Download Breast Cancer and Molecular Medicine - M. Piccart (Springer, 2006) WW PDF

TitleBreast Cancer and Molecular Medicine - M. Piccart (Springer, 2006) WW
TagsMedical
LanguageEnglish
File Size9.5 MB
Total Pages1046
Table of Contents
                            Contents
	1 Role of Modeling in Pharmacotherapeutics
	2 PET and Nuclear Medicine Imaging of the Breast
	3 Functional Radiologic Imaging in Breast Cancer
	4 Prevention of Breast Cancer
	5 DCIS: Pathology and Molecular Markers
	6 Ductal Carcinoma In Situ: a Modern Approach to Patient Management
	7 Ductal Carcinoma In Situ: Systemic Treatment
	8 Tailored Surgery for Early Breast Cancer: Surgical Techniques
	9 Tailored Surgery for Early Breast Cancer: Biological Aspects
	10 Tailored Surgery for Early Breast Cancer: the Very Young Woman
	11 Tailored Surgery for Older Women with Breast Cancer
	12 Tailored Radiotherapy for Breast Cancer Stages I and II: Technical Aspects
	13 Breast Cancer Management in the Era of Molecular Medicine: Tailored Radiotherapy – Clinical and Biological Aspects
	14 Early Breast Cancer (Stage I and II): Tailored Radiotherapy for Very Young Women
	15 The Elderly and Breast Cancer Radiotherapy
	16 Early Breast Cancer (Stage I and Stage II): Tailored Systemic Therapy for Endocrine-Resistant Breast Cancer
	17 Early Breast Cancer (Stage I and Stage II): Tailored Systemic Therapy for Endocrine-Responsive Breast Cancer
	18 Tailored Therapy for Breast Cancer in Very Young Women
	19 Tailored Systemic Therapy for the Elderly Woman
	20 Locoregional Therapy Following Neoadjuvant Chemotherapy: an Evolving Paradigm of Treatment Individualization
	21 Medical Therapy of Locally Advanced Breast Cancer
	22 Metastatic Breast Cancer: Tailored Endocrine Therapy for Premenopausal Women
	23 Metastatic Breast Cancer: Tailored Endocrine Therapy for Postmenopausal Women
	24 Metastatic Breast Cancer: Tailored Chemotherapy for the Elderly Woman
	25 Treatment of Brain Metastases from Breast Cancer
	26 Surgical Management of Breast Cancer Liver Metastases
	27 Individualization of Bisphosphonate Therapy
	28 Breast Cancer Metastases to the Eye
	29 Organ-Specific Approaches: Pain Management
	30 Genomic and Molecular Classification of Breast Cancer
	31 Applications of Proteomics to Clinical Questions in Breast Cancer
	32 Targeting the HER Family of Receptors in the Treatment of Advanced Breast Cancer
	33 Biological Therapies for Metastatic Breast Cancer: Antiangiogenesis
	34 Breast Cancer Gene Therapy
	35 Innovative Rational-Derived, Target- Based and Cytotoxic Therapies for Breast Cancer and Other Malignancies
	36 Mechanisms of Breast Cancer Resistance to Chemotherapy
	37 Mechanisms of Resistance to Hormone Therapy
	38 Novel Signaling Pathways in Breast Cancer
	39 Mechanisms of Apoptosis Resistance In Breast Cancer
	40 Breast Cancer and Pregnancy
	41 Hormone Replacement Therapy After Breast Cancer
	42 Male Breast Cancer
	43 Patients’ Preferences: What Makes Treatments Worthwhile?
	44 Breast Cancer: the Impact of Depression and its Treatment
	45 Molecular Profiling in Breast Cancer
	46 Clinical Trials in the Era of Treatment Tailoring
	Subject Index
Contributors
1 Role of Modeling in Pharmacotherapeutics
	1.1 Introduction
	1.2 The Skipper-Schabel Model and its Relevance
	1.3 Gompertzian Growth and the Norton-Simon Hypothesis
	1.4 The Impact Of Sequential Chemotherapy
	1.5 Dose Size
	1.6 Scheduling: What about Dose Density?
	1.7 Sequential Therapy and Dose Density in the Clinic
	1.8 Some Cautions Regarding Dose Density
	1.9 Gompertzian Growth is Biologically Driven
	References
	Editorial Comment
2 PET and Nuclear Medicine Imaging of the Breast
	2.1 Introduction
	2.2 18FDG-PET
	2.3 Primary Breast Cancer Detection
	2.4 Axillary Lymph Nodes
	2.5 Metastatic Disease and Staging
	2.6 Locally Advanced Breast Cancer: Response to Chemotherapy
	2.7 Prognostic Assessment
	2.8 Reimbursement
	2.9 99mTc-Sestamibi and 99mTc-Tetrofosmin
	2.10 Dedicated Devices for Nuclear Medicine Breast Imaging
	2.11 Summary
	References
	Editorial Comment
3 Functional Radiologic Imaging in Breast Cancer
	3.1 Introduction
	3.2 Magnetic Resonance Imaging
	3.3 Nuclear Medicine
	3.4 Monitoring Resistance to Chemotherapy
	3.5 Tumor Hypoxia
	3.6 Conclusion
	References
	Editorial Comment
4 Prevention of Breast Cancer
	4.1 Introduction
	4.2 Surgery For Breast Cancer Risk Reduction
	4.3 Chemoprevention of Breast Cancer
	4.4 Prevention of ER-Negative Breast Cancer
	4.5 Current Progress and Future Challenges
	References
	Editorial Commentary
5 DCIS: Pathology and Molecular Markers
	5.1 Introduction
	5.2 Histological Classification
	5.3 Genetic Alterations
	5.4 A Multistep Model for Breast Carcinogenesis
	5.5 Discussion and Future Prospects
	References
6 Ductal Carcinoma In Situ: a Modern Approach to Patient Management
	6.1 Introduction
	6.2 Treatment Options
	6.3 Biomarkers of Disease and Outcome
	6.4 Preventing Contralateral Breast Cancer
	6.5 Decision-Making Tools for Treatment of Ipsilateral DCIS
	6.6 Novel Therapies for Prevention
	6.7 Conclusions
	References
7 Ductal Carcinoma In Situ: Systemic Treatment
	7.1 Introduction
	7.2 Molecular Characteristics of DCIS
	7.3 Systemic Treatment of HR-Positive DCIS
	7.4 Tamoxifen Treatment for DCIS
	7.5 Aromatase Inhibitors as a Treatment for DCIS
	7.6 Treatment of Hormone-Independent DCIS
	7.7 Promising Novel Therapies for Hormone-Independent DCIS
	7.8 Future Directions In Treating DCIS
	References
	Editorial Comment
8 Tailored Surgery for Early Breast Cancer: Surgical Techniques
	8.1 Skin-Sparing Mastectomy
	8.2 Oncoplastic Surgery of the Breast
	References
9 Tailored Surgery for Early Breast Cancer: Biological Aspects
	9.1 Introduction
	9.2 Molecular Biology and Behavior of the Cancer in the Breast
	9.3 Prediction of Lymph Node Involvement from the Primary Tumor
	9.4 Predicting Further Lymph Node Involvement after SLN Biopsy
	9.5 Molecular Biology and Tailored Surgery for the Individual Patient: Conclusion
	References
10 Tailored Surgery for Early Breast Cancer: the Very Young Woman
	Abbreviations
	10.1 Incidence and Prevalence
	10.2 Risk Factors
	10.3 Presentation
	10.4 Clinical Assessment and Diagnostic Procedure
	10.5 Tumor Characteristics
	10.6 Treatment
	10.7 Local and Distant Recurrence Rates and Prognosis
	10.8 Late Effects of Treatment
	10.9 Conclusions
	References
11 Tailored Surgery for Older Women with Breast Cancer
	11.1 Introduction
	11.2 The Nature of Breast Cancer in Older Women
	11.3 Burden of Other Illness
	11.4 Early Diagnosis
	11.5 Treatment of the Axilla
	11.6 Mastectomy as a Treatment
	11.7 The Role of Tamoxifen
	11.8 The Role of Radiotherapy
	11.9 Selection of Local Treatment
	References
	Editorial Commentary
12 Tailored Radiotherapy for Breast Cancer Stages I and II: Technical Aspects
	12.1 Introduction
	12.2 Wide Excision Alone Trials
	12.3 Studies Addressing the Benefit of a Tumor-Bed Boost after Whole-Breast RT
	12.4 Tamoxifen as a Substitute for RT After Lumpectomy
	12.5 Accelerated, Whole-Breast RT Fractionation Schedules
	12.6 Accelerated, Partial-Breast Irradiation
	12.7 Three-Dimensional Conformal PBI Technique
	12.8 Three-dimensional Treatment Planning and Intensity-Modulated RT
	12.9 Conclusions
	References
13 Breast Cancer Management in the Era of Molecular Medicine: Tailored Radiotherapy – Clinical and Biological Aspects
	13.1 Overview
	13.2 Introduction
	13.3 Hormone Receptors
	13.4 Her2/neu Expression
	13.5 P53 Expression
	13.6 Proliferative Markers
	13.7 Other Selected Molecular Markers
	13.8 Genetic Factors and Local-Regional Management of Breast Cancer
	13.9 Conclusion
	References
14 Early Breast Cancer (Stage I and II): Tailored Radiotherapy for Very Young Women
	14.1 Introduction
	14.2 Age and Locoregional Recurrences
	14.3 Clinical, Pathological, and Biological Features Associated with Breast Cancer in Very Young Patients
	14.4 Respective Influence of Young Age and Other Associated Factors on the Risk of Breast Recurrence
	14.5 Tailoring Radiotherapy in Young Patients
	14.6 Conclusions
	References
15 The Elderly and Breast Cancer Radiotherapy
	15.1 Introduction
	15.2 Effects of Age
	15.3 Treatment
	15.4 Newer Techniques
	15.5 Palliative Radiotherapy
	15.6 Summary
	References
	Editorial Comment
16 Early Breast Cancer (Stage I and Stage II): Tailored Systemic Therapy for Endocrine-Resistant Breast Cancer
	16.1 Introduction
	16.2 The Use of Molecular Markers to Identify Low-Risk Endocrine-Resistant Disease
	16.3 The Use of Molecular Markers to Select Adjuvant Chemotherapy
	Summary
	References
17 Early Breast Cancer (Stage I and Stage II): Tailored Systemic Therapy for Endocrine-Responsive Breast Cancer
	17.1 Introduction
	17.2 Tailored Endocrine Therapy
	17.3 Tailored Chemotherapy
	17.4 Treatment Summary
	17.5 Future Directions
	References
18 Tailored Therapy for Breast Cancer in Very Young Women
	18.1 Introduction
	18.2 Incidence and Prevalence
	18.3 Age as a Prognostic Factor in Breast Cancer
	18.4 Prognostic Factors in the Young
	18.5 Age as an Independent Prognostic Factor
	18.6 Treatment of Breast Cancer in Young Women
	18.7 Special Considerations in the Young
	18.8 Conclusions and Caveats Regarding Tailored Therapy in Younger Women
	References
19 Tailored Systemic Therapy for the Elderly Woman
	19.1 Epidemiology
	19.2 Tumor Biology
	19.4 Life Expectancy for Older Women
	19.5 Comorbidities- Prevalence and Impact on Decision Making
	19.6 HER-2/neu Testing in Older Women with Early Stage Breast Cancer
	19.7 Adjuvant Systemic Therapy
	19.8 Neoadjuvant Therapy in Early Stage Disease
	19.9 Integrating the Data for Older Women into an Individualized Approach to Adjuvant Systemic Therapy
	19.10 Older Patients and Clinical Trials
	References
	Editorial Commentary
20 Locoregional Therapy Following Neoadjuvant Chemotherapy: an Evolving Paradigm of Treatment Individualization
	20.1 Introduction
	20.2 Appropriate Tumor Assessment Before, During, and After Neoadjuvant Chemotherapy and its Effects on Locoregional Management
	20.3 Locoregional Therapy Considerations Following Neoadjuvant Chemotherapy
	20.4 Future Directions in Locoregional Therapy after Neoadjuvant Chemotherapy
	References
21 Medical Therapy of Locally Advanced Breast Cancer
	21.1 Introduction
	21.2 Diagnosis
	21.3 Prognostic and Predictive Factors
	21.4 Therapy
	21.5 Inflammatory Breast Cancer
	21.6 Conclusion
	References
22 Metastatic Breast Cancer: Tailored Endocrine Therapy for Premenopausal Women
	22.1 Introduction
	22.2 Ovarian Ablation for Treatment of Metastatic Breast Cancer
	22.3 Tamoxifen for Treatment of Metastatic Breast Cancer
	22.4 Tamoxifen Compared to Ovarian Ablation or Suppression
	22.5 Combined Endocrine Therapy with Ovarian Suppression and Tamoxifen
	22.6 Aromatase Inhibitors for Treatment of Metastatic Breast Cancer
	22.7 Sex Steroids for Treatment of Metastatic Breast Cancer
	22.8 Future Considerations
	22.9 Conclusion
	References
23 Metastatic Breast Cancer: Tailored Endocrine Therapy for Postmenopausal Women
	23.1 Introduction
	23.2 Tailored Treatment Approaches to Endocrine Therapy for Breast Cancer
	23.3 Efficacy Issues in Tailored Endocrine Therapy for Advanced Disease
	23.4 Selective Estrogen-Receptor Downregulators
	23.5 High-Dose Estrogen
	23.6 The Use of HER2 to Tailor Endocrine Therapy for Advanced Disease?
	23.7 Combination Therapies with Signal Transduction Inhibitors
	23.8 New Technologies to Assess the Endocrine Therapy Resistance Problem
	23.9 Oncotype DX
	23.10 Conclusion
	References
24 Metastatic Breast Cancer: Tailored Chemotherapy for the Elderly Woman
	24.1 Introduction
	24.2 Clinical Definition of Age
	24.3 Assessment of the Elderly Patient with Cancer
	24.4 Cancer Chemotherapy in the Elderly Patient
	24.5 Clinical Trials
	24.6 Conclusion
	References
25 Treatment of Brain Metastases from Breast Cancer
	25.1 Clinical Features
	25.2 Radiosurgery: Definition
	25.3 Treatment Algorithm
	25.4 Radiobiological and Technical Principles for Radiation Treatment
	25.5 Toxicity
	25.6 Institutional Experience
	25.7 Conclusions
	References
26 Surgical Management of Breast Cancer Liver Metastases
	26.1 Introduction
	26.2 Surgical Management of Breast Cancer Liver Metastases: Rationale
	26.3 Surgical Management of Breast Cancer Liver Metastases: Options
	26.4 Conclusions
	References
27 Individualization of Bisphosphonate Therapy
	27.1 Introduction
	27.2 Breast-Cancer-Induced Hypercalcemia
	27.3 Metastatic Bone Pain
	27.4 Prevention of the Complications of Bone Metastases
	27.5 Prevention of Bone Metastases
	27.6 Prevention of Cancer-Treatment-Induced Bone Loss
	27.7 Conclusions and Perspectives
	References
28 Breast Cancer Metastases to the Eye
	28.1 Introduction
	28.2 Diagnosis and Treatment
	28.3 Treatment and Prognosis
	References
29 Organ-Specific Approaches: Pain Management
	29.1 Introduction
	29.2 Anatomy
	29.3 Modulation Within the Dorsal Horn
	29.4 Opioid Receptors
	29.5 Supraspinal Opioid Responses
	29.6 Conclusion
	References
30 Genomic and Molecular Classification of Breast Cancer
	30.1 Introduction
	30.2 Microarray technique
	30.3 A New Approach to Breast Cancer Classification
	30.4 Prediction of Metastatic Potential
	30.5 Classification of Hereditary and Familial Breast Cancer
	30.6 Gene Expression and Response to Treatment
	30.7 Concluding Remarks and Perspectives
	References
31 Applications of Proteomics to Clinical Questions in Breast Cancer
	31.1 Introduction
	31.2 The Proteomic Pipeline: a Primer on the Process
	31.3 Proteomics in Signaling Studies of Breast Cancer
	31.4 Proteomics in Biomarker Discovery
	31.5 Proteomics in the Treatment of Breast Cancer
	31.6 Conclusion
	References
32 Targeting the HER Family of Receptors in the Treatment of Advanced Breast Cancer
	32.1 Targeting the HER Family of Receptors: Rationale and Strategies
	32.2 Trastuzumab
	32.3 HER Dimerization Inhibitors (HDI): Pertuzumab
	32.4 Anti-HER Low-Molecular-Weight Tyrosine Kinase Inhibitors
	References
33 Biological Therapies for Metastatic Breast Cancer: Antiangiogenesis
	33.1 Introduction
	33.2 Tumor Vasculature During Angiogenesis
	33.3 Angiogenesis and Breast Carcinogenesis
	33.4 Angiogenic Molecules as Targets for Cancer Treatment
	33.5 Conclusions
	References
	Web Sites
34 Breast Cancer Gene Therapy
	34.1 Introduction
	34.2 DNA Delivery System in Breast Cancer Gene Therapy
	34.3 Strategies of Breast Cancer Gene Therapy
	34.4 Clinical Trials of Breast Cancer Gene Therapy
	34.5 Conclusion
	References
35 Innovative Rational-Derived, Target-Based and Cytotoxic Therapies for Breast Cancer and Other Malignancies
	35.1 Introduction
	35.2 Proliferative Signal Transduction Elements as Therapeutic Targets
	35.3 Targeting the Mitogen-Activated Protein Kinase Pathway (Ras/Raf/MEK)
	35.4 Targeting Insulin-Like Growth Factor Signaling
	35.5 Targeting the PI3K/Akt/PTEN Pathway
	35.6 Targeting mTOR
	35.7 Targeting Regulators of Apoptosis
	35.8 Targeting Regulators of Protein Trafficking
	35.9 Targeting Epigenetic DNA Modifications
	35.10 Novel Cytotoxic Compounds
	35.11 Targeting Mitotic Kinesins
	References
36 Mechanisms of Breast Cancer Resistance to Chemotherapy
	36.1 Introduction
	36.2 Mechanisms to Decrease Drug Uptake
	36.3 Mechanisms to Increase Drug Extrusion
	36.4 Mechanisms of Drug Inactivation Through Metabolism
	36.5 Modification of Drug Target or of Dependence on Drug Target
	36.6 Modification of Cell-Cycle Checkpoint Control and Apoptosis Mediators
	36.7 Repair of DNA Damage
	36.8 Impact of the Extracellular Environment
	36.9 Summary
	Acknowledgments
	References
37 Mechanisms of Resistance to Hormone Therapy
	37.1 Introduction
	37.2 Receptor Structure and Function
	37.3 ERα, ERβ, and Prediction of Response to Therapy
	37.4 Mechanisms of Resistance to Hormonal Therapies
	37.5 Future Directions
	37.6 Acknowledgements
	References
38 Novel Signaling Pathways in Breast Cancer
	38.1 Introduction
	38.2 Novel Insights into the ErbB Family of RTKs
	38.3 Novel Insights into the ER Pathway
	38.4 Conclusion
	References
39 Mechanisms of Apoptosis Resistance In Breast Cancer
	39.1 Introduction
	39.2 Apoptosis Signaling
	39.3 Apoptosis Effectors and Regulators in Human Normal and Breast Cancer Tissues
	References
	Editorial Comment
40 Breast Cancer and Pregnancy
	40.1 Introduction
	40.2 Diagnosis
	40.3 Pathological Characteristics
	40.4 Staging Investigations
	40.5 Treatment Options
	40.6 Termination of Pregnancy
	40.7 Prognosis
	40.8 Pregnancy After Breast Cancer
	40.9 Conclusions
	References
41 Hormone Replacement Therapy After Breast Cancer
	41.1 Introduction
	41.2 HRT in Healthy Women
	41.3 The Use of ERT/HRT in Women with a Previous Diagnosis of Breast Cancer
	41.4 Treatment Alternatives
	41.5 Summary
	References
42 Male Breast Cancer
	42.1 Introduction
	42.2 Incidence
	42.3 Risk Factors
	42.4 Genetics
	42.5 Diagnosis
	42.6 Treatment of Localized Disease
	42.7 Metastatic Disease
	42.8 Immunohistochemical Differences Between Male and Female BC
	42.9 Comparison of Outcome Between Male and Female BC
	42.10 Conclusions
	References
43 Patients’ Preferences: What Makes Treatments Worthwhile?
	43.1 Introduction
	43.2 Clinical Decision Making
	43.3 Breast Cancer
	43.4 Predictors of Preferences
	43.5 Rationality of Preferences
	43.6 Incorporating Preferences in Clinical Practice
	43.7 Implications for Research
	43.8 Conclusion
	References
44 Breast Cancer: the Impact of Depression and its Treatment
	44.1 Prevalence of Depression in Breast Cancer
	44.2 Depressive Symptomatology in the Woman with Breast Cancer
	44.3 Alterations of Mood and Hypothalamic-Pituitary-Gonadal Axis Function in Women with Breast Cancer
	44.4 Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Patients with Major Depression
	44.5 Depression, Immune Function, and Cancer
	44.6 Psychopharmacologic Treatment of Depression in Women with Breast Cancer
	44.7 Psychosocial Treatment of Depression in Women with Breast Cancer
	44.8 Summary
	References
45 Molecular Profiling in Breast Cancer
	45.1 Introduction
	45.2 Individual (Single) Prognostic and Predictive Markers
	45.3 Gene-Expression Profiling Techniques
	45.4 Molecular Profiling Data in Breast Cancer
	45.5 Limitations
	45.6 Future Trials
	45.7 Closing Remarks
	References
46 Clinical Trials in the Era of Treatment Tailoring
	46.1 Introduction
	46.2 Factors Influencing Treatment Tailoring for Breast Cancer
	46.3 Models of Clinical Trials Based on the Concept of Tailored Investigations
	46.4 Conclusion
	References
Subject Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	Y
	Z
                        
Document Text Contents
Page 1

Martine J. Piccart – William C. Wood
Chie-Mien Hung – Lawrence J. Solin
Fatima Cardoso (Eds.)

Breast Cancer
and Molecular
Medicine

With 134 Figures and 118 Tables

123

Page 2

Martine J. Piccart, MD, PhD
Dept. of Medical Oncology
Jules Bordet Institute
Boulevard de Waterloo, 215
1000 Brussels
Belgium
[email protected]

Fatima Cardoso, MD
Dept. of Medical Oncology
Jules Bordet Institute
Boulevard de Waterloo, 125
1000 Brussels
Belgium
[email protected]

Mien-Chie Hung, PhD
�e University of Texas MD
Anderson Cancer Center
1515 Holcombe Blvd
Houston, TX 77030-4095
USA
[email protected]

William Wood, MD
Dept. of Surgery
Emory University Hospital
1364 Cli�on Road NE B206
Atlanta, Georgia 30322-1059
USA
[email protected]

Lawrence J Solin, MD
Dept. of Radiation Oncology
Hospital of the University of
Pennsylvania
3400 Spruce Street
Philadelphia, Pennsylvania
19104-4283
USA
[email protected]

Library of Congress Control Number: 2006925084
ISBN 10 3-540-28265-3 Springer Berlin Heidelberg New York
ISBN 13 978-3-540-28265-5 Springer Berlin Heidelberg New York

�is work is subject to copyright. All rights reserved, whether the whole or part of the materialis con-
cerned, speci�cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting,
reproduction on micro�lm or in any otherway, and storage in databanks. Dupli-cation of this publication
or parts there of is permitted only under the provisions of the German Copyright Law of September, 9,
1965, in its current version, and permission for use must al-ways be obtained from Springer-Verlag. Vio-
lations are liable for prosecution under the German Copyright Law.

Springer is apart of Springer Science+Business Medias pringeronline.com
' Springer-Verlag Berlin Heidelberg 2006
Printed in Germany

�e use of general descriptive names, registered names, trademarks, etc. in this publication does not im-
ply, even in the absence of a speci�c statement,that such names are exempt from there levant protective
laws and regulations and there for e free for general use. Productliability: �e publisher cannot guarantee
the accuracy of any information about dosage and application contained in this book. In every individual
case the user must check such information by consulting there levant literature.

Editor: Dr. Ute Heilmann, Heidelberg
Deskeditor: Meike Stoeck, Heidelberg
Coverdesign: design & production GmbH, Heidelberg
Production & Typesetting: LE-TeX Jelonek, Schmidt & Vöckler GbR, Leipzig
Printed on acid-freepaper SPIN 10938713 21/3100/YL � 5 4 3 2 1 0

Page 523

488 Metastatic Breast Cancer: Tailored Chemotherapy for the Elderly Woman

Ta
b

le
24

.3
co

nt
in

ue
d

N
am

e
A

ct
iv

it
y

Pa
re

nt
C

om
po

un
d

A
ct

iv
e

M
et

ab
ol

it
e

E
lim

in
at

io
n

D
os

e
A

dj
us

tm
en

t

Pl
an

t D
er

iv
at

iv
es

E p
ip

od
op

hy
llo

to
xi

ns


Et
op

os
id

e
ye

s
no


m

ix
ed

h
ep

at
ic

a
nd

re
na

l
ye

s
re

du
ce

d

C
re

at
in

e
C

le
ar

an
ce



Te
ni

po
si

de


ye
s

no


m
ix

ed
h

ep
at

ic
a

nd
re

na
l

no


V
in

ca
A

lk
al

oi
ds



V
in

cr
is

tin
e

V
in

bl
as

tin
e

ye
s

no


bi
lia

ry


ye
s

V
in

or
el

bi
ne



Ta
xa

ne
s

Pa
c1

ita
xe

l
ye

s
no


he

pa
tic

m
et

ab
ol

is
m


?

D
oc

et
ax

el


ye
s

no


he
pa

tic
m

et
ab

ol
is

m


?

H
yd

ro
xy

ur
ea


ye

s
no


re

na
l

?

Page 524

and can reasonably assess kidney function in this setting, thus helping to modify
drug doses to maximize efficacy and reduce toxicity (Table 24.3) [11, 17, 28–30].
The issue with using serum creatinine alone is that it overestimates renal function
because less creatinine is produced due to the age-associated reduction of lean body
mass [11]. However, it is important to consider escalating the dose if no toxicity
occurs, to ensure the patient is not undertreated. Alternatively, the initial dose of
chemotherapy can be adjusted to the patient’s renal function using the formula of
Kintzel and Dorr [41]: Adjusted dose = (normal dose)×f[Kf–1]+1, where f is the
proportion of the agent or its active metabolite that is excreted through the kidneys,
and Kf is the patient’s creatinine clearance/120 ml/min.

Several chemotherapy agents, including anthracyclines and taxanes, need to be
given at modified doses in the presence of high levels of bilirubin, but there is little
data available on the precise adjustments necessary due to various liver-function
abnormalities [11]. Attention should also be paid to doses of those cytotoxic agents
that are metabolized by the liver, such as the anthracyclines, and to renal excretion
of their active metabolites [13].

24.4.2 Pharmacodynamics in the Elderly Patient

Retrospective studies of clinical trials have failed to demonstrate a relationship be-
tween age and chemotherapy-related toxicity [13, 17, 31–33]. However, these results
need cautious interpretation as the elderly patients who were eligible for these trials
were highly selective and unlikely to be representative of the true elderly population.
In addition, within these retrospective trials only a small proportion represented
those aged 75 years and over, and so it may be difficult to extrapolate these results
into this population [13, 17]. However, other studies have shown that the pharma-
codynamics of cytotoxic agents do differ in this older population, and this should
be taken into account when emphasizing the need to individualize treatment within
this age group to avoid unnecessary toxicity [35–36].

24.4.2.1 Myelotoxicity

Hemopoiesis becomes progressively impaired with age [34]. It has been observed
that in homeostasis, the hemopoietic reserve is sufficient for maintaining normal
concentrations of circulating blood elements in the older person. However, when
this reserve is under stress the older person may not be able to cope with the in-
creased destruction of blood elements by cytotoxic agents [17]. Dees et al. showed
in adjuvant treatment of breast cancer with doxorubicin and cyclophosphamide,
the risk, duration, and seriousness of neutropenia increased with age and was seen
particularly after the age of 75 years [35]. This increased risk of severe neutropenia
in elderly patients has also been reported in studies of non-Hodgkin’s lymphoma
[37–40]. These studies showed that the risk of grade 3 and 4 myelosuppression in-
creases with age and is about 50% after age 70 years with CHOP (cyclophosphamide,

24.4 Cancer Chemotherapy in the Elderly Patient 489

Page 1045

1026 Subject Index

Prophylactic Oophorectomy 66
PTHrP 547
pulmonary emboli 880

Q
quality of life 220, 553

R
radiation therapy 551
radioresistant 186
Radiotherapy 866
radiotherapy

bone 552
Raloxifene 893
Raloxifene chemoprevention 79

endometrial carcinoma 80
Study of Raloxifene and
Tamoxifen 81
thromboembolic events 80

randomized trial 220
randomized trials 221
rationality of preferences 937

adaption 937
cognitive dissonance reduction 937
psychological factors 937

receptor crosstalk 332
receptors

estrogen 885
hormone 892
progesterone 886

Replens 894
Response to endocrine therapy 451

Prediction of,
based on hormone receptor
expression 451

Retinoids 83
fenretinide 83

reverse transcriptase-polymerase chain
reaction (RT-PCR) 190

risk factors for local relapse 184

S
scintimammography 36
screening 217
sentinel node 32
sequencing of radiation 297





















SERMS 894
skeletal-related event 553
skeletal-related events (SREs) 545, 550
skeletal morbidity rate (SMR) 545
soy 895
spinal-cord compression 299
spinal cord compression 551
staging 34

axillary lymph nodes 33
internal mammary nodes 33
metastases 34

statins 894
Stockholm trial 892
stroke 880, 883
Surgery 866
surgery to bone 551

T
Tamoxifen 219, 221, 465, 468, 469,

870
Combined with ovarian
suppression 456
Effect on circulating estrogens 455
Mechanism of 454
Meta-analysis, compared with
ovarian ablation 455
Meta-analysis, comparing to ovarian
ablation 454
Sequential monotherapy with ovarian
ablation or suppression 456, 457
Withdrawal of 455

tamoxifen 35, 893
elderly 380
predicting response 35

Tamoxifen chemoprevention 70, 74
Dose 78
endometrial carcinoma 72, 76, 77
quality of life 72
risk:benefit ratio 76
The IBIS-I Trial 75
The Italian Prevention Trial 74
The NSABP P1 Trial 70
The Royal Marsden Prevention
Trial 74
thromboembolic events 72, 76

tamoxifen resistance 329































Page 1046

Subject Index 1027

HER2 330, 332, 333
PR 330
PR levels 329

taxanes
elderly 387

taxanes in elderly 493
Teratogenesis 868
The Early Breast Cancer

Trialist’s Collaborative Group
(EBCTCG) 329

The Immediate Preoperative
Anastrozole Tamoxifen or Combined
with Tamoxifen (IMPACT) 331

third-generation AIs 466, 469
Thromboembolism 888
tibolone 891
toxicity

elderly 386
toxicity management 492
tumor-negative margins 185
tumor biology

elderly 376
tumor size 184
type 101











U
UDH 104, 111, 112
Ultrasound 864
usual ductal hyperplasia 104

V
vasomotor 881
venlafaxine 895
vinorelbine in elderly 494
vitamin E 895

Y
young age 185

Z
zoledronate 551, 552, 553, 557

adjuvant 557
hypercalcemia 548
infusion time 552
multiple-events analysis 551
renal toxicity 551
skeletal morbidity rate 551
SRE 551
treatment induced bone loss 558










Similer Documents