Breast Cancer and Molecular Medicine

2 PET and Nuclear Medicine Imaging of the Breast......Page 8
4 Prevention of Breast Cancer......Page 9
6 Ductal Carcinoma In Situ: a Modern Approach to Patient Management......Page 10
9 Tailored Surgery for Early Breast Cancer: Biological Aspects......Page 11
11 Tailored Surgery for Older Women with Breast Cancer......Page 12
13 Breast Cancer Management in the Era of Molecular Medicine: Tailored Radiotherapy – Clinical and Biological Aspects......Page 13
16 Early Breast Cancer (Stage I and Stage II): Tailored Systemic Therapy for Endocrine-Resistant Breast Cancer......Page 14
18 Tailored Therapy for Breast Cancer in Very Young Women......Page 15
19 Tailored Systemic Therapy for the Elderly Woman......Page 16
20 Locoregional Therapy Following Neoadjuvant Chemotherapy: an Evolving Paradigm of Treatment Individualization......Page 17
22 Metastatic Breast Cancer: Tailored Endocrine Therapy for Premenopausal Women......Page 18
24 Metastatic Breast Cancer: Tailored Chemotherapy for the Elderly Woman......Page 19
26 Surgical Management of Breast Cancer Liver Metastases......Page 20
28 Breast Cancer Metastases to the Eye......Page 21
30 Genomic and Molecular Classification of Breast Cancer......Page 22
32 Targeting the HER Family of Receptors in the Treatment of Advanced Breast Cancer......Page 23
33 Biological Therapies for Metastatic Breast Cancer: Antiangiogenesis......Page 24
35 Innovative Rational-Derived, Target- Based and Cytotoxic Therapies for Breast Cancer and Other Malignancies......Page 25
37 Mechanisms of Resistance to Hormone Therapy......Page 26
39 Mechanisms of Apoptosis Resistance In Breast Cancer......Page 27
41 Hormone Replacement Therapy After Breast Cancer......Page 28
42 Male Breast Cancer......Page 29
43 Patients’ Preferences: What Makes Treatments Worthwhile?......Page 30
45 Molecular Profiling in Breast Cancer......Page 31
Subject Index......Page 32
Contributors......Page 33
1.1 Introduction......Page 53
1.2 The Skipper-Schabel Model and its Relevance......Page 54
1.3 Gompertzian Growth and the Norton-Simon Hypothesis......Page 57
1.4 The Impact Of Sequential Chemotherapy......Page 61
1.5 Dose Size......Page 65
1.6 Scheduling: What about Dose Density?......Page 66
1.7 Sequential Therapy and Dose Density in the Clinic......Page 67
1.8 Some Cautions Regarding Dose Density......Page 70
1.9 Gompertzian Growth is Biologically Driven......Page 73
References......Page 74
Editorial Comment......Page 79
2.2 18FDG-PET......Page 80
2.4 Axillary Lymph Nodes......Page 81
2.5 Metastatic Disease and Staging......Page 82
2.7 Prognostic Assessment......Page 83
2.9 99mTc-Sestamibi and 99mTc-Tetrofosmin......Page 84
2.10 Dedicated Devices for Nuclear Medicine Breast Imaging......Page 85
References......Page 87
Editorial Comment......Page 90
3.2 Magnetic Resonance Imaging......Page 91
3.3 Nuclear Medicine......Page 96
3.4 Monitoring Resistance to Chemotherapy......Page 103
3.5 Tumor Hypoxia......Page 104
3.6 Conclusion......Page 105
References......Page 107
Editorial Comment......Page 110
4.2 Surgery For Breast Cancer Risk Reduction......Page 111
4.3 Chemoprevention of Breast Cancer......Page 117
4.4 Prevention of ER-Negative Breast Cancer......Page 131
4.5 Current Progress and Future Challenges......Page 134
References......Page 135
Editorial Commentary......Page 144
5.1 Introduction......Page 146
5.2 Histological Classification......Page 148
5.3 Genetic Alterations......Page 151
5.4 A Multistep Model for Breast Carcinogenesis......Page 159
5.5 Discussion and Future Prospects......Page 160
References......Page 161
6.1 Introduction......Page 171
6.2 Treatment Options......Page 172
6.3 Biomarkers of Disease and Outcome......Page 174
6.4 Preventing Contralateral Breast Cancer......Page 176
6.5 Decision-Making Tools for Treatment of Ipsilateral DCIS......Page 177
6.6 Novel Therapies for Prevention......Page 179
References......Page 180
7.1 Introduction......Page 182
7.2 Molecular Characteristics of DCIS......Page 183
7.4 Tamoxifen Treatment for DCIS......Page 186
7.5 Aromatase Inhibitors as a Treatment for DCIS......Page 191
7.6 Treatment of Hormone-Independent DCIS......Page 193
7.7 Promising Novel Therapies for Hormone-Independent DCIS......Page 194
7.8 Future Directions In Treating DCIS......Page 196
References......Page 197
Editorial Comment......Page 203
8.1 Skin-Sparing Mastectomy......Page 205
8.2 Oncoplastic Surgery of the Breast......Page 216
References......Page 224
9.1 Introduction......Page 226
9.2 Molecular Biology and Behavior of the Cancer in the Breast......Page 227
9.3 Prediction of Lymph Node Involvement from the Primary Tumor......Page 229
9.4 Predicting Further Lymph Node Involvement after SLN Biopsy......Page 231
9.5 Molecular Biology and Tailored Surgery for the Individual Patient: Conclusion......Page 236
References......Page 237
10.2 Risk Factors......Page 242
10.4 Clinical Assessment and Diagnostic Procedure......Page 246
10.5 Tumor Characteristics......Page 247
10.6 Treatment......Page 248
10.7 Local and Distant Recurrence Rates and Prognosis......Page 249
10.8 Late Effects of Treatment......Page 252
References......Page 253
11.2 The Nature of Breast Cancer in Older Women......Page 257
11.4 Early Diagnosis......Page 259
11.5 Treatment of the Axilla......Page 260
11.6 Mastectomy as a Treatment......Page 262
11.7 The Role of Tamoxifen......Page 263
11.8 The Role of Radiotherapy......Page 265
11.9 Selection of Local Treatment......Page 267
References......Page 268
Editorial Commentary......Page 272
12.2 Wide Excision Alone Trials......Page 276
12.3 Studies Addressing the Benefit of a Tumor-Bed Boost after Whole-Breast RT......Page 277
12.5 Accelerated, Whole-Breast RT Fractionation Schedules......Page 279
12.6 Accelerated, Partial-Breast Irradiation......Page 280
12.7 Three-Dimensional Conformal PBI Technique......Page 284
12.8 Three-dimensional Treatment Planning and Intensity-Modulated RT......Page 286
References......Page 293
13.1 Overview......Page 298
13.2 Introduction......Page 299
13.3 Hormone Receptors......Page 300
13.4 Her2/neu Expression......Page 302
13.5 P53 Expression......Page 305
13.6 Proliferative Markers......Page 307
13.7 Other Selected Molecular Markers......Page 308
13.8 Genetic Factors and Local-Regional Management of Breast Cancer......Page 309
13.9 Conclusion......Page 314
References......Page 315
14.2 Age and Locoregional Recurrences......Page 320
14.3 Clinical, Pathological, and Biological Features Associated with Breast Cancer in Very Young Patients......Page 322
14.4 Respective Influence of Young Age and Other Associated Factors on the Risk of Breast Recurrence......Page 324
14.5 Tailoring Radiotherapy in Young Patients......Page 325
References......Page 327
15.2 Effects of Age......Page 331
15.3 Treatment......Page 334
15.4 Newer Techniques......Page 335
15.5 Palliative Radiotherapy......Page 339
References......Page 340
Editorial Comment......Page 347
16.2 The Use of Molecular Markers to Identify Low-Risk Endocrine-Resistant Disease......Page 348
16.3 The Use of Molecular Markers to Select Adjuvant Chemotherapy......Page 355
Summary......Page 360
References......Page 361
17.2 Tailored Endocrine Therapy......Page 366
17.3 Tailored Chemotherapy......Page 372
17.4 Treatment Summary......Page 378
References......Page 381
18.2 Incidence and Prevalence......Page 388
18.3 Age as a Prognostic Factor in Breast Cancer......Page 389
18.4 Prognostic Factors in the Young......Page 393
18.5 Age as an Independent Prognostic Factor......Page 396
18.6 Treatment of Breast Cancer in Young Women......Page 398
18.7 Special Considerations in the Young......Page 402
18.8 Conclusions and Caveats Regarding Tailored Therapy in Younger Women......Page 405
References......Page 406
19.2 Tumor Biology......Page 414
19.4 Life Expectancy for Older Women......Page 415
19.5 Comorbidities- Prevalence and Impact on Decision Making......Page 416
19.6 HER-2/neu Testing in Older Women with Early Stage Breast Cancer......Page 418
19.7 Adjuvant Systemic Therapy......Page 419
19.8 Neoadjuvant Therapy in Early Stage Disease......Page 427
19.9 Integrating the Data for Older Women into an Individualized Approach to Adjuvant Systemic Therapy......Page 428
References......Page 432
Editorial Commentary......Page 437
20.1 Introduction......Page 439
20.2 Appropriate Tumor Assessment Before, During, and After Neoadjuvant Chemotherapy and its Effects on Locoregional Management......Page 440
20.3 Locoregional Therapy Considerations Following Neoadjuvant Chemotherapy......Page 445
20.4 Future Directions in Locoregional Therapy after Neoadjuvant Chemotherapy......Page 453
References......Page 454
21.2 Diagnosis......Page 465
21.3 Prognostic and Predictive Factors......Page 466
21.4 Therapy......Page 467
21.5 Inflammatory Breast Cancer......Page 477
21.6 Conclusion......Page 478
References......Page 479
22.2 Ovarian Ablation for Treatment of Metastatic Breast Cancer......Page 487
22.3 Tamoxifen for Treatment of Metastatic Breast Cancer......Page 490
22.4 Tamoxifen Compared to Ovarian Ablation or Suppression......Page 491
22.5 Combined Endocrine Therapy with Ovarian Suppression and Tamoxifen......Page 492
22.6 Aromatase Inhibitors for Treatment of Metastatic Breast Cancer......Page 493
22.7 Sex Steroids for Treatment of Metastatic Breast Cancer......Page 494
22.9 Conclusion......Page 495
References......Page 496
23.2 Tailored Treatment Approaches to Endocrine Therapy for Breast Cancer......Page 501
23.3 Efficacy Issues in Tailored Endocrine Therapy for Advanced Disease......Page 502
23.4 Selective Estrogen-Receptor Downregulators......Page 505
23.6 The Use of HER2 to Tailor Endocrine Therapy for Advanced Disease?......Page 506
23.7 Combination Therapies with Signal Transduction Inhibitors......Page 507
23.9 Oncotype DX......Page 508
References......Page 510
24.2 Clinical Definition of Age......Page 514
24.3 Assessment of the Elderly Patient with Cancer......Page 516
24.4 Cancer Chemotherapy in the Elderly Patient......Page 519
24.6 Conclusion......Page 531
References......Page 532
25.1 Clinical Features......Page 539
25.2 Radiosurgery: Definition......Page 541
25.3 Treatment Algorithm......Page 542
25.4 Radiobiological and Technical Principles for Radiation Treatment......Page 544
25.5 Toxicity......Page 547
25.6 Institutional Experience......Page 548
References......Page 555
26.2 Surgical Management of Breast Cancer Liver Metastases: Rationale......Page 558
26.3 Surgical Management of Breast Cancer Liver Metastases: Options......Page 562
26.4 Conclusions......Page 571
References......Page 572
27.1 Introduction......Page 577
27.2 Breast-Cancer-Induced Hypercalcemia......Page 579
27.3 Metastatic Bone Pain......Page 581
27.4 Prevention of the Complications of Bone Metastases......Page 582
27.5 Prevention of Bone Metastases......Page 588
27.6 Prevention of Cancer-Treatment-Induced Bone Loss......Page 589
27.7 Conclusions and Perspectives......Page 591
References......Page 592
28.2 Diagnosis and Treatment......Page 597
28.3 Treatment and Prognosis......Page 598
References......Page 599
29.1 Introduction......Page 600
29.2 Anatomy......Page 601
29.3 Modulation Within the Dorsal Horn......Page 602
29.4 Opioid Receptors......Page 608
29.5 Supraspinal Opioid Responses......Page 613
29.6 Conclusion......Page 618
References......Page 619
30.1 Introduction......Page 624
30.2 Microarray technique......Page 625
30.3 A New Approach to Breast Cancer Classification......Page 627
30.4 Prediction of Metastatic Potential......Page 633
30.5 Classification of Hereditary and Familial Breast Cancer......Page 639
30.6 Gene Expression and Response to Treatment......Page 641
30.7 Concluding Remarks and Perspectives......Page 644
References......Page 646
31.1 Introduction......Page 651
31.2 The Proteomic Pipeline: a Primer on the Process......Page 652
31.3 Proteomics in Signaling Studies of Breast Cancer......Page 657
31.4 Proteomics in Biomarker Discovery......Page 659
31.5 Proteomics in the Treatment of Breast Cancer......Page 661
References......Page 664
32.1 Targeting the HER Family of Receptors: Rationale and Strategies......Page 669
32.2 Trastuzumab......Page 672
32.4 Anti-HER Low-Molecular-Weight Tyrosine Kinase Inhibitors......Page 684
References......Page 689
33.2 Tumor Vasculature During Angiogenesis......Page 697
33.3 Angiogenesis and Breast Carcinogenesis......Page 699
33.4 Angiogenic Molecules as Targets for Cancer Treatment......Page 703
33.5 Conclusions......Page 719
References......Page 720
Web Sites......Page 730
34.1 Introduction......Page 731
34.2 DNA Delivery System in Breast Cancer Gene Therapy......Page 732
34.3 Strategies of Breast Cancer Gene Therapy......Page 736
34.4 Clinical Trials of Breast Cancer Gene Therapy......Page 747
References......Page 753
35.2 Proliferative Signal Transduction Elements as Therapeutic Targets......Page 767
35.3 Targeting the Mitogen-Activated Protein Kinase Pathway (Ras/Raf/MEK)......Page 770
35.4 Targeting Insulin-Like Growth Factor Signaling......Page 777
35.5 Targeting the PI3K/Akt/PTEN Pathway......Page 778
35.6 Targeting mTOR......Page 779
35.7 Targeting Regulators of Apoptosis......Page 783
35.8 Targeting Regulators of Protein Trafficking......Page 787
35.9 Targeting Epigenetic DNA Modifications......Page 789
35.10 Novel Cytotoxic Compounds......Page 791
35.11 Targeting Mitotic Kinesins......Page 794
References......Page 795
36.1 Introduction......Page 808
36.2 Mechanisms to Decrease Drug Uptake......Page 810
36.3 Mechanisms to Increase Drug Extrusion......Page 812
36.4 Mechanisms of Drug Inactivation Through Metabolism......Page 816
36.6 Modification of Cell-Cycle Checkpoint Control and Apoptosis Mediators......Page 817
36.7 Repair of DNA Damage......Page 819
Acknowledgments......Page 821
References......Page 822
37.2 Receptor Structure and Function......Page 829
37.3 ERα, ERβ, and Prediction of Response to Therapy......Page 831
37.4 Mechanisms of Resistance to Hormonal Therapies......Page 832
37.5 Future Directions......Page 838
References......Page 839
38.2 Novel Insights into the ErbB Family of RTKs......Page 846
38.3 Novel Insights into the ER Pathway......Page 852
References......Page 858
39.1 Introduction......Page 863
39.2 Apoptosis Signaling......Page 864
39.3 Apoptosis Effectors and Regulators in Human Normal and Breast Cancer Tissues......Page 867
References......Page 873
Editorial Comment......Page 882
40.2 Diagnosis......Page 884
40.3 Pathological Characteristics......Page 885
40.4 Staging Investigations......Page 886
40.5 Treatment Options......Page 887
40.7 Prognosis......Page 892
40.8 Pregnancy After Breast Cancer......Page 893
References......Page 894
41.1 Introduction......Page 900
41.2 HRT in Healthy Women......Page 901
41.3 The Use of ERT/HRT in Women with a Previous Diagnosis of Breast Cancer......Page 909
41.4 Treatment Alternatives......Page 914
41.5 Summary......Page 917
References......Page 918
42.2 Incidence......Page 924
42.3 Risk Factors......Page 925
42.4 Genetics......Page 927
42.5 Diagnosis......Page 928
42.6 Treatment of Localized Disease......Page 930
42.7 Metastatic Disease......Page 932
42.8 Immunohistochemical Differences Between Male and Female BC......Page 934
42.9 Comparison of Outcome Between Male and Female BC......Page 937
42.10 Conclusions......Page 939
References......Page 940
43.2 Clinical Decision Making......Page 945
43.3 Breast Cancer......Page 949
43.4 Predictors of Preferences......Page 956
43.5 Rationality of Preferences......Page 957
43.6 Incorporating Preferences in Clinical Practice......Page 958
43.7 Implications for Research......Page 959
43.8 Conclusion......Page 960
References......Page 961
44.2 Depressive Symptomatology in the Woman with Breast Cancer......Page 965
44.3 Alterations of Mood and Hypothalamic-Pituitary-Gonadal Axis Function in Women with Breast Cancer......Page 968
44.4 Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Patients with Major Depression......Page 969
44.5 Depression, Immune Function, and Cancer......Page 972
44.6 Psychopharmacologic Treatment of Depression in Women with Breast Cancer......Page 974
44.7 Psychosocial Treatment of Depression in Women with Breast Cancer......Page 982
44.8 Summary......Page 983
References......Page 988
45.1 Introduction......Page 996
45.2 Individual (Single) Prognostic and Predictive Markers......Page 999
45.3 Gene-Expression Profiling Techniques......Page 1004
45.4 Molecular Profiling Data in Breast Cancer......Page 1007
45.5 Limitations......Page 1016
45.6 Future Trials......Page 1018
References......Page 1021
46.2 Factors Influencing Treatment Tailoring for Breast Cancer......Page 1026
46.3 Models of Clinical Trials Based on the Concept of Tailored Investigations......Page 1027
46.4 Conclusion......Page 1036
References......Page 1037
B......Page 1040
E......Page 1041
H......Page 1042
O......Page 1043
P......Page 1044
T......Page 1045
Z......Page 1046