, initially misdiagnosed as mastitis. Core needle biopsy revealed findings consistent with granulomatous lobular mastitis, and cultures were all negative for an infectious etiology. She was started on steroid therapy to which she initially responded well. A few weeks later she deteriorated and was found to have multiple breast abscesses. She underwent operative drainage and cultures grew Mycobacterium fortuitum. Granulomatous lobular mastitis is a rare inflammatory disease of the breast. The definitive diagnose entails a biopsy. Other causes of chronic or granulomatous mastitis should be ruled out, including atypical or rare bacteria such as Mycobacterium fortuitum. This is the first reported case of granulomatous mastitis secondary to Mycobacterium fortuitum. With pathologic confirmation of granulomatous mastitis, an infectious etiology must be ruled out. Atypical bacteria such as Mycobacterium fortuitum may not readily grow on cultures, as with our case. Medical management is appropriate, with surgical excision reserved for refractory cases or for drainage of abscesses. | Armin Kamyab | 2016 | World Journal of Clinical Cases2016，4，12： | 17 |
| 13 | Pathogenesis, prevention, diagnosis and treatment of breast cancer显示文摘Breast cancer is the most common cancer affecting women worldwide. Prediction models stratify a woman's risk for developing cancer and can guide screening recommendations based on the presence of known and quantifiable hormonal, environmental, personal, or genetic risk factors. Mammography remains the mainstay breast cancer screening and detection but magnetic resonance imaging and ultrasound have become useful diagnostic adjuncts in select patient populations. The management of breast cancer has seen much refinement with increased specialization and collaboration with multidisciplinary teams that include surgeons, oncologists, radiation oncologists, nurses, geneticist, reconstructive surgeons and patients. Evidence supports a less invasive surgical approach to the staging and management of the axilla in select patients. In the era of patient/tumor specific management, the advent of molecular and genomic profiling is a paradigm shift in the treatment of a biologically heterogenous disease. | Rupen Shah Kelly Rosso S David Nathanson | 2014 | World Journal of Clinical Oncology2014，5，3： | 17 |
| 14 | Contrast-enhanced ultrasound improved performance of breast imaging reporting and data system evaluation of critical breast lesions显示文摘AIM: To determine whether contrast-enhanced ultrasound(CEUS) can improve the precision of breast imaging reporting and data system(BI-RADS) categorization. METHODS: A total of 230 patients with 235 solid breast lesions classified as BI-RADS 4 on conventional ultrasound were evaluated. CEUS was performed within one week before core needle biopsy or surgical resection and a revised BI-RADS classification was assigned based on 10 CEUS imaging characteristics. Receiver operating characteristic curve analysis was then conducted to evaluate the diagnostic performance of CEUS-based BI-RADS assignment with pathological examination as reference criteria. RESULTS: The CEUS-based BI-RADS evaluation classified 116/235(49.36%) lesions into category 3, 20(8.51%), 13(5.53%) and 12(5.11%) lesions into categories 4A, 4B and 4C, respectively, and 74(31.49%) into category 5. Selecting CEUS-based BI-RADS category 4A as an appropriate cut-off gave sensitivity and specificity values of 85.4% and 87.8%, respectively, for the diagnosisof malignant disease. The cancer-to-biopsy yield was 73.11% with CEUS-based BI-RADS 4A selected as the biopsy threshold compared with 40.85% otherwise, while the biopsy rate was only 42.13% compared with 100% otherwise. Overall, only 4.68% of invasive cancers were misdiagnosed.CONCLUSION: This pilot study suggests that evaluation of BI-RADS 4 breast lesions with CEUS results in reduced biopsy rates and increased cancer-to-biopsy yields. | Jun Luo Ji-Dong Chen Qing Chen Lin-Xian Yue Guo Zhou Cheng Lan Yi Li Chi-Hua Wu Jing-Qiao Lu | 2016 | World Journal of Radiology2016，8，6： | 17 |
| 15 | Novel concepts in radiation-induced cardiovascular disease显示文摘Radiation-induced cardiovascular disease(RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy(RT).Cardiovascular complications include effusive or constrictive pericarditis,cardiomyopathy,valvular heart disease,and coronary/vascular disease.These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels.Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD,the increasing number of long-term cancer survivors,including those treated with older higher-dose RT regimens,will ensure a steady flow of afflicted patients for the foreseeable future.Thus,there is a pressing need for enhanced understanding of the disease mechanisms,and improved detection methods and treatment strategies.Newly characterized mechanisms responsible for the establishment of chronic fibrosis,such as oxidative stress,inflammation and epigenetic modifications,are discussed and linked to potential treatments currently under study.Novel imaging modalities may serve as powerful screening tools in RICVD,and recent research and expert opinion advocating their use is introduced.Data arguing for the aggressive use of percutaneous interventions,such as transcutaneous valve replacement and drug-eluting stents,are examined and considered in the context of prior therapeutic approaches.RICVD and its treatment options are the subject of a rich and dynamic body of research,and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardiooncology. | Jason R Cuomo Gyanendra K Sharma Preston D Conger Neal L Weintraub | 2016 | World Journal of Cardiology2016，8，9： | 17 |
| 16 | Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer显示文摘The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies. | Meng Zhao Bhuvaneswari Ramaswamy | 2014 | World Journal of Clinical Oncology2014，5，3： | 17 |
| 17 | Current medical treatment of estrogen receptor-positive breast cancer显示文摘Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of(1) ovarian function suppression(OFS), usually obtained using gonadotropinreleasing hormone agonists(Gn RHa);(2) selective estrogen receptor modulators or down-regulators(SERMs or SERDs); and(3) aromatase inhibitors(AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs(i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs(i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs(i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors(palbociclib) and mammalian target of rapamycin(m TOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness. | Franco Lumachi Davide A Santeufemia Stefano MM Basso | 2015 | World Journal of Biological Chemistry2015，6，3： | 16 |
| 18 | Adenoid cystic carcinoma of breast: Recent advances显示文摘Adenoid cystic carcinoma(ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features(i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. | Kosuke Miyai Mary R Schwartz Mukul K Divatia Rose C Anton Yong Wook Park Alberto G Ayala Jae Y Ro | 2014 | World Journal of Clinical Cases2014，2，12： | 16 |
| 19 | Cyclooxygenase-2 and the inflammogenesis of breast cancer显示文摘Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2(COX-2) is a ubiquitous driver of mammary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following:(1) COX-2 is constitutively expressed throughout breast cancer development and expression intensifies with stage at detection, cancer progression and metastasis;(2) essential features of mammary carcinogenesis(mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis and immunosuppression) are linked to COX-2-driven prostaglandin E2(PGE-2) biosynthesis;(3) upregulation of COX-2 and PGE-2 expression induces transcription of CYP-19 and aromatase-catalyzed estrogen biosynthesis which stimulates unbridled mitogenesis;(4) extrahe-patic CYP-1B1 in mammary adipose tissue converts paracrine estrogen to carcinogenic quinones with mutagenic impact; and(5) agents that inhibit COX-2 reduce the risk of breast cancer in women without disease and reduce recurrence risk and mortality in women with breast cancer. Recent sharp increases in global breast cancer incidence and mortality are likely driven by chronic inflammation of mammary adipose and upregulation of COX-2 associated with the obesity pandemic. The totality of evidence clearly supports the supposition that mammary carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive overexpression of COX-2 and the prostaglandin cascade in the 'inflammogenesis of breast cancer'. | Randall E Harris Bruce C Casto Zachary M Harris | 2014 | World Journal of Clinical Oncology2014，5，4： | 15 |
| 20 | Breast cancer-related lymphedema: Symptoms, diagnosis, risk reduction, and management显示文摘The global burden of breast cancer continues to increase largely because of the aging and growth of the world population. More than 1.38 million women worldwide were estimated to be diagnosed with breast cancer in 2008, accounting for 23% of all diagnosed cancers in women. Given that the 5-year survival rate for breast cancer is now 90%, experiencing breast cancer is ultimately about quality of life. Women treated for breast cancer are facing a life-time risk of developing lymphedema, a chronic condition that occurs in up to 40% of this population and negatively affects breast cancer survivors' quality of life. This review offers an insightful understanding of the condition by providing clinically relevant and evidence based knowledge regarding lymphedema symptoms, diagnosis, risk reduction, and management with the intent to inform health care professionals so that they might be better equipped to care for patients. | Mei R Fu | 2014 | World Journal of Clinical Oncology2014，5，3： | 15 |
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