Breast cancer chemoprevention: current challenges and a look toward the future.
There is a need to develop new prevention agents for breast cancer risk reduction that would have fewer side effects than the approved agent, tamoxifen, and/or would be effective in preventing estrogen receptor-negative or tamoxifen-resistant, estrogen receptor-positive breast cancers. There also is a need to improve the accuracy of present risk assessment models and to incorporate tissue-based biomarkers to supplement risk prediction tools. Candidate risk biomarkers include the serum hormones insulin-like growth factor-1 and its binding protein-3, mammographic breast density, nipple aspirate fluid production, and breast tissue evidence of proliferative breast disease (intraepithelial neoplasia). A variety of techniques have been developed to randomly sample breast tissue to detect precancerous changes and/or detect modulation of proliferation in response to a prevention agent. Based on molecular abnormalities observed in breast intraepithelial neoplasia, a number of drug classes and combinations are suggested as potential chemoprevention approaches. Clinical trial models have been developed to select the appropriate drug dose for subsequent biomarker modulation chemoprevention trials in which the use of surrogate endpoint biomarkers as indicators of efficacy is being explored. If these biomarkers can be validated and shown to reliably predict and monitor response in phase I/II prevention trials, and if favorable modulation is correlated with subsequent decreased cancer incidence, biomarkers may replace cancer incidence as the endpoint in future phase III trials, dramatically reducing the time and expense associated with new prevention drug development.
Fabian
Carol J
CJ
Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. cfabian@kumc.edu
Kimler
Bruce F
BF
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D018890:Chemoprevention / Q000639:trends*; D005260:Female; D006801:Humans
D016588:Anticarcinogenic Agents