Endocrine Treatment – ‘Old-Fashioned’ Therapy Becoming Redundant in an Era of Molecular Medicine?

摘要

For more than a century, endocrine therapy has been recognized as an effective, but palliative, treatment option for advanced breast cancer. Over the last 2 decades, 2 important observations have dramatically changed this conceptual view. The first observation was the finding that tamoxifen, but also ovarian ablation, causes sustainable relapse-free and overall survival benefits in the adjuvant setting [1, 2]. The second finding relates to the potential for improvement. While for decades, randomized studies comparing different endocrine regimens had revealed ‘no significant difference’ between the different endocrine treatment options regarding efficacy, third-generation aromatase inhibitors improved time to progression in metastatic disease [3] but also relapse-free survival in the adjuvant setting [4,5,6,7,8] compared to tamoxifen. In addition, studies have challenged the need for chemotherapy to hormone receptor-positive premenopausal low-risk patients, suggesting many patients may be well treated with endocrine therapy alone [9, 10], omitting the toxicity of chemotherapy. Ongoing studies are addressing important topics in adjuvant therapy. What is the optimal use of aromatase inhibitors (ta-moxifen upfront versus aromatase inhibitor monotherapy, optimal duration of treatment)? And how may we improve treatment for premenopausal women? Tamoxifen and an luteinizing hormone-releasing hormone (LHRH) analogue administered in concert has been shown to improve response rate compared to monotherapy in metastatic disease [11, 12], but we lack evidence whether this improves outcome compared to tamoxifen alone in the adjuvant setting.