Long-term Tamoxifen for Breast Cancer Patients Boosts Survival

Women over 50 years old with early breast cancer confined to one breast who took 20 mg of tamoxifen daily for 5 years were less likely to relapse than those who took the drug for 2 years. This is the finding of a long-term international breast cancer patient study by researchers at Cancer Research UK in London, England (DOI: 10.1200/JCO.2010.32.2933). 

Breast Cancer Reoccurrence on Tamoxifen

The study showed that women who took tamoxifen for 5 years had an 11% reduced chance of any breast-cancer associated event including relapse, cancer in the other breast, new tumor, or death compared to women who took the endocrine treatment for 2 years. There was a 9% reduction in the chance of death from breast cancer and a 17% reduction in the risk of recurrence.

Following tamoxifen treatment for 5 compared to 2 years resulted in a 30% statistically significant risk reduction in developing breast cancer in the other breast for women in the study. There was no relationship between age and either breast cancer reoccurrence or overall survival in this trial. There was also no effect of menopausal status on the outcome of a 5-year tamoxifen regimen.

Reduced Cardiovascular Risk

The study authors reported a significant reduction in the risk of both cardiovascular (CV) disease and death in all women on tamoxifen. The younger age cohort, those women between 50 and 59 had the greatest CV risk reductions. It should be pointed out that this reduced risk was not statistically significant. The benefit against CV events was seen as soon as patients started treatment. The effect on CV death was exhibited only after about 9 years of treatment. Based on the patient data, there could be approximately 3.3 fewer CV deaths for every 100 women between the ages of 50 and 59 taking tamoxifen for 5 vs 2 years.

According to the authors, this reduced cardiovascular risk is consistent with a previous Swedish Breast Cancer Group trial that studied women on tamoxifen for 2 and 5 years, as well as other trials that compared tamoxifen to placebo.

Tamoxifen or aromatase inhibitors for long-term adjuvant therapy?

Tamoxifen is a well-established adjuvant treatment, first used in the 1980s and still the standard of care for premenopausal women. In 2004, the American Society of Clinical Oncology (ASCO) issued new guidelines including the recommendation of aromatase inhibitors (AIs) for postmenopausal early breast cancer patients, which are FDA-approved for adjuvant treatment.

Both treatments reduce the growth of estrogen-sensitive tumors. Tamoxifen blocks the tumor’s ability to utilize estrogen while AIs reduce the amount of estrogen in the body. AIs cannot prevent the ovaries from producing estrogen, but can block the ability of other tissues in the body to produce the hormone. This is why AIs are predominantly used to treat postmenopausal women, those whose ovaries no longer produce estrogen.

AIs have been shown to be superior compared to tamoxifen in 5-year trials measuring disease-free survival. The paper sites 18% and 15% reduced risk of reoccurrence/death from two different studies.

Each treatment has its benefits and downsides. Tamoxifen is cheaper but has plenty of toxicity. Hot flashes, vaginal discharge, increased risk of thrombotic events, increased risk of endometrial cancer, uterine sarcoma, and a probable increased risk of cerebral vascular disease have all been well-documented on tamoxifen.

Aromatase inhibitors are more expensive (although will go off patent soon) but tend to cause fewer serious side effects. However, AIs come with their own troubles, including heart problems, osteoporosis, increased chance of bone fractures, and arthritis. Some patients are unsuitable for AI treatment (those with bone-health issues) or cannot tolerate it, making tamoxifen an affordable and still widely used treatment for women with low-risk, invasive breast cancer.

As the authors of the accompanying editorial point out, “ We now know from a variety of randomized trials that cardiovascular events and perhaps cardiovascular deaths are higher in women who are randomly assigned to receive AIs as compared with tamoxifen,” (DOI: 10.1200/JCO.2010.34.2766). Dr. Pritchard and Sousa from the Sunnybrook Odette Cancer Center in Toronto, Canada suggest that the appropriate therapy should be selected based on the patient’s underlying cardiovascular risk. They point out, however, that more long-term follow up data is necessary before clinicians can best advise women as to the optimal long-term therapy for their breast cancer. Prioritizing long-term patient follow-ups from studies such as this one is important to delineate best treatment options based on trial results and economic constraints of breast cancer patients.