After long-term follow-up, uPA/PAI-1 levels in primary tumor tissue reliably and strongly indicate an aggressive course of disease in lymph node-negative breast cancer independent of HER2 status. The particular prognostic effect of HER2 status on OS may reflect its ability to predict resistance to systemic therapy.
The gene coding for the human homologue of the Drosophila segment polarity gene patched (PTCH1) is mutated in several common human tumors. In mice, haplodeficiency at the Ptch1 locus results in severe histologic defects in mammary ductal structure. We found no mutations within the coding region of PTCH1 in 17 human primary breast carcinomas. However, the biallelic Pro1315Leu (C3944T ) polymorphism of PTCH1 was significantly associated with breast cancer in 41 Bavarian patients compared to 85 healthy controls. We investigated whether this variant influences susceptibility for breast cancer in 611 breast cancer patients diagnosed by age 50 years and 1,057 controls matched by age and study region in Germany and in 1,093 breast cancer patients from the United Kingdom. Allele and genotype frequencies were not different between cases and controls. However, multivariate logistic regression analysis revealed an effect modification of oral contraceptive use (OC) on breast cancer risk by Leu-carrier status. Compared to women who have Pro/Pro and never used OC, Pro/Pro OC users had an increased odds ratio for breast cancer of 1.7. The odds ratio was also 1.7 for Leu-carriers who never used OC, but this was attenuated among Leu-carriers who ever used OC by 20%.
Key words: genetic polymorphism; breast cancer; gene-environment interaction; oral contraceptivesThe tumor suppressor gene PTCH1 is a downstream receptor in the hedgehog family of cell signaling proteins and plays an essential role in many aspects of cell growth and cell differentiation. Germline mutations in PTCH1 have been detected in patients with nevoid basal cell carcinoma syndrome (NBCCS), in which patients are predisposed to developmental abnormalities and a variety of neoplasms including basal cell carcinoma and medulloblastoma. 1,2 In addition, somatic mutations in PTCH1 have been identified in sporadic cases of basal cell carcinomas and of medulloblastoma and in a variety of other tumors (see review). 3,4 Interestingly, nonsense mutations in PTCH1 have been reported in 2 of 7 breast carcinomas, 5 suggesting an involvement of the SHH/PTCH1 signaling pathway in development of this kind of tumor. Although a similar study in a larger sample of 45 breast carcinomas did not reveal any inactivating PTCH1 mutations, 6 the possible involvement of this gene in the formation of breast carcinoma has also been demonstrated in an animal model for Ptch1 haplodeficiency. 7 All postpubescent virgin mice heterozygous for Ptch1 developed ductal hyperplasia and dysplasia of the mammary glands, which reverted during late pregnancy and lactation but returned upon involution and gland remodeling. Treatment with estradiol and progesterone enhanced the mutant histologic phenotype. These data suggest a role for the Ptch1 signaling network in mammary growth and differentiation.To obtain further insights into the involvement of PTCH1 in breast carcinoma formation, we analyzed a series of breast carcinomas for PTCH1 mutations. In the process we observed that the biallelic Pro1315Leu (...
Background: Leiomyosarcoma of the fallopian tube is an extremely unusual gynecologic neoplasm. Since 1886, only 19 of about 35 sarcomas of the fallopian tube have been identified as leiomyosarcomas. As such, clinical diagnosis and therapy management are difficult. Case Report: We report on the case of a 59-year-old woman with leiomyosarcoma of the fallopian tube and liver metas-tases at the time of diagnosis. After initial tumor debulk-ing, she received palliative chemotherapy with gemcitabine 900 mg/m2 (d1+8) and docetaxel 100 mg/m2 (d8) (q21). For additional bone metastases, she started local radiation plus bisphosphonates (q28). After 2 cycles of chemotherapy, the disease progressed, and the patient died within 8 months of diagnosis. A review of the literature is given. Conclusions: Primary metastatic leiomy-osarcoma of the fallopian tube is a progressive disease with limited therapy options. For better prognostic evaluation and disease management in such rare cases, it is important to report and compare more cases regarding course of disease and outcome.
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