Endocrine therapy remains a mainstay in the treatment of endocrine-sensitive breast cancer. In the adjuvant setting, 5 years of endocrine therapy significantly reduces recurrence rate and mortality. Tamoxifen is the molecule of choice for premenopausal women, whereas for postmenopausal women aromatase inhibitors are currently part of the standard treatment. Endocrine therapy can induce side effects, which can affect patient's quality of life and lead to premature treatment interruption. Identification and adequately addressing these side effects is fundamental to maintain good treatment compliance and therefore improve breast cancer specific outcome.

Many complementary and alternatives medicines are offered to patients with cancer. Among them, herbal medicines have a substantial place. These plants are mainly used to reduce adverse effects of anticancer treatments and for specific anticancer properties. Our review shows that only few clinical data support medicinal plants effectiveness in cancer patients. Arguments rely mainly on usual indications and pharmacological data for minimization of treatments toxicity while for the anticancer properties, on epidemiological and preclinical data. To inform and counsel patients and people around, healthcare professionals need to evaluate benefit-risk balance on evidence-based information. Because the medical decision should be shared with the patient, his beliefs and preferences have to be considered. When no adverse effect or drug interaction is associated with herbal medicine, we state that their use is acceptable. This paper discuss of potential risk and benefit of the most used medicinal plants by cancer patients.

Mammalian target of rapamycine (mTOR) inhibitors are being increasingly prescribed as antitumoural drugs, and associated adverse cutaneous effects are frequent but poorly described. The aim of this study was to describe such adverse effects and to assess the quality of life of patients experiencing them.

Bevacizumab (Avastin(®)) is the first antiangiogenic therapy approved in non-small cell lung cancer (NSCLC). It is also currently the only agent in this family approved in NSCLC. This review focuses on results of clinical trials assessing bevacizumab in thoracic oncology. It also provides to clinicians practical advices for its prescription.

Most anticancer agents are thought to act through direct induction of tumoral, stromal and endothelial cell death by apoptosis or necrosis. In a 2008 issue of Bulletin de l'Académie Nationale de Médecine, we described an alternative (or complementary) theory whereby the immune system participates in the antitumoral effects of some chemotherapy or radiotherapy regimens by promoting an immunogenic cell death pathway. In particular, we showed the critical importance of two pre-mortem stressors that determine the immunogenicity of dying tumor cells. The first, an ER stress response culminating in calreticuline exposure at the tumor cell surface, is mandatory for the uptake and efficient phagocytosis of apoptotic bodies by dendritic cells. In the second, autophagy leads to the release of ATP by dying tumor cells, resulting in the recruitment of inflammatory phagocytes and antigen-presenting cells, and also triggering the inflammasome that causes IL-1beta release and CD8+ T cell polarization. The tumor microenvironment changes following chemotherapy, favoring sequential accumulation of a series of innate and cognate effectors that act in a coordinated fashion to promote tumor eradication. These findings will help to identify immune predictors of the response to conventional anticancer treatments and to design innovative combinatorial immunochemotherapy regimens.

Methotrexate (MTX) is a folic acid antagonist used at high-dose intravenously on 24 hours (24h) in the treatment of the acute lymphoblastic leukemia (ALL). To prevent potential toxicity, MTX is usually administered following the application of preventive measures. We report a case of an accidental shortening time for high dose MTX infusion and a literature review of accidental intoxications by the MTX. This case illustrates the importance of the respect of MTX high dose infusion time and the major role played by the therapeutic drug monitoring.

Imatinib, an antineoplastic drug used to treat certain cancers, has many side effects such as hematologic, neurologic or cutaneous toxicity. These toxicities seem to be due to a high imatinib plasmatic concentration and are frequently controlled by a discontinuation or a dosage reduction of the drug. We report here in 2 cases of cutaneous side effects induced by imatinib in order to demonstrate the necessity of drug monitoring in such cases. In our cases, imatinib is responsible in the occurrence of these side effects. Monitoring plasma levels of imatinib allowed us to judge if levels were toxic or not and to avoid discontinuation of imatinib in some cases.

Cancer and type II diabetes are two diseases that appear to be associated. In fact, diabetes increases the incidence of several cancers (colon, endometrium, rectum and breast). Retrospective epidemiological studies show that metformin, a drug commonly used in type II diabetes, has antitumor properties. Therefore, many experimental studies (in vivo and in vitro) have been initiated in recent years to understand the cellular and molecular mechanisms that may explain the protective effects of metformin against cancer. Two main mode of action have been proposed. The first, indirect, involves the decrease of insulinemia. The second, via a direct action on cells, results in the regulation of the activated AMPK kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, which plays a central role in many cellular processes such as energy metabolism, protein synthesis, autophagy and apoptosis. Here, we review recent results concerning the antitumor action of metformin: epidemiological, metabolic, cellular and molecular levels. Ongoing experimental and clinical trials should help us better understand the mechanisms of action of metformin and allow us to determine whether the drug can be used in the treatment of cancer.

The HER2 gene or c-erb B2 or neu is amplified in 15-25% of breast cancers. This amplification is associated with an aggressive course of disease. The trastuzumab is a monoclonal antibody targeting the extracellular domain of HER2. This is the first targeted molecule designed to treat breast cancer. In the firstline metastatic disease, trastuzumab in combination with chemotherapy significantly improved survival of patients with HER2-positive disease. In the adjuvant setting, trastuzumab has been evaluated in several randomized trials.

Most targeted anticancer therapies induce dermatological toxicities that are often predominant. In particular, pigmentary changes are frequent and relatively characteristic, and they present most often as depigmentation. In this review, we describe the main pigmentary disorders observed with these new therapies, which affect the skin, hair, nails and mucous membranes. Hyperpigmentation secondary to MEK or EGFR inhibitors will be described, as well as forms of hypopigmentation specific to several tyrosine kinase inhibitors (imatinib, sunitinib and pazopanib), blue dots induced by vandetanib, and eruptive naevus triggered by RAF inhibitors. Vitiligoid reactions to CTLA4 and PD1/PD-L1 blocking agents will also be described.

Crizotinib is a small orally-administered ALK inhibitor for patients with non-small cell lung cancer with EML4-ALK rearrangement (echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase). This fusion gene is detected with a break apart fluorescence in situ hybridization (FISH) assay. Phase I to III trials have shown an interesting disease control rate and acceptable tolerability. Crizotinib is available in France under temporary use authorization. New potentially effective therapeutics in ALK-positive NSCLC are being developed.

In recent decades, reproductive surgery and medicine have entered a new era of prevention. Oocyte freezing is at the heart of this new era, along with the preservation offemale fertility. Several options are being evaluated, and time will tell which one will prove most suitable for routine use. Currently, only the freezing and transplantation of ovarian tissue seems to have entered clinical practice. Animal studies demonstrated its effectiveness, with pregnancies and births in several species. These studies showed that both slow and rapid freezing (vitrification) allows the survival of more than 80 % of primordial follicles after thawing. Similar results have since been obtained in humans. Freezing allows satisfactory follicular survival Reimplantation of frozen ovarian tissue has helped to restore menstrual cycling and, more importantly, to obtain pregnancies and births, either spontaneously or by IVF This restoration of fertility offers great hopefor female patients having to confront not only their disease but also the prospect of permanent infertility. Related research has led to major advances in biology and reproductive medicine.

Girls who undergo treatment for cancer are at risk of ovarian hormonal dysfunction and subfertility due to the detrimental effects of some chemotherapeutic agents and/or radiotherapy on the gonads. Consequently, fertility-preserving techniques shouldbe discussed before starting gonadotoxic therapy. Ovarian tissue cryopreservation is currently the only option to preserve fertility in prepubertal girls and should be considered if the risk of premature ovarian failure is high. This promising approach involves the storage of a large number of follicles, which may subsequently be transplanted or cultured to obtain mature ovocytes. The results of ovarian tissue cryopreservation in adults are encouraging: at least twenty children have been born after orthotopic autografting of frozen-thawed ovarian cortex. It has been shown twice that transplantedprepubertal ovarian tissue can induce puberty, confirming the functional capacity of frozen-thawed prepubertal ovarian tissue.

The toxicity of cancer therapies can affect all organs and tissues. Some treatments damage spermatogonial stem cells (SSCs), with a risk of infertility. Storage and reimplantation of frozen testicular tissue is a recent approach tofertilitypreservationfor young boys. However, thawed frozen prepubertal testicular tissue must undergo a maturation process to restore sperm production. This process, currently being studied in animal models, can be achieved by in vivo transplantation of SSCs into seminiferous tubules or by testicular grafting, possibly following in vitro maturation.

Numerous cytotoxic drugs used to treat childhood cancers, as well as pelvic or hypothalamo- pituitary irradiation and gonadal surgery, can affect subsequent hormonal function and fertility. Prevention of these adverse consequences is based primarily on therapeutic de-escalation when possible, and now also on gonad or gamete preservation. These patients and their parents must receive thorough information, taking into account the child's age, the proposed treatments, and the length of follow-up. Teams treating childhood cancers must receive appropriate training, and access to innovative fertility-preserving techniques must be guaranteed at the national level.

Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.

Among the 35 new molecular entities approved by the FDA in 2011, 17 were particularly notable for their significant contributions to the health of patients, including abiraterone acetate, vandetanib, belatacept and fidaxomicin. Thus, abiraterone acetate, namely Zytiga®, was included as the first in a new class of drugs to treat late-stage prostate cancer. The ability of Zytiga® to prolong survival in these patients was considered as significant because they have few other treatments options and the benefits of Zytiga® outweighed the risks of reported side-effects. Vandetanib, namely Caprelsa®, was also considered as a relevant drug since it represents the first drug approved to treat particularly aggressive medullary thyroid cancer, an orphan disease. Despite huge progress in transplantation, renal transplantation remains a serious problem since patients treated with the calcineurin inhibitors cyclosporine and tacrolimus are at high risk of developing renal injury. With longer follow-up, the novel immunosuppressant belatacept continued to show better renal function compared with a cyclosporine-based regimen, as well as a consistent safety profile and comparable efficacy. It was approved by the Food and Drug Administration in June 2011 for the prophylaxis of organ rejection in adult recipients of a kidney transplant acting by a selective T-cell costimulation blocker given as an infusion. Clostridium difficile is currently the most important cause of infectious diarrhea in the United States. Fidaxomicin, a macrolide antibiotic, was recently approved for treatment of these infections (CDIs). It could be an alternative treatment for infection with C. difficile, with similar efficacy and safety to vancomycin. Fidaxomicin has minimal activity against Bacteroides species, which may be advantageous in maintaining colonization resistance and protecting the gastrointestinal tract from colonization by C. difficile.