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Key Words

Breast cancer, bone loss, anastrozole (Arimidex®), tamoxifen (Nolvadex®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁴.)

Summary

Postmenopausal women taking the drug anastrozole (Arimidex®) to prevent a recurrence of breast cancer suffered more bone loss than women taking tamoxifen (Nolvadex®), even while anastrozole provided better protection against relapse, according to a substudy of a major clinical trial comparing the two drugs. Doctors and patients need to consider all risks and benefits when deciding on the best adjuvant approach for women with hormone-positive, early-stage breast cancer.

Source

Journal of Clinical Oncology, March 1, 2008 (see the journal abstract ⁵).
(J Clin Oncol. 2008 Mar 1; 26(7): 1051-58)

Background

Postmenopausal women with hormone-positive, early-stage breast cancer have a number of medical options to lower the risk of a relapse after their initial treatment. Among these options are tamoxifen and various aromatase inhibitors (AIs), such as anastrozole, letrozole, or exemestane.

In addition to their potential benefits, these drugs have side effects that must be considered in the context of the patient’s overall health. For example, most women begin to lose bone density at menopause, which puts them at risk of osteoporosis. AIs such as anastrozole, it turns out, tend to cause bone loss. Tamoxifen protects against bone loss but also raises the risk of endometrial cancer and blood clot disorders, among other things.

The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blinded, phase III clinical trial in which postmenopausal women with hormone-positive, early-stage breast cancer were randomly assigned to one of three treatment groups. One received tamoxifen, another anastrozole (one of the AIs) , and a third group received a combination of the two. The combination group was discontinued when no benefit was seen at 33 months; these women were offered the chance to switch to one of the remaining two groups.

In 2005, ATAC researchers reported that anastrozole was better than tamoxifen at preventing breast cancer recurrence (see the related story ⁶). What follows is a summary of data from a prospective substudy of the ATAC trial concerned specifically with bone loss.

The Study

Of the 9,366 postmenopausal women enrolled in the original ATAC study, 108 completed the substudy reported here. Fifty-seven had been randomly assigned to the anastrozole-only group and 51 to the tamoxifen-only group. The substudy’s goal was to see how anastrozole and tamoxifen affected bone mineral density in the hip and the lumbar spine (lower back). Measurements were taken when the study began, and again at one, two, and five years.

The substudy’s principal investigator was Richard Eastell, M.D., of the University of Sheffield, England.

Results

At the five-year mark, women in the substudy’s tamoxifen group had actually gained bone mineral density: 2.77 percent to their lumbar spine and 0.74 percent to their hip. All gains occurred in the first two years and did not increase over the next three.

Women in the substudy receiving anastrozole for five years lost a median of 6.08 percent of bone mineral density from the lumbar spine and 7.24 percent from the hip. The spinal bone loss was faster during the first two years, whereas loss from the hip occurred at a steady rate.

When the substudy began, just under half of the women in each group had osteopenia (bone loss less severe than osteoporosis). Of these women, four from the anastrozole group progressed to osteoporosis during the five-year study period, compared to one woman from the tamoxifen group. Among women with normal bone density before the study began, 14 from the anastrozole group developed osteopenia, compared to three from the tamoxifen group.

Comments

Based on ATAC and trials with other AIs such as letrozole and exemestane, AIs are becoming the standard of care to prevent recurrence of early-stage breast cancer in this population. However, these cancer treatments do accelerate bone loss, says Jo Anne Zujewski, M.D., head of Breast Cancer Therapeutics with the National Cancer Institute’s Division of Cancer Treatment and Diagnosis. “Bone health is very important in this population, since it is estimated that half of all women over age 50 will suffer a fracture from osteoporosis. One in four of those will become disabled as a result, and one in five who break a hip die within a year.”

Fortunately, pre-existing bone loss “may represent a preventable and treatable condition. writes Eastell, Zujewski agrees.“Bisphosphonate drugs such as pamidronate and zoledronic acid are effective therapies for maintaining bone density,” she says.

“There is no single approach that is best for all women in the adjuvant treatment of hormone-positive, early-stage breast cancer,” says Zujewski. Ongoing trials will help to determine the best course for different groups of women. Patients should discuss the potential risk and benefits of any recommended treatment course with their doctor.

Glossary Terms

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

An anticancer drug that is used to decrease estrogen production and suppress the growth of tumors that need estrogen to grow. It is a type of nonsteroidal aromatase inhibitor.

A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone-dependent breast cancer.

A drug or substance used to treat hypercalcemia (abnormally high blood calcium) and bone pain caused by some types of cancer. Forms of bisphosphonates are also used to treat osteoporosis and for bone imaging. Bisphosphonates inhibit a type of bone cell that breaks down bone. Also called diphosphonate.

A clinical trial in which the medical staff, the patient, and the people who analyze the results do not know the specific type of treatment the patient receives until after the clinical trial is over.

A drug used to treat advanced breast cancer and to prevent recurrent breast cancer in postmenopausal women who have already been treated with tamoxifen. It is also being studied in the treatment of other types of cancer. Exemestane causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor. Also called Aromasin.

A drug used to treat advanced breast cancer in postmenopausal women. Letrozole causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor. Also called Femara.

A statistics term. The middle value in a set of measurements.

A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

Having to do with the time after menopause. Menopause (“change of life”) is the time in a woman's life when menstrual periods stop permanently.

In medicine, a study or clinical trial in which participants are identified and then followed forward in time.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with the standard of care. Also called best practice and standard therapy.

A drug used to treat certain types of breast cancer in women and men. It is also used to prevent breast cancer in women who have had ductal carcinoma in situ (abnormal cells in the ducts of the breast) and in women who are at a high risk of developing breast cancer. Tamoxifen is also being studied in the treatment of other types of cancer. It blocks the effects of the hormone estrogen in the breast. Tamoxifen is a type of antiestrogen. Also called tamoxifen citrate.