Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer

Background: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. Methods: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab. Results: NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls; further- more, NRG1 and Gal-3 were significantly increased after chemotherapy and were predictive of mortality at 1 year. Conclusions: Circulating NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes for breast cancer patients

Metronomic chemotherapy preserves quality of life ensuring efficacy in elderly advanced non small cell lung cancer patients

Metastatic non small cell lung cancers (NSCLC) are diseases with poor prognosis and platinum-based doublet chemotherapy still remains their standard cure. Elderly patients often present comorbidities that limit the utilization of this chemotherapy; therefore these patients should have a first-line treatment with low toxicity and capable to preserve the quality of life (QoL) but, at the same time, to ensure the best possible response. Furthermore, a first-line treatment allows patients to be fit for further treatments, prolonging overall survival. At this regard, metronomic chemotherapy can be an optimal choice for elderly, able to improve QoL and to obtain an optimal palliation. We retrospectively studied a cohort of 41 elderly advanced NSCLC patients with different histotypes, treated with metronomic chemotherapy (weekly carbo-paclitaxel or vinorelbine as single agent) as first choice and we analyzed the tolerability, the impact on QoL and the efficacy of these schedules: no toxicity of 3 and 4 grade was observed, together to a clinical benefit of 43%. We administered FACT-L test to evaluate QoL at baseline and after 4 months and found a significant improvement in all FACT-L parameters: physical, social, emotional and functional, confirming a QoL improvement. At a median follow-up of 20.2 months the progression free survival was of 6 months and the overall survival was of 15 months. These results suggest that metronomic chemotherapy can be an effective choice of treatment for elderly NSCLC patients and further trials with more patients are needed to confirm this proposal

Synchronous primary papillary breast cancer, medullary thyroid carcinoma and neuroendocrine tumor in postmenopausal woman.

Multiple endocrine neoplasia are syndromes involving two or more endocrine tissues, often correlated to RET proto-oncogene mutations. We herein present the first reported case of a 57-years-old woman with three synchronous primary cancers of breast (papillary), thyroid (medullary) and pancreas (neuroendocrine), the latter with liver metastasis. The patient first underwent surgery for papillary breast cancer with axillary lymph nodes metastases. A staging whole body computerized tomography (CT) showed a right lateral cervical lymph node, pancreatic inhomogeneity, peri-pancreatic nodes and a single liver metastasis. The poor response to an antracycline and taxane-based chemotherapy, the good performance status of patient, and associated symptoms, suggested a different origin for pancreatic and hepatic lesions. A careful re-evaluation of clinical history, an octreotide-labeled scan and an immunohistochemical analysis, on both hepatic and pancreatic tissues and on laterocervical lymph node, determined the diagnosis of synchronous papillary breast cancer, pancreatic neuroendocrine tumor (pNET) with liver metastasis and an occult medullary thyroid carcinoma in a patient who had proto-oncogene RET wild type

Are we ready to change clinical practice after the 'soft and text' results?

Luminal breast cancer is the most common subtype among molecular subgroups of breast cancer identified by gene profiling, and it accounts for more than half of all breast cancer cases around the world [1]. These cancers are characterized by hormonal receptors and low proliferative activity; in particular Luminal A (high rate of estrogen and progesterone receptors, low proliferative index, low grading) is the breast cancer type with the best prognosis, while Luminal B can be further subclassified into two phenotypes, depending of the expression of HER2 (Luminal B HER2 positive or Luminal B HER2 negative). Luminal B is characterized by low rate of estrogen and progesterone receptors and high proliferative index. The breast cancer incidence has increased in the last years, especially among younger women. The treatment of premenopausal women involves all the problems correlated to fertility preservation, an important issue for every woman affected by cancer [2]. The gold standard treatment for premenopausal women with hormone receptors positive early breast cancer is tamoxifen for 5 years, with or without ovarian suppression, which has demonstrated a significant effect on overall survival and in the reduction of relapses [3]. However, the association of ovarian suppression with aromatase inhibitors has emerged as a valid alternative in the adjuvant setting for premenopausal patients. The Phase III Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials conducted by the International Breast Cancer Study Group (IBCSG) in collaboration with the Breast International Group (BIG) and the North American Breast Cancer Group (NABCG), involved 4690 patients in 27 countries across 6 continents [4]. These researches demonstrated, for the first time, the superiority of exemestane in combination with the gonadotropin-releasing hormone analogue (GnRH-A) triptorelin, over tamoxifen plus ovarian suppression in the prevention of recurrence in young premenopausal women with hormone-sensitive early-stage breast cancer [4]. Exemestane and triptorelin treatment determined a decrease of 28% in the relative risk of developing a recurrence, with a disease-free survival at 5 years of 91.1%, compared with 87.3% in the tamoxifen group [4]. Despite the significant improvement in disease-free survival (DFS), an improvement in overall survival (OS) has not been demonstrated in the exemestane arm at a median follow-up of 5.7 years (68 months). The BIG1.98, ATAC and IES trials had previously confirmed the efficacy of aromatase inhibitors compared with tamoxifen in the adjuvant treatment of postmenopausal women in terms of risk of recurrence (range 15-25%) and distant metastases (around 27%) [5-7] and increased DFS, although no significant change in the OS and a small increase in cardiovascular risk were evidenced [5]

On and off metronomic oral vinorelbine in elderly women with advanced breast cancer

background: Elderly patients with metastatic breast cancer (MBC) have more problems receiving chemotherapy than younger patients, especially with the presence of multiple comorbidities, adverse drug events and function- al decline. Low-dose oral administration of cytotoxic agents such as vinorelbine, a semisynthetic vinca alkaloid that interferes with microtubule assembly, leading to arrest of cell division, is usually effective and well tolerated. Methods: From February 2010 to February 2014, 32 patients with MBC, median age 76 years (range 69-83) were treated with oral vinorelbine 30 mg (total dose), one day on and one day off, until disease progression or unac- ceptable toxicity levels were reported. Toxicity, quality of life and clinical benefit were evaluated. Matched t-tests were conducted to discern whether quality-of-life indicator (p<0.05 was considered significant) differed before and 6 months after treatment. Statistical analysis was performed using Graph Pad Prism 5.0 (GraphPad Software Inc., San Diego, CA, USA). Results: No grade 3 and 4 adverse events were reported. A clinical benefit of 50% was found in our cohort. On and off metronomic vinorelbine oral administration resulted in good tolerability and safe profile in our selected elderly population, and improved patient adherence to therapy. conclusions: The present study demonstrated that metronomic vinorelbine might be a potential treatment in elderly patients by reducing adverse effects and increasing quality of life, setting the stage for future extensive clinical trials

Taxane induced neuropathy in patients affected by breast cancer: literature review

Taxane induced neuropathy (TIN) is the most limiting side effect of taxane based chemotherapy, relative to the majority of breast cancer patients undergoing therapy with both docetaxel and paclitaxel. The symptoms begin symmetrically from the toes, because the tips of the longest nerves are affected for first. The patients report sensory symptoms such as paresthesia, dysesthesia, numbness, electric shock-like sensation, motor impairment and neuropathic pain. There is a great inter-individual variability among breast cancer women treated with taxanes, in fact 20-30% of them don't develop neurotoxicity. Actually, there is no standard therapy for TIN, although many medications, antioxidants and natural substances have been tested in vitro and in vivo. We will summarize all most recent literature data on TIN prevention and treatment, in order to reach an improvement in TIN management. Further studies are needed to evaluate new therapies that restore neuronal function and improve life quality of patients

Elderly woman with triple-negative metastatic breast cancer successfully treated with metronomic capecitabine.

Triple-negative breast cancer phenotype (estrogen receptor-, progesterone receptor- and human epidermal growth receptor 2-negative) is one of the most aggressive molecular subtypes, accounting for 15-20% of all breast tumors. There is no standard treatment for this setting of patients except anthracyclines and taxanes, but not all elderly patients can tolerate these kinds of agents. We describe the case of an elderly woman affected by triple-negative breast cancer with bone and brain metastases who has been treated for five years with metronomic capecitabine. At the moment, the patient has stable disease and enjoys good quality of life. She had initially been diagnosed with a poor Karnofsky index, which has actually improved from 50 to 90. Metronomic capecitabine treatment has clearly improved her quality of life, as documented by the results of the Functional Assessment of Cancer Therapy Breast. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.Triple-negative breast cancer phenotype (estrogen receptor-, progesterone receptor- and human epidermal growth receptor 2-negative) is one of the most aggressive molecular subtypes, accounting for 15-20% of all breast tumors. There is no standard treatment for this setting of patients except anthracyclines and taxanes, but not all elderly patients can tolerate these kinds of agents. We describe the case of an elderly woman affected by triple-negative breast cancer with bone and brain metastases who has been treated for five years with metronomic capecitabine. At the moment, the patient has stable disease and enjoys good quality of life. She had initially been diagnosed with a poor Karnofsky index, which has actually improved from 50 to 90. Metronomic capecitabine treatment has clearly improved her quality of life, as documented by the results of the Functional Assessment of Cancer Therapy Breast. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved

Metastasis to the Pancreas from Breast Cancer: Difficulties in Diagnosis and Controversies in Treatment

Background: Metastasis to the pancreas originating from malignant tumours is a rare event and, in the literature, we have found only 11 reported cases of solitary pancreatic metastases originating from breast cancer. Case Report: We report a case of a 51-year-old woman with primary breast cancer who developed obstructive jaundice and epigastric pain after 2 years without any symptoms. The pancreatic mass revealed by computed tomography (CT) scan and magnetic resonance imaging (MRI) was not recognised as a metastasis from breast cancer and the patient underwent cephalic pancreaticoduodenectomy. Conclusions: We discuss all aspects of the case management, stressing the importance of a careful evaluation of the clinical history and the primary cancer features and the usefulness of a multi-disciplinary approach. These aspects are of main importance for a correct diagnostic process and an appropriate therapeutic choice when a pancreatic lesion develops in a patient with prior neoplasm

Prevention of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates

Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption and are widely used in the treatment of bone metastases. Osteonecrosis of the jaw (ONJ) is the worst side-effect related to BP use. At our Center, we have implemented internal guidelines regarding the management of patients with bone metastases from solid tumors. Our analysis includes 200 patients affected by solid tumors with bone metastases who received zoledronic acid. They underwent a baseline mouth assessment to evaluate their dental conditions and to perform dental care; a dental follow-up was performed every six months. All patients received calcium and vitamin D daily. Dental examination and application of preventive measures led to a total reduction in ONJ in our patients treated with zoledronic acid. The keystone in management of ONJ is prevention, and the risk of developing ONJ during treatment with zoledronic acid is reduced by implementing preventive measures