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Her2 positive breast cancer

Emanuela Risi, Andrea Grilli, Ilenia Migliaccio, Chiara Biagioni, Amelia McCartney, Cristina Guarducci, Martina Bonechi, Matteo Benelli, Stefania Vitale, Laura Biganzoli, Silvio Bicciato, Angelo Di Leo, Luca Malorni
PURPOSE: HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients...
March 22, 2018: Breast Cancer Research and Treatment
Sally Agersborg, Christopher Mixon, Thanh Nguyen, Sramila Aithal, Sucha Sudarsanam, Forrest Blocker, Lawrence Weiss, Robert Gasparini, Shiping Jiang, Wayne Chen, Gregory Hess, Maher Albitar
PURPOSE: While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Alternative probes may be used in equivocal cases. We present a single community-based institution's experience in further evaluating these cases. PATIENTS AND METHODS: Between 2014 and 2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA...
March 22, 2018: Breast Cancer Research and Treatment
E Martínez de Dueñas, J Gavila-Gregori, S Olmos-Antón, A Santaballa-Bertrán, A Lluch-Hernández, E J Espinal-Domínguez, M Rivero-Silva, A Llombart-Cussac
Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy...
March 21, 2018: Clinical & Translational Oncology
Balázs Győrffy, Lőrinc Pongor, Giulia Bottai, Xiaotong Li, Jan Budczies, András Szabó, Christos Hatzis, Lajos Pusztai, Libero Santarpia
BACKGROUND: Sequence variations in coding and non-coding regions of the genome can affect gene expression and signalling pathways, which in turn may influence disease outcome. METHODS: In this study, we integrated somatic mutations, gene expression and clinical data from 930 breast cancer patients included in the TCGA database. Genes associated with single mutations in molecular breast cancer subtypes were identified by the Mann-Whitney U-test and their prognostic value was evaluated by Kaplan-Meier and Cox regression analyses...
March 21, 2018: British Journal of Cancer
Hope S Rugo, Jean-Pierre Delord, Seock-Ah Im, Patrick A Ott, Sarina A Piha-Paul, Phillipe L Bedard, Jasgit Sachev, Christophe Le Tourneau, Emilie M J van Brummelen, Andreea Varga, Roberto Salgado, Sherene Loi, Sanatan Saraf, Dina Pietrangelo, Vassiliki Karantza, Antoinette R Tan
PURPOSE: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor‒positive (ER+)/human epidermal growth factor receptor 2-negative (HER2- ) advanced breast cancer with programmed death ligand 1‒positive (PD-L1‒positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. EXPERIMENTAL DESIGN: Patients with ER+/HER2- advanced breast cancer with PD-L1‒positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shih-Fan Lai, Yu-Hsuan Chen, Tony Hsiang-Kuang Liang, Che-Yu Hsu, Huang-Chun Lien, Yen-Sen Lu, Chiun-Sheng Huang, Sung-Hsin Kuo
INTRODUCTION: Whole brain (WB) re-irradiation for breast cancer patients with progressive brain metastasis after first-course WB radiotherapy (WBRT) is controversial. In this study, we sought to investigate the association between the molecular sub-classifications and breast-specific Graded Prognostic Assessment (GPA, which includes the Karnofsky performance status, molecular subtypes, and age as its indices) and the outcomes of breast cancer patients who received WB re-irradiation. METHODS: Twenty-three breast cancer patients who received WB re-irradiation for relapsed and progressive intracranial lesions after first-course WBRT between 2004 and 2016 were retrospectively reviewed...
March 20, 2018: Journal of Neuro-oncology
Geneviève Gauthier, Patrick Gagnon-Sanschagrin, Annie Guérin, Rebecca Burne, Tania Small, Polly Niravath, Anand A Dalal
INTRODUCTION: Premenopausal women with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) have complex treatment needs and may receive sequential combinations of endocrine therapy (ET) or chemotherapy. This study describes healthcare utilization (HRU) and costs among premenopausal women with HR+/HER2- mBC in real-world settings from a payer's perspective. METHODS: In this retrospective cohort study, premenopausal women with HR+/HER2- mBC who received ET or chemotherapy were identified from the Truven Health Analytics MarketScan database (1 January 2006-31 December 2015)...
March 20, 2018: Advances in Therapy
Diego F Munoz, Cong Xu, Sylvia K Plevritis
We present a Monte Carlo simulation model that reproduces US invasive breast cancer incidence and mortality trends from 1975 to 2010 as a function of screening and adjuvant treatment. This model was developed for multiple purposes, including to quantify the impact of screening and adjuvant therapy on past and current trends, predict future trends, and evaluate potential outcomes under hypothetical screening and treatment interventions. The model first generates the life histories of individual breast cancer patients by determining the patient's age, tumor size, estrogen receptor (ER) status, human epidermal growth factor 2 (HER2) status, SEER (Surveillance, Epidemiology, and End Results) historic stage, detection mode at time of detection, preclinical tumor course, and death age and cause of death (breast cancer v...
April 2018: Medical Decision Making: An International Journal of the Society for Medical Decision Making
Diego F Munoz, Sylvia K Plevritis
BACKGROUND: As molecular subtyping of breast cancer influences clinical management, the evaluation of screening and adjuvant treatment interventions at the population level needs to account for molecular subtyping. Performing such analyses are challenging because molecular subtype-specific, long-term outcomes are not readily accessible; these markers were not historically recorded in tumor registries. We present a modeling approach to estimate historical survival outcomes by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status...
April 2018: Medical Decision Making: An International Journal of the Society for Medical Decision Making
Xin Zhao, Jing Wei, Xiaoxin Li, Haochang Yang, Pei Wang, Susheng Cao
Adequate lymph node evaluation is recommended for optimal staging in patients with malignant neoplasms including breast cancer. However, the role of negative lymph nodes (LNs) remains unclear in breast cancer according to N substage (N1, N2, and N3). In this study, for the first time, we analyzed the prognostic significance of negative LNs in breast cancer patients. A critical relationship was observed between negative LN count and survival, independent of patient characteristics and other related molecular variables including estrogen receptor (PR) status, progesterone receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, depth of tumor invasion and degree of differentiation...
2018: PloS One
Catherine L Forse, Dushanthi Pinnaduwage, Shelley B Bull, Anna Marie Mulligan, Irene L Andrulis
The proper handling of unstained paraffin slides for immunohistochemistry has been a matter of debate, with several studies demonstrating loss of antigenicity with prolonged storage at room temperature, 4°C and -20°C. The purpose of this study was to determine whether long-term storage of unstained slides at -80°C would impact the staining intensity and expression distribution of markers used to molecularly subtype breast cancer specimens [estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), and Ki67]...
March 17, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Gaochen Lan, Jie Li, Qiaomei Wen, Lin Lin, Libin Chen, Liyu Chen, Xi Chen
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) serves an important role in inhibiting anti-tumor immune response in the majority of solid tumors. However, a limited number of studies reported the function of CTLA-4 in luminal B HER2-negative breast cancer. Immunohistochemistry was performed to evaluate the expression of tumor and interstitial CTLA-4 in luminal B HER2-negative breast cancer tissues. The percentage of patients with tumor and interstitial CTLA-4+ was 41.2% (42/102) and 46.1% (47/102), respectively...
April 2018: Oncology Letters
Cheng-Liang Yuan, Zhao-Hong Liu, Ning Zou, Ya-Li Wang, Zhong-Yao Chen
It is designed to discuss the relationship between the expression of chemokine receptor 7 (chemokine receptor 7, CXCR7) and nuclear transcription factor-κB (nuclear factor kappa B, NF-κB) and the occurrence of the breast cancer and lymphatic metastasis. METHOD: 80 samples were excised and confirmed as breast cancer through our hospital pathology from January 2014 to December 2016 and tumor tissues and normal mammary tissues 2 cm from the tumor edges were taken as an experimental group and a control group, respectively...
December 2017: Saudi Journal of Biological Sciences
Hayato Kaida, Koichi Azuma, Uhi Toh, Akihiko Kawahara, Eiji Sadashima, Satoshi Hattori, Jun Akiba, Nobuhiro Tahara, Axel Rominger, Kazunai Ishii, Takamichi Murakami, Masatoshi Ishibashi
OBJECTIVE: To assess the correlations between dual-phase fluorine-18 fluorodeoxyglucose (18 F-FDG) uptake and clinicopathological and immunohistochemical prognostic factors in patients with surgically resected breast cancer. SUBJECTS AND METHODS: We retrospectively analyzed the cases of 105 patients. We calculated the maximum standardized uptake value (SUVmax) at 85min (SUV1), SUVmax at 125min (SUV2) and the retention index [RI]. Spearman's rank correlation test, the Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were performed to assess the association between18 F-FDG uptake and the clinicopathological and immunohistochemical factors: glucose transporter-1 (Glut-1), estrogen receptor alpha (ERα), ERβ, progesterone receptor (PR), human epidermal growth factor 2 (Her2), mammalian target of rapamycin (mTOR), and P70S6kinase (P70S6)...
March 20, 2018: Hellenic Journal of Nuclear Medicine
Shahryar Khoshtinat Nikkhoi, Fatemeh Rahbarizadeh, Saeed Ranjbar, Sepideh Khaleghi, Alireza Farasat
Breast cancer is the leading cause of mortality among all cancers. HER2, human epidermal growth factor receptors type 2, a receptor tyrosine kinase that induces interminable cell proliferation, is overexpressed in 20-25 percent of breast cancers. In spite of significant progress in nanomedicine in the past decade, being subjected to genetic drift that hides many paramount epitopes has rendered targeting HER2 as a big challenge. In the present study, we developed monovalent and bivalent monospecific along with bivalent bispecific VHH targeting different epitopes on HER2, and showed that bivalent bispecific VHH has the highest affinity among other tested modalities...
March 14, 2018: Molecular Immunology
Timothy Kwang Yong Tay, Aye Aye Thike, Nirmala Pathmanathan, Ana Richelia Jara-Lazaro, Jabed Iqbal, Adeline Shi Hui Sng, Heng Seow Ye, Jeffrey Chun Tatt Lim, Valerie Cui Yun Koh, Jane Sie Yong Tan, Joe Poh Sheng Yeong, Zi Long Chow, Hui Hua Li, Chee Leong Cheng, Puay Hoon Tan
Background: Ki67 positivity in invasive breast cancers has an inverse correlation with survival outcomes and serves as an immunohistochemical surrogate for molecular subtyping of breast cancer, particularly ER positive breast cancer. The optimal threshold of Ki67 in both settings, however, remains elusive. We use computer assisted image analysis (CAIA) to determine the optimal threshold for Ki67 in predicting survival outcomes and differentiating luminal B from luminal A breast cancers...
February 20, 2018: Oncotarget
Fernanda Ramos-Gomes, Julia Bode, Alyona Sukhanova, Svetlana V Bozrova, Mara Saccomano, Miso Mitkovski, Julia Eva Krueger, Anja K Wege, Walter Stuehmer, Pavel S Samokhvalov, Daniel Baty, Patrick Chames, Igor Nabiev, Frauke Alves
Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single- and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA)...
March 15, 2018: Scientific Reports
Volkmar Müller, Michael Clemens, Jacek Jassem, Nedal Al-Sakaff, Petra Auclair, Eveline Nüesch, Debbie Holloway, Mona Shing, Yung-Jue Bang
BACKGROUND: Trastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively)...
March 15, 2018: BMC Cancer
Michael Untch, Gunter von Minckwitz, Bernd Gerber, Christian Schem, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Sibylle Loibl
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308)...
March 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Kelly Kyker-Snowman, Bracha Erlanger Avigdor, Mansoor Nasim, Ashley Cimino-Mathews, Sarah J Wheelan, Pedram Argani, Ben Ho Park
BACKGROUND/PURPOSE: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative...
March 15, 2018: Breast Cancer Research and Treatment
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