Innovative approaches to tamoxifen administration for breast cancer prevention

Brandy M. Heckman-Stoddard, Oukseub Lee, Matteo Lazzeroni, Seema Khan, Andrea DeCensi, Barbara K. Dunn*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Tamoxifen has long been a mainstay of treatment of estrogen receptor (ER)-positive breast cancer in both the metastatic and adjuvant settings. In 1998, results from the large phase III Breast Cancer Prevention Trial (conducted by the National Surgical Adjuvant Breast and Bowel Project/NSABP) led to the Food and Drug Administration's approvalof tamoxifen for reduction of breast cancer incidence in high-risk women. 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 use is the investigation of novel, and potentially safer, modes of delivery of this agent. Two novel approaches are discussed in this paper. Low-dose tamoxifen, expected to confer fewer adverse events, is being examined by varying both dose and interval of administration. Low-dose tamoxifen is being investigated in in both clinical biomarker-based trials and observational studies. Modulation of systemic biomarkers, including lipid and IGF levels, and tissue biomarkers, including Ki-67, which are known to be favorably affected by conventional tamoxifen dosing, has been observed. These findings suggest possible beneficial clinical prevention effects from novel low-dose tamoxifen regimens. An alternative approach is administration of topical forms of tamoxifen directly to breast tissue in high-risk women. Avoidance of systemic administration is expected to limit the distribution of drug to tissues susceptible to tamoxifen-induced toxicity. While clinical trials of topical tamoxifen are still ongoing, laboratory data suggest that appropriate formulations of drug successfully penetrate the skin to reach breast tissue, where a preventive effect is expected.

Original languageEnglish (US)
Title of host publicationTamoxifen Concepts and Cancer
Subtitle of host publicationNew Paradigms
PublisherNova Science Publishers, Inc.
Pages61-86
Number of pages26
ISBN (Print)9781620815205
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Fingerprint Dive into the research topics of 'Innovative approaches to tamoxifen administration for breast cancer prevention'. Together they form a unique fingerprint.

  • Cite this

    Heckman-Stoddard, B. M., Lee, O., Lazzeroni, M., Khan, S., DeCensi, A., & Dunn, B. K. (2012). Innovative approaches to tamoxifen administration for breast cancer prevention. In Tamoxifen Concepts and Cancer: New Paradigms (pp. 61-86). Nova Science Publishers, Inc..