Hormonal Therapy of Breast Cancer: Introduction

Article Outline

• Copyright

The hormonal therapy of breast cancer often has been viewed as secondary to chemotherapy in the impact on the survival of these patients. However, recent trials such as the Arimidex or Tamoxifen Alone or in Combination (ATAC) trial have changed the attitudes and approach to this integral aspect of treatment. The goal of this issue of Seminars in Oncology is to provide a comprehensive overview of the hormonal therapy from receptor to prevention to treatment.

Cordera and Jordan present a complete overview of the estrogen and progesterone receptors and the molecular basis for response and resistance to treatment. They illustrate beautifully how the knowledge of the mechanisms behind signal transduction should impact therapeutic decisions in the hormonal treatment of breast cancer. Their article further elucidates the molecular mechanisms behind the development of resistance to these therapies, which should impact the choice of sequential therapies and the design of future clinical trials.

Chan and Morris next discuss the use of hormonal therapy in the prevention of breast cancer in high-risk populations such as women with lobular carcinoma-in-situ and BRCA1 or BRCA2 mutation carriers, or those women with a Gail model score greater than 1.66.

The discussion of chemoprevention would not be complete without a report devoted to the use of tamoxifen in ductal carcinoma-in-situ (DCIS). Daly reviews the clinical evidence for the use of tamoxifen in this ever-growing population of patients. This article is a wonderful reference for the clinician discussing the risk benefit-ratio with these patients on a daily basis.

As DCIS is a precursor for invasive breast cancer, we then move on to the use of endocrine therapy in the neoadjuvant treatment of breast cancer. Chemotherapy traditionally has been used in the United States to allow for breast conservation; however, Ma and Ellis bring to us the evidence that endocrine therapy, specifically with an aromatase inhibitor, will promote breast conservation as well. They astutely point out that a less toxic therapeutically superior adjuvant treatment in postmenopausal patients logically should continue to be evaluated in the neoadjuvant setting.

The choice of endocrine therapy in the premenopausal patient at first blush appears straightforward. However, Brown and Davidson bring to light the mitigating factors that impact the choice of agent and the duration and timing of use. It is for these patients, many of whom have their reproductive years ahead of them, that the choice may be most difficult.

Park et al cover the flip side of the coin for these premenopausal patients. What hormonally can be done to preserve their fertility? What impact if any do subsequent pregnancies play on the risk of recurrence of their breast cancer? These are questions often at the forefront of premenopausal women’s minds when deciding on adjuvant therapy, both chemotherapeutic and hormonal. This work is an excellent review and reference for the clinician counseling these women.

The next discussion regards the choice of endocrine therapy for the postmenopausal patient. Wheler and colleagues review the landmark trials in this patient population. Their first table summarizes the schema and results of these trials and their paper astutely analyzes and discusses the results.

The choice of endocrine therapy in both pre- and postmenopausal patients, if not complex enough, now appears to be impacted by the Her-2/neu status of their tumor. Cordera and Jordan set the stage for resistance to endocrine therapy seen in tumors that overexpress Her-2/neu on the molecular level. Armstrong and Prowell discuss the clinical data available in the small percentage of tumors that express both Her-2/neu and hormone receptors.

From treatment always stems side effects. Pandya and Morris review the toxicities associated with aromatase inhibitors and how best to treat or ameliorate them. Bruno and Feeney discuss the impact of menopausal symptoms brought on by treatment, both endocrine and chemotherapeutic. Our patients come to us with questions regarding the safely and benefit of complementary therapies used to treat the often disabling symptoms of menopause. Our report provides the knowledge to recommend or reject these therapeutic interventions.

This issue concludes with an intellectually stimulating report on hormesis by Prehn and Berd. While the bulk of breast cancer literature focuses on hormonal deprivation as therapy, these authors remind us that breast cancer will adapt to its environment. Thus, they propose a “whipsaw effect” of exposing the tumor to alternating high and low levels of hormone as therapy. It is ideas such as these that inspire us to develop treatment outside of the bounds of convention.

In conclusion, we would like to thank the authors for the obvious effort they have put into these papers. Collectively they have produced an excellent comprehensive review of the hormonal therapy of breast cancer that should prove to be a reference for oncologists for years to come. Enjoy.