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Key Words: breast cancer, fulvestrant, postmenopausal women. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ².)

A new drug called fulvestrant (Faslodex®) was as effective as another drug, anastrozole (Arimidex®), in postmenopausal women with advanced, previously treated breast cancer, according to two studies published in the August 15, 2002, issue of the Journal of Clinical Oncology.

The women in the studies had been previously treated with the drug tamoxifen, only to have their breast cancer return. Anastrozole belongs to a class of drugs called aromatase inhibitors ³ (AIs). Drugs from this class are the current standard therapy for breast cancer that has recurred or progressed after treatment with tamoxifen.

The new fulvestrant results "mean that patients with advanced breast cancer and their doctors now have an additional treatment option," said Jeff Abrams, M.D., of the National Cancer Institute's Cancer Therapy Evaluation Program.

The first of the two studies, led by C.K. Osborne, M.D., of Baylor College of Medicine in Houston, Texas, involved 400 patients in the United States and Canada who were randomly assigned to receive either fulvestrant or anastrozole (see the journal abstract). Fulvestrant is given as a monthly injection, anastrozole as a daily pill, so the researchers included in their study two placebos, or dummy treatments. Patients who received the fulvestrant injection also received a dummy pill; those who were given the anastrozole pill were also injected with a dummy substance. Neither patients or their doctors knew which was the active treatment. This kind of "double-blind" approach helps to prevent the kind of bias that can weaken study results.

After an average of 17 months of follow-up, fulvestrant delayed disease progression by 5.4 months on average, compared with 3.4 months for anastrozole. This difference, however, was not statistically significant (that is, it could have occurred by chance). In patients who responded to treatment, the average duration of response was 19 months for those treated with fulvestrant and 11 months for those who received anastrozole. The number of patients experiencing adverse effects of treatment, as well as the severity of those adverse effects, were similar in both groups.

In the second study, led by A. Howell, M.D., of Christie Hospital National Health Service Trust in Manchester, United Kingdom, 451 patients in Europe, South Africa, and Australia were randomly assigned to receive either fulvestrant by monthly injection or anastrozole in a daily pill (see the journal abstract). Unlike the U.S.-Canadian study, this study was not designed in a double-blinded fashion. Thus, both patients and their doctors knew who was receiving which treatment.

The results of this study were very similar to those of the U.S.-Canadian study. Response rates and delays in disease progression were about the same in both groups of patients.

(Note: After an extended follow-up, combined data from the two studies were subseqently published in the July 15, 2005, issue of the journal Cancer. These results showed that "fulvestrant was similar to anastrozole with respect to overall survival in the second-line treatment of postmenopausal women" with advanced breast cancer. See the journal abstract.)

Now that fulvestrant appears to be as effective as anastrozole, doctors and patients should consider several factors, including the patient's prior treatment and each drug's side effects, when making treatment decisions, said Abrams.

"If a patient gets tamoxifen as first-line therapy," said Abrams, "then either fulvestrant or an AI is a reasonable second-line choice. However, some patients are getting AIs first-line now, so the actual choice for some may be between fulvestrant and tamoxifen."

Fulvestrant has been shown to work in patients whose tumors progressed after treatment with tamoxifen. But it's not yet known whether the opposite is true -- that is, whether tamoxifen helps patients whose tumors have recurred after treatment with fulvestrant. For this reason, said Abrams, "it would be reasonable to use tamoxifen or an AI first and save fulvestrant for second-line therapy."

Tamoxifen, AIs, and fulvestrant are effective only in patients whose tumors are sensitive to the hormones estrogen and progesterone. The drugs work in different ways to prevent these hormones from stimulating breast cancer growth.

Tamoxifen attaches to the estrogen receptor in the tumor, which blocks estrogen's effect on the cancer cells in breast tissue but may mimic the effect of estrogen elsewhere, such as the uterus or bone. AIs, by contrast, reduce overall estrogen levels by inhibiting the body's production of the hormone. Fulvestrant, like tamoxifen, attaches to the estrogen receptor but, unlike tamoxifen, it destroys the receptor, thereby blocking all estrogen activity.

Because of their different mechanisms of action, the drugs have different side effects, explained Abrams. "Tamoxifen has protective effects against osteoporosis because it stimulates the estrogen receptor in bone. AIs and fulvestrant do not seem to have this protective effect on bone, whereas tamoxifen, by stimulating the estrogen receptor in the uterus, increases the risk of endometrial cancer. AIs and fulvestrant are unlikely to have this effect on the uterus."

Finally, tamoxifen is effective in premenopausal women with breast cancer whereas AIs are not, said Abrams. Clinical studies have not yet shown whether fulvestrant is effective in premenopausal women.

Glossary Terms

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.

Having to do with the endometrium (the layer of tissue that lines the uterus).

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

A drug used to treat certain types of breast cancer in postmenopausal women. It is also being studied in the treatment of other types of cancer. Fulvestrant blocks estrogen activity in the body and is a type of antiestrogen. Also called Faslodex and ICI 182780.

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

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.

A type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone can also be made in the laboratory. It may be used as a type of birth control and to treat menstrual disorders, infertility, symptoms of menopause, and other conditions.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

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

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.