Tamoxifen or Nolvadex

Tamoxifen is generally well tolerated and much less toxic than chemotherapy. The biggest patient concerns have to do with blood clots and uterine cancer. (Results from NSABP P-1 trials showed that patients taking tamoxifen without a history of pulmonary emboli experienced a statistically significant increase in pulmonary emboli and a nonstatistically significant increase in deep-vein thrombosis and stroke and an increased incidence of endometrial cancer, older patients were more at risk go here.)

A recent study showed that the risk of blood clots was highest during the first two years (go here). Obviously patients need to balance the benefits and the risks before deciding on taking this drug. This is one of the most widely studies drugs and a search of Medline will produce thousands of articles. A table of the risks and benefits is noted below and some of the data is summarized below and more on the drug and safety from the many on-line drug information sites and the Nolvadex safety page. (see the NCCN guidelines for indications and for monitoring women on the drug.)

**Number of Cases per Year Per 1000 Women in Tamoxifen Prevention Study**
Effects	Tamoxifen	No Tamoxifen
Side Effects
endometrial cancer	2.29	0.92
pulmonary embolus	0.75	0.25
deep vein thromboses	1.26	0.79
stroke	1.43	1.00
cataracts	25	22.5
Good or neutral effects
breast cancer develops	3.58	6.49
hip fracture	0.38	0.84
heart disease	2.57	2.47

Monitoring Patients on Tamoxifen NCCN 2005

Endometrial Cancer

The increased risk for endometrial cancer in postmenopausal women treated with tamoxifen requires monitoring. Early reports that tamoxifen-associated endometrial cancer may be more aggressive than other endometrial cancers have not been confirmed on further study. In the NSABP Breast Cancer Prevention Trial, the only death from endometrial cancer occurred in a placebo-treated subject. Recent analysis from the NSABP data has noted a small number of uterine sarcomas among the number of patients taking tamoxifen with an intact uterus. These patients have already been included in the reported number of patients diagnosed with endometrial cancer. Overall, the rate of sarcoma in women taking tamoxifen was 0.17 per 1,000 women years. This translates to less than one-tenth of 1%. a new “black box” Food and Drug Administration warning on tamoxifen has been added to highlight the uterine cancer risk (both endometrial and uterine sarcoma) and will also include pulmonary embolism and stroke risks. Annual pelvic examination should include an age-appropriate Papanicolaou smear if the woman has an intact uterus. The vast majority of women with tamoxifen-associated endometrial cancer present with vaginal spotting as an early symptom of cancer. Therefore, prompt evaluation of vaginal spotting in the postmenopausal woman is essential. At present, there is insufficient evidence to recommend the performance of uterine ultrasonography or endometrial biopsy for routine screening in asymptomatic women. In women diagnosed with endometrial cancer while taking tamoxifen, the drug should be discontinued until the endometrial cancer has been fully treated. The panel believes that it is safe and reasonable to resume tamoxifen therapy after completion of treatment for early stage endometrial carcinoma.

Retinopathy and Cataract Formation

Tamoxifen is associated with the rare occurrence of retinopathy and with a 1.14 relative risk of cataract formation, compared with placebo. Individuals developing cataracts while on tamoxifen have a relative risk for cataract surgery of 1.57, compared with placebo. Thus, in patients experiencing visual symptoms, prompt ophthalmologic evaluation is appropriate.

Bone Mineral Density

Although tamoxifen is associated with an increase in bone mineral density in postmenopausal women, there is concern that it may be associated with a decrease in bone mineral density in premenopausal women. Thus, monitoring bone mineral density in premenopausal women may be considered.

Thromboembolic Disease

The prospective intermittent screening of women for thromboembolic disease is unlikely to be of value. However, women taking tamoxifen should be educated regarding the symptoms associated with deep vein thrombosis and pulmonary emboli. They should also be instructed to contact their physicians immediately if they develop symptoms of deep vein thrombosis or pulmonary emboli. Women with documented thromboembolic disease should be treated appropriately for the thromboembolic process and should discontinue tamoxifen permanently.