AT THE SAN ANTONIO Breast Cancer Symposium, several breast cancer experts interviewed by The ASCO Post noted that the approved dose of tamoxifen was arbitrarily set, and the optimal dose is actually unknown. Studies of lower-dose tamoxifen, therefore, are welcomed.
Virginia G. Kaklamani, MD
Virginia G. Kaklamani, MD, Professor of Medicine at The University of Texas Health Science Center at San Antonio and leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, noted that drugs are often “rushed out” for clinical use, and their indications are based on the maximum tolerated dose. “For many drugs, we use higher doses than we need, and this is an example,” she said. “Drugs don’t work unless patients take them, and if we can find ways of getting patients to do this—such as giving lower doses that are better tolerated—then patients will benefit.”
Dr. Kaklamani noted that the new data particularly supported lower doses of tamoxifen in patients with atypical ductal hyperplasia and lobular carcinoma in situ. “For ductal carcinoma in situ (DCIS), I think we need more follow-up before changing practice,” she said. “But if I have a patient with DCIS who is not tolerating tamoxifen at 20 mg/d, I would be extremely happy to lower the dose to 5 mg based on this study.”
Monica Morrow, MD
Could Increase Patient Acceptance of Tamoxifen
MONICA MORROW, MD, Chief of the Breast Service at Memorial Sloan Kettering Cancer Center, New York, pointed out, “The dose of tamoxifen was arbitrarily determined many years ago, but the data that were shown here for a lower dose were pretty convincing in terms of benefit. The population was fairly heterogeneous—this was a pure-prevention population in the setting of [atypical ductal hyperplasia] and [lobular carcinoma in situ], and then there were women with DCIS who had surgery and radiotherapy—so it’s a bit mixed. On the other hand, the effect we have seen across those groups in other tamoxifen studies (at least for contralateral breast cancer in DCIS) is fairly consistent, so you’d think it would be the same with tamoxifen at a lower dose.”
Dr. Morrow said she is hopeful the findings might convince more women to accept treatment with tamoxifen. “This is exciting news in light of the fact that tamoxifen acceptance is so low, courtesy of the Internet. Whether or not this will change anything, we don’t yet know, but we haven’t seen much new in chemoprevention for a long time.”
John Cole, MD
John Cole, MD, of the Ochsner Health System in New Orleans, said that the side-effect profile of antiestrogen agents hinders chemoprevention, and heretofore the benefits have been thought to be relatively modest, anyway. “The risk-reduction data in the [TAM01] study were as good as those for full-dose tamoxifen in other studies. In fact, the risk reduction in contralateral breast cancer was even better. You need to balance things out,” he said. “If you can reduce the side-effect profile and, in this case, also the cost—10 mg every other day costs one-quarter of what a patient normally spends on a monthly basis—then I think this will improve compliance.”
He added, “The data will make me enthusiastic about perhaps cutting back on the dose for a patient who is not tolerating tamoxifen. This will help me keep the patient on the drug.” ■
DISCLOSURE: Drs. Kaklamani, Morrow, and Cole reported no conflicts of interest.
A VERY LOW DOSE of tamoxifen—5 mg/d, given for 3 years rather than 5 years—halved the risk of breast cancer recurrence or new lesions over placebo in women with breast intraepithelial neoplasia, without producing the usual toxicities seen with the standard dose, Italian researchers reported at the...