Alvaro Macieira-Coelho is a Research Director at the French National Institute of Health. He received a MD from the University of Lisbon, Portugal, and a PhD from the University of Uppsala Sweden. He did an internship at the University Hospital in Lisbon and was a Research Associate at the Wistar Institute in Philadelphia (USA) and at the Department of Cell Biology of the University of Uppsala (Sweden). He became the Head of the Department of Cell Pathology at the Cancer Institute in Villejuif (France) and was a Visiting Professor at the University of Linkoping (Sweden). He has published 150 papers in professional journals and 9 books on Cancer and Aging. He has received the following awards: Fritz Verzar Prize (University of Vienna, Austria), “Seeds of Science”, Career Prize (Lisbon, Portugal), Dr. Honoris Causa (University of

Linkoping, Sweden), Johananof International Visiting Professor (Institute Mario Negri, Milano, Italy).

Breast cancers have been extensively studied, which renders them quite representative of the nature of neoplastic disease. While describing the pathogenesis, one has to consider the organism as a whole, the tumor microenvironment, and the tumor cells proper. The permanent evolution of the organism from the embryonic stage up to senescence can create variable vulnerability factors for the growth of breast cancers, influenced by environmental factors. We have found that a population of fibroblasts in connective tissue has abnormal growth characteristics, which shows that the whole organism participates in the neoplastic process. This population of fibroblasts is present long before the cancer becomes apparent. Micro environmental factors such as genes expressed and factors secreted by stromal cells also influence tumor growth. Gene expression by tumor cells shows that breast cancers are not a single disease and constitute a group of molecularly distinct neoplastic disorders.

Finally, during senescence the incidence of breast cancers declines due to tissue, cellular and molecular modifications occurring

in the organism during the last developmental stage of the human life span.

Liane Deligdisch has graduated from the Carol Davila University of Medicine and Pharmacy, Romania and is trained in Obstetrics-Gynecology and Pathology in Israel. She was a Resident in Pathology at the Boston Free Hospital for Women (Harvard Medical School), Visiting Professor at Magee Women's Hospital, Pittsburgh and was a Fellow in Perinatal Pathology at the Mount Sinai School of Medicine, New York. Currently, she is a Professor of Pathology and Obstetrics-Gynecology at the Mount Sinai School of Medicine, New York, USA. She founded the Division of Gynecologic Pathology and the Course of Gynecologic Pathology at the Mount Sinai School of Medicine. She is a Member of the French National Academy of Medicine, has authored 145 articles in peer-reviewed journals and has also edited 7 textbooks.

The endometrial tissue is exquisitely sensitive to steroid sex hormones and able to modify structures and functions with

promptness and versatility. Hormonal-induced changes occur physiologically during menstrual cycles and menopause and pathologically may result in dysfunctional fertility and abnormal growth ranging from hyperplasia to carcinoma. Hormone therapy is used by women of all ages, including oral contraceptives and ovulation stimulation for premenopausal women, hormone replacement therapy for postmenopausal women and adjuvant therapy for breast and uterine cancer. The most commonly used hormones are Estrogen (E) and Progesterone (P), normally present and responsible for reproductive functions in premenopausal women. Prolonged and unopposed E may result in abnormal proliferation and neoplasms often seen in patients with metabolic abnormalities (obesity, diabetes) and polycystic ovarian disease that can be reverted with hormonal therapy. Endometrial cancer (EC), the most common gynecologic cancer in the USA and in most industrialized countries associated with hyperestrogenism ,Type I, has often a better outlook than "independent" (from hormones),Type II EC seen in older postmenopausal patients: this was seen in studies of E and P Receptor studies correlated with the the degree of severity of the EC. Tamoxifen a non-steroidal synthetic triethylene estrogene derivative is successfully used in Breast Cancer due to

its antiestrogenic effect on breast tissue; on the Endometrium it can have an agonist estrogen effect in elderly patients who may develop polyps and cancer as shown by this author and team in the largest series (700 cases) published. While hormonal effect is the most common known etiologic factor in EC a possible cofactor has been recently been demonstrated by this team: Human Mammary Tumor Virus (HMTV) identified in 23,3 % of EC containing env gene sequences absent in all control benign endometrial tissue.

Tatiana Massarrah obtained her degree in Nursing at Pontifical University of Salamanca, Salus Infirmorum Nursing School in 1991. Her professional career has developed as a Clinical Nurse in Oncology department, in its various areas, Medical Oncology, Palliative Care and Oncohematology and Bone Marrow Transplantation. Currently, she

coordinates the Oncology Research Unit in Medical Oncology department. Advisory and training patients in drugs side effects, adverse events management and care are the area of her job development as part of the Clinical Research Unit Team.

Clinical research in oncology means walking through the future in cancer treatment and care. Oncology nursing has acquired over the years expertise in cancer care, detecting and helping in the management of adverse events (AE) as well as participating in the field of advisory and advocating for cancer patients. Main objectives in oncology clinical trials are safety and efficacy, accomplishing regulatory rules and principles of Good Clinical Practice (GCP). New research pathways reveal new treatments, new toxicities and new standards of care. Informing and educating patients and care givers in the environment of clinical research is the principal reason to design an Oncology Clinical Research Nurse Consulting (OCRNC). Improving treatment compliance, training patients and care givers how to report side effects or any AE and how to manage them, are target for the OCRNC. In addition, the information received from patients, description of AE and the concomitant medication registry will be necessary for medical investigators to grade events and relate them to the study drug or not. The purpose of

this communication is to highlight the importance of the work of the oncology nurse in the clinical research setting and his/her role in informing and educating patients to preserve safety, adherence and compliance under the GCP rules. Oncology patients are part involved in the treatment decision making and a well-performed clinical trial is a way to honor their altruistic and voluntary contribution to the development of treatments and the progress of medicine and the society in general. Quality of data in clinical research requires not only a rigorous physical patient assessment, also a careful and empathic listening of both social and emotional issues, giving crucial information for final results of the study. Patients will be the main source of information in the clinical research context.

Sherry A Bradford has attended undergraduate school at SUNY at Buffalo and has done her PhD in Biochemistry from the University of Buffalo. During her clinical laboratory vocation, she was solicited by the Chief of Surgery at Millard Fillmore Hospital, Buffalo, NY, to direct the Surgical Research Laboratory. She was awarded for Excellence in Research by the American Federation for Clinical Research, and for the Excellence in Research – SUNY at Buffalo. Currently, she sits on the Editorial Board of many reputed national and international journals and has authored and co-authored a number of scientific peer-reviewed manuscripts. She is also a member of many professional organizations including: International Metabolic Cancer Group, AACR, ASCO and GLIFCA.

Despite significant increase in the number of women surviving breast cancer, there still exist a large number of women who die each year despite treatment. It remains a challenging disease to treat, in part, due to the heterogeneity of the malady. It is widely accepted that breast cancer is a highly heterogeneous disease and that subpopulations of cells within a single tumor can exhibit distinct genomic, protein and metabolic profiles. These profound complex profiles result in perspicacious and variable phenotypic cellular portraits. Furthermore, tumor cells experience a range of microenvironmental cues, which would in turn, translate into a range of phenotypic manifestations, contributing to morphologically dissimilar cellular lineages and tissues, within the tumor milieu. Thus, interactions of tumor cells with their microenvironment mutually shape tumor behavior and phenotype. Likewise, plasticity of tumor cell phenotypes would necessarily also influence the apoptotic and autophagic responses. The clinical relevance is that this disparate and divergent heterogenicity contributes significantly to the efficacy of drug therapy and therefore imparts considerable inter-individual variation in pharmacotherapy and clinical response to a myriad of agents. Accordingly, this tumor intra-/inter- incongruence in breast cancer patients, underscores the necessity to

personalize therapeutic regimens favoring more personalized patient care throughout monitoring disease progression, relapse and remission states. Our lab briefly delineates a reliable in-vitro test that employs a more scientific and logical approach to identify drug(s) and drug combinations that may be efficacious against a specific patient’s tumor in-vivo. The patient’s own tumor mass is fully disaggregated and as such, all cells (microenvironment) that compose the tumor are subjected to cytotoxic/cytolytic agents. The end-point is cell death (not cell-growth), which correlates to clinical outcomes of progression-free and overall survival in cancer patients. Though, the entirety our tumor studies are not shown, our studies do validate that in-vitro testing does qualify as a tool that can assist and guide oncologists to the most efficacious therapy(s) for their patients and the necessity to individualize chemotherapeutic regimes.

Aleksandar Stefanovic has completed his PhD in Medical Faculty, University of Belgrade. He is the Director of Clinic for Gynecology and Obstetrics, Clinical Center of Serbia, Belgrade, Serbia and President of Association of Gynecologist and Obstetricians of Serbia, Montenegro and Republic Srpska. He is also a Member of FIGO. He has published more than 46 papers in reputed journals and has been serving as an Editorial Board Member of repute. He was invited speaker in more than 60 international congresses.

Standard surgical approach to invasive cervical cancer carries risks of unfulfilled reproductive plans and morbidity, which could influence quality of life to a greater extent. Radical trachelectomy is a fertility sparing procedure with the aim to preserve reproductive potential of the patient with unchanged oncologic outcome. The procedure can be performed by vaginal or abdominal approach. Abdominal trachelectomy offers greater radicality concerning the parametrial resection with an easier learning curve, although studies demonstrate slightly lower reproductive success. Vaginal radical trachelectomy is combined with minimally invasive lymphadenectomy (laparoscopic or robotic). The procedure is applied to patients with early-stages of cervical cancer, FIGO staged as Ia1, Ia2 and smaller Ib1 tumours. Since the procedure is combined with an ex-tempore hystologic analysis, organization and experience of team is of crucial importance. Oncologic outcome is excellent and comparable to standard procedure. Fertility rates are between 40 and 70%, with an increased rate of pregnancies achieved by assisted reproductive procedures (about 1/3). The rate of pregnancy complication is higher, and include increased rates of abortions, preterm deliveries, chorioamnionitis and cesarean sections. In an attempt to further decrease morbidity and to optimize reproductive outcome, some institutions perform less radical approaches – conisation or amputation of cervix, precedeed by pelvic lympadenectomy. Novel approaches include sentinel node biopsies and neoadjuvant chemotherapy followed by fertility sparing procedures. Since the oncologic safety of these procedures is yet to be determined, for now these procedures have to be considered as experimental. More studies, concerning the safety of above mentioned procedures, are needed, before they can fully be utilized in routine practice.