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9780521496322

Medical Therapy of Breast Cancer

by
  • ISBN13:

    9780521496322

  • ISBN10:

    0521496322

  • Format: Hardcover
  • Copyright: 2003-01-27
  • Publisher: Cambridge University Press

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Summary

This wide-ranging account will be essential for breast cancer specialists, trainees in oncology and clinical research scientists.

Author Biography

Zenon Rayter is Consultant Surgeon at Bristol Royal Infirmary and Honorary Senior Lecturer at the University of Bristol. He is Director of the Bristol Breast Unit and Vice President of the Surgical Section of the Royal Society of Medicine Janine Mansi is Consultant Medical Oncologist and Honorary Senior Lecturer at St George's Hospital Medical School, and also Lead Clinician for cancer services for the Trust, and an executive member of the Association of Cancer Physicians

Table of Contents

List of contributors
xvii
History of breast cancer therapy
1(36)
Zenon Rayter
History of surgery for breast cancer
1(6)
Introduction
1(1)
The empiric period
2(1)
The pessimistic period
2(1)
The optimistic period
3(3)
The realistic period
6(1)
The rise and fall of endocrine surgery for metastatic disease
6(1)
Introduction of radiation therapy for breast cancer
7(3)
History
7(1)
Influence of radiotherapy on local control and survival
8(2)
Timing of radiotherapy
10(1)
Theoretical considerations in the spread of breast cancer
10(3)
Evolution of conservative surgery for breast cancer
13(13)
Surgery of the breast
13(3)
Axillary surgery
16(2)
Sentinel node biopsy in the management of the axilla
18(6)
Timing of surgery
24(1)
Reconstructive surgery
25(1)
Need for systemic therapy in early breast cancer
26(1)
Conclusion
27(1)
References
28(9)
Chemoprevention of breast cancer
37(24)
Tamas Hickish
Introduction
37(1)
Chemoprevention as a strategy in breast cancer
38(1)
Rationale for tamoxifen chemoprevention trials
39(1)
The Royal Marsden Tamoxifen Prevention Trial
39(3)
The NSABP-P1 trial
42(1)
The Italian Tamoxifen Prevention Study
42(1)
Overview of the reported tamoxifen breast cancer prevention trials
43(2)
Compliance and statistical power
44(1)
The differences between the trials in terms of risk of breast cancer among the participants
44(1)
The use of HRT
45(1)
Adverse effects of tamoxifen in the breast cancer prevention trials
45(4)
Menopausal symptoms and anxiety
45(1)
Vascular events
46(1)
Endometrial cancer
46(1)
Ocular effects
47(1)
Cardiovascular disease
47(1)
Bone density and fractures
48(1)
Risk--benefit calculation
49(3)
Evolving chemoprevention
52(3)
Raloxifene
52(1)
Nutriceuticals -- breast cancer prevention with phyto-oestrogens
53(1)
Fenretinide breast cancer prevention
54(1)
Conclusion and future directions
55(1)
References
55(6)
Familial breast cancer
61(11)
H. Gogas
V. Murday
Introduction
61(1)
BRCA1
61(1)
BRCA2
62(1)
Other genes associated with increased risk of breast cancer
63(1)
Referral, assessment and clinical management of women for familial breast cancer
64(5)
Referral
64(1)
Assessment
65(3)
Clinical management
68(1)
Conclusion
69(1)
References
69(3)
Hormone replacement therapy and breast cancer
72(31)
J. Marsden
N. P. M. Sacks
Introduction
72(2)
The incidence of oestrogen deficiency symptoms in women with breast cancer
74(1)
Alternatives to HRT for the management of postmenopausal oestrogen deficiency
75(3)
Is serum oestradiol an important indicator of the risk of developing breast cancer recurrence?
78(3)
Indirect evidence that HRT may not have an adverse effect in breast cancer survivors
81(1)
HRT, breast density and mammography
82(1)
HRT and its effect on tumour biology and breast cancer mortality
83(1)
HRT and breast cancer risk in women at high risk of developing breast cancer
84(3)
Familial breast cancer
86(1)
Benign breast disease
86(1)
Observational studies of HRT in breast cancer survivors
87(3)
Potential antagonism between tamoxifen and HRT
90(1)
Is a randomized trial of HRT in breast cancer survivors feasible?
91(1)
Conclusion
92(1)
References
92(11)
Screening for breast cancer
103(23)
Rosalind Given-Wilson
Introduction
103(1)
Why screen?
103(1)
The principles of screening and their application to breast cancer
104(3)
Evaluation of screening benefit
107(1)
Bias in survival evaluation
107(1)
Lead time bias
107(1)
Length bias
108(1)
Randomized controlled trials
108(1)
What is the evidence that screening works in different age groups?
109(2)
Screening in women aged 50--64 years of age
109(1)
Screening in women over the age of 65
110(1)
Screening women aged 40--49 years
110(1)
Screening for women under 40 years old
111(1)
Organization aspects of screening -- the UK model
111(4)
Sensitivity and specificity of screening -- the performance of the UK NHSBSP
112(3)
Benefits and adverse effects of breast screening
115(2)
Future developments
117(2)
Challenges facing screening programmes -- resources
117(1)
Best practice for screening programmes, two views, two readers and extension of age
118(1)
Digital technology and computer aided detection
118(1)
Nonoperative diagnosis
119(1)
`Family history' screening of younger women
119(3)
Ultrasound for screening
120(1)
Magnetic resonance imaging
121(1)
Conclusion
122(1)
References
122(4)
The management of in situ breast cancer
126(27)
Zenon Rayter
Introduction
126(1)
Epidemiology
127(2)
Pathology of DCIS
129(1)
Classification of DCIS
129(1)
Natural history of DCIS
130(2)
Molecular biology of DCIS
132(1)
Interphase cytogenetics
132(1)
Oncogenes and steroid receptors
132(1)
Diagnosis of DCIS
133(2)
Treatment of DCIS
135(10)
Historical perspective
135(3)
Breast-conserving surgery
138(4)
Role of radiotherapy
142(1)
Role of adjuvant medical therapy
143(1)
Role of axillary surgery
144(1)
Follow-up
144(1)
Future studies
145(1)
Conclusion
145(1)
References
145(8)
Adjuvant systematic therapy
153(25)
T. R. J. Evans
The rationale for systemic adjuvant therapy
153(1)
Adjuvant chemotherapy
154(2)
Node-negative patients
156(2)
The place of anthracyclines
158(2)
Poor risk patients and dose intensification
160(2)
High-dose adjuvant chemotherapy
160(1)
Toxicity
161(1)
Adjuvant endocrine therapy
162(4)
Ovarian ablation
162(1)
Adjuvant tamoxifen
163(2)
Duration of tamoxifen
165(1)
Side-effects of tamoxifen
166(1)
Adjuvant aromatase inhibitors
166(1)
Combined chemotherapy and endocrine therapy
167(2)
Premenopausal women with node-positive, receptor-positive breast cancer
168(1)
Postmenopausal women with node-positive, receptor-positive breast cancer
169(1)
Tamoxifen and chemotherapy for node-negative, receptor-positive breast cancer
169(1)
Concurrent versus sequential chemohormonal therapy
169(1)
Future prospects
169(1)
References
170(8)
Adjuvant radiotherapy in the management of breast cancer
178(31)
Gillian Ross
David Landau
Andrew Tutt
Introduction
178(1)
Radiotherapy and breast conservation
178(2)
Risk factors for recurrence following breast-conserving surgery
180(1)
Natural history of and risk factors for local recurrence
181(1)
The importance of local recurrence
182(1)
The balance between optimal local control and cosmesis
183(1)
Margin status and local recurrence risk
183(2)
The effect of radiotherapy dose escalation
185(2)
The influence of systemic therapy on local recurrence following breast conservation
187(1)
The effect of re-excision
188(1)
Postmastectomy radiotherapy
188(8)
Optimizing breast conservation with adjuvant tadiotherapy
196(1)
Variation in UK radiotherapy practices for women with breast cancer: the Start study
196(2)
Sequencing of chemotherapy and radiotherapy
198(1)
Radiotherapy and postmastectomy breast reconstruction
199(3)
Radiotherapy and implant reconstruction
200(1)
Dose distribution
201(1)
Radiotherapy and TRAM flap reconstruction
201(1)
Conclusion
202(1)
Summary
203(1)
References
203(6)
Predictors of response and resistance to medical therapy
209(1)
Cell kinetic parameters and response to therapy
210(10)
R. S. Camplejohn
Introduction
210(1)
DNA flow cytometry
211(1)
Predictors of response to therapy
212(5)
Adjuvant chemotherapy for node-negative breast cancer
212(1)
Prediction of response to neoadjuvant chemotherapy
212(2)
Adjuvant chemotherapy for node-positive breast cancer
214(1)
Hormonal therapy
214(1)
Tumour p53 status as a possible predictor of response to therapy
214(2)
Potential predictors of response in clinical trials
216(1)
Conclusion
217(1)
References
217(3)
Predictors of response and resistance to medical therapy: endocrine therapy
220(26)
Zenon Rayter
Introduction
220(1)
Oestrogen receptor (ER)
221(4)
Structure and function of the oestrogen receptor
221(1)
Measurement of ER
222(1)
ER as a predictor of hormone response
223(2)
Oestrogen-regulated proteins predictive of hormone response
225(2)
Progesterone receptor (PR)
225(1)
Oestrogen-inducible protein (pS2)
225(1)
Heat shock protein 27(HSP27)
226(1)
Markers of lack of response to endocrine therapy
227(1)
Epidermal growth factor receptor (EGFR) and c-erbB-2 (HER-2/neu)
227(1)
Urokinase
227(1)
Transforming growth factor &alpha
228(1)
Prolactin
228(1)
Prostate-specific antigen (PSA)
228(1)
Mechanisms of endocrine resistance
228(6)
Oestrogen receptor mechanisms
229(2)
Tumour cell elimination of antioestrogens
231(1)
Clonal selection
231(1)
Acquisition of steroidogenic metabolic pathways
232(1)
Constitutive production of mitogens
233(1)
Messenger system interactions
233(1)
Effects of oncogenes on cell cycle control
234(1)
Alteration of secreted proteins
234(1)
The use of steroid receptors in clinical trials
234(2)
Conclusion
236(1)
References
237(9)
Predictors of response and resistance to medical therapy: chemotherapy
246(18)
Stephen R. D. Johnston
Introduction
246(1)
Laboratory studies -- potential mechanisms for drug resistance
247(6)
Proximal mechanisms
247(2)
Drug-specific targets
249(1)
Distal response: apoptosis regulatory oncogenes
250(2)
Extrachromosomal DNA and drug resistance
252(1)
Clinical studies -- predictive markers of chemotherapy response/resistance
253(4)
HER-2/neu
253(1)
Changes in cell proliferation and apoptosis
254(3)
Opportunities for therapy
257(1)
Modulation of chemoresistance
257(1)
Targeted therapy
257(1)
Conclusion
258(1)
References
258(6)
Primary medical therapy in breast cancer
264(19)
Janine L. Mansi
Introduction
264(1)
Primary medical therapy in locally advanced breast cancer
265(1)
Primary chemotherapy in operable primary breast cancer
266(2)
Primary medical therapy in patients with small tumours
268(1)
Chemotherapy regimens used in primary medical therapy
268(2)
Duration of primary medical therapy
270(1)
Type of surgery
270(2)
The timing of radiotherapy
272(1)
Local recurrence rates after combined modality treatment
272(2)
The use of adjuvant therapy after surgery/radiotherapy
274(1)
Endocrine therapy as primary medical therapy
275(1)
Prognostic factors in primary medical therapy
275(1)
Impact of primary medical therapy on survival
276(1)
Conclusion
276(2)
References
278(5)
Medical therapy of advanced disease
283(26)
Alison Jones
Karen McAdam
Introduction
283(1)
Principles of treatment
284(1)
Endocrine versus cytotoxic treatment?
285(4)
Selective oestrogen receptor modulators (SERMS)
286(2)
Ovarian suppression
288(1)
Aromatase inhibitors
289(2)
Progestins
291(1)
Combination endocrine treatment
292(1)
Chemotherapy
292(10)
Duration of treatment
293(1)
Single-agent versus combination therapy
294(1)
Anthracylines
294(1)
Taxanes
295(2)
Vinorelbine
297(1)
Fluoropyramidines
297(1)
Dose intensification
298(1)
Bisphosphonates
298(1)
Trastuzumab
299(1)
Specific problems
300(2)
Conclusion
302(1)
References
302(7)
Experimental approaches
309(1)
High-dose chemotherapy in breast cancer
310(19)
John Crown
R. C. F. Leonard
Background: chemotherapy of breast cancer -- theory and practice
310(1)
Chemotherapy dose-response effect
311(1)
Haematopoietic support of high-dose chemotherapy
312(1)
High-dose chemotherapy strategies
313(3)
Primary high-dose chemotherapy
313(1)
Late intensification
313(1)
High-dose sequential
314(1)
Multicycle high-dose chemotherapy
315(1)
Single-arm trials of high-dose chemotherapy with autograft support in breast cancer
316(2)
Metastatic disease
316(2)
Adjuvant treatment of high-risk early stage disease
318(1)
Randomized trials of high-dose chemotherapy with autograft support in breast cancer
318(4)
Metastatic disease
318(2)
Adjuvant treatment of high-risk early stage disease
320(2)
Critical analysis of the literature of randomized trials of high-dose chemotherapy in breast cancer
322(1)
Research priorities and future directions
323(1)
References
324(5)
New immunological approaches to treatment for breast cancer
329(11)
A. G. Dalgleish
Introduction
329(1)
Cancer and the immune system
329(1)
Solid tumour oncogenesis
330(1)
Potential for therapy
331(2)
Evidence of an immune response to breast cancer
333(1)
Current immunotherapeutic clinical studies
334(1)
Vaccines
334(1)
Antibodies (Herceptin)
334(1)
Future approaches
335(1)
Suicide gene therapy
335(1)
Angiogenesis and telomerase inhibitors
335(1)
The immediate future
336(1)
References
337(3)
The place of bisphosphonates in the management of breast cancer
340(17)
A. H. G. Paterson
Introduction
340(1)
The clinical problem
340(1)
Normal and abnormal bone remodelling
341(1)
`Seed and soil' theories
342(1)
Bone metastases
342(2)
Incidence and morbidity
342(1)
Bone pain
343(1)
General principles of management
343(1)
Bisphosphonates
344(1)
Clinical trials of bisphosphonates in breast cancer
345(2)
Hypercalcaemia
345(1)
Skeletal complications
345(2)
Bone pain
347(1)
Trials of adjuvant bisphosphonates
347(4)
Patients with recurrent disease but no bone metastases
347(1)
Patients with operable breast cancer
348(3)
Conclusions
351(1)
References
352(5)
Palliative care in breast cancer
357(29)
Janet Hardy
Introduction
357(1)
Pain
357(6)
Special pain situations in breast cancer
363(9)
Bone metastases
363(5)
Pathological fractures
368(1)
Incident pain
368(1)
Liver capsular pain
369(1)
Neuropathic pain
369(2)
Headache
371(1)
Spiritual pain
371(1)
Fatigue
371(1)
Depression
372(1)
Nausea
372(1)
Dyspnoea
373(2)
Limb weakness/paraplegia
375(1)
Confusion
376(1)
Skin metastases and locally advanced disease
377(1)
Abdominal distension
378(1)
Terminal care
379(3)
Conclusion
382(1)
References
383(3)
Index 386

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