Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer.

BACKGROUND: Tamoxifen use has been associated with increased risk of thromboembolic events (TEs) in women with breast cancer and women at high risk for the disease. Factor V Leiden (FVL) is the most common inherited clotting factor mutation and also confers increased thrombosis risk. We investigated whether FVL was associated with TE risk in women with early-stage breast cancer who took adjuvant tamoxifen. METHODS: A case-control study was conducted among 34 Cancer and Leukemia Group B (CALGB) institutions. We matched each of 124 women who had experienced a documented TE while taking adjuvant tamoxifen for breast cancer (but who were not necessarily on a CALGB treatment trial) to two control subjects (women who took adjuvant tamoxifen but did not experience TE) by age at diagnosis (+/-5 years). DNA from blood was analyzed for FVL mutations. Conditional logistic regression was used to estimate odds ratios (ORs) and to evaluate other potential factors associated with TE and tamoxifen use. All P values are based on two-sided tests. RESULTS: FVL mutations were identified in 23 (18.5%) case and 12 (4.8%) control subjects (OR = 4.66, 95% confidence interval = 2.14 to 10.14, P < .001). In the multivariable model, FVL mutation was associated with TE (OR = 4.73, 95% confidence interval = 2.10 to 10.68, P < .001). Other statistically significant factors associated with TE risk were personal history of TE and smoking. CONCLUSIONS: Among women taking adjuvant tamoxifen for early-stage breast cancer, those who had a TE were nearly five times more likely to carry a FVL mutation than those who did not have a TE. Postmenopausal women should be evaluated for the FVL mutation before prescription of adjuvant tamoxifen if a positive test would alter therapeutic decision making.

Extrapulmonary small cell carcinoma of the bladder.

Among the many sites for primary small cell cancer is the genitourinary system. The majority of cases have been observed in the bladder and prostate. Small cell carcinoma accounts for less than 1% of all bladder tumors. Definitive predisposing factors are unknown; however, small cell carcinoma of the bladder has been associated with cigarette smoking, long-standing cystitis, bladder calculus, and augmented cystoplasty. Contrary to the early theory of derivation from Kulchitsky cells, it is now believed that small cell carcinoma of the bladder originates from the totipotent stem cells present in the submucosa of the bladder wall. A number of chromosomal aberrations have been reported in small cell cancer of the bladder. There are no specific clinical features that differentiate these patients from transitional cell carcinoma of the bladder; however, some patients may have associated paraneoplastic conditions. Diagnosis is established by cystoscopic-assisted biopsy. Like small cell carcinoma of the lung, small cell carcinoma of the bladder has a propensity for early metastases. There is no standard therapy for small cell carcinoma of the bladder and the prognosis is poor; however, patients treated with cisplatin-based chemotherapy regimens seem to have a better prognosis.

Small cell carcinoma of the breast.

Small cell carcinoma of the breast (SCCB) is an uncommon neoplasm that accounts for less than 1% of primary breast cancers. Histologically, these tumors have striking similarities to small call carcinoma of the lung, usually with evidence of associated ductal carcinoma-in-situ (DCIS) with areas of ductal, lobular, or papillary differentiation. Immunoreactivity for neuroendocrine markers is documented in two thirds of cases, while 33% to 50% are positive for estrogen receptor (ER) or progesterone receptor (PR). Her2/neu expression has not been reported in SCCB. Treatment, which may include surgery, radiotherapy, and combination chemotherapy, is based on clinical stage and the presence of metastases. Prognosis is variable and is dependent on the initial stage of disease.

Small cell cancer of the pleura, kidney, and thymus.

Small cell carcinoma is a distinct clinicopathologic entity that usually arises in the lung but also can originate in extrapulmonary sites, such as the pleura, thymus, and kidney. Small cell carcinoma of the kidney and renal pelvis is rare. Most patients present with large tumors and have evidence of extensive locoregional spread and distant metastases, despite a short duration of symptoms. Although nephrectomy has been used for treatment it does not appear to confer any significant benefit. Cisplatin-based chemotherapy has improved the median survival from 8 months to 20 months. Only isolated cases of small cell carcinoma of the pleura and thymus have been reported. Both tumors have a tendency for aggressive local invasion and distant metastases. Surgery, radiation, and chemotherapy have been used in the management of these tumors with variable results.

Vascular toxicity of antineoplastic agents.

Among the various deleterious effects of cancer chemotherapy, vascular toxicity is the least well recognized. This lack of recognition may be because the vasculotoxic phenomena are not unique to antineoplastic agents, can occur in patients without exposure to these agents, and the fact cancer itself may produce a hypercoagulable state. As a result, many vascular events either go unnoticed, are ignored, and/or are attributed to the underlying malignancy. Many antineoplastic therapies are associated with various vascular phenomena that range from simple phelibitis to lethal microangiopathy. Recognition of these events is important to minimize the morbidity and even prevent unnecessary deaths. Herein we review the vascular syndromes that have been reported in association with antineoplastic agents.

Hepatotoxicity of chemotherapy.

The selection of a chemotherapeutic regimen for the oncology patient is based on a thorough assessment of potential hazards relating to the patient's clinical condition and the toxicities of chemotherapy. Liver function abnormalities are commonly seen in this patient population and deducing their aetiology may be difficult. Immunosuppression, paraneoplastic phenomena, infectious disease, metastases and polypharmacy may all confound the clinical picture. While criteria for standardising liver injury have been established, dose modifications often rely on empirical clinical judgement. Therefore, a comprehensive understanding of hepatotoxic manifestations for the most common chemotherapeutic agents is essential. This article reviews the hepatotoxicity of commonly utilised antineoplastic agents.