Study Demonstrates That Low Dose Tamoxifen May Be Effective in Treating Breast Cancer
Behind the Cancer Headlines®
April 11, 2003
Administering tamoxifen at lower doses
than the current standard dose appears to effectively reduce breast cancer
proliferation while causing fewer side effects, according to data presented at
the Annual Meeting of the American Association for Cancer Research (AACR).
Unlike standard chemotherapy,
estrogen-based agents such as tamoxifen work by saturating the estrogen
receptor. Once saturation occurs, there is no longer any treatment benefit
regardless of regimen frequency or dosing, and additional drugs may cause an
increase in side effects.
"This study demonstrates that
tamoxifen doses as low as one milligram per day maintain clinical effect against
the treatment of breast cancer," said Andrea Decensi, M.D., Director of the
Division of Cancer Prevention, European Institute of Oncology, Milan, Italy.
"Since lower tamoxifen doses may also reduce the risks of potential serious
side effects such as endometrial cancer, this study concludes that more drug may
not be necessarily better."
The study protocol randomized 120
women with estrogen receptor (ER)-positive breast cancer toeither one, five or
20 milligrams (mg) of tamoxifen daily for four weeks prior to surgery. Results
in these women were compared with two non-randomized control groups – one of
34 women with ER-negative breast cancer who were recruited concurrently during
the trial, and one of 29 women with ER-positive breast cancer who were recruited
after randomization was complete.
Changes in Ki-67 (the key identifying
marker that measures tumor proliferation and which is associated with tumor
shrinkage and prognosis in breast cancer) were measured in cancer tissue before
and after tamoxifen treatment. Tamoxifen significantly reduced Ki-67
(p<0.001) but there was no dose response (p=0.81). All three doses reduced
Ki-67 levels equally. Although more drug was measured in the tumor at the 20 mg
dose, there was no correlation to increased Ki-67 reduction.
"Tamoxifen is the most widely
prescribed agent in the world for the prevention and treatment of breast
cancer," said Decensi. "Although tamoxifen has been studied since the
1970s, we have yet to determine the optimal biologic dose."
While there may be potential benefits
to lower doses of drug in terms of cancer prevention, the study identified other
disease markers that were dose-dependent, specifically circulating biomarkers
reflecting drug estrogenicity such as insulin-like growth factor-I, cholesterol,
triglycerides and antithrombin-III. Lower doses of tamoxifen might therefore
reduce its preventative effects in cardiovascular disease and osteoporosis, but
also reduce important adverse events such as venous thrombosis. There was also a
direct link to the decreased reduction of cholesterol and low dose tamoxifen.
Proceedings for the
2003 Annual Meeting of the American Association for Cancer Research, April 8,
2003, Toronto, Canada