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Endocrine Therapy in Breast Cancer

2002 Edition, March 8, 2002

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Active, Most Current

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ISBN: 978-0-8247-0787-3
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Product Details:

  • Revision: 2002 Edition, March 8, 2002
  • Published Date: March 8, 2002
  • Status: Active, Most Current
  • Document Language: English
  • Published By: CRC Press (CRC)
  • Page Count: 395
  • ANSI Approved: No
  • DoD Adopted: No

Description / Abstract:


The knowledge that hormones influence both the risk of developing and the natural history of breast cancer is not new (indeed, Beatson, working in Scotland over a century ago, made the pioneering observation that ovarian ablation in premenopausal women produced regression of breast cancer). However, the recent development of new specific and highly potent endocrine agents makes it timely to examine the "new horizons" they create. To this end, 50 clinicians and basic scientists—experts at the forefront of endocrine research in breast cancer—convened a workshop in Gleneagles, Scotland, to evaluate progress and to assess future potential and needs. This volume summarizes the developments discussed in that workshop.

Part I sets the scene with Chapter 1 addressing the question "Why endocrine therapy?" The book is then divided into four interrelated subject areas: advanced breast cancer, early breast cancer, neoadjuvant therapy, and chemoprevention.

The status of endocrine agents in the treatment of advanced breast cancer is discussed in Part II by individual experts with firsthand experience in their use: tamoxifen (Chap. 2); aromatase inhibitors (Chap. 3); other selective estrogen receptor modulators (SERMs) (Chap. 4), as well as other endocrine agents and therapies directed at molecular targets (Chap. 5). Part III uses the same approach to cover early breast cancer: tamoxifen (Chap. 6); aromatase inhibitors (Chap. 7); and other SERMs (Chap. 8). In addition, because treatment of early breast cancer often involves adjuvant therapy over relatively long periods of time, surrogate markers of response to, and side effects of, treatment are reviewed in Chapter 9.

While the conventional sequence of treatment in most patients with early breast cancer is surgery followed by systemic therapy, Part IV reviews primary or neoadjuvant therapy, in which drug treatment is given prior to surgery with the tumor still within the breast. This strategy offers both potential clinical benefits to patients and unique opportunities for research. Until recently, the use of endocrine therapy in this setting had been relatively ignored, but this gap is filled in Chapter 10 (which presents the subject from a medical perspective); Chapter 11 (from a surgical perspective); and Chapter 12 (from a pathological perspective). Chapter 13 focuses on research opportunities.

Neoadjuvant therapy may also be exploited to study mechanisms of resistance (which is a major obstacle to increasing survival by endocrine measures), but other model systems are providing interesting results. These data are covered in Chapter 14.

Part V is concerned with chemoprevention. The etiology of breast cancer has a strong hormonal component. Chapter 15 reviews the epidemiological basis for believing endocrine manipulation may prevent most breast cancers. Evidence that estrogen may have a direct carcinogenic effect and initiate breast cancer is presented in Chapter 16. The relative advantages and disadvantages of using either antiestrogens or aromatase inhibitors are summarized in Chapters 17 and 18. Throughout this volume, discussion sessions are presented in an unabridged form so that the areas of controversy can be identified and points of detail clarified.

A consensus was reached at the workshop in Gleneagles. First, it was agreed that these are momentous times in terms of the development of new endocrine agents. On the one hand, the new generation of aromatase inhibitors can inhibit estrogen biosynthesis more potently and specifically than ever before. On the other hand, the SERMs can block the mechanism of estrogen action differentially in different tissue, thus offering the promise of selectively turning off the estrogen stimulus to malignant growth while maintaining the same signal in normal tissues. Results from clinical trials in advanced disease have established that aromatase inhibitors such as letrozole, anastrozole, and exemestane are at least as efficacious as other endocrine agents when used as second-line therapy after tamoxifen and, indeed, may be superior to tamoxifen when used as first-line therapy. Similar promising clinical benefits have been observed when, for example, letrozole was compared with tamoxifen in the neoadjuvant setting. Indeed, when used neoadjuvantly against estrogen-receptor-rich tumors, clinical and pathological response can be remarkable high, rivaling that previously seen only after chemotherapy. The benefits of neoadjuvant therapy stretch beyond clinical outcomes because of the opportunity to have easy and sequential access to the tumor. Combining this approach with molecular technology will allow us to define accurately the phenotype of responsive tumors and the mechanism of endocrine resistance; thus treatment will be optimized.

The transfer of these observations to earlier stages of the disease and cancer prevention is underway and, in the next few years, we will know whether the newer SERMs and aromatase inhibitors can continue the trend of improved survival attributed to tamoxifen.

The epidemiology and etiology of breast cancers suggest that hormonal measures, if implemented earlier and used correctly, can prevent the appearance of breast cancer. The challenge is to identify high-risk groups and develop acceptable regimes (perhaps by offering other health benefits such as contraception at the same time). In this context, if estrogens are genotoxic carcinogens, aromatase inhibitors (by reducing levels of estrogen rather than blocking interaction at receptor sites) may be more effective chemopreventatives than tamoxifen and other SERMs.

Since the era of Beatson, there has been no more exciting time to be associated with endocrine therapy. It is thus highly appropriate that this volume emanated from a workshop in Beatson's homeland. It is patently clear that there are unprecedented opportunities for advancing the science and understanding of breast cancer and improving the care of our patients with this disease. We hope this volume will stimulate and extend your horizons in the field of endocrine therapy in breast cancer.