To determine prospectively the factors associated with reconstruction failure (i.e. requiring expander removal) and capsular contracture in patients undergoing mastectomy and immediate two-stage breast reconstruction with a tissue expander and implant, and radiotherapy for breast cancer. This is a multi-institutional prospective nonrandomized trial.

The purpose of this review is to update the reader on the impact of cancer treatment on fertility, the options of fertility preservation, and the new markers to assess ovarian function.

Colorectal cancer (CCR), which is one of the most common causes of cancer, has benefited from the major advances in the understanding of the intracellular signaling pathways implicated in the initiation, growing and local and metastasis dissemination of tumor, which have occurred during the 20 past years. The pharmacogenomics approach, especially the determination of the genetic polymorphisms, tries to find prognosis and predictive biomarkers permitting to identify patients who could benefit from a particular treatment or those exhibiting higher risks of toxicity. Among the numerous biomarkers, which have been studied, few are currently in use in clinical practice. The phenotyping of DPD and UGT1A1 activities, and to a lesser extent, its genotyping, appears as the most useful tool in terms of prediction of toxicities induced by two major drugs: 5-FU and irinotecan. For oxaliplatin, the determination of the polymorphisms of reparases and detoxification systems such as GSTpi seems interesting, but its exact place should be more defined. It is in the field of targeted therapies that the pharmacogenomics approach seems to be the more relevant. KRAS mutation is a dramatic example of single nucleotide polymorphism, which is able to identify a priori patients that could receive or not an anti-EGFR monoclonal antibody such as cetuximab or panitumumab. It is obvious that pre-clinical identification of molecular biomarkers predictive of the sensitivity of the drug targets, which subsequently implicate the selection of patients and the rational evaluation of responses, will be the cornerstone of any clinical trials concerning targeted therapies. Besides the determination of drug target polymorphisms, it is also important to consider those related to the distribution and metabolism. In this area, the determination of enzymatic activities should recover its place besides the genomic profiling.

Since the middle of 1990s, the development of combinatorial chemistry along with the high throughput screening have led to some lack of interest for natural products from the pharmaceutical industry. Moreover, purification and optimization of natural compounds are very often difficult and animal experimentations need enough supply of natural sources or alternatively need sophisticated total synthesis. In oncology, this increased disinterest was also closely connected with the rapid expansion of monoclonal antibodies and synthetic protein kinase inhibitors. However since 2005, with the approval of five new drugs by the FDA (trabectedin, ixabepilone, temsirolimus, everolimus and Vinflunine), it appears that natural products are still present as direct or indirect sources of drugs. On the other hand, a third generation of natural product has arisen, which relies upon bioengineering using genetically altered producer organisms. This is particularly true of the polyketides where bioengineering harnesses their natural flexibility to expand their structural diversity. Several programs are going on to produce antibiotics, anticancer drugs or immunosuppressant. This combinatorial approach makes drug discovery by bioengineering complementary with conventional medicinal chemistry. With the approval of Mylotarg by the FDA, increased interest has also been devoted to immunoconjugates, which represent a way by which highly cytotoxic natural products such as dolastatin, calicheamycin, duocarmycin and maytansin may be targeted to cancer cells while limiting their side-effects.

Ionizing radiation is frequently used for cancers with a curative intent for many patients. The total dose delivered on the tumour plays a major factor for locoregional control. Increasing the dose to the tumour volume is generally correlated with an increased dose to normal tissue. Dose constraints to organs at risk must be taken into account for the planning of external beam radiation. A high dose will generate more acute and late side effects. Medical doctors should record these toxicities prospectively. Registration and grading should be simple, reproducible and sensitive in order to obtain an accurate and appropriate evaluation for each organ. Several scales have been published in the literature (WHO, EORTC/RTOG, LENT-SOMA, NCI CTCAE) but none have a satisfactory level. The National Cancer Institute has proposed several version of the CTCAE and its latest version 4.0, currently appears to be the most adapted. The advantage of using only this common and universal classification will be to harmonize practices and have a common language.

Zoledronate, just as other bisphosphonates, inhibit osteoclast mediated bone resorption. This is the reason why they are used in the treatment of bone metastasis, in order to block osteolysis. Zoledronate and some other bisphosphonates (clodronate, pamidronate, ibandronate, alendronate, risédronate, minodronate) also exhibit antitumor properties in vitro. They act directly on tumor cells by blocking tumor cell adhesion, invasion and proliferation, and by inducing tumor cell apoptosis. However, their high bone mineral affinity decreases their bioavailability to a significant extent and, thus, should weaken their in vivo antitumor potential. Despite of this, several studies (most of them being performed with zoledronate) show that bisphosphonates have an in vivo antitumor activity. This review focuses on zoledronate and on results obtained in several experimental models showing that this bisphosphonate interferes with the growth of tumors and metastases which are thriving in tissues others than the skeletal tissue. The significance of these findings is discussed in the light of several ongoing clinical trials which examine the benefits of using zoledronate and other bisphosphonates in the adjuvant treatment of cancers at an early stage of the disease.

Recent progress in cancer therapy has dramatically modified the course and prognosis of some malignancies. Chemo and radiotherapy, along with newer targeted treatments, are given to control symptoms, postpone relapse, or attempt cure. However, many of these regimens are associated with adverse cardiovascular effects such as impaired left ventricular function, myocardial ischemia, hypertension, and arrhythmia. Awareness of potential cardiotoxicity is important, as it may allow practitioners to recognize early signs of cardiac complications and to adapt therapy in order to limit detrimental effects. Diagnosis of cardiovascular complications may iustify the introduction of cardiologic therapies, and may require the reassessment of risk/benefit ratios related to specific cancer therapy. Screening and follow up strategies are proposed.

Despite major progress in the understanding of biological mechanisms underlying metastatic prostate cancer, the treatment of men with advanced prostate cancer remains challenging. Several randomized controlled trials with promising or positive results are underway or just released. Here we discuss new treatments which might be used in clinic in the near future: hormonal treatments (Abiraterone and MDV3100), a new chemotherapy (Cabazitaxel), a cellular vaccine (Sipuleucel-T), anti-angiogenic drugs (Bevacizumab, Aflibercept), a new radioactive treatment (Alpharadin) and a new bone-protective agent (Deno-sumab).

The formation of new vessels (aka neo-angiogenesis) is critical for tumoral progression. Although anti-angiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway are employed since less than ten years in human patients, they are now a key player in the treatment of advanced stage malignant tumors. An endothelial syndrome, characterized by hypertension and glomerular proteinuria, complicates this treatment in roughly 25% of patients. From a pathophysiological perspective, this may be considered as a preeclampsia-like syndrome. While the most severe forms require the interruption of the regimen, this syndrome is usually mild or moderate, and should be treated by the addition of an anti-hypertensive drug.

Evaluate efficacy and safety of epoetin beta in anaemic patients receiving chemotherapy for a non-myeloid malignancy.

Bladder cancer often occurs in patients with high risk of acute toxicity under chemotherapy. So-called unfit patients are a heterogenous population, sharing a contra-indication for cisplatin and presenting either chronic renal failure, and/or elderly, and/or altered performance status, and/or severe co-morbidities. Therefore, it is necessary to develop chemotherapy protocols feasible in renal insufficient patients, and well tolerated in frail patients. The medical evaluation prior to initiate chemotherapy is of major importance to screen for chronic disorders and to anticipate the potential acute complications following chemotherapy. Chemotherapy of elderly patients with severe comorbidities is a common situation in bladder cancer, and will concern all cancer patients. The evaluation of the benefit/risk ratio of the chemotherapy protocol is a typical expertise of medical oncologists, which requires to integrate the complex links between the patient, the antitumor agent, and toxicity. The physician must also have a honest dialogue to inform, advise, listen to the patients priorities. Medical oncologists have to have in mind this situation and to adapt their clinic and their vocabulary to this emerging reality.

Direct side effects of the inhibition of activation of VEGF receptors are well known and could be easily explained (HTA). The indirect toxicity of the inhibitors of tyrosinekinases is much less known and several hypotheses appear. Usually, the common side effects of the inhibitors of tyrosine-kinases can be easily managed and are reversible when the treatment is stopped. Their management is essentially based on prevention measures. It is necessary to stop definitively or temporarily the treatment in case of intensification of pre-existing comorbidities or side effects of rank 3 or 4. There is no predictive factor of treatment toxicity and, at the moment, there is thus no indication in a previous dose adaptation.

Anti-angiogenic therapies induce an ischemic necrosis of tumoral tissue, which exposes to a risk of hemorrhagic complications. The frequency and the intensity of the symptoms may differ according to molecules and according to studies. The risk seems to be maximal with tyrosin kinase inhibitors, particularly with sunitinib, with 26% of hemorrhagic complications. In most cases, events are grade 1 or 2, severe adverse effects (grade 3 or 4) appear rarely. Intra-cerebral bleeding remains rare and seems to be observed essentially in case of cerebral metastases. The hemorrhagic risk seems to be correlated with arterial high blood pressure and concomitant thrombopenia. The management of hemorrhagic risk is essentially based on precautionary measures. For any surgical procedure, it is advised to interrupt the treatment at least 4 weeks before and 4 weeks later, in order to avoid parietal complications.

Since the discovery of the remarkable efficacy of imatinib in the metastatic GIST, several studies advanced our knowledge on the care of this pathology. In the localized GIST, the efficacy of the adjuvant treatment by imatinib was proved, but the duration, the indication and the management in case of relapse after imatinib are not still consensual. The imatinib is also used in neoadjuvant setting to optimize the quality of resection, the main treatment remaining the maximal tumor resection. In metastatic setting, imatinib remains the standard of care first-line treatment. It must be administered until progress or intolerance. Nevertheless, secondary resistance to imatinib is a substantial problem in routine clinical practice; in second line, sunitinib demonstrated its efficacy. Several inhibitors of tyrosine-kinases are ongoing evaluated in all the therapeutic lines. Clearly, a better knowledge of the molecular profile and the pharmacokinetics underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine-kinase inhibitors may allow in the near future new individualized therapeutic strategies for GIST patients.