Hormones and Cancer: Breast and Prostate, An Issue of Endocrinology and Metabolism Clinics of North America

Alice C. Levine

Description

This issue of Endocrinology Clinics brings the reader up to date on the latest information about hormones and cancer of the breast and prostate. The first section focuses on the breast, and topics covered include the following. The role of sex steroids and their receptors in normal breast development; estrogen carcinogenesis in breast cancer; hormonal mechanisms underlying the relationship between obesity and breast cancer; postmenopausal hormone replacement therapy and the risk of breast cancer; aromatase inhibitors, anti-estrogen and SERMS in the treatment of breast cancer; and androgens in breast cancer in men and women. The second section is devoted to the prostate, and topics covered include the following. Overview of prostate anatomy, histology, and pathology; the critical role of sex steroids in normal prostate development; estrogens and androgens in prostate cancer development and the rationale for hormonal chemopreventive therapies; weighing the clinical evidence regarding the timing and extent of androgen ablative therapy for prostate cancer treatment; new hormonal therapies for castration-resistant prostate cancer; and the management of the side effects of castration therapy.

Sujets

• Médecine
• Spécialités médicales
• Medical
• Metabolism
• Endocrinology

Informations

• Publié par: Saunders
• Date de parution: 28 septembre 2011
• Nombre de lectures: 0
• EAN13: 9781455712397
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Hormones and Cancer: Breast and Prostate , Vol. 40, No. 3, September 2011
ISSN: 0889-8529
doi: 10.1016/S0889-8529(11)00081-8

Contributors
Endocrinology Clinics of North America
Hormones and Cancer: Breast and Prostate
GUEST EDITOR: Alice C. Levine, MD
CONSULTING EDITOR: Derek LeRoith, MD, PhD
ISSN  0889-8529
Volume 40 • Number 3 • September 2011

Hormones and Cancer: Breast and Prostate , Vol. 40, No. 3, September 2011
ISSN: 0889-8529
doi: 10.1016/S0889-8529(11)00082-X

Contents
Cover
Contributors
Forthcoming Issues
Hormones and Cancer: Breast and Prostate
Preface
The Pivotal Role of Insulin-Like Growth Factor I in Normal Mammary Development
Estrogen Carcinogenesis in Breast Cancer
Hormonal Mechanisms Underlying the Relationship Between Obesity and Breast Cancer
Postmenopausal Hormone Therapy and Breast Cancer Risk: Current Status and Unanswered Questions
Hormonal Modulation in the Treatment of Breast Cancer
Androgens and Breast Cancer in Men and Women
Management of Bone Disease in Patients Undergoing Hormonal Therapy for Breast Cancer
Overview of Prostate Anatomy, Histology, and Pathology
The Critical Role of Androgens in Prostate Development
Estrogens and Prostate Cancer: Etiology, Mediators, Prevention, and Management
The Timing and Extent of Androgen Deprivation Therapy for Prostate Cancer: Weighing the Clinical Evidence
New Hormonal Therapies for Castration-Resistant Prostate Cancer
Androgens and Prostate Cancer Bone Metastases: Effects on Both the Seed and the Soil
Management of Side Effects of Androgen Deprivation Therapy
Index
Hormones and Cancer: Breast and Prostate , Vol. 40, No. 3, September 2011
ISSN: 0889-8529
doi: 10.1016/S0889-8529(11)00083-1

Forthcoming Issues
Hormones and Cancer: Breast and Prostate , Vol. 40, No. 3, September 2011
ISSN: 0889-8529
doi: 10.1016/j.ecl.2011.05.015

Foreword
Hormones and Cancer: Breast and Prostate

Derek LeRoith, MD, PhD ,
Division of Endocrinology, Metabolism, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, Altran 4-36, New York, NY 10029, USA
E-mail address: [e-mail]

Derek LeRoith, MD, PhD, Consulting Editor
This current issue of Endocrinology and Metabolism Clinics of North America compiled by Dr Alice Levine covers the important topic of hormones and cancer and focuses on two hormone-dependent cancers, breast and prostate. The first seven articles cover the mammary gland and breast cancer and the second seven articles cover the prostate gland and prostate cancer.
In the opening article, Dr Kleinberg discusses the development of the adult mammary gland that is seen at puberty and is the result of multiple hormonal interactions. Both estrogen and progesterone are critical, estrogen for mammary ductal morphogenesis, while the combination of both is required for lobulo-alveolar development. On the other hand, growth hormone is also needed for ductal morphogenesis and GH plus prolactin are required for lobulo-alveolar development. Importantly, IGF-1 apparently mediates all the effects of GH on mammary development.
Estrogens are well known to be important for breast development, but also play a role in breast cancer. In her article, Dr Germain describes the emerging studies that show that in addition to estrogen and estrogen receptor’s nuclear effects on gene transcription, the ER also has significant nongenomic effects that emanate from the plasma membrane and cytosolic compartment. The nuclear events involve activation or suppression of co-activators or co-repressors, whereas the extranuclear effects of ER activation involve intracellular signaling pathways.
Epidemiological studies have established an increased risk for developing breast cancer in obese individuals. A number of factors have been identified that may be causative. These include sex hormones, the insulin/IGF-1 axis, leptin, and inflammatory cytokines such as IL-6. Furthermore, Drs Perks and Holly describe how lifestyle changes have been shown to affect the prevalence of breast cancer in obesity.
Following publication of the results from the Women’s Health Initiative, the use of hormonal replacement therapy (HRT) has decreased significantly. However, as estrogens remain the most effective therapy for hormonal symptoms, many questions still remain. Dr Chen’s article reviews the literature data on postemenopausal HRT and breast cancer risk. It seems clear that women who have had breast cancer or have other associated risk factors should refrain from HRT. However, it is apparent that estrogen therapy is less harmful than the combination of estrogen and progestin and is still commonly used by women with postmenopausal (PMP) symptoms.
In their article on the use of hormonal modulation, Drs Adelson, Germain, Raptis, and Biran describe its use as primary cancer prevention, as adjuvant therapy, and even as palliative therapy, in cases of breast cancer. Traditionally tamoxifen therapy is used in cases of premenopausal cancer, whereas aromatase inhibitors are the mainstay for PMP cases. However, as the authors discuss, more research is required to determine if these are the optimal approaches.
Dr Dimitrakakis discusses an interesting concept, namely, that androgens inhibit mammary epithelial proliferation. Furthermore, conventional estrogen therapy inhibits endogenous androgen production and the balance favors mammary epithelial proliferation. Thus the possibility that needs to be tested is the addition of androgens to estrogen/progestin (E2/P) therapies to decrease the impact of E2/P on breast cancer risk.
In PMP women with breast cancer, tamoxifen has been used as an anti-estrogen for the cancer and pro-estrogen protecting, to some degree, against bone loss. Aromatase inhibitors decrease circulating and possibly local estrogen levels and when used to treat breast cancer generally cause a reduction in BMD. As discussed by Dr Mirza in her article, bisphosphonates have been successful in preventing the PMP bone loss associated with aromatase inhibitors. The recent addition of the RANKL as a therapy for bone loss may prove to be another important way to prevent bone loss in these patients.
Drs Lee, Akin-Olugbade, and Kirschenbaum describe many aspects of the prostate gland, including its anatomy, histology and pathology with particular relevance to two common disorders, benign prostatic hyperplasia, and prostate cancer. They underscore the marked heterogeneity of the gland, which is particularly relevant in prostate cancer. In addition, they review the current understanding of the location and characterization of prostate epithelial stem cells. As they discuss, while there is a large body of information on all these aspects, further research on molecular aspects may help in our understanding of the normal and abnormal gland and in the development of both biological markers that predict disease progression and more efficacious, targeted therapies for both hyperplasia and cancer.
Dr Wilson describes the critical role of androgens in prostate differentiation, early development, and hyperplasia later in life. A complex interplay between prostate stromal and epithelial cells, under the influences of androgens, dictates fetal, pubertal, and adult growth of the gland. Androgen deprivation, conversely, results in apoptosis and a reduction in prostate cell number. The relative roles of testosterone and its metabolite, dihydrotestosterone, have been dissected at both the biologic and the molecular levels. Despite these well-known effects, Dr Wilson reports that downstream events of androgen action, particularly gene expression, is not well defined and awaits further research.
While androgens are traditionally considered to play important roles in prostate cancer (PCa) and anti-androgen therapy is often used especially in metastatic PCa, there is accumulating evidence that estrogens may also play a role. As discussed by Drs Ho, Lee, Lam, and Leung, both genomic and noncanonical effects of the ER maybe involved. For example, alterations in the estrogen/androgen ratios, changes in sex hormone binding globulin, and the potential genotoxic carcinogenic effects may all be involved. Thus, estrogen and anti-estrogens may be important in the etiology as well as potential therapeutics for PCa.
In their article Drs Ginzburg and Albertsen discuss the history, clinical trials, and current indications for androgen ablation therapy for PCa. Although castration therapy has long been the mainstay of treatment for bone-metastatic, symptomatic disease, it is not indicated for localized disease as it has serious side effects and has no proven long-term benefit in that setting. Neo-adjuvant androgen deprivation when combined with external beam radiation does improve survival for men with locally advanced disease. Androgen deprivation therapy, with orchiectomy or with GnRH agonists or antagonists, is the current standard of care. They underscore that more randomized clinical trials are needed to guide clinicians as to the proper use of androgen deprivation therapy in men with prostate cancer at various stages of the disease.
Although most patients with advanced, metastatic prostate cancer will respond to androgen deprivation, the majority of cancers inevitably relapse and progress. The majority of castrate-resistant prostate cancers still express androgen receptors (AR) and depend on AR-signaling for their survival and continued proliferation. Recent studies have demonstrated that prostate cancer cells are capable of de novo synthesis of androgens under castrate conditions, reviving the interest in targeting the androgen/AR pathway even in so-called castrate-resistant disease. Therapeutic strategies designed to more effectively ablate tumoral androgen activity are required to improve clinical efficacy and prevent disease progression. Thus newer forms of anti-