Oral low dose and topical tamoxifen for breast cancer prevention

modern approaches for an old drug

Matteo Lazzeroni, Davide Serrano, Barbara K. Dunn, Brandy M. Heckman-Stoddard, Oukseub Lee, Seema Khan, Andrea Decensi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Tamoxifen is a drug that has been in worldwide use for the treatment of estrogen receptor (ER)-positive breast cancer for over 30 years; it has been used in both the metastatic and adjuvant settings. Tamoxifen's approval for breast cancer risk reduction dates back to 1998, after results from the Breast Cancer Prevention Trial, co-sponsored by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project, showed a 49% reduction in the incidence of invasive, ER-positive breast cancer in high-risk women. Despite these positive findings, however, the public's attitude toward breast cancer chemoprevention remains ambivalent, and the toxicities associated with tamoxifen, particularly endometrial cancer and thromboembolic events, have hampered the drug's uptake by high-risk women who should benefit from its preventive effects. Among the strategies to overcome such obstacles to preventive tamoxifen, two novel and potentially safer modes of delivery of this agent are discussed in this paper. Low-dose tamoxifen, expected to confer fewer adverse events, is being investigated in both clinical biomarker-based trials and observational studies. A series of systemic biomarkers (including lipid and insulin-like growth factor levels) and tissue biomarkers (including Ki-67) are known to be favorably affected by conventional tamoxifen dosing and have been shown to be modulated in a direction consistent with a putative anti-cancer effect. These findings suggest possible beneficial clinical preventive effects by low-dose tamoxifen regimens and they are supported by observational studies. An alternative approach is topical administration of active tamoxifen metabolites directly onto the breast, the site where the cancer is to be prevented. Avoidance of systemic administration is expected to reduce the distribution of drug to tissues susceptible to tamoxifen-induced toxicity. Clinical trials of topical tamoxifen with biological endpoints are still ongoing whereas pharmacokinetic studies have already shown that appropriate formulations of drug successfully penetrate the skin to reach breast tissue, where a preventive effect is sought.

Original languageEnglish
Article number214
JournalBreast Cancer Research
Volume14
Issue number5
DOIs
Publication statusPublished - Oct 29 2012

Fingerprint

Tamoxifen
Breast Neoplasms
Pharmaceutical Preparations
Biomarkers
Estrogen Receptors
Observational Studies
Breast
Topical Administration
Drug Compounding
National Cancer Institute (U.S.)
Chemoprevention
Somatomedins
Risk Reduction Behavior
Endometrial Neoplasms
Pharmacokinetics
Clinical Trials
Lipids
Skin
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Oral low dose and topical tamoxifen for breast cancer prevention : modern approaches for an old drug. / Lazzeroni, Matteo; Serrano, Davide; Dunn, Barbara K.; Heckman-Stoddard, Brandy M.; Lee, Oukseub; Khan, Seema; Decensi, Andrea.

In: Breast Cancer Research, Vol. 14, No. 5, 214, 29.10.2012.

Research output: Contribution to journalArticle

Lazzeroni, Matteo ; Serrano, Davide ; Dunn, Barbara K. ; Heckman-Stoddard, Brandy M. ; Lee, Oukseub ; Khan, Seema ; Decensi, Andrea. / Oral low dose and topical tamoxifen for breast cancer prevention : modern approaches for an old drug. In: Breast Cancer Research. 2012 ; Vol. 14, No. 5.
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