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Triple negative breast cancer

Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
Hui Yao, Guangchun He, Shichao Yan, Chao Chen, Liujiang Song, Thomas J Rosol, Xiyun Deng
Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers, does not express estrogen receptor (ER) or progesterone receptor (PR) and lacks human epidermal growth factor receptor 2 (HER2) overexpression or amplification. These tumors have a more aggressive phenotype and a poorer prognosis due to the high propensity for metastatic progression and absence of specific targeted treatments. Patients with TNBC do not benefit from hormonal or trastuzumab-based targeted therapies because of the loss of target receptors...
September 27, 2016: Oncotarget
Anthony Gonçalves, François Bertucci, Arnaud Guille, Severine Garnier, José Adelaide, Nadine Carbuccia, Oliver Cabaud, Pascal Finetti, Serge Brunelle, Gilles Piana, Jeanne Tomassin-Piana, Maria Paciencia, Eric Lambaudie, Cornel Popovici, Renaud Sabatier, Carole Tarpin, Magali Provansal, Jean-Marc Extra, François Eisinger, Hagay Sobol, Patrice Viens, Marc Lopez, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Max Chaffanet, Daniel Birnbaum
BACKGROUND: Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population. RESULTS: Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%)...
October 18, 2016: Oncotarget
Ion Cristobal, Blanca Torrejón, Manuel Pedregal, Federico G Rojo, Jesús García-Foncillas
Dear Editor, We have read with great interest the recent published manuscript by Caiazza et al. (2016), which provides novel exciting findings about the potential therapeutic value of enzalutamide in patients with androgen receptor (AR)-positive triple negative breast cancer (TNBC). Some previous studies have shown promising antitumor effects of this drug in breast tumors. Thus, enzalutamide-mediated AR inhibition has been reported to reduce proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis of TNBC cells in vitro and decrease viability of TNBC xenografts in vivo (Cochrane et al...
October 20, 2016: Endocrine-related Cancer
Marc A Becker, Xiaonan Hou, Piyawan Tienchaianada, Brian B Haines, Sean C Harrington, S John Weroha, Sriram Sathyanarayanan, Paul Haluska
BACKGROUND: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years...
October 20, 2016: BMC Cancer
Hae Jin Park, Kyung Hwan Shin, Jin Ho Kim, Seung Do Ahn, Ja Young Kim, Won Park, Yong Bae Kim, Yeon-Joo Kim, Jin Hee Kim, Kyubo Kim, Kyung Ran Park, Hyun Soo Shin, Bae Kwon Jeong, Sun Young Lee, Suzy Kim
Purpose: In a recent meta-analysis, post-mastectomy radiotherapy (PMRT) reduced any first recurrence (AFR) and improved survival in N1 and N2 patients. We investigated risk factors for AFR in N1 after optimal systemic therapy without PMRT, to define a subgroup of patients who may benefit from PMRT. Materials and Methods: 1,382 pT1-2N1M0 breast cancer patients treated with mastectomy without PMRT between 2005 and 2010 were retrospectively analyzed. Only 0.6% had no systemic therapy...
October 19, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Cortney L Lawrence, Albert S Baldwin
Enhancer of zeste homology 2 (EZH2) is the methyltransferase component of the polycomb repressive complex (PRC2) which represses gene transcription via histone H3 trimethylation at lysine 23 (H3K27me3). EZH2 activity has been linked with oncogenesis where it is thought to block expression of certain tumor suppressors. Relative to a role in cancer, EZH2 functions to promote self-renewal and has been shown to be important for the tumor-initiating cell (TIC) phenotype in breast cancer. Recently a non-canonical role for EZH2 has been identified where it promotes transcriptional activation of certain genes...
2016: PloS One
Uhi Toh, Shuko Saku, Mina Okabe, Nobutaka Iwakuma, Yuko Kimitsuki, Momoko Akashi, Etsuyo Ogo, Akira Yamada, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi
Our previous phase II clinical trial showed that therapeutically selected personalized peptide vaccines(PPVs)were effective at boosting anticancer immunity; the immune response after PPV was associated with a clinical outcome as a prognostic factor for metastatic breast cancer(mBC). We conducted an early phase II study to evaluate the safety and efficacy of a new regimen using multiple peptide vaccines(KRM-19)for patients with metastatictriple -negative breast cancer. KRM-19 consisted of 19 mixed peptides chosen from the previously reported 31 PPVs according to their anti-tumor immunologiceffec ts and safety profiles for patients with mBC...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yoshinori Nio, Shiro Imai, Kayo Uesugi, Mikako Tamaoki, Masashi Tamaoki, Riruke Maruyama
Triple-negative breast cancers(TNBCs)are associated with early recurrence after surgery and unfavorable prognoses. To date, no effective therapies for TNBCs have been established. The present study was designed to evaluate the efficacy of adjuvant chemotherapy(ACT)for 111 TNBCs using a retrospective multivariate analysis(MVA). The intravenous(iv)ACTs included docetaxel, epirubicin, gemcitabine, and vinorelbine. The oral ACTs included UFT, doxifluridine, and cyclophosphamide. The 10-year disease-free survival(DFS)and overall survival(OS)rates were 77...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Naoki Hayashi, Madoka Iwase, Tomohiro Ochi, Akina Seki, Naoko Matsuda, Hideko Yamauchi
Following the discovery that the prognostic impact of preoperative chemotherapy depends on the primary breast cancer subtype, the treatment strategy for primary breast cancer changed. Pathologic complete response(pCR)with preoperative chemotherapy is predictive of a favorable prognosis in patients with HER2 type or triple-negative type breast cancer, but not in patients with ER-positive/HER2-negative, the so-called Luminal type, breast cancer. However, the role of preoperative chemotherapy in patients with Luminal-B type breast cancer who may need chemotherapy should be further assessed...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
W Liu, J B Li, T Wang, L Bian, S H Zhang, H Q Zhang, J M Zhou, S T Song, Z F Jiang
Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS)...
September 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Meiou Dai, Chenjing Zhang, Ayad Ali, Xinyuan Hong, Jun Tian, Chieh Lo, Nadège Fils-Aimé, Sergio A Burgos, Suhad Ali, Jean-Jacques Lebrun
Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients...
October 19, 2016: Scientific Reports
Wayne O Miles, Antonio Lembo, Angela Volorio, Elena Brachtel, Bin Tian, Dennis Sgroi, Paolo Provero, Nicholas Dyson
Alternative polyadenylation (APA) is a process that changes the post-transcriptional regulation and translation potential of mRNAs via addition or deletion of 3'UTR sequences. To identify post-transcriptional regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3'UTR region found that APA-mediated removal of Pumilio Regulatory Elements (PRE) was unusually common. Breast tumor sub-type specific APA profiling identified triple-negative breast tumors as having the highest levels of APA...
October 10, 2016: Cancer Research
Ken Takai, Annie Le, Valerie M Weaver, Zena Werb
Increased collagen expression in tumors is associated with increased risk of metastasis, and triple-negative breast cancer (TNBC) has the highest propensity to develop distant metastases when there is evidence of central fibrosis. Transforming growth factor-β (TGF-β) ligands regulated by cancer-associated fibroblasts (CAFs) promote accumulation of fibrosis and cancer progression. In the present study, we have evaluated TNBC tumors with enhanced collagen to determine whether we can reduce metastasis by targeting the CAFs with Pirfenidone (PFD), an anti-fibrotic agent as well as a TGF-β antagonist...
October 14, 2016: Oncotarget
Ahmed R H Ahmed
Identification of metastatic potential of breast cancer cells is necessary for proper management of this disease. This work aimed to estimate likelihood of axillary lymph node (ALN) involvement in breast cancer patients based on human epidermal growth factor receptor 2 (HER2) expression. Primary tumors of 317 breast cancer patients were evaluated for estrogen receptor (ER), progesterone receptor (PR) and HER2 expression by immunohistochemistry. The validity of these molecules to predict ALN metastasis was measured statistically and compared to predictive effect of other clinicopathological parameters...
October 15, 2016: Journal of the Egyptian National Cancer Institute
Suleyman Sahin, Gokmen U Erdem, Fatih Karatas, Aydin Aytekin, Ali R Sever, Yavuz Ozisik, Kadri Altundag
BACKGROUND: Body mass index (BMI) is defined as a poor prognostic factor in patients with breast cancer (BC). However, there are controversial results regarding the various effects of BMI on BC, hence the exact pathophysiology of the relation between obesity and BC is still under debate, and remains unclear. This paper aims to investigate the association between BMI at presentation and BC subtypes defined according to the immunohistochemical classification in both premenopausal and postmenopausal patients with BC...
October 15, 2016: Breast: Official Journal of the European Society of Mastology
Mustapha Abubakar, Nick Orr, Frances Daley, Penny Coulson, H Raza Ali, Fiona Blows, Javier Benitez, Roger Milne, Herman Brenner, Christa Stegmaier, Arto Mannermaa, Jenny Chang-Claude, Anja Rudolph, Peter Sinn, Fergus J Couch, Peter Devilee, Rob A E M Tollenaar, Caroline Seynaeve, Jonine Figueroa, Mark E Sherman, Jolanta Lissowska, Stephen Hewitt, Diana Eccles, Maartje J Hooning, Antoinette Hollestelle, John W M Martens, Carolien H M van Deurzen, kConFab Investigators, Manjeet K Bolla, Qin Wang, Michael Jones, Minouk Schoemaker, Jelle Wesseling, Flora E van Leeuwen, Laura Van 't Veer, Douglas Easton, Anthony J Swerdlow, Mitch Dowsett, Paul D Pharoah, Marjanka K Schmidt, Montserrat Garcia-Closas
BACKGROUND: The value of KI67 in breast cancer prognostication has been questioned due to concerns on the analytical validity of visual KI67 assessment and methodological limitations of published studies. Here, we investigate the prognostic value of automated KI67 scoring in a large, multicentre study, and compare this with pathologists' visual scores available in a subset of patients. METHODS: We utilised 143 tissue microarrays containing 15,313 tumour tissue cores from 8088 breast cancer patients in 10 collaborating studies...
October 18, 2016: Breast Cancer Research: BCR
Eva Gross, Harm van Tinteren, Zhou Li, Sandra Raab, Christina Meul, Stefanie Avril, Nadja Laddach, Michaela Aubele, Corinna Propping, Apostolos Gkazepis, Manfred Schmitt, Alfons Meindl, Petra M Nederlof, Marion Kiechle, Esther H Lips
BACKGROUND: Triple-negative breast cancer (TNBC) with a BRCA1-like molecular signature has been demonstrated to remarkably respond to platinum-based chemotherapy and might be suited for a future treatment with poly(ADP-ribose)polymerase (PARP) inhibitors. In order to rapidly assess this signature we have previously developed a multiplex-ligation-dependent probe amplification (MLPA)-based assay. Here we present an independent validation of this assay to confirm its important clinical impact...
October 19, 2016: BMC Cancer
Shaheenah Dawood, Hope S Rugo
PURPOSE OF REVIEW: This article describes the role of the PD-1 axis and reviews current data and future directions inhibiting PD-1 and PD-L1 in breast cancer. RECENT FINDINGS: Four phase I monotherapy expansion trials in patients with metastatic breast cancer have demonstrated low but durable single agent responses to PD-1 and PD-L1 inhibitors, ranging from 4.8 to 19%. Higher response rates are seen in triple negative breast cancer, compared with hormone receptor positive disease...
October 15, 2016: Current Opinion in Supportive and Palliative Care
M E Cazzaniga, L Cortesi, A Ferzi, L Scaltriti, F Cicchiello, M Ciccarese, S Della Torre, F Villa, M Giordano, C Verusio, M Nicolini, A R Gambaro, L Zanlorenzi, E Biraghi, L Legramandi, E Rulli
PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS)...
October 17, 2016: Breast Cancer Research and Treatment
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