Breast Cancer : Prognosis, Treatment, and Prevention

ISBN: 9780824707125 | 0824707125
Cover: Hardcover
Copyright: 7/17/2002

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Summary

This reference examines the biological factors and genetic and molecular pathways potentially responsible for the development and progression of breast cancer-analyzing the latest therapeutic strategies as well as breakthroughs in endocrine treatments, angiogenesis, and non-hormonal approaches to predict, control, and inhibit the formation and growth of cancerous cells.

Preface

iii

Contributors

xix

Mechanisms Involved in Carcinogenesis of the Breast

(18)

Jose Russo

Irma H. Russo

Introduction

(1)

Developmental Pattern of the Human Breast from Adolescence to Maturity

(2)

Hormonal Influences on the Development of the Breast

(5)

Architectural Pattern of the Normal Breast at Menopause

(1)

Breast Development, Hormones, and the Pathogenesis of Breast Cancer

(2)

Future Perspectives

(7)

References

(6)

The Fetus, Pregnancy, and Breast Cancer

(54)

Jorge R. Pasqualini

Introduction

(2)

Hormones and Pregnancy

(4)

Breast Cancer and Pregnancy

(12)

Breast Cancer During Pregnancy

(8)

Breast Cancer Detected During Lactation or Postpartum

(1)

Pregnancies in Patients with a Previous Breast Cancer

(3)

Fetal and Perinatal Factors and Breast Cancer

(10)

The Fetal Hormonal Hypothesis: Its Possible Role in Breast Cancer

(1)

The Fetal Enzyme Hypothesis: Its Possible Role in Breast Cancer

(1)

Birth Weight as a Risk Factor for Breast Cancer

(1)

Multiple Births and Maternal Risk of Breast Cancer

(1)

Duration of Pregnancy and Risk of Breast Cancer

(2)

Gender of Offspring and Maternal Breast Cancer Risk

(1)

Pre- and Perinatal Mechanism and Other Factors Involved in the Risk of Breast Cancer

(1)

Lifestyle During Pregnancy and Risk of Breast Cancer

(2)

Abortion and Risk of Breast Cancer

(4)

Induced Abortion

(1)

Abortion and Risk of Breast Cancer as Associated with the Gestational Age of the Fetus

(1)

Abortion and Risk of Breast Cancer with Maternal Age

(1)

Effect of Single Versus Multiple Induced Abortions

(1)

Spontaneous Abortion

(1)

Spontaneous Versus Induced Abortion and Breast Cancer Risk

(1)

BRCA-1 and BRCA-2 in Pregnancy

(1)

The Fetal and Maternal Immune Systems: Possible Role in Breast Cancer

(3)

Pregnancy-Induced Immunity

(1)

The Fetal Antigen Hypothesis for Breast Cancer Risk

(1)

Other Factors in a Possible Relationship Between the Pregnancy Immunosystem and Breast Cancer Risk

(1)

Can a Woman ``Vaccinate'' Herself Against Breast Cancer by Becoming Pregnant?

(1)

Conclusions

(19)

References

(17)

Control of proliferation in the Normal and Neoplastic Breast

(20)

Robert B. Clarke

Anthony Howell

Elizabeth Anderson

Introduction

(1)

The Normal and Neoplastic Mammary Gland

(2)

Human Breast Development

(1)

Epithelial Cell Types in the Human Breast

(1)

Breast Tumor Pathogenesis

(1)

Factors Controlling Epithelial Proliferation

(7)

Ovarian Steroids: Estrogen and Progesterone

(3)

Local Growth Factors

(2)

Intracellular Pathways Leading to Cell Growth

(2)

Targets for the Therapeutic Manipulation of Cell Proliferation

(1)

Summary

(9)

References

(9)

Prognostic and Predictive Factors and Targets for Therapy in Breast Cancer

(32)

Jan G. M. Klijn

Els M. J. J. Berns

John A. Foekens

Introduction

(2)

Prognostic and Predictive Factors

(15)

Patient Characteristics

(2)

Variables Determined in Blood

(1)

Tumor Characteristics

(12)

Final Conclusions on Prognostic and Predictive Factors

109

(1)

Molecular Target--Directed Therapies

110

(15)

Short Overview

110

(2)

Future Aspects

112

(1)

References

112

(13)

Inhibition of Cell Growth and Induction of Apoptosis

125

(24)

Bent Formby

T. S. Wiley

Introduction

125

(1)

What Is the Core Apoptotic Machinery?

126

(1)

Important Genes Related to Apoptosis

127

(1)

Function of CD44 in Tumor Cells

128

(1)

Sex Steroid Cell Cycle Phase--Specific Actions and Apoptosis

128

(1)

Molecular Effects of Sex Steroids on the Occurrence of Apoptosis in Breast Cancer Cell Lines

129

(5)

Experimental Studies on Apoptotic Regulators in the Breast Tumor Cell Lines T-47D, MCF-7, and MDA-MD-231

134

(5)

Concluding Remarks

139

(10)

The Menstrual Cycle and Aggressiveness of Breast Carcinomas

139

(1)

Molecular Effects of Progesterone on Breast Tumor Cells In Vitro

139

(2)

In Vivo Effects of Progesterone on Normal Human Breast Epithelial Cells

141

(1)

Progesterone-Induced Apoptosis in Breast Cancer Cells May Be Relevant for Therapeutic Purposes

142

(1)

Progesterone May Act on Tumor Cells' Ability to Escape

143

(1)

References

144

(5)

The Importance of the Estrogen Receptor in Breast Cancer

149

(38)

Rachel Schiff

Suzanne A. W. Fuqua

Introduction

149

(1)

ER-Mediated Processes in Normal and Cancer Breast Cells

150

(1)

ER Genes and mRNA Transcriptional Regulation

151

(2)

ER Expression in Premalignant Disease and Breast Cancer

152

(1)

Transcriptional Regulation

152

(1)

Molecular Mechanism of ER Action as a Ligand-Dependent Transcription Factor

153

(8)

ERα Structure and Functional Domains

154

(2)

Erβ

156

(2)

Nuclear Receptor Coactivator and Corepressor Proteins

158

(3)

ER Cross-Talk with Other Signal Transduction Pathways and Alternative Signaling

161

(3)

Cross-Talk with Other Transduction Pathways at the ER

161

(2)

Nonclassical Binding---ER Pathways Through AP-1

163

(1)

Rapid Nongenomic Signaling---Membrane-Bound ER

164

(1)

Endocrine Therapies

164

(2)

Selective Estrogen-Receptor Modulators (SERMs) and Pure Antiestrogens

164

(2)

Aromatase Inhibitors

166

(1)

Methods for the Measurement of ER in Breast Cancer

166

(2)

Assay Methodology

166

(1)

Cutoff Point

167

(1)

ER in the Clinical Management of Breast Cancer Patients

168

(5)

ER as a Prognostic Factor

168

(1)

ER as a Predictive Factor

169

(1)

ER in Prevention

170

(1)

ER Mutations and Variants in Clinical Breast Cancer

170

(3)

Summary and Conclusions

173

(14)

References

173

(14)

The Selective Estrogen Enzyme Modulators (SEEM) in Breast Cancer

187

(64)

Jorge R. Pasqualini

Gerard S. Chetrite

Introduction

187

(1)

Estrogen Concentrations in Breast Cancer

188

(3)

Estrone Sulfatase and Its Control in Breast Cancer

191

(11)

Estrone Sulfatase: Structure, Function, and Enzymatic Characteristics

191

(2)

Estrone Sulfatase in Breast Cancer

193

(2)

Control of Estrone Sulfatase

195

(6)

Expression and Control of Estrone Sulfatase mRNA

201

(1)

Sulfatase Versus Aromatase Activities in Breast Tissues

202

(2)

In Breast Cancer Tissues

202

(1)

In Breast Fibroadenoma

203

(1)

Sulfotransferase and Its Control in Breast Cancer

204

(12)

Mechanism of Sulfoconjugation

204

(1)

Sulfotransferase (ST) Superfamilies

205

(1)

Sulfotransferases in Normal and Carcinomous Breast

206

(4)

Control of Sulfotransferase Activities in the Breast

210

(4)

Sulfotransferase Expression and Its Control in Breast Cancer

214

(2)

17β-Hydroxysteroid Dehydrogenase and Its Control in Breast Cancer

216

(7)

17β-Hydroxysteroid Dehydrogenase Isoforms: Nomenclature, Structure, and Function

216

(2)

17β-Hydroxysteroid Dehydrogenase in Normal and Tumoral Breast Tissues

218

(3)

Control of 17β-Hydroxysteroid Dehydrogenase Activity in the Breast

221

(2)

Proliferation of the Breast Cell and Its Control by Progestins

223

(5)

In the Normal Breast Cell

223

(1)

In the Breast Cancer Cell

224

(1)

Progestins and the Mechanism of Cell Growth

225

(1)

Hypothetical Correlation of Sulfotransferase Activity and Proliferation of the Breast Cancer Cell

226

(2)

Conclusions

228

(23)

References

231

(20)

Aromatase Inhibitors and Their Application to the Treatment of Breast Cancer

251

(20)

Angela M. H. Brodie

Introduction

251

(1)

Aromatase Expression

252

(1)

Aromatase as Target for Inhibition

253

(1)

Selective Aromatase Inhibitors

253

(3)

Enzyme Inactivators

254

(1)

Nonsteroidal Aromatase Inhibitors

255

(1)

Clinical Efficacy of Aromatase Inhibitors

256

(3)

Treatment for Advanced Breast Cancer

256

(3)

Aromatase Inhibitors as First-Line Therapy

259

(1)

Exemestane

259

(1)

Anastrozole

259

(1)

Letrozole

260

(1)

Intratumoral Aromatase Mouse Model as a Guide for Future Trials

260

(5)

Conclusion

265

(6)

References

265

(6)

Selective Estrogen Receptor Modulation

271

(16)

Anait S. Levenson

V. Craig Jordan

Introduction

271

(2)

Recognition of Selective Estrogen Receptor Modulation

273

(1)

Tamoxifen

273

(1)

Raloxifene

273

(1)

Clinical Demonstration of SERM Principles

274

(3)

D351Y ER

277

(3)

Conclusions

280

(7)

References

280

(7)

Cathepsin D in Breast Cancer---20 Years Later

287

(14)

Henri Rochefort

J. F. Rouayrenc

Pascal Roger

Introduction

287

(1)

A Cytosolic Marker Associated with Poor Prognosis in Breast Cancer

288

(2)

Cathepsin D Expression Assessed by Immunohistochemistry

290

(2)

The Clinical Value of Cath-D Level or Activity Depends on the Validation of the Assay

292

(1)

An Overview on the Mode of Action of Overexpressed Cathepsin D in Breast Cancer

292

(2)

Conclusions

294

(7)

References

295

(6)

The Breast Cancer Phenotype and Endocrine Response: Implications for New Drug Development Initiatives

301

(42)

Julia M. W. Gee

Robert I. Nicholson

Introduction

301

(1)

Estrogen-Receptor Signal Transduction

302

(1)

Growth-Factor Signal Transduction

303

(2)

Signaling Interactions

305

(3)

The Estrogen Receptor Is a Target for Growth-Factor--Induced Kinase Activity

305

(1)

Estrogens Stimulate Positive Elements of Growth-Factor Signaling Pathways, Including Cell Attachment Factors that May Facilitate Growth-Factor--Directed Cell Proliferation

305

(1)

Estrogens Inhibit Negative Elements of Growth-Factor Signaling Pathways

306

(1)

The Estrogen Receptor Interacts with Growth-Factor--Induced Nuclear Transcription Factors, Coactivators/Corepressors, and Additional Proteins to Target a Diversity of Response Elements

307

(1)

Steroid Hormone and Growth-Factor Signaling Pathways Influence Common Growth Regulatory Genes

308

(1)

Changes in the Tumor Cell Phenotype Are Likely to Perturb ``Cross-Talk'' Between Estrogen and Growth-Fact r Signaling Pathways in Endocrine-Unresponsive Disease

308

(10)

EGFR and Additional Members of the erbB Receptor Tyrosine Kinase Family

309

(1)

Transforming Growth Factor Alpha and Additional erbB Receptor Ligands

310

(1)

Insulin-Like Growth-Factor Family

311

(1)

Intracellular Components of Growth Factor Signaling Pathways

312

(1)

Nuclear Transcription Factors

313

(1)

Negative Elements of Growth-Factor Signaling Pathways

314

(1)

Genetic Events in Growth-Factor Expression and Cell Cycle Control

315

(2)

Estrogen Receptor Loss, Receptor Variants/Mutations, and Subtypes

317

(1)

Model of Endocrine Response and New Therapeutic Targets

318

(1)

New Therapeutic Targets

319

(4)

ER: Pure Antiestrogens and Antisteroid Hormone Receptor Regimes

319

(1)

Growth Factor Receptors: Antiligand and Receptor Regimes

320

(1)

Signal Transduction Pathways

321

(1)

Nuclear Transcription Factors

322

(1)

Summary and Conclusions

323

(20)

References

323

(20)

Recent Developments in the Hormonal Treatment of Breast Cancer

343

(30)

Irene M. Boeddinghaus

Mitch Dowsett

Introduction

343

(1)

GnRH Agonists and Antagonists

343

(5)

Advanced Disease

345

(1)

Adjuvant Therapy

346

(1)

Neoadjuvant Therapy

347

(1)

Prevention

347

(1)

GnRH Antagonists

348

(1)

Aromatase Inhibitors

348

(5)

Advanced Disease

349

(2)

Adjuvant Therapy

351

(1)

Primary Therapy

352

(1)

Prevention

352

(1)

Tamoxifen

353

(3)

Advanced Disease

353

(1)

Adjuvant Therapy

353

(2)

Primary Therapy

355

(1)

Prevention

355

(1)

Selective Estrogen Receptor Modulators

356

(3)

Advanced Disease

358

(1)

Adjuvant Therapy

358

(1)

Primary Therapy

358

(1)

Prevention

359

(1)

Pure Antiestrogens

359

(1)

Advanced Disease

360

(1)

Adjuvant Therapy

360

(1)

Primary Therapy

360

(1)

Progestins and Antiprogestins

360

(1)

Sequential/Combination Treatment

361

(1)

Advanced Disease

361

(1)

Summary and Conclusions

362

(11)

References

362

(11)

Hormone Replacement Therapy, the Menopause, and Breast Cancer

373

(32)

Jo Marsden

Introduction

373

(1)

Evidence for the Estrogen Dependency of Breast Cancer

374

(1)

HRT and the Risk of Developing Breast Cancer

375

(8)

Does HRT Increase the Risk of Developing Breast Cancer?

375

(3)

Combined HRT and Breast Cancer Risk

378

(1)

HRT, Breast Density, and Mammography

379

(1)

The Influence of HRT on Breast Tumor Biology

380

(1)

The Effect of HRT on Breast Cancer Mortality

381

(2)

The Use of HRT in Women with a Previous Diagnosis of Breast Cancer

383

(10)

The Incidence of Estrogen Deficiency Symptoms in Women with Breast Cancer

383

(2)

Alternatives to HRT for the Management of Estrogen Deficiency in Breast Cancer Patients

385

(8)

Conclusion

393

(12)

References

393

(12)

Adjuvant Therapy of Breast Cancer in Premenopausal Women: Hormone Therapy, Chemotherapy, or Both?

405

(12)

Moise Namer

Introduction

405

(1)

Randomized Controlled Trials Comparing Hormone Therapy and Chemotherapy

406

(3)

Castration Versus Chemotherapy

406

(2)

Tamoxifen Versus Chemotherapy

408

(1)

Which Hormone Therapy Can Be the Best Comparator with Chemotherapy?

409

(2)

Should Hormone Therapy Be Combined with Chemotherapy?

411

(3)

Combining Castration with Chemotherapy

411

(2)

Combining Tamoxifen with Chemotherapy

413

(1)

Conclusions

414

(3)

References

414

(3)

Cytotoxic Therapy and Other Nonhormonal Approaches for the Treatment of Metastatic Breast Cancer

417

(56)

Joseph A. Sparano

Introduction

417

(1)

Effect of Cytotoxic Therapy on Survival and Symptom Palliation

417

(2)

Definition of Response and Other Endpoints

419

(1)

Patterns and Timing of Recurrence

420

(1)

Prognostic Factor Models

420

(1)

Commonly Used Chemotherapy Agents/Regimens

421

(2)

Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF)

423

(1)

Doxorubicin

424

(2)

Mechanism of Action and Metabolism

424

(1)

Phase III Trials of Doxorubicin

424

(1)

Cardiac Toxicity of Doxorubicin

425

(1)

Phase III Trials of Doxorubicin and Dexrazoxane

425

(1)

Liposomal Anthracyclines

426

(4)

Liposomal Preparations

426

(1)

Tumor Penetration of Liposomal Anthracyclines

427

(1)

Comparison of D-99 with Doxorubicin and Epirubicin

428

(1)

Clinical Trials of Pegylated Liposomal Doxorubicin

429

(1)

Epirubicin

430

(2)

Mechanism of Action and Pharmacology

430

(1)

Comparison of Epirubicin with Doxorubicin

430

(1)

Evaluation of the Optimal Dose of Epirubicin

430

(1)

Evaluation of the Optimal Schedule of Epirubicin

430

(1)

Comparison of Single-Agent Epirubicin with Combination Therapy

431

(1)

Mitoxantrone

432

(1)

Mechanism of Action of Metabolism

432

(1)

Comparison of Mitoxantrone with Doxorubicin

432

(1)

Taxanes

433

(8)

Mechanism of Action and Metabolism

433

(1)

Single-Agent Paclitaxel: Duration of Infusion

434

(1)

Single-Agent Paclitaxel: Evaluating the Optimal Dose

435

(1)

Single-Agent Paclitaxel Compared with Other Agents or Combinations

436

(2)

Single-Agent Docetaxel Compared with Other Agents or Combinations

438

(1)

Taxane-Anthracycline Combinations

439

(1)

Taxane-Based Combinations Compared with Other Combinations

439

(2)

Weekly Taxanes

441

(1)

Vinorelbine

441

(1)

Mechanism of Action and Metabolism

441

(1)

Phase II and Phase III Trials

441

(1)

Capecitabine

442

(1)

Mechanism of Action and Metabolism

442

(1)

Phase II Trials

443

(1)

Gemcitabine

443

(1)

Mechanism of Action and Metabolism

443

(1)

Phase II Trials

444

(1)

Platinum Analogues

444

(1)

Mechanism of Action and Metabolism

444

(1)

Phase II Trials

444

(1)

Duration of Chemotherapy

445

(2)

Less Than 4 Months of Therapy

445

(1)

CMF Maintenance Beyond 4 Months

445

(2)

Epirubicin-Based Maintenance Therapy

447

(1)

High-Dose Therapy Plus Stem Cell Transplantation

447

(1)

Trastuzumab

448

(3)

HER2 as a Therapeutic Target

448

(1)

Efficacy of Trastuzumab

448

(1)

Cardiac Toxicity of Trastuzumab

449

(2)

Bisphosphonates

451

(1)

Colony-Stimulating Factors

452

(1)

Systematic Review of Cytotoxic Therapy

453

(1)

Chemotherapy Versus Hormonal Therapy

454

(1)

Chemotherapy Versus Chemohormonal Therapy

454

(1)

General Approach to Treatment

455

(1)

Nonlocalized (Disseminated) Disease

455

(1)

One Site of Disease

455

(1)

Clinical Trials

456

(1)

Conclusions

457

(16)

References

457

(16)

Management of Locally Advanced Breast Cancer

473

(24)

Ummekalsoom R. Malik

Joseph A. Sparano

Introduction

473

(1)

Prognostic Features

474

(1)

Diagnosis and Pretreatment Evaluation

475

(1)

Management of Locally Advanced Breast Cancer

475

(1)

Rationale for Primary Systemic (Neoadjuvant) Chemotherapy

475

(1)

Randomized Trials Comparing Primary Systemic with Adjuvant Chemotherapy

476

(3)

Prognostic Significance of Clinical and Pathological Response to Primary Systemic Chemotherapy

479

(1)

Randomized Trials Comparing Different Regimens for Primary Systemic Therapy

480

(2)

Nonrandomized Trials of Primary Systemic Chemotherapy in Locally Advanced and Non-Locally Advanced Breast Cancer

482

(3)

Randomized Trials of Irradiation Following Mastectomy

485

(2)

Randomized Trials Evaluating Local and/or Systemic Therapy

487

(2)

Randomized Trials Evaluating Adjuvant Therapy Following Neoadjuvant Chemotherapy

489

(1)

Inflammatory Breast Cancer

489

(1)

Prognostic Factors

489

(1)

Management of Inflammatory Breast Cancer

490

(2)

Surgery and Irradiation

490

(1)

Nonrandomized Studies of Chemotherapy Plus Local Therapy

490

(1)

High-Dose Chemotherapy for Locally Advanced Breast Cancer

491

(1)

Conclusions

492

(5)

References

492

(5)

Angiogenesis Research: Possible Prognostic and Therapeutic Applications in Breast Cancer

497

(30)

Giampietro Gasparini

Biological Background

497

(4)

Angiogenesis

497

(4)

Lymphangiogenesis

501

(1)

Prognostic Applications of Surrogate Markers of Angiogenesis

501

(8)

Intratumoral Microvessel Density (IMD)

501

(2)

Angiogenic Factors

503

(6)

Antiangiogenic Therapy

509

(6)

General Principles

509

(2)

Studies on Breast Cancer

511

(4)

Conclusions and Future Directions of Research

515

(12)

References

516

(11)

Phytoestrogens and Breast Cancer

527

(1)

Herman Adlercreutz

Witold Mazur

Satu-Maarit Heinonen

Katariina Stumpf

Introduction

527

(1)

Isoflavones

528

(1)

Plant Lignans and Formation of Mammalian Lignans

529

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Breast Cancer : Prognosis, Treatment, and Prevention

Summary

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