HER2-positive breast cancer is associated with an aggressive clinical course and poor prognosis. At present, these patients may be offered targeted therapies directed against a specific molecular target, i.e. HER2 receptor. Standard agents of this class include trastuzumab (monoclonal antibody) and lapatinib (small-molecule inhibitor of HER2-receptor-associated tyrosine kinase). As estimated, about 25% of breast tumors are HER2-positive, and these patients are candidates for trastuzumab therapy. A precondition for initiation of the treatment is confirmation of overexpression of HER2 protein or amplification of HER2 gene in tumor cells. Trastuzumab administered as adjuvant treatment improves recurrence-free survival by 7% and overall survival by 3%. On the other hand, the same drug combined with chemotherapy in patients with disseminated breast cancer increases objective response rate, improves progression-free survival and overall survival as compared with chemotherapy alone. As estimated, only about 50% of HER2-positive patients obtained a clinical benefit following trastuzumab-based palliative treatment. There are several theories explaining the phenomenon of primary and secondary resistance to antibody-treatment. Patients previously undergoing with anthracycline- and taxoid-based chemotherapy, who experience recurrence or progression after trastuzumab, may benefit from administration of lapatinib, a HER1/HER2-associated small-molecule tyrosine kinase inhibitor, combined with capecitabine. Studies of novel therapeutic strategies in patients with HER2-positive breast cancer are underway, testing both new anti-HER2 antibodies (T-DM1, pertuzumab) and other small-molecule tyrosine kinase inhibitors (neratinib).
Aim of paper: Epidemiological analysis of malignant tumors developing within the female genital system in Polish population. Material and method: Data concerning incidence were obtained in the National Tumor Registry; data on mortality were obtained at the Head Statistical Bureau. Data on mortality in other European countries come from the WHO database (WHO Statistical Information System). Analysis of time trends was based on coefficients standardized with respect to global population. Results: Malignancies of the female genital system account for about 20% of malignant tumors in Polish females. Most common are: endometrial cancer (over 5000 new cases per year), ovarian cancer (about 3500) and cervical cancer (over 3100). Over the past 4 decades, we are witnessing a rapid increase of incidence of endometrial cancer and a trend towards decreasing mortality. A decline in both incidence and mortality is seen in cervical cancer. Ovarian cancer has reached stable coefficients of morbidity and mortality since about two decades. In Poland, 5-year survival indices are worse than mean values reported in most European countries. Conclusions: In the area of female genital malignancies, reduction of incidence is seen only in cervical cancer, while reduction of mortality – both in cervical and in endometrial cancer. Popularization and reorganization of national screening programs designed to early detection of malignant tumors, combined with promulgation of awareness of risk factors of carcinogenesis are fundamental to control the “tumor epidemic”.
The technique for producing monoclonal antibodies is presently quite advanced. These antibodies comprise not only murine antibodies, which block a particular receptor, but also recombinant human monoclonal antibodies which are often hybrid compounds (combined with another active antitumor substance). Since we are currently able to design monoclonal antibodies that are directed against particular receptors, the practical application of the principles of “tailored therapy” (more recently known as “personalized medicine”) is now a reality. From the point of view of gynecologic-oncologic clinical practice, however, the technique of producing monoclonal antibodies is not the key issue; of more importance is the issue of how to use this still new generation of agents for the maximum benefit of patients with genital malignancies as well as the related issue of what remains to be done in order to safely improve the overall survival rate of the patient who uses these drugs. This paper reviews the current literature devoted to the use of monoclonal antibodies in oncologic gynecology. In part I, we discuss how monoclonal antibodies, particularly bevacizumab, block the molecular mechanisms that regulate neoangiogenesis. We also seek to determine whether oncologic gynecology, like modern hemato-oncology, can continue to function without monoclonal antibodies.
Milstein and Köhler’s discovery of monoclonal antibodies has resulted in their widespread use in various fields of medicine. Monoclonal antibodies constitute a separate group of drugs that do not behave as either classic cytostatics or inhibitors of particular components of intracellular signaling pathways. Monoclonal antibodies are essentially highly specific biological agents able to block a particular receptor by showing a higher affinity for that receptor than its natural ligand. This property has been exploited in order to design monoclonal antibodies that block the receptors of the EGFR family and in order to develop drugs that block the receptors needed for the transmission of the signal controlling the activity of the host immune system. The next step in increasing the clinical use of monoclonal antibodies is the creation of hybrid drugs. The base for this kind of drug is an active substance with strong cytotoxic properties for which the monoclonal antibody serves as a carrier. While in the first part of this paper we reviewed the current literature on the use of monoclonal antibodies in oncologic gynecology, in this second part, we discuss monoclonal antibodies that block the molecular mechanisms involved in the regulation of the response of the immune system and signal the pathway associated with the EGFR receptor. We ask whether the time has not arrived when oncologic gynecology, like hemato-oncology, can no longer function without monoclonal antibodies.
Endometriosis is a benign proliferative process, where tissues of the uterine mucosa are present ectopically, generally manifesting by infertility and pain. Awareness of similarity between endometriosis and neoplastic process, as well as of oncological risk associated therewith is low. Since 1925, when Sampson was the first to highlight the fact that endometriosis may transform into a malignant lesion, several papers appeared in the medical literature extensively documenting the correlation between endometriosis and tumors, in particular with ovarian cancer. The aim of this paper was to examine correlations linking endometriosis with the neoplastic process by reviewing medical literature published in English in the aspect of epidemiological evidence of endometriosis – cancer correlation, comparison of clinical-pathological features of both entities and comparison of molecular and genetic features of endometriosis with the “cancer phenotype” as defined by Hanahan and Weinberg in their paper The hallmarks of cancer. A large body of evidence has been collected documenting similarity of endometriosis to the neoplastic process, its association with malignant transformation and increased risk of cancer and other malignant tumors. It is not clear, whether endometriotic lesions may undergo malignant transformation directly, indirectly with an intermediate phase, the so-called atypical endometriosis, or endometriosis and cancer possess common initial antecedent mechanisms and/or predisposing factors (e.g. genetic susceptibility, sensitivity to exposure to environmental toxins) with subsequent divergence on the molecular level. Incidence of endometriosis undoubtedly creates an oncological risk, necessitating elucidation by further genetic and molecular studies.
Hemorrhagic cystitis (HC) is a common complication in oncologic patients undergoing chemotherapy, radiotherapy or auto- and allotransplantation of hematopoietic stem cells. Cytostatics most prone to cause diffuse inflammation of the urinary bladder with concomitant bleeding include alkylating agents (e.g. cyclophosphamide and ifosfamide). The direct toxic agent are their metabolites, mainly acrolein. Nearly 20% of patients undergoing radiotherapy for pelvic malignancies experience bladder-associated complications, including HC. On the other hand, HC caused by cytostatics administered in the scope of conditioning protocol, affects 1-25% of patients undergoing transplantation. There are two forms of HC – early and delayed. The former is a result of preparatory protocols preceding graft injection or previous therapy and the flatter has usually viral etiology. Traditional means to prevent HC include adequate hydration, implementation of the so-called forced diuresis and administration of mesna, which contributed to a significant reduction of incidence of early HC. Effective treatment of delayed HC appears to rely on timely administration of antiviral drugs. Delayed diagnosis of HC or inadequate treatment may lead to urine retention with subsequent renal failure and even death. This paper presents, based on current literature, guidelines concerning prevention, diagnosis and treatment of HC.
Standard treatment for ovarian cancer is systemic therapy; as a rule it comprises surgical excision, chemotherapy and, in selected cases, radiotherapy. The scope of the surgical excision and its relation to chemotherapy recently underwent certain changes. On the one hand, the use of taxanes and platinum derivates has enhanced the role of chemotherapy; on the other hand, progress in surgery has enabled what only a few years ago were limitations to be overcome. Already in the 1970s, a link was suggested between the completeness of the surgical excision and the prolongation of the time period for both overall and progression-free survival. Now after the publication of several randomized trials, a direct correlation has been made between complete cytoreduction performed during the primary surgery and the prolongation of the time period for both overall and progression-free survival. It appears that non-resectability depends mainly on the experience of the surgeon and the degree of infiltration of the bowels and superior mesenteric vessels and bile ducts. Imaging studies are of no use in determining the resectability of lesions. Consequently, patients should not be qualified for lymphadenectomy based solely on the results of imaging studies. Systemic excision of pelvic and para-aortic lymph nodes is a permanent component of the surgical treatment of ovarian cancer in: 1) patients in the early clinical stages within the scope of staging; 2) patients with clinically positive nodes as a component of cytoreduction; 3) patients after complete cytoreduction as a prognosis-improving factor.