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E-raamat: Tamoxifen: Pioneering Medicine in Breast Cancer

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Tamoxifen is a pioneering medicine for the treatment and prevention of breast cancer. It is the first drug targeted therapy in cancer to be successful. Tamoxifen targets the tumor estrogen receptor. The therapy is known to have saved the lives of millions of women over the past 40 years.This monograph, written by V. Craig Jordan - known as the “father of tamoxifen” - and his Tamoxifen Team at the Georgetown University Washington DC, illustrates the journey of this milestone in medicine. It includes a personal interview with V. Craig Jordan about his four decades of discovery in breast cancer research and treatment. V. Craig Jordan was there for the birth of tamoxifen as he is credited for reinventing a “failed morning after contraceptive” to become the “gold standard” for the treatment of breast cancer. He contributed to every aspect of tamoxifen application in therapeutics and all aspects of tamoxifen’s pharmacology. He discovered the selective estrogen receptor modulators (SERMs) and explored the new biology of estrogen-induced apoptosis.

Tamoxifen is a pioneering medicine for the treatment and prevention of breast cancer. This monograph, written by V. Craig Jordan, the “Father of tamoxifen,” and his team at Georgetown University illustrates the journey of this milestone in medicine.

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From the book reviews:

This is a book that had to be written. This book should be available in every oncology department. The story will interest clinicians and laboratory scientists alike. It has both historical value and value as a guide that will illuminate the path to successful involvement in cancer research for younger cancer researchers. (R. M. Lowenthal, Inflammopharmacology, Vol. 22 (3), June, 2014)

This is a very well-written, readable book for anyone who has an interest in the prevention and treatment of breast cancer, ranging from those involved in drug discovery to those who are treating and taking care of patients with breast cancer. Likewise, anyone who has a loved one who has, or is at high risk for, breast cancer will find this an excellent read. It is a well-done and interesting read. (Thomas L. Pazdernik, Doodys Book Reviews, November, 2013)

1 Discovery and Pharmacology of Nonsteroidal Estrogens and Antiestrogens
1(30)
Introduction
1(1)
Testing Methods for Estrogen
2(1)
Structure-Activity Relationships of Estrogens
3(3)
Estrogen Action
6(1)
Nonsteroidal Antiestrogens
7(1)
Structure-Activity Relationships in the Rat
7(1)
Substituted Tripheny lethylenes
7(2)
Bicyclic Antiestrogens
9(3)
The Molecular Modulation of the Estrogen Receptor by Nonsteroidal Antiestrogens
12(4)
Effect of Antiestrogens in Different Species
16(1)
Mouse
17(1)
Rat
18(2)
Chick
20(1)
Conclusion
20(2)
References
22(9)
2 Tamoxifen Goes Forward Alone
31(16)
Introduction
31(2)
ICI 46,474: The Early Years
33(4)
ICI 46,474 to Tamoxifen
37(2)
Patenting Problems
39(1)
Conclusion
40(2)
References
42(5)
3 Metabolites of Tamoxifen as the Basis of Drug Development
47(22)
Introduction
47(1)
Basic Mechanisms of Tamoxifen Metabolism
48(4)
Metabolic Mimicry
52(3)
Tamoxifen Metabolism Today
55(2)
Clinical Correlations
57(3)
References
60(9)
4 Adjuvant Therapy: The Breakthrough
69(16)
Introduction
69(1)
Adjuvant Therapy with Tamoxifen
70(3)
Studies in Premenopausal Women
73(1)
Overview of Clinical Trials
74(2)
Arrival of Aromatase Inhibitors as Adjuvant Therapy
76(1)
Increasing Survivorship Following 5 Years of Adjuvant Tamoxifen
77(3)
References
80(5)
5 The Wisconsin Story in the 1980s: Discovery of Target Site-Specific Estrogen Action
85(16)
Introduction
85(1)
Laboratory Studies on the Target Site-Specific Pharmacology of "Nonsteroidal Antiestrogens"
86(3)
The Wisconsin Tamoxifen Study
89(1)
Translational Research
90(6)
References
96(5)
6 Carcinogenesis and Tamoxifen
101(14)
Introduction
101(1)
Tamoxifen and the Endometrial Carcinoma
102(1)
Deaths from Endometrial Carcinoma
103(1)
Tamoxifen and the Stage of Endometrial Carcinoma
104(1)
Incidence of Endometrial Cancer with Tamoxifen
105(2)
Tamoxifen and Rat Liver Carcinogenesis
107(1)
Tamoxifen and DNA Adduct Formation
108(1)
Doses of Tamoxifen in Animals and Man
109(1)
Testing at Comparable Therapeutic Levels
110(1)
Conclusion
111(2)
References
113(2)
7 Chemoprevention: Cinderella Waiting for the Ball
115(20)
Introduction
115(1)
The Link Between Estrogen and Breast Cancer
116(1)
Prevention of Mammary Cancer in Rodents
117(2)
Tamoxifen: The First SERM for the Prevention of Breast Cancer in High-Risk Populations
119(1)
Royal Marsden Study
120(2)
NSABP/NCI P-1 Study
122(3)
Italian Study
125(1)
The International Breast Cancer Intervention Study (IBIS-I)
126(1)
Follow-Up of Chemoprevention Studies with Tamoxifen
127(1)
Two Approaches to the Chemoprevention of Breast Cancer
127(1)
Raloxifene: Abandoned and Resurrected
128(3)
Conclusion
131(1)
References
131(4)
8 Tamoxifen and Raloxifene Head to Head: The STAR Trial
135(8)
References
141(2)
9 Acquired Resistance to Tamoxifen: Back to the Beginning
143(22)
Introduction
143(1)
The MCF-7 Breast Cancer Cell Line
144(1)
Tamoxifen Metabolism Hypothesis
145(1)
Growth Factor-Driven Acquired and Intrinsic Resistance
146(1)
An Evolving Model of Acquired Resistance to SERMs and Aromatase Inhibitors
147(2)
Back to the Beginning
149(1)
Mechanisms of Estrogen-Induced Apoptosis
150(2)
A New Classification of Estrogens
152(1)
Final Thoughts on Four Decades of Discovery to Advance the Value of the ER Target in Breast Cancer
153(4)
References
157(8)
10 The Legacy of Tamoxifen
165(14)
Introduction
165(1)
Pure Antiestrogens
166(2)
SERM Successes
168(1)
Lasofoxifene (CP-336156, Fablyn)
169(1)
Bazedoxifene (TSE-424, WAY-140424)
170(1)
Ospemifene (FC-1271a)
170(1)
Refining the SERM Concept Further
171(3)
References
174(5)
Appendix A Four Decades of Discovery in Breast Cancer Research and Treatment: An Interview with V. Craig Jordan 179(18)
Appendix B Selected Awards That Recognize the Contribution of Tamoxifen and Raloxifene to Medicine 197
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