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Breast Cancer: Targets and Therapy

Marta Venturelli, Giorgia Guaitoli, Claudia Omarini, Luca Moscetti
Endocrine treatment represents the cornerstone of endocrine-sensitive premenopausal early breast cancer. The estrogen blockade plays a leading role in the therapeutic management of hormone receptor-positive breast cancer together with surgery, radiotherapy, and selective antiestrogen treatments. For several years, selective estrogen receptor modulators, such as tamoxifen, have represented the mainstay of therapy. The role of amenorrhea has been extensively elucidated in the past year: the benefit observed with chemotherapy-induced amenorrhea has strengthened its therapeutic role...
2018: Breast Cancer: Targets and Therapy
Joshua R Niska, Sameer R Keole, Barbara A Pockaj, Michele Y Halyard, Samir H Patel, Donald W Northfelt, Richard J Gray, Nabil Wasif, Carlos E Vargas, William W Wong
Background: Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT...
2018: Breast Cancer: Targets and Therapy
Carmen Criscitiello, Giulia Viale, Giuseppe Curigliano, Aron Goldhirsch
Alteration of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin signaling pathway is key for the growth and survival of several cancers, including breast cancer. In addition, dysregulation of PI3K signaling may contribute to resistance to several anticancer agents. PI3K inhibitors may, therefore, be effective as antineoplastic therapy. Buparlisib is a potent and highly specific oral inhibitor of the pan-class I PI3K family. Buparlisib specifically inhibits class I PIK3 in the PI3K/AKT kinase signaling pathway in an ATP-competitive manner, thus inhibiting the production of the secondary messenger phosphatidylinositol (3,4,5)-trisphosphate and activation of the PI3K signaling pathway...
2018: Breast Cancer: Targets and Therapy
Alison E Hunter-Smith, Zenon Rayter
Breast cancer is the most common cancer in women, worldwide, and 1,400 deaths per day are attributed to it. The success of national screening programs has seen breast cancers being diagnosed at an earlier stage. With conservative surgery to the breast demonstrating equivalent long-term outcomes, the last 10 years have seen a growing interest in the safety of less invasive management for the axilla in breast cancer patients. One-step nucleic acid amplification (OSNA) is a validated, reliable, and efficient tool in identifying micro- and macro-metastases intraoperatively...
2018: Breast Cancer: Targets and Therapy
Monica Szmyd, Victoria Lloyd, Kelly Hallman, Katie Aleck, Viktoria Mladenovik, Christina McKee, Mia Morse, Tyler Bedgood, Sumi Dinda
The North American plant Cimicifuga racemosa, also known as black cohosh (BC), is a herb that recently has gained attention for its hormonal effects. As the usage of hormone replacement therapy is declining due to its adverse effects in women with cancer, many are turning to herbal remedies like BC to treat menopausal symptoms. It is crucial to determine whether the effects of BC involve estrogen receptor-alpha (ERα). Previous studies from our laboratory have shown ERα to be a possible molecular target for BC...
2018: Breast Cancer: Targets and Therapy
Leopoldo Costarelli, Domenico Campagna, Alessandra Ascarelli, Francesco Cavaliere, Maria Helena Colavito, Tatiana Ponzani, Laura Broglia, Massimo La Pinta, Elena Manna, Lucio Fortunato
Background: Pleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic. Materials and methods: We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC) and 574 cases of high-grade invasive ductal carcinoma (HG-IDC). We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment...
2017: Breast Cancer: Targets and Therapy
Dumessa Edessa, Mekonnen Sisay
In normal cell cycle progression, transition of G0/G1 phase to synthesis (S) phase for breast and other cells is regulated by association of cyclin D and cyclin-dependent kinases 4 and 6 (CDK4/6) that leads to phosphorylation of retinoblastoma (Rb) protein. Imbalance of this cyclin D-CDK4/6-inhibitors of CDK4/6-Rb phosphorylation pathway is associated with tumorigenesis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Despite effective first-line endocrine therapy, HR+/HER2- metastatic breast cancers remain still incurable...
2017: Breast Cancer: Targets and Therapy
Renae D Van Wyhe, Omar M Rahal, Wendy A Woodward
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are medications that have been used for decades to lower cholesterol and to prevent or treat cardiovascular diseases. Since their approval by the US Food and Drug Administration in the 1980s, other potential uses for statins have been speculated on and explored. Basic science and clinical research suggest that statins are also effective in the management of breast cancer. Specifically, in various breast cancer cell lines, statins increase apoptosis and radiosensitivity, inhibit proliferation and invasion, and decrease the metastatic dissemination of tumors...
2017: Breast Cancer: Targets and Therapy
Sophie Seité, René-Jean Bensadoun, Jean-Michel Mazer
More than half the number of patients with cancer, who are treated with radiotherapy, will have radiodermatitis at some point during their treatment. Radiodermatitis either occurs early on in the treatment period or appears months or up to several years later. Acute radiodermatitis is a burn injury that varies in severity according to both treatment and inherent patient factors. Most acute radiodermatitis reactions resolve after several weeks but some reactions persist and can cause complications. Late-onset radiodermatitis is characterized by telangiectasia that forms on atrophic and fragile skin...
2017: Breast Cancer: Targets and Therapy
Nelson Rangel, Victoria E Villegas, Milena Rondón-Lagos
One area of great importance in breast cancer (BC) research is the study of gene expression regulated by both estrogenic and antiestrogenic agents. Although many studies have been performed in this area, most of them have only addressed the effects of 17β-estradiol (E2) and tamoxifen (TAM) on MCF7 cells. This study aimed to determine the effect of low doses of E2 and TAM on the expression levels of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC cell lines differentially expressing estrogen receptor (ER) α and HER2 (MCF7, T47D, BT474, and SKBR3)...
2017: Breast Cancer: Targets and Therapy
Sacha J Howell, Kimberley Hockenhull, Zena Salih, D Gareth Evans
Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by mutation/deletion of the NF1 gene. The gene product, neurofibromin, is a tumor suppressor which represses the activity of the Ras oncogene. Central nervous system (CNS) tumors have long been associated with NF1, but their association with several other malignancies has been demonstrated. In this review, we summarize the epidemiological data that irrefutably support a link between NF1 and an increased risk of early-onset breast cancer, to levels at which annual mammography is currently recommended in national high-risk screening programs...
2017: Breast Cancer: Targets and Therapy
Esther Jennifer Campbell, Laszlo Romics
Oncoplastic breast conservation surgery (OBCS) is increasingly becoming part of routine breast cancer surgical management. OBCS may be viewed as an extension of standard breast conservation surgery for resecting tumors of larger sizes without compromising on cosmetic outcome, or as an alternative to mastectomy. High quality evidence to support the oncological safety and benefits of OBCS is lacking. This review will focus on the best available level of evidence and address key issues regarding oncological safety in OBCS, such as tumor resection margins and re-excision rates, local recurrence and patient outcome, postoperative complications and adjuvant therapy delivery, and briefly discuss cosmetic outcome in OBCS...
2017: Breast Cancer: Targets and Therapy
Elyse E Lower, Shagufta Khan, Diane Kennedy, Robert P Baughman
BACKGROUND: Hormone receptor and HER-2/neu discordance between the primary lesion and first metastasis has been reported. This study was performed to determine further biomarker discordance rates between the first and subsequent metastatic breast cancer lesions. METHODS: We performed a retrospective review of paired biomarkers from primary breast cancers compared to first reported and subsequent metastases from 103 patients with breast cancer. The estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status were reported at all three time points...
2017: Breast Cancer: Targets and Therapy
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
Yayun Liang, Sandy Goyette, Salman M Hyder
Clinical trials and studies have shown that postmenopausal women undergoing combination hormone replacement therapy containing estrogen and progestin have an increased risk of breast cancer compared with women taking estrogen or placebo alone. Using animal models, we have previously shown that synthetic progestins, including medroxyprogesterone acetate (MPA), which is widely used clinically, accelerate breast cancer tumor growth and promote metastasis. Furthermore, we have found that MPA elevates CD44 protein expression and aldehyde dehydrogenase (ALDH) activity, two markers of cancer stem cells (CSCs), and increases mammosphere formation, another hallmark of stem cells, in hormone-dependent T47-D human breast cancer cells...
2017: Breast Cancer: Targets and Therapy
Paola Arnaboldi, Silvia Riva, Chiara Crico, Gabriella Pravettoni
Stress has been extensively studied as a psychosomatic factor associated with breast cancer. This study aims to review the prevalence of post-traumatic stress disorder (PTSD), its associated risk factors, the role of predicting factors for its early diagnosis/prevention, the implications for co-treatment, and the potential links by which stress could impact cancer risk, by closely examining the literature on breast cancer survivors. The authors systematically reviewed studies published from 2002 to 2016 pertaining to PTSD, breast cancer and PTSD, and breast cancer and stress...
2017: Breast Cancer: Targets and Therapy
Roberta Piva, Flavia Ticconi, Valentina Ceriani, Federica Scalorbi, Francesco Fiz, Selene Capitanio, Matteo Bauckneht, Giuseppe Cittadini, Gianmario Sambuceti, Silvia Morbelli
In the last decades, in addition to conventional imaging techniques and magnetic resonance imaging (MRI), (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has been shown to be relevant in the detection and management of breast cancer recurrence in doubtful cases in selected groups of patients. While there are no conclusive data indicating that imaging tests, including FDG PET/CT, produce a survival benefit in asymptomatic patients, FDG PET/CT can be useful for identifying the site of relapse when traditional imaging methods are equivocal or conflicting and for identifying or confirming isolated loco-regional relapse or isolated metastatic lesions...
2017: Breast Cancer: Targets and Therapy
Yilin Hou, Man Zhou, Jing Xie, Ping Chao, Qiyu Feng, Jun Wu
Hyperglycemia or diabetes mellitus (DM), which is characterized by high blood glucose levels, has been linked to an increased risk of cancer for years. However, the underlying molecular mechanisms of the pathophysiological link are not yet fully understood. In this study, we demonstrate that high glucose levels promote the proliferation of breast cancer cells by stimulating epidermal growth factor receptor (EGFR) activation and the Rho family GTPase Rac1 and Cdc42 mediate the corresponding signaling induced by high glucose levels...
2017: Breast Cancer: Targets and Therapy
João Marcos de Azevedo Delou, Giselle Maria Vignal, Vanessa Índio-do-Brasil, Maria Theresa de Souza Accioly, Taiana Sousa Lopes da Silva, Diogo Nascimento Piranda, Marcelo Sobral-Leite, Marcelo Alex de Carvalho, Márcia Alves Marques Capella, Rosane Vianna-Jorge
ABCB1 gene encodes an adenosine 5'-triphosphate-binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, ABCB1 expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of ABCB1 in breast tumors as a function of genetic, clinical, and histopathological variables...
2017: Breast Cancer: Targets and Therapy
Alissar El Chediak, Raafat S Alameddine, Ayman Hakim, Lara Hilal, Sarah Abdel Massih, Lana Hamieh, Deborah Mukherji, Sally Temraz, Maya Charafeddine, Ali Shamseddine
BACKGROUND: Several retrospective studies have reported that younger age at presentation is associated with a worse prognosis for nonmetastatic breast cancer patients. In this study, we prospectively assessed the association between different baseline characteristics (age, tumor characteristics, mode of treatment, etc) and outcomes among newly diagnosed nonmetastatic Lebanese breast cancer patients. METHODS: We recruited a sample of 123 women newly diagnosed with nonmetastatic breast cancer presenting to American University of Beirut Medical Center...
2017: Breast Cancer: Targets and Therapy
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