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Breast Cancer

Breast cancer is the most common type of cancer among women, the risk of breast cancer increases with age, it is most common after the age of 50. Each breast has 15- 20 sections (lobes), each of which has many smaller sections (lobules). The lobes and lobules are connected by thin tubes (ducts). The most frequent type of breast cancer is that starting in the ducts (ductal cancer), other types include cancer beginning in the lobes or lobules (lobular carcinoma), less common is Inflammatory breast cancer which causes the breast to be red, and swollen. The incidence of breast cancer has been increasing in Western countries, the rate of increase has been faster in younger women, however, the cause of most breast cancers remains unknown. World-wide about 794,000 women are diagnosed with breast cancer each year.

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  • PubMed search for publications about Breast Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Breast Cancer
    MeSH term: Breast Neoplasms
    International US National Library of Medicine
    qualityPubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.

See also: Molecular Biology of Breast Cancer

Breast Cancer Organisations (11 links)

See also: National Cancer Organisations

Specialist Journals (12 links)

See also: Oncology Journals

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Lv L, Qiu K, Yu X, et al.
Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumin Co-Delivery to Reverse Multidrug Resistance in Breast Cancer.
J Biomed Nanotechnol. 2016; 12(5):973-85 [PubMed] Related Publications
Development of multidrug resistance against chemotherapeutic drugs is one of the major obstacles to successful cancer therapy in the clinic. Thus far, amphiphilic polymeric micelles and chemosensitizers have been used to overcome multidrug resistance in cancer. The goals of this study were to prepare poly(ethylene glycol)-bock-poly(lactide) (PEG(2k)-PLA(5k)) micelles for co-delivery of the chemotherapeutic drug doxorubicin (DOX) with a chemosensitizer curcumin (CUR), investigate the potential of the dual drug-loaded micelles ((DOX+CUR)-Micelles) to reverse multidrug resistance, and explore the underlying mechanisms. (DOX + CUR)-Micelles were prepared using an emulsion solvent evaporation method. The cellular uptake, drug efflux, down-regulation of P-glycoprotein expression and inhibition of ATP activity of (DOX+ CUR)-Micelles were studied in drug-resistant MCF-7/ADR cells. In vitro analyses demonstrated that (DOX + CUR)-Micelles were superior to free DOX, free drug combination (DOX + CUR), and DOX-loaded micelles in inhibiting proliferation of MCF-7/ADR cells. This effect of (DOX + CUR)-Micelles was partially attributable to their highest cellular uptake, lowest efflux rate of DOX, and strongest effects on down-regulation of P-glycoprotein and inhibition of ATP activity. Additionally, (DOX+CUR)-Micelles showed increased tumor accumulation and strong inhibitory effect on tumor growth in the xenograft model of drug-resistant MCF-7/ADR cells compared to that of other drug formulations. These results indicate that (DOX + CUR)-Micelles display potential for application in the therapy of drug-resistant breast carcinoma.

Tran TA, Krishnamoorthy K, Cho SK, Kim SJ
Inhibitory Effect of Zinc Sulfide Nanoparticles Towards Breast Cancer Stem Cell Migration and Invasion.
J Biomed Nanotechnol. 2016; 12(2):329-36 [PubMed] Related Publications
Cancer stem cells are demonstrated to be a highly malignant cancer with an extremely high migratory ability and conventional therapies have little effect on preventing cancer migration and invasion. In this study, we investigated the inhibitory effect of zinc sulfide (ZnS) nanoparticles towards the migration and invasion of breast cancer stem cells MCF-7-SC. The cytotoxicity studies and the Hoechst staining experiments suggested that there is no obvious toxicity of ZnS has been observed upto a concentration of 400 µg/mL. ZnS nanoparticles significantly inhibited the wound healing in the MCF-7-SC cells. The cell invasion assay and western blot analysis results suggested that ZnS nanoparticles inhibited the metastasis of MCF-7-SCs in dose-dependent manner by suppressing epithelial-mesenchymal transition process. Overall, our experimental analysis suggested that nano ZnS has the ability to inhibit cancer stem cell migration and invasion, which can open up new insights in the cancer therapy.

Graham EG, Wailes EM, Levi-Polyachenko NH
Multi-Walled Carbon Nanotubes Inhibit Breast Cancer Cell Migration.
J Biomed Nanotechnol. 2016; 12(2):308-19 [PubMed] Related Publications
According to the American Cancer Society, breast cancer is the second leading cause of cancer death in the US. Cancerous cells may have inadequate adhesions to the extracellular matrix and adjacent cells. Previous work has suggested that restoring these contacts may negate the cancer phenotype. This work aims to restore those contacts using multi-walled carbon nanotubes (MWNTs). Varying concentrations of carboxylated MWNTs in water, with or without type I collagen, were dried to create a thin film upon which one of three breast cell lines were seeded: cancerous and metastatic MDA- MB-231 cells, cancerous but non-metastatic MCF7 cells, or non-cancerous MCF10A cells. Proliferation, adhesion, scratch and autophagy assays, western blots, and immunochemical staining were used to assess adhesion and E-cadherin expression. Breast cancer cells grown on a MWNT-collagen coated surface displayed increased adhesion and decreased migration which correlated with an increase in E-cadherin. This work suggests an alternative approach to cancer treatment by physically mediating the cells' microenvironment.

Anulika Aweto H, Akinbo SR, Olawale OA
Effects of Combined Aerobic and Stretching Exercises on the Cardiopulmonary Parameters of Premenopausal and Postmenopausal Breast Cancer Survivors.
Nig Q J Hosp Med. 2015 Jul-Sep; 25(3):177-83 [PubMed] Related Publications
BACKGROUND: Therapeutic approaches that will improve the reduced cardiopulmonary functions of breast cancer (BC) survivors are of optimal importance. The effects of aerobic exercise on health-related outcomes of BC survivors have been reported while there is a dearth of information on the effects of combined aerobic and stretching exercises on cardiopulmonary parameters of female BC survivors.
OBJECTIVE: This study investigated the effects of combined aerobic and stretching exercises on cardiopulmonary functions of premenopausal and postmenopausal Breast cancer (BC) survivors.
METHODS: Fifty-four eligible BC survivors participated in the study but four-eight completed it. They were randomly' assigned to groups A and B and each group had two subgroups; subgroup 1 (premenopausal) and subgroup 2 (postmenopausal). Group A underwent combined aerobic exercise using treadmill and stretching exercises for 12 weeks while Group B was the control group.
RESULTS: Significant changes were observed in the cardiovascular parameters of participants in Groups A,,,,, (Resting systolic blood pressure (A1:p = 0.01*; A2: p = 0.01*), Resting diastolic blood pressure (A1: p = 0.01*; A2: p = 0.004*), Resting rate pressure product (A1: p 0.001*; A2: p = 0.02*). Significant changes were also observed in the pulmonary parameters of participants of Groups A(1&2) (Arterioxyhaemoglobin saturation (A,:p = 0.001*; A2:p = 0.02*), Forced vital capacity (A1:p = 0.13; A2: p = 0.05*), maximal oxygen uptake (A1:p = 0.03*; A2: p = 0.15).
CONCLUSION: Combined aerobic and stretching exercises brought about significant therapeutic effects on selected cardiopulmonary parameters in female BC survivors.

Songtish D, Akranurakkul P, Chaiaroon W
The Prevalence and Related Factors of Complementary and Alternative Medicine Used in Thai Breast Cancer Patients.
J Med Assoc Thai. 2015; 98 Suppl 10:S1-7 [PubMed] Related Publications
OBJECTIVE: This study's aim is to identify the prevalence and types of complementary and alternative medicine (CAM) used among Thai breast cancer patients and investigate the factors influencing the use of CAM by these patients.
MATERIAL AND METHOD: We interviewed 220 Thai breast cancer patients who visited the HRH Princess Maha Chakri Sirindhorn Medical Center and the Maha Vajiralongkorn Cancer Center during the period from October 2008 to September 2010 and collected data about their socio-economic status, history of cancer treatments and complications, the cancer staging, their Quality of life (QoL) and types and reasons of CAM used.
RESULTS: The prevalence of CAM usage in Thai breast cancer patients was 560 in every 1,000 patients. Factors which influenced CAM usage were; the patients' educational level, amount of income per month, the duration of the individuals' breast cancer diagnoses, menopausal status, the type of axillary surgery used in the course of their treatment, the incidences of systemic recurrence and physical components as measured by the SF-36.
CONCLUSION: The results have shown that most Thai breast cancer patients used CAM for the treatment of their breast cancer and had used CAM after being diagnosed with breast cancer Healthcare providers should recognize and provide pros and cons to patients and their family if CAM were used during breast cancer treatment.

Ozkavruk Eliyatkin N, Aktas S, Ozgur H, et al.
The role of p95HER2 in trastuzumab resistance in breast cancer.
J BUON. 2016 Mar-Apr; 21(2):382-9 [PubMed] Related Publications
PURPOSE: Trastuzumab, the HER2 oncogene targeting drug, shows remarkable clinical efficacy in HER2-amplified breast cancer patients. Despite of robust activity, some of the patients with HER2-positive breast cancers do not get the benefit due to trastuzumab resistance. Overexpression of p95HER2 is one of the molecular mechanisms of trastuzumab resistance. The purpose of this study was to investigate whether p95HER2 overexpressing breast cancers were resistant to trastuzumab.
METHODS: p95HER2 (truncated HER2) and HER2 were determined by real-time polymerase chain reaction (RT-PCR) analysis. HER2 protein expression and HER2 gene amplification were also determined by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). Archival material from 80 formalin-fixed paraffin-embedded (FFPE) breast cancer tumor tissues was used for the study. None of the cases had metastases at the initial diagnosis. HER2-positive cases were treated with trastuzumab with/without chemotherapy.
RESULTS: Of 80 breast cancer cases 39 (48.7%) were HER2-positive and had trastuzumab treatment. Of these 39 cases 11 (28.2%) were trastuzumab-resistant and 28 (71.8%) were not, 17 (43.6%) were recurrent cases and 22 (56.4%) were not. Three patients died during follow-up. p95HER2 mean ratio was 11.01±19.73 in 11 cases which were trastuzumab-resistant, while p95HER2 mean ratio was 1.99±1.37 in 28 cases without trastuzumab resistance. If p95HER2 ratio was low, there was no trastuzumab resistance. However, when p95HER2 ratio was high, there was trastuzumab resistance (p=0.210, Mann-Whitney U test).
CONCLUSION: p95HER2 was correlated with trastuzumab resistance, but it was not an independent factor of trastuzumab resistance. We claim that p95HER2 is sensitive but not specific for the prediction of trastuzumab resistance.

Ates O, Babacan T, Kertmen N, et al.
Efficacy and safety of eribulin monotherapy in patients with heavily pretreated metastatic breast cancer.
J BUON. 2016 Mar-Apr; 21(2):375-81 [PubMed] Related Publications
PURPOSE: Eribulin is a non-taxane microtubule inhibitor, which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated MBC patients.
METHODS: In this single-center trial, a total of 66 MBC patients who received eribulin monotherapy in Hacettepe University Cancer Institute between 2013 and 2015 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values <0.05 were considered as statistically significant.
RESULTS: Sixty-six patients who received at least one cycle of eribulin were registered. Most patients were heavily pretreated with a median of 4 (range 2-7) previous chemotherapy lines prior to eribulin. Median patient age was 50 years (range 28-67). Most patients were treated with eribulin at 4th or 5th line (33.3 and 27.3%, respectively). Brain metastases were present in 19 (28.8%) patients at the time of initial eribulin administration. Median PFS was 5 (95% CI 4.1-5.8) and median OS was 8 (95% CI 6-9.9) months. Fifteen patients (22.7%) responded to treatment with partial remission (PR) and 36 (54%) had stable disease (SD). No hypersensitivity reactions and no toxic deaths were observed. Three (5%) patients experienced grade 4 neurotoxicity. Fourteen (21.5%) patients developed grade 3-4 neutropenia.
CONCLUSION: Eribulin monotherapy is an effective and safe regimen for MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease in its intravenous administration make this agent a preferable option for both physicians and patients.

Lykholat T, Lykholat O, Antonyuk S
Tsitol Genet. 2016 Jan-Feb; 50(1):40-51 [PubMed] Related Publications
Immunohistochemical and biochemical study of infiltrative ductal breast carcinoma and tissue adjacent to the tumour revealed a particular molecular profile and characteristics of the oxidant-antioxidant status neoplasms depending on the age of the patients and the presence of metastases in regional lymph nodes. Some causes of high aggressiveness and low hormone sensitivity of tumours in premenopausal women, as well as stability and high metastatic potential of tumours in postmenopausal women have been found.

Mertins P, Mani DR, Ruggles KV, et al.
Proteogenomics connects somatic mutations to signalling in breast cancer.
Nature. 2016; 534(7605):55-62 [PubMed] Related Publications
Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.

Ben-David MA, Elkayam R, Gelernter I, Pfeffer RM
Melatonin for Prevention of Breast Radiation Dermatitis: A Phase II, Prospective, Double-Blind Randomized Trial.
Isr Med Assoc J. 2016 Mar-Apr; 18(3-4):188-92 [PubMed] Related Publications
BACKGROUND: Radiation-induced dermatitis is commonly seen during radiotherapy for breast cancer. Melatonin-based creams have shown a protective effect against ultraviolet-induced erythema and a radioprotective effect in rats.
OBJECTIVES: To evaluate the efficacy of melatonin-containing cream in minimizing acute radiation dermatitis.
METHODS: In this phase II, prospective, randomized, placebo-controlled double-blind study, patients who underwent breast-conserving surgery for stage 0-2 breast cancer were randomly allocated to melatonin emulsion (26 women) or placebo (21 women) for twice daily use during radiation treatment and 2 weeks following the end of radiotherapy. All women received 50 Gy whole breast radiation therapy with 2 Gy/fx using computed tomography-based 3D planning. Patients were examined and completed a detailed questionnaire weekly and 2 weeks following the end of treatment.
RESULTS: The occurrence of grade 1/2 acute radiation dermatitis was significantly lower (59% vs. 90%, P = 0.038) in the melatonin group. Women older than 50 had significantly less dermatitis than younger patients (56% vs. 100%, P = 0.021). The maximal radiation dermatitis in the study group was grade 2 in 15% of the treated patients.
CONCLUSIONS: Patients treated with melatonin-containing emulsion experienced significantly reduced radiation dermatitis compared to patients receiving placebo.

Wilhelm IN, Penman EJ
Radiation Associated Angiosarcoma: Case Series from a Community Cancer Center and Review of the Literature.
Del Med J. 2016; 88(3):78-82 [PubMed] Related Publications
BACKGROUND: Radiation associated angiosarcoma (RAAS) of the breast is a rare, but lethal complication of breast conserving surgery (BCS). Early recognition and knowledge of treatment modalities is imperative for successful treatment. We present the experience of a large community cancer center, with review of the literature.
METHODS: The Christiana Care Department of Pathology and the Helen F. Graham Cancer Center and Research Institute databases were queried from 2001-2011 and 2011-2015 respectively for soft tissue neoplasms of the breast. A total of 2,153 patients with diagnosis of malignant neoplasm of the breast not otherwise specified (NOS) were identified. There were seven cases of RAAS identified.
RESULTS: Seven patients with RAAS were identified. Average age at presentation was 70 years with a range of 58-87. Time from radiation therapy to diagnosis was 8.5 years with a range of 4.0 years to 14.9 years. Five of seven patients presented with skin lesions, all with varying clinical signs. Clinical lymphedema was not identified in any of these patients.
CONCLUSION: Radiation associated angiosarcoma of the breast is an aggressive tumor with poor prognosis. Larger studies are needed to evaluate adjuvant treatments; however the small number of cases makes this prohibitive. Genetic testing and potentially targeted therapies are emerging as options for treatment and prevention of this complicated disease process.

Mittendorf EA, Peoples GE
Injecting Hope--A Review of Breast Cancer Vaccines.
Oncology (Williston Park). 2016; 30(5):475-81, 485 [PubMed] Related Publications
There is significant interest in investigating immunotherapeutic strategies to be used for the treatment of breast cancer patients. One form of immunotherapy under active investigation is the cancer vaccine. Vaccines are a form of active immune therapy designed to stimulate the immune system to recognize tumor cells as foreign. Vaccines include an antigen that serves as the target for the immune response, and an immunoadjuvant, which is a nonspecific stimulator of the immune response that promotes an environment conducive to immune stimulation. Vaccines are an appealing therapeutic strategy because they are specific and are associated with minimal toxicity. In addition, they stimulate the adaptive immune system, thereby producing a memory response allowing for sustained effect without repeated therapy. Currently, there are no US Food and Drug Administration-approved breast cancer vaccines; however, there are multiple vaccines and treatment strategies employing these vaccines that are being actively investigated in clinical trials.

Lin B, Li D, Zhang L
Oxymatrine mediates Bax and Bcl-2 expression in human breast cancer MCF-7 cells.
Pharmazie. 2016; 71(3):154-7 [PubMed] Related Publications
UNLABELLED: The aim of this study was to explore the effects of oxymatrine in treating breast cancer patients using biomolecular methodology. Human breast cancer MCF-7 cells were treated with oxymatrine at concentrations of 0 (control), 25, 50 and 100 µg/mL. Apoptosis assay by Annexin/PI staining was performed to examine the effects of oxymatrine on apoptotic rates of MCF-7 cells at time points of 24 h, 48 h, and 72 h after treatment. Real-time PCR was performed for the mRNA abundance of Bax and Bcl-2 after the cells were treated with oxymatrine at concentration of 0, 25, 50, and 100 µg/mL at the time points of 24, 48, and 72 h. Western blotting was performed when the cells were treated with oxymatrine at various concentrations for 72h. High concentration of oxymatrine at 100 µg/mL enhanced apoptosis by 6.4-fold at 72 h compared with control (33.16% vs. 4.47%; t= 9.82, p< 0.001). Oxymatrine at 100 µg/mL up regulated Bax mRNA abundance by 169 % at 72 h (t = 18.32, p = 0.001), and reduced Bcl-2 mRNA abundance by 24 % at 72 h (t = 6.30, p = 0.001) compared with control. Oxymatrine enhanced the expression of Bax protein while reduced the expression of Bcl-2 protein. Oxymatrine treatment showed pro-apoptotic effects in breast cancer MCF-7 cells, and these effects correlated with the up regulation of Bax transcription and protein expression and the down regulation of Bcl-2 transcription and protein expression in a time- and dose-dependent manner.
CONCLUSION: Oxymatrine had effects in promoting apoptosis in human breast cancer MCF-7 cells by mediating the mRNA and protein expression levels of Bax and Bcl-2.

Do JH, Kim W, Cho YK, et al.
Lymphology. 2015; 48(4):184-96 [PubMed] Related Publications
The incorporation of resistance exercises into the lifestyle of patients with lymphedema is understudied and an emerging interest. We investigated the effectiveness and results of adding a moderate intensity resistance exercise program for 8 weeks in conjunction with intensive CDT for 1 or 2 weeks (depending on severity) on arm volume, arm function, QOL, and muscular strength in patients with breast cancer-related lymphedema. This prospective, pilot trial included forty-four patients with a history of breast cancer who were beginning complex decongestive therapy for lymphedema. They were assigned to either the intervention (n = 22) or control (n = 22). groups. The intervention comprised of resis- tance band exercises 5 times a week for 8 weeks. These were initially supervised during the intensive lymphedema treatment, but performed independently during the study period. Limb volume, muscular strength, and the European Organization for Research and Treatment of Cancer QOL Questionnaire C30 (EORTC QLQ-C30), EORTC-Breast Cancer-Specific QOL Questionnaire (EORTC QLQ-BR23), and Disabilities of Arm, Shoulder, and Hand (DASH) questionnaires were assessed at baseline and at 8 weeks. After 8 weeks, the intervention group demonstrated statistically significant differences (p < 0.05) in the DASH score and muscular strength compared to the control group. Our results indicate that upper body resistance exercise demonstrates a positive effect on arm function and muscular strength without increasing arm volume in breast cancer related lymphedema during and shortly post intensive CDT lymphedema treatment.

Zhero SV, Hotko YS, Tsyhyka DY, et al.
Peculiarities of breast cancer incidence rate in urban population and implementation of screening programs in health care system.
Wiad Lek. 2016; 69(1 Pt 2):61-3 [PubMed] Related Publications
INTRODUCTION: In the structure of illnesses connected with malignant tumors (MT) among women's population of Ukraine breast cancer (BC) holds a leading position and was at the level of 19.3% in 2014.
THE AIM: The aim of research is a comparative analysis of BC illnesses among women's population in regional centers of Prydniprovsk-Donetsk which is an intensive industrial zone (Dnipropetrovsk city) and Transcarpathian region, clean natural area (Uzhgorod city). The latter belongs to a recreational area because of its natural and climatic features. Also, the aim is to estimate an influence of screening program implementation on mortality of women from BC within one year period from diagnosis date. O bject and methods: We have used data of state statistics records as per F-7 and F-35 forms, which were received while processing the primary medical documentation (№ 090/о, № 027-1/о and № 30-6/о). The said was carried out by means of regional branches of National Cancer Register of Ukraine. Rough indexes of BC incidence rate and part of lethal outcomes among BC patients before one year after diagnosis in regional centers were considered.
RESULTS: A considerable increase of incidence rate of BC has been detected in administrative centers of both regions. This incidence rate has reached 90 cases out of 100,000 female population. Substantial change in gender behavior due to influence of urban surrounding is a possible factor of high BC incidence rate of urban population.
CONCLUSIONS: Mammography screening implementation contributes to general and annual decrease of BC mortality among women's population.

Taylor-Phillips S, Wallis MG, Jenkinson D, et al.
Effect of Using the Same vs Different Order for Second Readings of Screening Mammograms on Rates of Breast Cancer Detection: A Randomized Clinical Trial.
JAMA. 2016; 315(18):1956-65 [PubMed] Related Publications
IMPORTANCE: Interpreting screening mammograms is a difficult repetitive task that can result in missed cancers and false-positive recalls. In the United Kingdom, 2 film readers independently evaluate each mammogram to search for signs of cancer and examine digital mammograms in batches. However, a vigilance decrement (reduced detection rate with time on task) has been observed in similar settings.
OBJECTIVE: To determine the effect of changing the order for the second film reader of batches of screening mammograms on rates of breast cancer detection.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-blind, cluster randomized clinical trial conducted at 46 specialized breast screening centers from the National Health Service Breast Screening Program in England for 1 year (all between December 20, 2012, and November 3, 2014). Three hundred sixty readers participated (mean, 7.8 readers per center)-186 radiologists, 143 radiography advanced practitioners, and 31 breast clinicians, all fully qualified to report mammograms in the NHS breast screening program.
INTERVENTIONS: The 2 readers examined each batch of digital mammograms in the same order in the control group and in the opposite order to one another in the intervention group.
MAIN OUTCOMES AND MEASURES: The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers.
RESULTS: Among 1,194,147 women (mean age, 59.3; SD, 7.49) who had screening mammograms (596,642 in the intervention group; 597,505 in the control group), the images were interpreted in 37,688 batches (median batch size, 35; interquartile range [IQR]; 16-46), with each reader interpreting a median of 176 batches (IQR, 96-278). After completion of all subsequent diagnostic tests, a total of 10,484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, -0.02% to 0.04% points; recall rate, 24,681 [4.14%] vs 24,894 [4.17%]; difference, -0.03% points; 95% CI, -0.10% to 0.04% points; or rate of reader disagreements, 20,471 [3.43%] vs 20,793 [3.48%]; difference, -0.05% points; 95% CI, -0.11% to 0.02% points).
CONCLUSIONS AND RELEVANCE: Interpretation of batches of mammograms by qualified screening mammography readers using a different order vs the same order for the second reading resulted in no significant difference in rates of detection of breast cancer.
TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN46603370.

Nik-Zainal S, Davies H, Staaf J, et al.
Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
Nature. 2016; 534(7605):47-54 [PubMed] Article available free on PMC after 02/12/2016 Related Publications
We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.

Shintia C, Endang H, Diani K
Assessment of pathological response to neoadjuvant chemotherapy in locally advanced breast cancer using the Miller-Payne system and TUNEL.
Malays J Pathol. 2016; 38(1):25-32 [PubMed] Related Publications
BACKGROUND: Responses to neoadjuvant (before surgery) chemotherapy in locally advanced breast cancer (LABC) consist of clinical and pathological responses. Evaluating chemotherapy response is essential to predict survival rate and guide future chemotherapy. Until now, the evaluation of pathological response mainly involves quantitative assessment and is often inconsistent with clinical response. We explored the evaluation of pathological responses by both quantitative and qualitative methods, i.e. by evaluating the cellularity of tumour cells and the percentage of apoptosis.
MATERIALS AND METHOD: A cross-sectional analytical retrospective study was conducted on tissue of LABC diagnosed between 2010 and 2014 at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia Cipto Mangunkusumo Hospital and Division of Surgical Oncology, Cipto Mangunkusumo Hospital. Biopsy and resection specimens were compared to evaluate reduction in cellularity, which were subsequently categorized into stages of Miller-Payne (MP) classification. The resection specimens were stained with TUNEL and the percentage of apoptosis was calculated. Reduction in cellularity between biopsy and mastectomy specimens with TUNEL staining is evaluated as a modification of the MP method.
RESULTS: We found no association between clinical responses with percentage of apoptosis, MP pathological responses and modified MP. There was a correlation between the dead cell evaluated by MP and by modified MP (p=0.000).
CONCLUSION: Modified MP increases the degree or grading of pathological responses, but it does not improve the correlation with clinical response.

Toh YF, Cheah PL, Looi LM, et al.
Phyllodes tumours of the breast: retrospective analysis of a University Hospital's experience.
Malays J Pathol. 2016; 38(1):19-24 [PubMed] Related Publications
Taking cognizance of the purported variation of phyllodes tumours in Asians compared with Western populations, this study looked at phyllodes tumours of the breast diagnosed at the Department of Pathology, University of Malaya Medical Centre over an 8-year period with regards to patient profiles, tumour parameters, treatment offered and outcome. Sixty-four new cases of phyllodes tumour were diagnosed during the period, however only 30 (21 benign, 4 borderline and 5 malignant) finally qualified for entry into the study. These were followed-up for 4-102 months (average = 41.7 months). Thirteen cases (8 benign, 3 borderline, 2 malignant) were Chinese, 9 (all benign) Malay, 7 (4 benign, 1 borderline, 2 malignant) Indian and 1 (malignant) Indonesian. Prevalence of benign versus combined borderline and malignant phyllodes showed a marginally significant difference (p=0.049) between the Malays and Chinese. Patients' ages ranged from 21-70 years with a mean of 44.9 years with no significant difference in age between benign, borderline or malignant phyllodes tumours. Except for benign phyllodes tumours (mean size = 5.8 cm) being significantly smaller at presentation compared with borderline (mean size = 12.5 cm) and malignant (mean size = 15.8 cm) (p<0.05) tumours, history of previous pregnancy, breast feeding, hormonal contraception and tumour laterality did not differ between the three categories. Family history of breast cancer was noted in 2 cases of benign phyllodes. Local excision was performed in 17 benign, 2 borderline and 3 malignant tumours and mastectomy in 4 benign, 2 borderline and 2 malignant tumours. Surgical clearance was not properly recorded in 10 benign phyllodes tumours. Six benign and all 4 borderline and 5 malignant tumours had clearances of <10 mm. Two benign tumours recurred locally at 15 and 49 months after local excision, however information regarding surgical clearance was not available in both cases. One patient with a malignant tumour developed a radiologically-diagnosed lung nodule 26 months after mastectomy, was given a course of radiotherapy and remained well 8-months following identification of the lung nodule.

Manea E, Munteanu A
Rev Med Chir Soc Med Nat Iasi. 2016 Jan-Mar; 120(1):192-6 [PubMed] Related Publications
Bilateral breast cancer incidence is appreciated to be between 0.3 to 12% and is determined either by a hereditary load associated with chromosomal instability under the effect of environmental factors, or by the evolution in a particular hormonal context which gives biological aggressiveness. We present the case of a patient, aged 38 years, clinically, imagistic and bioptic diagnosed with left axillary lymph node metastases of breast carcinoma NST invasive G3, IHC-RE = 60%, RP = 30%, HER2neu = 2 +, Ki67 = 20%, in August 2013. Patient followed neoadjuvant chemotherapy treatment during September-October 2013. In December 2013 she was clinically and imaging diagnosed with bilateral breast cancer, for which surgical intervention was done which consisted of bilateral radical Madden mastectomy with bilateral axillary lymphadenectomy. BAP-invasive carcinoma NST: left breast-pT2mN3a G2, right breast--pT3mN3a G2, IHC-RE = 90%, RP =70% HER2neu = 2 +, Ki67 = 50%. During the period of January-March 2014, the patient followed adjuvant chemotherapy and Herceptin. Bilateral breast ultrasound assessment in April 2014 revealed: left axilla--liquid blade 29 / 6mm; right axilla--oval ganglion 9/5 mm. Abdominal and pelvic ultrasound: empty uterine cavity, bosselated contour; at left ovary level multiple cystic formations. During the period of May-June 2014, adjuvant radiation therapy and ovarian irradiationwas administered to the patient. Subsequently hormone therapy was initiated. Following CHT / ovarian irradiation patient continues to experience intermittent uterine bleeding, which is why a total hysterectomy with bilateral ovariectomy was done, and BAP: cervical, endometrialand left ovary with tumor multifocal infiltration with histopathological aspect of invasive breast carcinoma NST. Periodic imaging evaluations do not reveal local or distant recurrence. The particularity of this case is synchronous bilateral breast cancer diagnosis in a young patient complicated in its evolution by ovarian metastases. This form of metastasis is rare in young women and occurs in advanced stages of the disease.

Owsley J, Jimeno A, Diamond JR
Palbociclib:CDK4/6 inhibition in the treatment of ER-positive breast cancer.
Drugs Today (Barc). 2016; 52(2):119-29 [PubMed] Related Publications
Maintaining cell-cycle control has become a mainstay in treatment for many cancers. Cell-cycle manipulation can be especially valuable in breast cancer tumor cells that will often express hormone receptors that are amenable to anti-hormone receptor-targeted therapies. Despite these treatments, patients often progress, leading to other targeted agents being investigated to help promote progression-free survival. Cyclin-dependent kinases (CDKs) have been identified as contributors in the process of cell division. Combining inhibitors of CDKs with traditional endocrine treatments has shown significant progression-free survival in patients with metastatic breast cancer. One such CDK inhibitor, palbociclib, has shown great promise in the treatment of hormone receptor-positive breast cancer. In this article we review the traditional hormonal treatments of breast cancer, how CDK inhibition is beneficial in the treatment of this disease, and the preclinical and clinical data supporting the use of this medication.

Song XX, Song XD, Wang M, et al.
Integration of gene expression data and genetic variations involved in breast cancer.
J BUON. 2016 Jan-Feb; 21(1):61-9 [PubMed] Related Publications
PURPOSE: The studies of transcriptome and genome involved in breast cancer are effectively promote the understanding of biological processes and the development of novel targeted therapies. Here we performed an integrated analysis of gene expression and genetic variation to disclose the molecular pathogenesis in breast cancer.
METHODS: Gene expression profiles were applied to identify differential expression levels of genes between breast cancer and normal subjects. DNA sequencing data were extracted to analyze gene mutational information including number of mutations, number of mutated genes and their chromosomal distributions. Correlation analysis of gene mutations and differential expression was performed. Network-based approach was applied to compare the topological properties between the differentially expressed (DE) genes prone to mutation and those that(were not. Two-tailed p<0.05 was considered as statistically significant.
RESULTS: Statistical analysis showed that DE genes presented significantly positive correlation with the number of mutations (p=1.267E(-05)), mutated genes (p=0.00001) and total genes in the genome (p=2.489E(-06)). There were 81 genes, both DE and mutant, and they were distributed on chromosome 4 (N=51), chromosome 15 (N=29), and chromosome 18 (N=1). These 81 genes showed an increase in the number of genes interacting with in the protein-protein network.
CONCLUSION: Analysis of the integration of transcriptome and genome in breast cancer disclosed distinctive topology between the DE genes prone to mutation and those that were not.

Angelousi A, Nonni A, Kassi E, Kontzoglou K
Expression of sodium iodide symporter in human breast tissues.
J BUON. 2016 Jan-Feb; 21(1):53-60 [PubMed] Related Publications
PURPOSE: Sodium iodide symporter (NIS) expression in breast cancer (BC) tissues suggests the possibility of using radioiodine for diagnostic and therapeutic purposes. This study evaluated NIS protein expression in primary BC samples and its association with BC prognostic markers and thyroid functional parameters.
METHODS: Fifty-six breast tissue samples from 52 operated women (41 BC, 11 benign breast diseases (BBD) and 4 peritumoral adjacent to the carcinoma tissues samples) were analyzed by immunohistochemistry using monoclonal anti-NIS antibody. Measurements of baseline levels of thyroid hormones and antibodies were also analysed in association with NIS protein expression.
RESULTS: NIS presented positive cytoplasmic immunoreactivity in the majority of BBD samples (45% ) and in 3 out of 4 breast tissues adjacent to carcinoma. Immunoreactivity was extremely faint in BC samples. Mean thyroid hormones levels and thyroid antibodies positivity did not differ statistically between patients with NIS positive (faint expression) and NIS negative BC. NIS expression appeared to be independent of estrogen (ER) and progesterone receptor (PR) expression as well as of lymph node status.
CONCLUSIONS: BC samples expressed only faintly and mainly cytoplasmic NIS protein, suggesting the presence of a non-functional NIS protein. The hypothesis of the downregulation of NIS expression during carcinogenesis cannot be excluded.

Ekici K, Gokce T, Karadogan I, et al.
Is helical tomotherapy-based intensity-modulated radiotherapy feasible and effective in bilateral synchronous breast cancer? A two-center experience.
J BUON. 2016 Jan-Feb; 21(1):46-52 [PubMed] Related Publications
PURPOSE: This study describes the early clinical results and dosimetric parameters of intensity-modulated radiation therapy (IMRT) using a tomotherapy device in patients with primary bilateral synchronous breast cancer (PSBBC).
METHODS: Fourteen patients with bilateral breast cancer were treated with tomotherapy between January 2011 and October 2014. The treatment planning objectives were to cover 95% of the planning target volume using a 95% isodose, with a minimum dose of 90% and a maximum dose of 107%. The organs at risk (OAR), such as the lungs, heart, esophagus and spinal cord, were contoured. Acute toxicity was recorded during and after radiation therapy.
RESULTS: The advantages included better treatment conformity with lower dosages to minimize the risk to susceptible organs, such as the lungs, heart and spinal cord. There was improved coverage of the planning target volume, including the regional nodes, without any field junction problems. The median homogeneity index was 0.13 and the median conformity index 1.32. The median V20, V15, V10 and V5 for the total lungs were 18.5, 23.3, 24.2 and 60%, respectively. Skin acute toxicity was grade 1 in 72% and grade 2 in 14% of the patients. Esophageal acute toxicity was grade 1 in 43% of the patients.
CONCLUSION: Tomotherapy delivers treatment that is well-tolerated, with high homogeneity and coverage indexes and the capability to reduce the irradiation dose received by the lungs and heart in PSBBC patients. This technique is therefore feasible and safe for the treatment of bilateral breast cancer.

Vasiljevic S, Paunovic V, Konevic S
The importance of quality control in the implementation of breast cancer screening program in the Health Center Zemun.
J BUON. 2016 Jan-Feb; 21(1):42-5 [PubMed] Related Publications
PURPOSE: To investigate whether the differences in implementation between opportunistic and organized breast cancer screening affect the results, as well as the significance of quality control during the implementation of organized breast cancer screening.
METHODS: Testing was performed in 2013 (opportunistic screening) and 2014 (organized screening) in the Health Centre Zemun. This included female population aged 50-69 years, belonging to the target population according to the national breast cancer screening programs. The Health Centre Zemun database of insured patients from the National Health Insurance Fund of the municipality of Zemun and Surcin was used for the evaluation of the screening performance. Statistical data processing was done with the statistical package SPSS-20.0.
RESULTS: There was a highly significant difference (p=0.000) in the implementation of opportunistic and organized screening, whereby the response of women in organized screening was much greater (11.48%) than of the women responding to opportunistic screening (0.27%). The low response of women noticed in the summer in organized screening was attributed to the fact that the majority of women in Serbia take their holidays in that period.
CONCLUSION: Performance and quality of screening depends on the control of all segments of the activities carried out in the screening process. Previous experience in organizing and controlling the quality of the implementation of screening can serve as a proven model, which by a multidisciplinary approach in practice can provide a better and safer healthcare.

Li C, Zhang T
Human mammaglobin: A specific marker for breast cancer prognosis.
J BUON. 2016 Jan-Feb; 21(1):35-41 [PubMed] Related Publications
PURPOSE: In this study, we examined the expression of human mammaglobin (hMAM) mRNA and the protein levels in patients with breast cancer and their relationship with prognostic clinicopathological parameters.
METHODS: hMAM mRNA expression in leucocytes from peripheral blood samples from patients diagnosed with primary invasive breast cancer (IC), carcinoma in situ (CIS), or benign breast diseases was analyzed using RT-PCR. The hMAM protein levels and expression patterns in tissue from 3 patient groups were evaluated by immunohistochemical staining, and several non-breast neoplasms were selected as negative controls, undergoing the same examination.
RESULTS: The expression of hMAM mRNA was significantly higher in patients with IC or CIS compared to those with benign tumors (both<0.01). Immunohistochemical staining revealed similar results, where patients with IC or CIS had higher levels of hMAM protein (p<0.01 and p<0.01, respectively), while none of the negative controls expressed hMAM. Further analyses showed a strong correlation between hMAM protein/mRNA expression and clinicopathological factors, such as histological grade, clinical stage, and lymph node status, in patients with IC.
CONCLUSION: The hMAM mRNA and protein expression profiles validate the potential of hMAM as a specific marker for breast cancer diagnosis and target treatment delivery.

Sendur MA, Aksoy S, Ozdemir NY, et al.
Effect of body mass index on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.
J BUON. 2016 Jan-Feb; 21(1):27-34 [PubMed] Related Publications
PURPOSE: Obesity has been confirmed to be an adverse prognostic factor in patients who were treated with aromatase inhibitors; however, such relationship has never been thoroughly investigated in patients treated with tamoxifen. The purpose of this study was to examine the effect of body mass index (BMI) on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.
METHODS: Newly diagnosed premenopausal and non-metastatic hormone receptor-positive breast cancer patients were enrolled in the study. Patients with BMI ranging between 18.5 and 24.9 kg/m(2) were considered as normal weight patients (Arm A, n = 408), and/patients with a BMI ≥ 25 kg/m(2) were considered as overweight and obese patients (Arm B, n = 418).
RESULTS: In both normal weight and overweight patients, the baseline clinicopathologic properties and the treatment history with radiotherapy and chemotherapy were similar and no statistical significant difference could be detected. Tamoxifen in combination with luteinizing hormone-releasing hormone (LHRH) agonist was used in 33% (136/408) of the patients in Arm A and in 22% (91/418) of patients in Arm B (p<0.001). Three-year disease free survival (DFS) rates were 89% and 87% in arm A and arm B, respectively (p=0.39). Three-year overall survival (OS) rates were 99% in arm A and 94% in arm B which appeared to be of significance (p=0.028). In univariate analysis no statistical significant effect of LHRH agonist usage on DFS (p=0.58) and OS (p=0.96) was found.
CONCLUSION: Although BMI had no negative effect on recurrence risk, poor OS was observed in overweight and obese premenopausal breast cancer patients with hormone-receptor positive tumors who were treated with tamoxifen.

Ozguzer A, Bayol U, Pala EE, et al.
Does single receptor positive breast carcinoma differ with regard to age, tumor grade, and HER2 amplification status?
J BUON. 2016 Jan-Feb; 21(1):21-6 [PubMed] Related Publications
PURPOSE: To investigate whether there is a difference in patient and tumor characteristics in cases with single receptor positive (SRP) (ER-/PR+ and ER+/PR-) breast carcinoma in comparison with the double receptor positive (DRP) (ER+/PR+) and double receptor negative (DRN) (ER-/PR-) tumors.
METHODS: A total of 255 breast cancer patients were categorized on the basis of their tumor hormonal receptor phenotype, age, grade, and HER2 amplification status. The study focused on the SRP phenotype (ER+/PR- and ER-/PR+) and compared it with the DRP (ER+/PR+rpar; and DRN (ER-/PR-) tumors.
RESULTS: There were 103 (40.3%) DRP tumors, 98 (38.4%) DRN tumors and 54 (21%) SRP tumors, 41 (16.1%) of which were ER+/PR- and 13 (5.1%) were ER-/PR+. Compared to DRP tumors, the SRP group was more likely to be associated with grade 3 tumors and higher frequency of HER2 amplification status. ER-/PR+ tumors were more likely to be associated with younger age at diagnosis compared to ER+/PR- tumors. HER2 amplification, age, and grade were not significantly different between ER-/PR+ and DRN groups. Compared to the DRN group, the ER+/PR- group had lower grade.
CONCLUSIONS: Our findings demonstrated that SRP phenotype including ER+/PR- and ER-/PR+ tumors is different from DRP group with regard to age, grade, and HER2 amplification status. Moreover, our data showed that ER-/PR+ tumors are associated with younger age.

Beyer KM, Zhou Y, Matthews K, et al.
Breast and Colorectal Cancer Survival Disparities in Southeastern Wisconsin.
WMJ. 2016; 115(1):17-21 [PubMed] Related Publications
BACKGROUND: Cancer health disparities by race, ethnicity, socioeconomic status, and geography are a top public health priority. Breast and colorectal cancer, in particular, have been shown to exhibit significant disparities and contribute a large proportion of morbidity and mortality from cancer. In addition, breast and colorectal cancer offer targets for prevention and control, including nutrition, physical activity, screening, and effective treatments to prolong and enhance the quality of survival. However, despite the investment of significant time and resources over many years, breast and colorectal cancer disparities persist, and in some cases, may be growing.
METHODS: This paper examines breast and colorectal cancer survival disparities in an 8-county region in southeastern Wisconsin, including the City of Milwaukee. Cox proportional hazards models were used to examine survival trends, and a new adaptation of adaptive spatial filtering--a disease mapping method--was used to examine spatial patterns of survival.
RESULTS: Disparities by race and ethnicity are revealed, and spatial analyses identify specific areas within the study region that have lower than expected survival rates.
CONCLUSIONS: Cancer control efforts in southeastern Wisconsin should focus on black/African American and Hispanic/Latina women to reduce breast cancer survival disparities, and black/African American populations to reduce colorectal cancer disparities. Evidence indicates that targeted interventions may be needed to serve populations in the Milwaukee and Kenosha metropolitan areas, as well as areas of Walworth, Ozaukee, and Waukesha counties.

Zhang Y, Ma AD, Jia HX
Correlation between molybdenum target mammography signs and pathological prognostic factors of breast cancer.
J Biol Regul Homeost Agents. 2016 Jan-Mar; 30(1):219-25 [PubMed] Related Publications
This study explores the correlation between molybdenum target (mo-target) mammography signs and pathological prognostic factors of breast cancer. We selected 320 breast cancer patients who were treated between January 2014 and January 2016; using single-factor and multiple-factor logistic regression method, we made correlation analysis on their clinical features, pathological features and mo-target mammography signs. Among mo-target mammography signs, lumps accompanied with calcification and blurry edge were associated with high histologic grades; lumps accompanied with calcification and clear edge were associated with Ki-67 positive; compared with the patients who had lumps with non-stellate edges, positive rates of estrogen receptor (ER) and progesterone receptor (PR) were significantly higher for the patients who had lumps with stellate edges (p < 0.01), while positive rate of human epidermal growth factor receptor-2 (HER-2) and tumor proliferative activity were significantly lower (p < 0.05, p < 0.01). According to the study, we can conclude that mo-target mammography signs mainly include lumps and calcification. Mo-target mammography can improve the accuracy of diagnosis and reduce misdiagnosis or missed diagnosis. Part of mo-target mammography signs are associated with clinical pathology prognostic factors; by grasping the relation, breast cancer patient conditions are expected to be relieved.

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