Targeting RANKL in breast cancer: bone metastasis and beyond.

In breast cancer, RANK ligand (RANKL) appears to play an important role in the process of chemotaxis between circulating tumor cells and the bone microenvironment, which enables RANK-expressing breast cancer cells to migrate into the bone. Mounting clinical evidence has further demonstrated that the anti-RANKL monoclonal antibody; denosumab is the most effective approach in the prevention of skeletal-related events. On the other hand, inhibiting RANKL in preclinical models, not only reduced breast cancer formation but also decreased the development of lung metastases, suggesting RANKL as a novel target for breast cancer chemoprevention. In addition, recent data have pointed to a potential role of RANKL in the biology of breast cancer arising at a young age. Hence, RANKL emerges as a key molecule, not only in the field of breast cancer bone metastasis but also in the biology of breast cancer as a whole.info:eu-repo/semantics/publishe

Breast cancer arising at a young age: do we need to define a cut-off?

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Potential Therapeutic Targets in Triple Negative Breast Cancer

Triple negative breast cancers (TNBC) are often described as biologically aggressive tumors, with poorer survival compared to other breast cancer subtypes. The fact that TNBC lacks an obvious target like estrogen receptor and HER2 represents a major challenge in the management of these patients. Genomic analyses have revealed that TNBC comprises a diverse group of cancers, which have distinct molecular profiles and different prognosis. These studies also highlighted molecular aberrations that could serve as potential treatment targets. On the other hand, a high percentage of TNBCs express some important surface receptors that have been already exploited in the development of promising targeted therapies, which are currently tested in clinical trials. In this review, we will provide an overview on the molecular diversity of TNBC with special emphasis on the evolving role of some potential biomarkers that may be utilized in the near future.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Has the time come for genomic tests to guide the use of adjuvant chemotherapy in node-positive breast cancer?

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Managing cancer during pregnancy

This book provides hands-on information on how to manage pregnant cancer patients in clinical practice. In this context a multidisciplinary perspective is essential, and contributions are accordingly presented from experts in surgical management, medical oncology, radiotherapy, pharmacokinetics, obstetric care, psychological care, neonatal and pediatric care. In addition a series of chapters focused on management in particular disease settings are presented, including breast cancer, melanoma, cervical cancer, ovarian tumors, lymphoma, leukemia, and thoracic cancers. The book reflects the major progress that has been achieved in the care of pregnant cancer patients in the recent years as important data have become available on patient management, and fetal safety in addition to valuable preclinical research on the impact of pregnancy on pharmacokinetics of anti-cancer agents. Edited and authored by worldwide leaders in the field, it will serve as a valuable resource not only for oncologists but also for obstetricians, gynecologists, neonatologists, and pediatricians caring for pregnant cancer patients and their newborns.SCOPUS: bk.binfo:eu-repo/semantics/publishe

Cancer du sein chez la jeune femme: impact de la grossesse sur la biologie et le résultats.

In this work, we found that proliferation-related prognostic gene signatures could aid treatment decision-making independent of age. This is clinically relevant for the younger breast cancer population given the potential long-term side effects of adjuvant systemic chemotherapy and hence the need to identify patients who are less likely to benefit adjuvant chemotherapy. In addition, it was clear that young age at diagnosis adds extra biological complexity, which is independent of differences in breast cancer subtype distribution. This includes enrichment with known breast cancer targets like RANKL. Whilst these results require further validation, either experimentally or in other clinical data sets, it suggests that separate therapeutic approaches may need to be specifically designed in order to improve outcomes for breast cancer arising in young women. In this regard, and based on our results and supportive evidence from other studies, we initiated a proof-of-concept prospective phase II neoadjuvant study investigating the role of denosumab, a RANKL inhibitor on modulating tumor biology in young premenopausal breast cancer patients. We found that diagnosis during pregnancy does not significantly influence the classic pathological features or the prevalence of breast cancer subtypes. We also did not find obvious differences in the distribution of PIK3CA mutations. However, we found that tumors diagnosed during pregnancy have activated serotonin receptor signaling and high expression of potential breast cancer targets; of particular interest IGF1, and PDL1. Such differences appeared to be reflected in the normal pregnant breast underscoring the potential role of the pregnant breast microenvironment on the tumor transcriptome. We were not able to associate these genes with prognosis, which could be partly due to lack of statistical power. Of note, we cannot confirm whether any of these aberrations are key drivers of the biology of tumors diagnosed during pregnancy. Nevertheless, this remains the first study to look into the biology of this relatively rare disease and hence we believe it would serve as a very valuable resource for future research in this field. We are planning to perform targeted gene sequencing to further refine our understanding of the potential effect of pregnancy on the biology of these tumors. In the last part of this work addressing the safety of pregnancy following breast cancer diagnosis, we identified that available studies suffered major limitations related to study design including selection bias and lack of information on patients with history of an ER-positive disease. This has resulted in advising against pregnancy in women with prior history of breast cancer. Our subsequent study has robustly addressed most of the limitations in older studies and clearly showed that pregnancy following breast cancer is safe even in women with a history of ER-positive disease. Hence, this study would provide a very important resource for the oncology community, which would aid adequate fertility counseling for young breast cancer survivors. This work is currently serving as the basis for a new prospective study by the IBCSG to test the safety of early interruption of tamoxifen in young women with early breast cancer seeking subsequent pregnancy. Doctorat en Sciences biomédicales et pharmaceutiquesinfo:eu-repo/semantics/nonPublishe

Clinical development of new formulations of cytotoxics in solid tumors.

To discuss the clinical development of new formulations of old cytotoxic agents and highlight the value of adopting this strategy.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Breast cancer in young women - Special Issue.

info:eu-repo/semantics/publishe

Managing pregnancy-associated breast cancer: Is more really better?

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Understanding the factors associated with the surgical management of early breast cancer.

info:eu-repo/semantics/publishe