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Ki67 neoadjuvant Breast Sequencing

Isabel Echavarria, Sara López-Tarruella, Antoni Picornell, Jose Ángel García-Saenz, Yolanda Jerez, Katherine Hoadley, Henry L Gómez, Fernando Moreno, María Del Monte-Millan, Iván Márquez-Rodas, Enrique Alvarez, Rocío Ramos-Medina, Javier Gayarre, Tatiana Massarrah, Inmaculada Ocaña, María Cebollero, Hugo Fuentes, Agusti Barnadas, Ana Isabel Ballesteros, Uriel Bohn, Charles M Perou, Miguel Martin
Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues...
April 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Cynthia X Ma, Vera Suman, Matthew P Goetz, Donald Northfelt, Mark E Burkard, Foluso Ademuyiwa, Michael Naughton, Julie Margenthaler, Rebecca Aft, Richard Gray, Amye Tevaarwerk, Lee Wilke, Tufia Haddad, Timothy Moynihan, Charles Loprinzi, Tina Hieken, Erica K Barnell, Zachary L Skidmore, Yan-Yang Feng, Kilannin Krysiak, Jeremy Hoog, Zhanfang Guo, Leslie Nehring, Kari B Wisinski, Elaine Mardis, Ian S Hagemann, Kiran Vij, Souzan Sanati, Hussam Al-Kateb, Obi L Griffith, Malachi Griffith, Laurence Doyle, Charles Erlichman, Matthew J Ellis
Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER+ ) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA -mutant ER+ breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER+ breast cancer. Experimental Design: Potential eligible patients with clinical stage II/III ER+ /HER2- breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Silvia Guil-Luna, Jan Stenvang, Nils Brünner, Francisco Javier De Andrés, Eva Rollón, Víctor Domingo, Raquel Sánchez-Céspedes, Yolanda Millán, Juana Martín de Las Mulas
BACKGROUND: Progesterone receptors play a key role in the development of canine mammary tumours, and recent research has focussed on their possible value as therapeutic targets using antiprogestins. Cloning and sequencing of the progesterone receptor gene has shown that the receptor has two isoforms, A and B, transcribed from a single gene. Experimental studies in human breast cancer suggest that the differential expression of progesterone receptor isoforms has implications for hormone therapy responsiveness...
2014: BMC Veterinary Research
Muhammad Alamgeer, Vinod Ganju, Beena Kumar, Jane Fox, Stewart Hart, Michelle White, Marion Harris, John Stuckey, Zdenka Prodanovic, Michal Elisabeth Schneider-Kolsky, D Neil Watkins
INTRODUCTION: Although neoadjuvant chemotherapy (NAC) for locally advanced breast cancer can improve operability and local disease control, there is a lack of reliable biomarkers that predict response to chemotherapy or long-term survival. Since expression of aldehyde dehydrogenase-1 (ALDH1) is associated with the stem-like properties of self-renewal and innate chemoresistance in breast cancer, we asked whether expression in serial tumor samples treated with NAC could identify women more likely to benefit from this therapy...
April 24, 2014: Breast Cancer Research: BCR
N Tominaga, Y Naoi, K Shimazu, T Nakayama, N Maruyama, A Shimomura, S J Kim, Y Tamaki, S Noguchi
BACKGROUND: The aim of this study was to investigate the clinicopathological characteristics of GATA binding protein 3 (GATA3)-positive breast cancers as well as the association of GATA3 expression with response to chemotherapy. PATIENTS AND METHODS: Tumor specimens obtained before neoadjuvant chemotherapy [paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide)] from breast cancer patients (n = 130) were subjected to immunohistochemical and mutational analysis of GATA3 and DNA microarray gene expression analysis for intrinsic subtyping...
December 2012: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Nyam-Osor Chimge, Sanjeev K Baniwal, Jingqin Luo, Simon Coetzee, Omar Khalid, Benjamin P Berman, Debu Tripathy, Matthew J Ellis, Baruch Frenkel
PURPOSE: To assess the clinical significance of the interaction between estrogen and Runx2 signaling, previously shown in vitro. EXPERIMENTAL DESIGN: MCF7/Rx2(dox) breast cancer cells were treated with estradiol and/or doxycycline to induce Runx2, and global gene expression was profiled to define genes regulated by estradiol, Runx2, or both. Anchorage-independent growth was assessed by soft-agar colony formation assays. Expression of gene sets defined using the MCF7/Rx2(dox) system was analyzed in pre- and on-treatment biopsies from hormone receptor-positive patients undergoing neoadjuvant letrozole treatment in two independent studies, and short-term changes in gene expression were correlated with tumor size reduction or Ki67 index at surgery...
February 1, 2012: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Gais Kadra, Pascal Finetti, Yves Toiron, Patrice Viens, Daniel Birnbaum, Jean-Paul Borg, François Bertucci, Anthony Gonçalves
Microtubule-targeting agents, including taxanes (Tax) and ixabepilone (Ixa), are important components of modern breast cancer chemotherapy regimens, but no molecular parameter is currently available that can predict for their efficiency. We sought to develop pharmacogenomic predictors of Tax- and Ixa-response from a large panel of human breast tumor cell lines (BTCL), then to evaluate their performance in clinical samples. Thirty-two BTCL, representative of the molecular diversity of breast cancers (BC), were treated in vitro with Tax (paclitaxel (Pac), docetaxel (Doc)), and ixabepilone (Ixa), then classified as drug-sensitive or resistant according to their 50% inhibitory concentrations (IC50s)...
April 2012: Breast Cancer Research and Treatment
Hiroyuki Yasojima, Atsushi Shimomura, Yasuto Naoi, Kazuki Kishi, Yousuke Baba, Kenzo Shimazu, Takahiro Nakayama, Seung Jin Kim, Yasuhiro Tamaki, Shinzaburo Noguchi
BACKGROUND: The aim of this study was to investigate whether c-myc amplification in human breast cancer is associated with response to neoadjuvant chemotherapy comprising paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC). METHODS: Tumour tissue samples were obtained before neoadjuvant chemotherapy (P-FEC) from 100 primary breast cancer patients (stage II/III). C-myc and HER2 amplification were examined by FISH, and oestrogen receptor (ER), progesterone receptor (PR), Ki67, and topoisomerase 2α (TOP2A) expression were examined immunohistochemically...
August 2011: European Journal of Cancer
Anita K Dunbier, Helen Anderson, Zara Ghazoui, Janine Salter, Joel S Parker, Charles M Perou, Ian E Smith, Mitch Dowsett
Considerable heterogeneity exists amongst oestrogen receptor positive (ER+ve) breast cancer in both its molecular profile and response to therapy. Attempts to better define variation amongst breast tumours have led to the definition of four main "intrinsic" subtypes of breast cancer with two of these classes, Luminal A and B, composed almost entirely of ER+ve cancers. In this study we set out to investigate the significance of intrinsic subtypes within a group of ER+ve breast cancers treated with neoadjuvant anastrozole...
July 2011: Steroids
Bhuvanesh Dave, Ilenia Migliaccio, M Carolina Gutierrez, Meng-Fen Wu, Gary C Chamness, Helen Wong, Archana Narasanna, Anindita Chakrabarty, Susan G Hilsenbeck, Jian Huang, Mothaffar Rimawi, Rachel Schiff, Carlos Arteaga, C Kent Osborne, Jenny C Chang
PURPOSE: Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be associated with trastuzumab resistance. Trastuzumab, the humanized human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and lapatinib, an epidermal growth factor receptor/HER2 tyrosine kinase inhibitor, are both established treatments for HER2-overexpressing breast cancers. Understanding of the cellular response to HER2-targeted therapies is needed to tailor treatments and to identify patients less likely to benefit...
January 10, 2011: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Yasuto Naoi, Kazuki Kishi, Tomonori Tanei, Ryo Tsunashima, Naoomi Tominaga, Yosuke Baba, Seung Jin Kim, Tetsuya Taguchi, Yasuhiro Tamaki, Shinzaburo Noguchi
BACKGROUND: The aim of the present study was to investigate the prognostic value of the genomic grade index for lymph node-negative and estrogen receptor (ER)-positive breast cancers of Japanese women treated with adjuvant hormonal therapy alone, as well as the relation between genomic grade index and pathological complete response (CR) to neoadjuvant chemotherapy. METHODS: Genomic grade index was determined by DNA microarray (U133plus2.0; Affymetrix, Santa Clara, Calif) in tumor tissues obtained from lymph node-negative and ER-positive breast cancers (n = 105) treated with adjuvant hormonal therapy alone or in breast tumor biopsy specimens (n = 84, Mammotome) obtained before neoadjuvant chemotherapy (paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphomide) to investigate the prognostic and predictive values of genomic grade index...
February 1, 2011: Cancer
Vicky S Sabine, Andrew H Sims, E Jane Macaskill, Lorna Renshaw, Jeremy S Thomas, J Michael Dixon, John M S Bartlett
There is growing evidence that uncontrolled activation of the PI3K/Akt/mTOR pathway contributes to the development and progression of breast cancer. Inhibition of this pathway has antitumour effects in preclinical studies and efficacy in combination with other agents in breast cancer patients. The aim of this study is to characterise the effects of pre-operative everolimus treatment in primary breast cancer patients and to identify potential molecular predictors of response. Twenty-seven patients with oestrogen receptor (ER)-positive breast cancer completed 11-14 days of neoadjuvant treatment with 5-mg everolimus...
July 2010: Breast Cancer Research and Treatment
Alfonso Sánchez-Muñoz, R Dueñas-García, A Jaén-Morago, E Carrasco, I Chacón, A M García-Tapiador, A L Ortega-Granados, E Martínez-Ortega, N Ribelles, M Fernández-Navarro, C de la Torre-Cabrera, B Dueñas, A I Rueda, J Martínez, C Ramírez Tortosa, M D Martín-Salvago, P Sánchez-Rovira
PURPOSE: To evaluate the pathologic complete response (pCR) rate of a combination of epirubicin (E) and cyclophosphamide (C) followed by paclitaxel (P) and gemcitabine (G) (+ trastuzumab[T]) in Her2+ patients) in a sequential and dose-dense schedule as neoadjuvant chemotherapy for stages II and III patients with breast cancer. Secondary endpoints: clinical response rate, disease free survival, safety and correlation between pCR and biologic markers. PATIENTS AND METHODS: Eligible patients were treated with E (90 mg/m²) and C (600 mg/m²) for 3 cycles (first sequence) followed by P (150 mg/m²) and G (2500 mg/m²) (second sequence) for 6 cycles...
October 2010: American Journal of Clinical Oncology
O C Freedman, E Amir, W Hanna, H Kahn, F O'Malley, G Dranitsaris, D E C Cole, S Verma, E Folkerd, M Dowsett, M Clemons
Several adjuvant endocrine strategies exist for postmenopausal women with breast cancer. This study compared the effect of two sequences of aromatase inhibitor use [steroidal (exemestane) and non-steroidal (anastrozole)] on serological and pathological biomarkers when given in the neoadjuvant setting to postmenopausal women with breast cancer. Thirty women were assigned to receive exemestane 25 mg or anastrozole 1 mg each given for 8 weeks in a randomized sequence. The effect of this treatment on serum estrone sulfate and estradiol levels, as well as tumor changes in the proliferation biomarker Ki67 were evaluated at baseline, 8 weeks and 16 weeks...
January 2010: Breast Cancer Research and Treatment
Cynthia X Ma, Cesar G Sanchez, Matthew J Ellis
Endocrine therapy is one of the most effective treatment strategies for breast cancer. However, in the adjuvant setting, up to 40% to 50% of patients with estrogen receptor (ER)-positive breast cancers relapse despite these interventions. Although ER and HER2 analysis has increased our ability to predict which patients will benefit from endocrine therapy, further improvement is needed, most specifically for patients with ER-positive, HER2-negative disease. Recent advances in genomic technology have made it possible to classify breast cancers into risk categories with significant prognostic implications...
February 2009: Oncology (Williston Park, NY)
William R Miller, T J Anderson, S White, A Larionov, J Murray, D Evans, A Krause, J M Dixon
Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis...
May 2005: Journal of Steroid Biochemistry and Molecular Biology
W R Miller, T J Anderson, J M Dixon
The use of drugs, which inhibit estrogen biosynthesis, is an attractive treatment for postmenopausal women with hormone-dependent breast cancer. Estrogen deprivation is most specifically achieved using inhibitors which block the last stage in the biosynthetic sequence, i.e., the conversion of androgens to estrogens by the aromatase enzyme. Recently, a new generation of aromatase inhibitors has been developed. Among these, letrozole (Femara) appears to be the most potent. When given orally in milligram amounts per day to postmenopausal women, the drug almost totally inhibits peripheral aromatase and causes a marked reduction in circulating estrogens to levels that are often undetectable in conventional assays...
2002: Cancer Investigation
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