Cancer venous thromboembolism

Due to the presence of oestrogens there is increased risk of breast, endometrial and ovarian cancer, venous thromboembolism and stroke, but they alleviate vaginal atrophy and vasomotor instability, and reduce osteoporosis. 

Patients with cancer who develop a venous thromboembolism may benefit from long-term therapy with a low molecular weight heparin (at least the first 3-6 mo of pharmacotherapy) instead of oral warfarin... 

Combined estrogen plus progestin should not be used in the prevention of chronic diseases because it increases the risk of CHD, stroke, breast cancer, and venous thromboembolism. 

Venous thromboembolism Breast cancer Gallbladder disease Progestins... 

HRT on the incidence of venous thromboembolism, breast cancer, or CHD. Lower-dose HRT provides women with an alternative to standard-dose HRT for menopausal symptoms but also should be recommended only for a short duration. Although many women have switched to lower-dose HRT,... 

Adverse effects of estrogen include nausea, headache, breast tenderness, and heavy bleeding. More serious adverse effects include increased risk for coronary heart disease, stroke, venous thromboembolism, breast cancer, and gallbladder disease. Transdermal estrogen is less likely than oral estrogen to cause nausea, headache, breast tenderness, gallbladder disease, and deep vein thrombosis. 

Low-dose hormone therapy (conjugated equine estrogen 0.45 mg and medroxyprogesterone acetate 1.5 mg/day) has demonstrated equivalent symptom relief and bone density preservation without an increase in endometrial hyperplasia. Whether such lower doses will be safer (cause less venous thromboembolism and breast cancer) remains to be seen. 

Tamoxifen is discussed in Chap. 61, Breast Cancer raloxifene is discussed in Chap. 3, Osteoporosis. Raloxifene decreases bone loss in recently menopausal women without affecting the endometrium and has estrogen-like actions on lipid metabolism. It may exacerbate vasomotor symptoms, and it increases the risk of venous thromboembolism and stroke. 

Decensi A, Maisonneuve P, Rotmenz N et al. (2005) Effect of Tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation 111 650-656... 

Cancer is a complicated process consisting of well-coordinated multiple steps. Randomized trials to study the effectiveness of LMW heparins as compared with unfractionated heparin in treating venous thromboembolism in cancer patients led to a surprising observation that treatment with heparin... 

Treatment of postmenopausal women with osteoporosis with raloxifene (60mg/day or 120mg/day for 36 months) was found to significantly increase bone mineral density in the spine and femoral neck and decrease the risk of vertebral fracture compared to the placebo treatment.Treatment with raloxifene increased the risk of venous thromboembolism compared to the placebo group and was also associated with a lower risk of breast cancer and did not cause breast pain or vaginal bleeding. 

An extensive literature review has provided a useful assessment of the benefit to harm balance of raloxifene (20). The findings were reassuring. One large fracture prevention trial provided the best evidence that raloxifene 60 mg/day for 3 years reduced the relative risk of vertebral fractures by 30-50% in women with prevalent fractures or osteoporosis. The extraskeletal effects of raloxifene include a reduction in total cholesterol and low density lipoprotein cholesterol concentrations. Raloxifene was not associated with endometrial hyperplasia, and there was a 72% reduction in the incidence of invasive breast cancer. Adverse events associated with raloxifene included an increase in the absolute risk of venous thromboembolism and increased risks of hot... 

Table 1 Incidences of venous thromboembolism with and without breast cancer taking various treatments (37) ...

The risks of venous thromboembolism in women with and without breast cancer have been analysed and are summarized in Table 1 (37). In one case tamoxifen was associated with myocardial infarction (38). 

Deitcher SR, Gomes MPV. The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma a systematic review. Cancer 2004 101 439-49. 

Decensi A, Maisonneuve P, Rotmensz N, Bettega D, Costa A, Sacchini V, Salvioni A, Travaglini R, Oliviero P, D Aiuto G, Gulisano M, Gucciardo G, Del Turco MR, Pizzichetta MA, Conforti S, Bonanni B, Boyle P, Veronesi U. Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation 2005 111 650-6. 

The current consensus is that the contemporary low-dose preparations pose minimal risks in women who have no predisposing risk factors and, in fact, may provide certain beneficial health effects (e.g., protection against endometrial and ovarian cancer). Oral contraceptive pills have been associated with increased risk for myocardial infarction, stroke, and venous thromboembolism. However, studies have been published that suggest that these risks are minimal in appropriately chosen low-risk women. 

Stroke is a very uncommon event in childbearing women, occurring in approximately 11 per 100,000 women over a 1-year period of time. Therefore, even a doubling of this risk with oral contraceptive pills would have minimal effect on attributable risk. The estimated risk of myocardial infarction associated with oral contraceptive pill use in nonsmokers is 3 per million women over 1 year. The estimated risk of venous thromboembolism attributable to oral contraceptive pills is less than 3 per 10,000 women per year. However, the risk may be increased in women who smoke or have other predisposing factors to thrombosis or thromboembolism. In fact, it should be emphasized that the risk of serious cardiovascular side effects is particularly marked in women over 35 years of age who are heavy smokers (e.g., more than 15 cigarettes per day). Additionally, the literature suggests that there may be an increased risk of breast cancer associated with long-term oral contraceptive pill use in women under the age of 35. However, because the incidence of breast cancer is so relatively low in this population, the attributable risk of breast cancer from birth control pill use is small. 

Finally, the RUTH study (Raloxifene Use for the Heart)38 was a placebo-controlled clinical trial following over 10,000 postmenopausal women with coronary heart disease (CHD) or with multiple risk factors for CHD.44 16 This trial demonstrated 44% reduced incidence of invasive breast cancer versus placebo, with 0.6% absolute risk reduction,47 thus confirming the findings from MORE and CORE, while also demonstrating that raloxifene did not increase or decrease risk for coronary events or stroke. However, there was an increase in stroke mortality and incidence of venous thromboembolic events (VTEs) as compared to placebo, already seen in MORE, which resulted in a recommendation that raloxifene should not be used for the prevention or reduction of the risk of cardiovascular disease.21... 

The risks and benefits of HRT should be carefully assessed on an individual basis. This is particularly important in women with predisposing risk factors, such as a personal or family history of deep vein thrombosis or pulmonary embolism, severe varicose veins, obesity or prolonged bed-rest [2], because HRT increases the risk of venous thromboembolism and stroke. HRT has also been observed to increase the risk of gallbladder disease, breast cancer and endometrial cancer. It is recommended that the minimum effective dose should be used for the shortest period of time, with treatment being reviewed at least once a year [2]. 

The more serious complications are venous thromboembolism and cancer of the endometrium or breast. These risks are small in absolute terms, particularly so for the risks of cancer during the first 5 years of treatment. 

Home MK 3rd, Figg WD, Arlen P, Gulley J, Parker C, Lakhani N, Parnes H, Dahut WL. Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer. Pharmacotherapy 2003 23(3) 315-18. 

Patients with a high risk for clotting require thromboprophylaxis. Some risk factors for venous thromboembolism include age greater than 40 years, prolonged immobility, history of prior venous thromboembolism (DVT, pulmonary embolism [PE]), cancer, major surgery (abdominal, pelvic, or lower extremity), fracture (pelvis, hip, or leg), CHF, Ml, stroke, obesity, and high-dose estrogen use. 

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