[Therapy-related hematologic neoplasias after breast cancer. Epidemiologic, etiologic and cytogenetic aspects and new risk factors according to published data and own results].
BACKGROUND
Breast cancer is the most frequent solid tumor in women. The incidence is increasing. In Germany, about 45,000 women are newly diagnosed each year. The general strategy aims for the best local control of the tumor by surgery and radiotherapy. This strategy is supplemented by systemic adjuvant chemotherapy and/or anti-hormonal therapy. The following substances have shown their efficacy in clinical trials: alkylating agents, antimetabolites, anthracyclines, topoisomerase inhibitors, platinum derivatives, and taxanes. Due to intensified treatment schedules remission rates and overall survival could be significantly improved. On the other hand, the long-term toxicity of this antineoplastic therapy is an increasing problem.
Therapy-associated secondary leukemias frequently occur after treatment for malignant lymphomas and multiple myelomas. However, they can also be observed after antineoplastic therapy of solid tumors such as cancers of the breast, lung, testicles and ovaries and sarcomas. The highest risk for secondary leukemias has been attributed to concurrent radiochemotherapy. Therapy-associated hematologic neoplasias are a severe medical problem due to the high incidence of breast cancer and the dismal outcome of secondary leukemias, which occur in 0.3-5% of patients receiving antineoplastic therapy.


METHODS
The delineation of new individual risk factors is urgently required to improve the safety of modern breast cancer treatment, which includes intensive combined radiochemotherapy. Candidate mechanisms could be polymorphisms in DNA repair and/or xenobiotic-metabolizing enzymes. Preliminary data suggest that the resulting deficiencies in xenobiotic-metabolizing enzymes such as glutathione S-transferases increase the risk for therapy-induced hematologic neoplasias in patients with breast cancer.
Haase
Detlef
D
Abteilung Hämatologie und Onkologie, Georg-August-Universität, Göttingen. haase.onkologie@med.uni-goettingen.de
Hanf
Volker
V
Schulz
Thomas
T
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D002869:Chromosome Aberrations; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004260:DNA Repair; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D007938:Leukemia / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D007953:Leukemia, Radiation-Induced / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011878:Radiotherapy / Q000009:adverse effects*; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013997:Time Factors; D015262:Xenobiotics / Q000378:metabolism
D000970:Antineoplastic Agents; D015262:Xenobiotics; D005982:Glutathione Transferase
Therapieinduzierte hämatologische Neoplasien nach Mammakarzinomen. Epidemiologie und Atiologie, zytogenetische Charakteristika und Etablierung neuer Risikofaktoren unter Berücksichtigung eigener Daten.