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    2591 results match your criteria Breast Cancer Research[Journal]

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    The endonuclease EEPD1 mediates synthetic lethality in RAD52-depleted BRCA1 mutant breast cancer cells.
    Breast Cancer Res 2017 Nov 16;19(1):122. Epub 2017 Nov 16.
    Department of Medicine and the Cancer Center, University of Florida Health, 1600 SW Archer Rd, Gainesville, FL, 32610, USA.
    Background: Proper repair and restart of stressed replication forks requires intact homologous recombination (HR). HR at stressed replication forks can be initiated by the 5' endonuclease EEPD1, which cleaves the stalled replication fork. Inherited or acquired defects in HR, such as mutations in breast cancer susceptibility protein-1 (BRCA1) or BRCA2, predispose to cancer, including breast and ovarian cancers. Read More

    Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells.
    Breast Cancer Res 2017 Nov 15;19(1):121. Epub 2017 Nov 15.
    Department of Pediatrics, Stanford University School of Medicine, 150E Clark Center, 318 Campus Drive, Stanford, CA, 94305-5427, USA.
    Background: Approximately 70% of all breast cancers express the estrogen receptor, and are regulated by estrogen. While the ovaries are the primary source of estrogen in premenopausal women, most breast cancer is diagnosed following menopause, when systemic levels of this hormone decline. Estrogen production from androgen precursors is catalyzed by the aromatase enzyme. Read More

    Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.
    Breast Cancer Res 2017 Nov 14;19(1):120. Epub 2017 Nov 14.
    Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Postbox 4953 Nydalen, 0424, Oslo, Norway.
    Background: The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy.

    Methods: Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death. Read More

    Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study.
    Breast Cancer Res 2017 Nov 7;19(1):119. Epub 2017 Nov 7.
    Department of Oncology, Leuven Multidisciplinary Breast Cancer, University Hospital Leuven, KU Leuven, Leuven, Belgium.
    Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.

    Methods: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). Read More

    Addition of T2-guided optical tomography improves noncontrast breast magnetic resonance imaging diagnosis.
    Breast Cancer Res 2017 Oct 24;19(1):117. Epub 2017 Oct 24.
    Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
    Background: While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast cancer based on endogenous contrast are of growing interest. In this study, endogenous near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to explore whether the combined imaging modality, which does not require contrast injection or involve ionizing radiation, can achieve acceptable diagnostic performance. Read More

    Roles of BCCIP deficiency in mammary tumorigenesis.
    Breast Cancer Res 2017 Oct 18;19(1):115. Epub 2017 Oct 18.
    Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
    Background: Dysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions. Read More

    A novel and fully automated mammographic texture analysis for risk prediction: results from two case-control studies.
    Breast Cancer Res 2017 Oct 18;19(1):114. Epub 2017 Oct 18.
    Centre for Imaging Science, School of Health Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
    Background: The percentage of mammographic dense tissue (PD) is an important risk factor for breast cancer, and there is some evidence that texture features may further improve predictive ability. However, relatively little work has assessed or validated textural feature algorithms using raw full field digital mammograms (FFDM).

    Method: A case-control study nested within a screening cohort (age 46-73 years) from Manchester UK was used to develop a texture feature risk score (264 cases diagnosed at the same time as mammogram of the contralateral breast, 787 controls) using the least absolute shrinkage and selection operator (LASSO) method for 112 features, and validated in a second case-control study from the same cohort but with cases diagnosed after the index mammogram (317 cases, 931 controls). Read More

    Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study.
    Breast Cancer Res 2017 Oct 13;19(1):113. Epub 2017 Oct 13.
    School of Cancer Studies, CRUK King's Health Partners Centre, King's College London, Guy's Campus, London, SE1 1UL, UK.
    Background: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.

    Methods: A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Read More

    Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as prognostic factors.
    Breast Cancer Res 2017 Oct 11;19(1):112. Epub 2017 Oct 11.
    Department of Gynaecology, Martin-Luther-University, Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
    Background: Breast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, are less well-understood. Profiling of metabolism-related proteins harbors the potential to establish new patient stratification regimes and biomarkers promoting individualized therapy. In our study, we aimed to examine the relationship between metabolism-associated protein expression profiles and clinicopathological characteristics in a large cohort of breast cancer patients. Read More

    FUT8 promotes breast cancer cell invasiveness by remodeling TGF-β receptor core fucosylation.
    Breast Cancer Res 2017 Oct 5;19(1):111. Epub 2017 Oct 5.
    Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
    Background: Core fucosylation (addition of fucose in α-1,6-linkage to core N-acetylglucosamine of N-glycans) catalyzed by fucosyltransferase 8 (FUT8) is critical for signaling receptors involved in many physiological and pathological processes such as cell growth, adhesion, and tumor metastasis. Transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) regulates the invasion and metastasis of breast tumors. However, whether receptor core fucosylation affects TGF-β signaling during breast cancer progression remains largely unknown. Read More

    Endophilin A2 promotes HER2 internalization and sensitivity to trastuzumab-based therapy in HER2-positive breast cancers.
    Breast Cancer Res 2017 Oct 3;19(1):110. Epub 2017 Oct 3.
    Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
    Background: Human epidermal growth factor receptor-2 (HER2) is amplified and a clinical target in a subset of human breast cancers with high rates of metastasis. Targeted therapies involving the antibody trastuzumab and trastuzumab-emtansine (T-DM1) have greatly improved outcomes for HER2-positive (HER2+) breast cancer patients. However, resistance to these targeted therapies can develop and limit their efficacy. Read More

    Alcohol consumption and breast tumor gene expression.
    Breast Cancer Res 2017 Sep 12;19(1):108. Epub 2017 Sep 12.
    Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, 715 N Pleasant Street, Amherst, MA, 01003, USA.
    Background: Alcohol consumption is an established risk factor for breast cancer and the association generally appears stronger among estrogen receptor (ER)-positive tumors. However, the biological mechanisms underlying this association are not completely understood.

    Methods: We analyzed messenger RNA (mRNA) microarray data from both invasive breast tumors (N = 602) and tumor-adjacent normal tissues (N = 508) from participants diagnosed with breast cancer in the Nurses' Health Study (NHS) and NHSII. Read More

    Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors.
    Breast Cancer Res 2017 Sep 11;19(1):107. Epub 2017 Sep 11.
    Department of Laboratory Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
    Background: Poly(ADP-ribose) polymerase inhibitors (PARPi), coupled to a DNA damaging agent is a promising approach to treating triple negative breast cancer (TNBC). However, not all patients respond; we hypothesize that non-response in some patients may be due to insufficient drug penetration. As a first step to testing this hypothesis, we quantified and visualized veliparib and carboplatin penetration in mouse xenograft TNBCs and patient blood samples. Read More

    Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.
    Breast Cancer Res 2017 Sep 11;19(1):106. Epub 2017 Sep 11.
    Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, Arcispedale Santa Maria Nuova - IRCCS, Viale Umberto I, No. 50, 42123, Reggio Emilia, Italy.
    Background: Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. Read More

    ErbB3 drives mammary epithelial survival and differentiation during pregnancy and lactation.
    Breast Cancer Res 2017 Sep 8;19(1):105. Epub 2017 Sep 8.
    Department of Cancer Biology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Rm 749 Preston Research Building, Nashville, TN, 37232, USA.
    Background: During pregnancy, as the mammary gland prepares for synthesis and delivery of milk to newborns, a luminal mammary epithelial cell (MEC) subpopulation proliferates rapidly in response to systemic hormonal cues that activate STAT5A. While the receptor tyrosine kinase ErbB4 is required for STAT5A activation in MECs during pregnancy, it is unclear how ErbB3, a heterodimeric partner of ErbB4 and activator of phosphatidyl inositol-3 kinase (PI3K) signaling, contributes to lactogenic expansion of the mammary gland.

    Methods: We assessed mRNA expression levels by expression microarray of mouse mammary glands harvested throughout pregnancy and lactation. Read More

    SPEN, a new player in primary cilia formation and cell migration in breast cancer.
    Breast Cancer Res 2017 Sep 6;19(1):104. Epub 2017 Sep 6.
    Division of Experimental Medicine, Department of Oncology and Surgery, McGill University, Montréal, PQ, H3A 0G4, Canada.
    Background: The primary cilium is a microtubule-based and nonmotile organelle functioning as a cellular antenna that is involved in the regulation of cell proliferation, differentiation, and migration. In breast cancer cells, the primary cilium is a structure that decreases in incidence with increasing degrees of transformation and may be biologically more important in estrogen receptor (ERα)-negative breast cancer cells. Split ends (SPEN) is an ERα corepressor that we have identified as a tumor suppressor protein in ERα-positive breast cancer cells whose hormone-independent roles in breast cancer have never been explored. Read More

    Breast Tissue Organisation and its Association with Breast Cancer Risk.
    Breast Cancer Res 2017 Sep 6;19(1):103. Epub 2017 Sep 6.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Background: Mammographic percentage density is an established and important risk factor for breast cancer. In this paper, we investigate the role of the spatial organisation of (dense vs. fatty) regions of the breast defined from mammographic images in terms of breast cancer risk. Read More

    Pathobiology of the 129:Stat1 (-/-) mouse model of human age-related ER-positive breast cancer with an immune infiltrate-excluded phenotype.
    Breast Cancer Res 2017 Sep 2;19(1):102. Epub 2017 Sep 2.
    Center for Comparative Medicine, University of California at Davis, Davis, CA, USA.
    Background: Stat1 gene-targeted knockout mice (129S6/SvEvTac-Stat1 (tm1Rds)) develop estrogen receptor-positive (ER(+)), luminal-type mammary carcinomas at an advanced age. There is evidence for both host environment as well as tumor cell-intrinsic mechanisms to initiate tumorigenesis in this model. In this report, we summarize details of the systemic and mammary pathology at preneoplastic and tumor-bearing time points. Read More

    The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting.
    Breast Cancer Res 2017 Aug 25;19(1):99. Epub 2017 Aug 25.
    Agendia NV, Amsterdam, The Netherlands.
    Background: Patients with BRCA1-like tumors correlate with improved response to DNA double-strand break-inducing therapy. A gene expression-based classifier was developed to distinguish between BRCA1-like and non-BRCA1-like tumors. We hypothesized that these tumors may also be more sensitive to PARP inhibitors than standard treatments. Read More

    Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer.
    Breast Cancer Res 2017 Aug 29;19(1):101. Epub 2017 Aug 29.
    City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA.
    Background: Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. Read More

    Tissue-based associations of mammographic breast density with breast stem cell markers.
    Breast Cancer Res 2017 Aug 29;19(1):100. Epub 2017 Aug 29.
    Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN, 55905, USA.
    Background: Mammographic breast density is a well-established, strong breast cancer risk factor but the biology underlying this association remains unclear. Breast density may reflect underlying alterations in the size and activity of the breast stem cell pool. We examined, for the first time, associations of CD44, CD24, and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) breast stem cell markers with breast density. Read More

    Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.
    Breast Cancer Res 2017 Aug 22;19(1):98. Epub 2017 Aug 22.
    Centre de Recherche en Cancérologie de Lyon, INSERM U1052 - Centre Léon Bérard, 28 rue Laennec, 69373, Lyon, France.
    Background: Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. Read More

    The ninth ENBDC Weggis meeting: growth and in-depth characterisation of normal and neoplastic breast cells.
    Breast Cancer Res 2017 Aug 22;19(1):96. Epub 2017 Aug 22.
    INSERM U1218, Institut Bergonie, University of Bordeaux, 229 cours de l'Argonne, 33076, Bordeaux, France.
    Mammary gland biologists gathered for the ninth annual workshop of the European Network for Breast Development and Cancer (ENBDC) at Weggis on the shores of Lake Lucerne in March 2017. The main themes were oestrogen receptor alpha signalling, new techniques for mammary cell culture, CRISPR screening and proteogenomics. Read More

    Combining quantitative and qualitative breast density measures to assess breast cancer risk.
    Breast Cancer Res 2017 Aug 22;19(1):97. Epub 2017 Aug 22.
    Department of Radiology, University of California, San Francisco, CA, USA.
    Background: Accurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk.

    Methods: We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. Read More

    White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
    Breast Cancer Res 2017 Aug 18;19(1):94. Epub 2017 Aug 18.
    Department of Civil and Environmental Engineering, University of Massachusetts, Amherst, MA, 01003, USA.
    Background: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk.

    Methods: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. Read More

    Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion.
    Breast Cancer Res 2017 Aug 18;19(1):95. Epub 2017 Aug 18.
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
    Background: We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1.

    Methods: Electrophoretic mobility shift assay-mass spectrometry was performed to identify proteins binding to the ZNF423 SNP and coordinating with estrogen receptor alpha (ERα). Read More

    Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer.
    Breast Cancer Res 2017 Aug 15;19(1):93. Epub 2017 Aug 15.
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
    Background: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo.

    Methods: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Read More

    Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer.
    Breast Cancer Res 2017 Aug 9;19(1):92. Epub 2017 Aug 9.
    Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine III, Technical University Dresden, Fetscherstraße 74, D-01307, Dresden, Germany.
    Background: The mammalian target of rapamycin inhibitor everolimus is approved as an antitumor agent in advanced estrogen receptor-positive breast cancer. Surrogate bone marker data from clinical trials suggest effects on bone metabolism, but the mode of action of everolimus in bone biology remains unclear. In this study, we assessed potential bone-protective effects of everolimus in the context of osteotropic tumors. Read More

    Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance.
    Breast Cancer Res 2017 Aug 7;19(1):91. Epub 2017 Aug 7.
    Department of Pathology, Yale University School of Medicine, 310 Cedar St, PO Box 208023, New Haven, CT, 06520-8023, USA.
    Background: The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy.

    Methods: Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy. Read More

    Inhibition of basal-like breast cancer growth by FTY720 in combination with epidermal growth factor receptor kinase blockade.
    Breast Cancer Res 2017 Aug 4;19(1):90. Epub 2017 Aug 4.
    Kolling Institute, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
    Background: New molecular targets are needed for women with triple-negative breast cancer (TNBC). This pre-clinical study investigated the combination of the EGFR inhibitor gefitinib with the sphingosine kinase (SphK) inhibitor FTY720 (Fingolimod), aiming to block tumorigenic signaling downstream of IGFBP-3, which is abundantly expressed in basal-like TNBC.

    Methods: In studies of breast cancer cell growth in culture, proliferation was monitored by IncuCyte live-cell imaging, and protein abundance was determined by western blotting. Read More

    AKT1(low) quiescent cancer cells persist after neoadjuvant chemotherapy in triple negative breast cancer.
    Breast Cancer Res 2017 Aug 1;19(1):88. Epub 2017 Aug 1.
    Massachusetts General Hospital Cancer Center, Richard B. Simches Research Building, 185 Cambridge Street, Boston, MA, 02114, USA.
    Background: Absence of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) correlates with poor long-term survival in patients with triple negative breast cancer (TNBC). These incomplete treatment responses are likely determined by mechanisms that enable cancer cells to resist being killed. However, the detailed characterization of a drug-resistant cancer cell state in residual TNBC tissue after NACT has remained elusive. Read More

    A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer.
    Breast Cancer Res 2017 Aug 2;19(1):89. Epub 2017 Aug 2.
    Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
    Background: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. Read More

    Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.
    Breast Cancer Res 2017 Jul 27;19(1):87. Epub 2017 Jul 27.
    Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
    Background: The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies.

    Methods: Baseline tumour biopsies were available from 74 patients with HER2-positive breast cancer who were enrolled in the phase II TCHL neoadjuvant study (ICORG 10-05) assessing TCH (docetaxel, carboplatin, trastuzumab) (n = 38) versus TCL (docetaxel, carboplatin, lapatinib) (n = 10) versus TCHL (docetaxel, carboplatin, trastuzumab, lapatinib) (n = 40), each for six cycles. Read More

    Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin.
    Breast Cancer Res 2017 Jul 27;19(1):86. Epub 2017 Jul 27.
    Invasion and Metastasis Unit, St. Vincent's Institute, Melbourne, VIC, Australia.
    Background: Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently with decreased proliferation. Proliferation may be restored in secondary metastases by mesenchymal-to-epithelial transition (MET). We tested whether E-cadherin maintains epithelial proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic colonization in severe combined immunodeficiency (SCID) mice. Read More

    Body size in early life and risk of breast cancer.
    Breast Cancer Res 2017 Jul 21;19(1):84. Epub 2017 Jul 21.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77, Stockholm, Sweden.
    Background: Body size in early life is inversely associated with adult breast cancer (BC) risk, but it is unclear whether the associations differ by tumor characteristics.

    Methods: In a pooled analysis of two Swedish population-based studies consisting of 6731 invasive BC cases and 28,705 age-matched cancer-free controls, we examined the associations between body size in early life and BC risk. Self-reported body sizes at ages 7 and 18 years were collected by a validated nine-level pictogram (aggregated into three categories: small, medium and large). Read More

    Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population.
    Breast Cancer Res 2017 Jul 19;19(1):83. Epub 2017 Jul 19.
    Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Background: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history. Read More

    Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case-control study in the Northern Sweden Maternity Cohort.
    Breast Cancer Res 2017 Jul 18;19(1):82. Epub 2017 Jul 18.
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Background: Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones.

    Methods: We conducted a nested case-control study in the Northern Sweden Maternity Cohort (1975-2007). Read More

    Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.
    Breast Cancer Res 2017 Jul 10;19(1):81. Epub 2017 Jul 10.
    Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
    Background: The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies.

    Methods: Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Read More

    The footprint of the ageing stroma in older patients with breast cancer.
    Breast Cancer Res 2017 Jul 3;19(1):78. Epub 2017 Jul 3.
    Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium.
    Background: Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression. Read More

    Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.
    Breast Cancer Res 2017 Jul 3;19(1):77. Epub 2017 Jul 3.
    Department of Oncology, Georgetown University, Research Building, Room E407, 3970 Reservoir Road, NW, Washington, DC, 20057, USA.
    Background: Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk.

    Methods: Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Read More

    Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis.
    Breast Cancer Res 2017 Jul 3;19(1):79. Epub 2017 Jul 3.
    Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3517 Cullen Blvd, Houston, TX, 77204, USA.
    Background: Upregulation of estrogen receptor beta (ERβ) in breast cancer cells is associated with epithelial maintenance, decreased proliferation and invasion, and a reduction in the expression of the receptor has been observed in invasive breast tumors. However, proof of an association between loss of ERβ and breast carcinogenesis is still missing.

    Methods: To study the role of ERβ in breast oncogenesis, we generated mouse conditional mutants with specific inactivation of ERβ and p53 in the mammary gland epithelium. Read More

    Ex vivo expanded natural killer cells from breast cancer patients and healthy donors are highly cytotoxic against breast cancer cell lines and patient-derived tumours.
    Breast Cancer Res 2017 Jul 1;19(1):76. Epub 2017 Jul 1.
    Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, 1280 Main Street West, MDCL 4015, Hamilton, ON, Canada.
    Background: Natural killer (NK) cells play a critical role in cancer immunosurveillance. Recent developments in NK cell ex-vivo expansion makes it possible to generate millions of activated NK cells from a small volume of peripheral blood. We tested the functionality of ex vivo expanded NK cells in vitro against breast cancer cell lines and in vivo using a xenograft mouse model. Read More

    Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.
    Breast Cancer Res 2017 Jun 30;19(1):74. Epub 2017 Jun 30.
    Department of Cancer Biology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Rm 749 Preston Research Building, Nashville, TN, 37232, USA.
    Background: The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear. Read More

    Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival.
    Breast Cancer Res 2017 Jun 30;19(1):75. Epub 2017 Jun 30.
    Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, SRB 4, Tampa, FL, 33612, USA.
    Background: Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients.

    Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database provided by the National Institutes of Health to derive an analytic dataset of 250,195 female patients with early-stage breast cancer who received RT before (n = 2554; 1. Read More

    MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer.
    Breast Cancer Res 2017 Jun 21;19(1):73. Epub 2017 Jun 21.
    Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
    Background: Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive.

    Methods: We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 (sf/+) ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. Read More

    Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes.
    Breast Cancer Res 2017 Jun 19;19(1):71. Epub 2017 Jun 19.
    H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
    Background: A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer.

    Methods: Affymetrix gene expression profiles were used to interrogate the CS by the principal component method. Read More

    miR-629-3p may serve as a novel biomarker and potential therapeutic target for lung metastases of triple-negative breast cancer.
    Breast Cancer Res 2017 Jun 19;19(1):72. Epub 2017 Jun 19.
    Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No.651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong, 510060, People's Republic of China.
    Background: Different breast cancer subtypes show distinct tropisms for sites of metastasis. Notably, the lung is the most common site for the first distant recurrence in triple-negative breast cancer (TNBC). The identification of novel biomarkers for lung metastasis is of great importance to improving the outcome of TNBC. Read More

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