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Proliferation residual neoadjuvant breast

Prachi Namjoshi, Lori Showalter, Brian J Czerniecki, Gary K Koski
A recent neoadjuvant vaccine trial for early breast cancer induced strong Th1 immunity against the HER-2 oncodriver, complete pathologic responses in 18% of subjects, and for many individuals, dramatically reduced HER-2 expression on residual disease. To explain these observations, we investigated actions of Th1 cytokines (TNF-α and IFN-γ) on murine and human breast cancer cell lines that varied in the surface expression of HER-family receptor tyrosine kinases. Breast cancer lines were broadly sensitive to the combination of IFN-γ and TNF-α, as evidenced by lower metabolic activity, lower proliferation, and enhanced apoptosis, and in some cases a reversible inhibition of surface expression of HER proteins...
June 25, 2016: Oncotarget
Tarek M A Abdel-Fatah, Devika Agarwal, Dong-Xu Liu, Roslin Russell, Oscar M Rueda, Karen Liu, Bing Xu, Paul M Moseley, Andrew R Green, Alan G Pockley, Robert C Rees, Carlos Caldas, Ian O Ellis, Graham R Ball, Stephen Y T Chan
BACKGROUND: Proliferation markers and profiles have been recommended for guiding the choice of systemic treatments for breast cancer. However, the best molecular marker or test to use has not yet been identified. We did this study to identify factors that drive proliferation and its associated features in breast cancer and assess their association with clinical outcomes and response to chemotherapy. METHODS: We applied an artificial neural network-based integrative data mining approach to data from three cohorts of patients with breast cancer (the Nottingham discovery cohort (n=171), Uppsala cohort (n=249), and Molecular Taxonomy of Breast Cancer International Consortium [METABRIC] cohort; n=1980)...
July 2016: Lancet Oncology
Marie Klintman, Richard Buus, Maggie Chon U Cheang, Amna Sheri, Ian E Smith, Mitch Dowsett
PURPOSE: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression. EXPERIMENTAL DESIGN: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffin-embedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies...
May 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Maurizio Callari, Vera Cappelletti, Francesca D'Aiuto, Valeria Musella, Antonio Lembo, Fabien Petel, Thomas Karn, Takayuki Iwamoto, Paolo Provero, Maria Grazia Daidone, Luca Gianni, Giampaolo Bianchini
PURPOSE: In spite of improvements of average benefit from adjuvant/neoadjuvant treatments, there are still individual patients with early breast cancer at high risk of relapse. We explored the association with outcome of robust gene cluster-based metagenes linked to proliferation, ER-related genes, and immune response to identify those high-risk patients. EXPERIMENTAL DESIGN: A total of 3,847 publicly available gene-expression profiles were analyzed (untreated, N = 826; tamoxifen-treated, N = 685; chemotherapy-treated, N = 1,150)...
January 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Belinda Yeo, Mitch Dowsett
Neoadjuvant endocrine treatment has become of increasing interest for downstaging primary ER+ breast cancers as it has become clear that the pathologic complete response rate of luminal tumours to chemotherapy is much lower than that of non-luminal and differs little from that to endocrine therapy. There is much more experience in postmenopausal than premenopausal women. Aromatase inhibitors are generally the agent of choice. Responses are lower in those with the low levels of ER. While duration of endocrine treatment in clinical trials has usually been standardized at around three to four months it is clear that volume reductions continue to occur beyond that time in a large proportion of cases and routine clinical practice is often to treat to maximum response...
November 2015: Breast: Official Journal of the European Society of Mastology
Shenduo Li, Sturgis Payne, Fang Wang, Peter Claus, Zuowei Su, Jeffrey Groth, Joseph Geradts, Gustaaf de Ridder, Rebeca Alvarez, Paul Kelly Marcom, Salvatore V Pizzo, Robin E Bachelder
INTRODUCTION: Chemotherapy remains the only available treatment for triple-negative (TN) breast cancer, and most patients exhibit an incomplete pathologic response. Half of patients exhibiting an incomplete pathologic response die within five years of treatment due to chemo-resistant, recurrent tumor growth. Defining molecules responsible for TN breast cancer chemo-resistance is crucial for developing effective combination therapies blocking tumor recurrence. Historically, chemo-resistance studies have relied on long-term chemotherapy selection models that drive genetic mutations conferring cell survival...
2015: Breast Cancer Research: BCR
Debajyoti Chatterjee, Amanjit Bal, Ashim Das, Gurpreet Singh
For locally advanced breast cancer, pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) is associated with good disease-free survival. In several studies, response to chemotherapy according to various parameters has shown strong inter-individual variability. We investigated whether different prognostic factors, including ALDH1 expression, might predict response to NACT in female patients with locally advanced breast carcinoma. ER, PR, Her2/neu, Ki-67 and ALDH1 immunohistochemistry were performed on the initial biopsy and subsequent resection specimens...
September 2015: Virchows Archiv: An International Journal of Pathology
Mark Jesus M Magbanua, Denise M Wolf, Christina Yau, Sarah E Davis, Julia Crothers, Alfred Au, Christopher M Haqq, Chad Livasy, Hope S Rugo, Laura Esserman, John W Park, Laura J van 't Veer
INTRODUCTION: The molecular biology involving neoadjuvant chemotherapy (NAC) response is poorly understood. To elucidate the impact of NAC on the breast cancer transcriptome and its association with clinical outcome, we analyzed gene expression data derived from serial tumor samples of patients with breast cancer who received NAC in the I-SPY 1 TRIAL. METHODS: Expression data were collected before treatment (T1), 24-96 hours after initiation of chemotherapy (T2) and at surgery (TS)...
2015: Breast Cancer Research: BCR
Flavio Crippa, Roberto Agresti, Marco Sandri, Gabriella Mariani, Barbara Padovano, Alessandra Alessi, Giulia Bianchi, Emilio Bombardieri, Ilaria Maugeri, Mario Rampa, Maria Luisa Carcangiu, Giovanna Trecate, Claudio Pascali, Anna Bogni, Gabriele Martelli, Filippo de Braud
PURPOSE: We evaluated whether (18)F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). METHODS: In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery...
May 2015: European Journal of Nuclear Medicine and Molecular Imaging
Zijing Zhang, Wei Zhang, Yiting Jin, Hongying Wang, Fei Gu, Jian Zhou, Zhengyin Lao, Zude Xu, Feng Tang, Liping Zou, Weijun Tang, Rong Lu, Qiang Zou
OBJECTIVE: In order to evaluate the therapeutic response to neoadjuvant chemotherapy (NAC) for breast cancer, this research focused on the changes in expression of tumor biomarkers and the correlations associated with changes of magnetic resonance imaging (MRI) pre- and post-NAC. We also compared the accuracy of MRI and pathology in terms of residual tumor extent after NAC. METHODS: MRI was performed before and after four courses of cyclophosphamide, epirubicin and paclitaxel (CET) NAC on 114 patients treated in Huashan Hospital (Fudan University) from December 2009 to January 2013...
June 2014: Journal of Thoracic Disease
Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kennedy, Victoria L Seewaldt, Salvatore V Pizzo, Robin E Bachelder
Although many tumors regress in response to neoadjuvant chemotherapy, residual tumor cells are detected in most cancer patients post-treatment. These residual tumor cells are thought to remain dormant for years before resuming growth, resulting in tumor recurrence. Considering that recurrent tumors are most often responsible for patient mortality, there exists an urgent need to study signaling pathways that drive tumor dormancy/recurrence. We have developed an in vitro model of tumor dormancy/recurrence. Short-term exposure of tumor cells (breast or prostate) to chemotherapy at clinically relevant doses enriches for a dormant tumor cell population...
2014: PloS One
Amy S Clark, Jinbo Chen, Shiv Kapoor, Claire Friedman, Carolyn Mies, Laura Esserman, Angela DeMichele
Laboratory studies suggest that vitamin D (vitD) enhances chemotherapy-induced cell death. The objective of this study was to determine whether pretreatment vitD levels were associated with response to neoadjuvant chemotherapy (NACT) in women with breast cancer. Study patients (n = 82) were enrolled on the I-SPY TRIAL, had HER2-negative tumors, and available pretreatment serum. VitD levels were measured via DiaSorin radioimmunoassay. The primary outcome was pathologic residual cancer burden (RCB; dichotomized 0/1 vs...
June 2014: Cancer Medicine
Libero Santarpia, Takayuki Iwamoto, Angelo Di Leo, Naoki Hayashi, Giulia Bottai, Martha Stampfer, Fabrice André, Nicholas C Turner, W Fraser Symmans, Gabriel N Hortobágyi, Lajos Pusztai, Giampaolo Bianchini
DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. We evaluated Affymetrix gene expression profiles for 145 DNA repair genes in untreated breast cancer (BC) patients (n = 684) and BC patients treated with regimens containing neoadjuvant taxane/anthracycline (n = 294) or anthracycline (n = 210). We independently assessed estrogen receptor (ER)-positive/HER2-negative, HER2-positive, and ER-negative/HER2-negative subgroups for differential expression, bimodal distribution, and the prognostic and predictive value of DNA repair gene expression...
2013: Oncologist
Ivett Teleki, Tibor Krenacs, Marcell A Szasz, Janina Kulka, Barna Wichmann, Cornelia Leo, Barbel Papassotiropoulos, Cosima Riemenschnitter, Holger Moch, Zsuzsanna Varga
BACKGROUND: Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST) are still missing. Deregulation of gap junction channel forming connexins (Cx) has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems...
2013: BMC Cancer
Gunter von Minckwitz, Michael Untch, Sibylle Loibl
PURPOSE OF REVIEW: Neoadjuvant treatment is used by an increased number of patients with breast cancer. This study reviews the current literature on how new research findings have impacted patients and treatment selection. RECENT FINDINGS: The prognostic value of pathological complete response (pCR) is different in various breast cancer subtypes. pCR rate after neoadjuvant chemotherapy is associated with better outcome only for patients with human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor negative or HER2-negative/hormone receptor negative (triple-negative) and some more aggressive HER2-negative/hormone receptor positive tumours...
February 2013: Current Opinion in Obstetrics & Gynecology
J Grim, P Jandík, I Slánská, E Doležalová-Brčáková, L Fuksa, A Ryška, J Knížek, J Petera, S Mičuda, H Hornychová
The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The pre- and post- NCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry...
2012: Folia Biologica (Praha)
Sven Rottenberg, Jos Jonkers
Lack of eradication of disseminated breast cancer by chemotherapy is a central clinical problem. Even tumors that show substantial shrinkage after drug treatment frequently relapse and eventually become refractory to all drugs available. The mechanisms underlying this lack of eradication are largely undefined and it is therefore difficult to develop curative strategies using systemic anti-cancer therapy. In a recent article low DUSP4 expression was reported to activate RAS-ERK signaling in residual breast cancer after neoadjuvant chemotherapy...
2012: Breast Cancer Research: BCR
Y Z Chen, J Y Xue, C M Chen, B L Yang, Q H Xu, F Wu, F Liu, X Ye, X Meng, G Y Liu, Z Z Shen, Z M Shao, J Wu
PURPOSE: Neoadjuvant chemotherapy for advanced breast cancer may improve the radicality for a subset of patients, but others may suffer from severe adverse drug reactions without any benefit. To predict the responses to chemotherapy, we performed a phase II trial of neoadjuvant chemotherapy using a weekly PCb [paclitaxel (Taxol) plus carboplatin] regimen for stage II/III breast cancer and assessed the correlation between baseline gene expression and the tumor response to treatment. METHODS: A total of 61 patients with stage II-III breast cancer were included and administered four cycles of preoperative PCb...
November 2012: Cancer Chemotherapy and Pharmacology
Joanna Szkandera, Gudrun Absenger, Nadia Dandachi, Peter Regitnig, Sigurd Lax, Michael Stotz, Hellmut Samonigg, Wilfried Renner, Armin Gerger
To elucidate the role of predictive factors on individual's drug response, based on genetic variation, we examined the association between eight germline polymorphisms in genes involved in protection against oxidative stress, apoptosis, oncogenic transformation, proliferation, immune response and DNA repair (TP53, NQO1, IL6, TLR4 and XRCC1) and the pathological response to anthracycline-based neoadjuvant chemotherapy in 70 patients with breast cancer. The DNA was genotyped for eight polymorphisms in five genes (TP53, NQO1, IL6, TLR4 and XRCC1) by 5'-exonuclease (TaqMan™) technology...
September 2012: Molecular Genetics and Genomics: MGG
Justin M Balko, Rebecca S Cook, David B Vaught, María G Kuba, Todd W Miller, Neil E Bhola, Melinda E Sanders, Nara M Granja-Ingram, J Joshua Smith, Ingrid M Meszoely, Janine Salter, Mitch Dowsett, Katherine Stemke-Hale, Ana M González-Angulo, Gordon B Mills, Joseph A Pinto, Henry L Gómez, Carlos L Arteaga
Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status...
July 2012: Nature Medicine
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