TY - JOUR
T1 - Strategies for the application of biomarkers for risk assessment and efficacy in breast cancer chemoprevention trials
AU - Dhingra, Kapil
AU - Vogel, Victor
AU - Sneige, Nour
AU - Sahin, Aysegul
AU - Aldaz, Marcelo
AU - Hortobagyi, Gabriel N.
AU - Hittelman, Walter
PY - 1993
Y1 - 1993
N2 - Current chemoprevention trial designs based on epidemiological risk assessment and occurrence of cancer as an endpoint are inefficient and expensive. Novel biomarkers are needed to facilitate the development of chemopreventive interventions. The following four categories of biomarkers may be useful in prevention trials: histologic and morphometric markers; phenotypic markers of dysregulated proliferation, differentiation, and cell loss; specific oncogenes and growth regulators which are qualitatively or quantitatively altered in breast cancers; and markers of genetic and epigenetic instability. Some of these markers will be generally useful regardless of the chemopreventive approach used, whereas others may be uniquely useful in trials of specific chemopreventive agents [e.g., upregulation of progesterone receptor (PR) expression in response to tamoxifen]. The development of these markers requires three phases of study: “Phase I”: assessing the prevalence of the putative marker in malignant and premalignant tissue from individuals who have developed breast cancer; “Phase II”: assessing in vivo modulation of the biomarker by the proposed chemopreventive agent; and “Phase III”: applying the proposed biomarker in larger‐scale trials of chemopreventive agent in high‐risk populations, either before or after the development of a primary breast malignancy. The use of these biomarkers may also allow identification of novel targets for chemoprevention.
AB - Current chemoprevention trial designs based on epidemiological risk assessment and occurrence of cancer as an endpoint are inefficient and expensive. Novel biomarkers are needed to facilitate the development of chemopreventive interventions. The following four categories of biomarkers may be useful in prevention trials: histologic and morphometric markers; phenotypic markers of dysregulated proliferation, differentiation, and cell loss; specific oncogenes and growth regulators which are qualitatively or quantitatively altered in breast cancers; and markers of genetic and epigenetic instability. Some of these markers will be generally useful regardless of the chemopreventive approach used, whereas others may be uniquely useful in trials of specific chemopreventive agents [e.g., upregulation of progesterone receptor (PR) expression in response to tamoxifen]. The development of these markers requires three phases of study: “Phase I”: assessing the prevalence of the putative marker in malignant and premalignant tissue from individuals who have developed breast cancer; “Phase II”: assessing in vivo modulation of the biomarker by the proposed chemopreventive agent; and “Phase III”: applying the proposed biomarker in larger‐scale trials of chemopreventive agent in high‐risk populations, either before or after the development of a primary breast malignancy. The use of these biomarkers may also allow identification of novel targets for chemoprevention.
KW - Breast cancer
KW - chemoprevention
KW - genetic instability
KW - intermediate biomarkers
KW - multistep carcinogenesis
UR - http://www.scopus.com/inward/record.url?scp=0027792992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027792992&partnerID=8YFLogxK
U2 - 10.1002/jcb.240531106
DO - 10.1002/jcb.240531106
M3 - Article
C2 - 8007707
AN - SCOPUS:0027792992
SN - 0730-2312
VL - 53
SP - 37
EP - 43
JO - Journal of cellular biochemistry
JF - Journal of cellular biochemistry
IS - S17G
ER -