Optimal management of hormone receptor positive metastatic breast cancer in 2016

Abstract

Hormone receptor positive tumors represent the most common form of breast cancer and account for most of the deaths from the disease. Endocrine therapy represents the main initial therapeutic strategy for these patients and has been associated with significant clinical benefits in a majority of patients. While in early stages endocrine therapy is administered as part of a curative approach once clinical metastases develop, the disease is considered incurable and the main management objectives are tumor control and quality of life. The two major clinical paradigms of always indicating endocrine therapy in the absence of visceral crises and sequencing endocrine treatments have been guiding our therapeutic approach to these patients. However, for many decades, we have delivered endocrine therapy with a 'one size fits all' approach by applying agents that interfere with hormone receptor signaling equally in every clinical patient scenario. We have been unable to incorporate the well-known biologic principle of different degrees of hormone receptor dependency in our therapeutic recommendations. Recent developments in the understanding of molecular interactions of hormone signaling with other important growth factor, metabolic and cell division pathways have opened the possibility of improving results by modulating hormone signaling and interfering with resistance mechanisms yet to be fully understood. Unfortunately, limitations in the design of trials conducted in this area have made it difficult to develop predictive biomarkers and most of the new combinations with targeted agents, even though showing improvements in clinical endpoints, have been directed to an unselected population of patients. In this review we explore some of the current and most relevant literature in the management of hormone receptor positive advance breast cancer.

Confronting the therapeutic misconception

“…The patient seems to be an acceptable operative candidate from a medical perspective, and oophorectomy has a long history as an acceptable endocrine therapy for breast cancer, even when metastatic or highly advanced. 25 This patient’s cancer has progressed despite standard-of-care endocrine therapies, but it is possible that the operation itself would provide some additional therapeutic benefit. Furthermore, current National Comprehensive Cancer Network guidelines for breast cancer treatment recommend that premenopausal patients with advanced breast cancer who progress on tamoxifen receive either pharmacologic ovarian suppression or oophorectomy and then be treated as postmenopausal.…”

Efficacy and safety of palbociclib plus endocrine therapy in North American women with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative metastatic breast cancer

“…In this setting, endocrine therapy (ET) is the preferred option for patients who are not symptomatic or in visceral crisis . Recent advances have enabled the development of combination strategies to delay progression and limit resistance to monotherapy, including targeting the cyclin‐dependent kinase (CDK) 4/6 pathway …”

Development of a high‐performance liquid chromatography method with fluorescence detection for the routine quantification of tamoxifen, endoxifen and 4‐hydroxytamoxifen in plasma from breast cancer patients

“…Hormone‐dependent breast cancer (HDBC) is diagnosed by the presence of estrogen/progesterone receptor‐positive tumors. The adjuvant therapy is based on tamoxifen (Del Re, Michelucci, Simi, & Danesi, ), which is prescribed in both pre‐ (Gu et al, ) and post‐menopausal (Regan et al, ) women with early (Freedman et al, ) and metastatic HDBC (Reinert & Barrios, ). A five‐year treatment used to be standard, but an increase to 10 years was proposed after publication of the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial results (Davies et al, ).…”