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Updated: Mar 24, 2026
Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
Incorporating Biomarkers in Studies of Chemoprevention
Carol J Fabian1, Bruce F Kimler2
1University of Kansas Medical Center, 3901 Rainbow Boulevard, 66160, Kansas City, KS, USA. cfabian@kumc.edu.
Abstract:
Despite Food and Drug Administration approval of tamoxifen and raloxifene for breast cancer risk reduction and endorsement by multiple agencies, uptake of these drugs for primary prevention in the United States is only 4% for risk eligible women likely to benefit from their use. Side effects coupled with incomplete efficacy and lack of a survival advantage are the likely reasons. This disappointing uptake, after the considerable effort and expense of large Phase III cancer incidence trials required for approval, suggests that a new paradigm is required. Current prevention research is focused on (1) refining risk prediction, (2) exploring behavioral and natural product interventions, and (3) utilizing novel translational trial designs for efficacy. Risk biomarkers will play a central role in refining risk estimates from traditional models and selecting cohorts for prevention trials. Modifiable risk markers called surrogate endpoint or response biomarkers will continue to be used in Phase I and II prevention trials to determine optimal dose or exposure and likely effectiveness from an intervention. The majority of Phase II trials will continue to assess benign breast tissue for response and mechanism of action biomarkers. Co-trials are those in which human and animal cohorts receive the same effective dose and the same tissue biomarkers are assessed for modulation due to the intervention, but then additional animals are allowed to progress to cancer development. These collaborations linking biomarker modulation and cancer prevention may obviate the need for cancer incidence trials for non-prescription interventions.
Insights
Low uptake of breast cancer risk reduction drugs like tamoxifen and raloxifene necessitates new prevention strategies. Research now focuses on improved risk prediction and novel trial designs using biomarkers for better efficacy assessment.
Area of Science:
- Oncology
- Preventive Medicine
- Biomarker Research
Background:
- Tamoxifen and raloxifene are FDA-approved for breast cancer risk reduction but have low U.S. uptake (4%) among eligible women.
- Reasons for low uptake include side effects, incomplete efficacy, and lack of survival benefit.
- Current breast cancer prevention research requires a new paradigm beyond traditional large-scale incidence trials.
Purpose of the Study:
- To address the low uptake of breast cancer preventive medications.
- To explore novel strategies for breast cancer prevention research.
- To highlight the role of biomarkers in refining risk prediction and evaluating intervention efficacy.
Main Methods:
- Focus on refining risk prediction models.
- Investigation of behavioral and natural product interventions.
- Utilization of translational trial designs incorporating risk and response biomarkers.
- Assessment of benign breast tissue for biomarkers in Phase II trials.
- Implementation of co-trials with human and animal cohorts to link biomarker modulation with cancer prevention.
Main Results:
- Risk biomarkers are crucial for improving risk estimates and selecting trial cohorts.
- Surrogate endpoint or response biomarkers will guide dose optimization and effectiveness in early-phase trials.
- Co-trials may reduce the need for cancer incidence trials for non-prescription interventions by linking biomarker changes to prevention outcomes.
Conclusions:
- A shift towards biomarker-driven research is essential for advancing breast cancer prevention.
- Novel translational trial designs, including co-trials, offer a more efficient pathway for evaluating interventions.
- Biomarker research holds the potential to overcome limitations of current prevention strategies and improve drug uptake.
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