Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update

Abstract

Purpose To update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment. Methods ASCO conducted a systematic review of randomized clinical trials from 2012 to 2018. Guideline recommendations were based on the Panel’s review of the evidence from six trials. Results The six included studies of AI treatment beyond 5 years of therapy demonstrated that extension of AI treatment was not associated with an overall survival advantage but was significantly associated with lower risks of breast cancer recurrence and contralateral breast cancer compared with placebo. Bone-related toxic effects were more common with extended AI treatment. Recommendations The Panel recommends that women with node-positive breast cancer receive extended therapy, including an AI, for up to a total of 10 years of adjuvant endocrine treatment. Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. The Panel noted that the benefits in absolute risk of reduction were modest and that, for lower-risk node-negative or limited node-positive cancers, an individualized approach to treatment duration that is based on considerations of risk reduction and tolerability was appropriate. A substantial portion of the benefit for extended adjuvant AI therapy was derived from prevention of second breast cancers. Shared decision making between clinicians and patients is appropriate for decisions about extended adjuvant endocrine treatment, including discussions about the absolute benefits in the reduction of breast cancer recurrence, the prevention of second breast cancers, and the impact of adverse effects of treatment. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients’ preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer

“…Current guidelines unequivocally indicate endocrine therapy as the preferred systemic treatment in the vast majority of patients with advanced HR-positive, HER2-negative BC [2][3][4]. However, this is in contrast to treatment reality; 43% of these patients are primarily subjected to first-line chemotherapy with > 80% receiving first-line chemotherapy when aged ≤50 years [19].…”

“…Current international guidelines recommend endocrine therapy as the first-line treatment of choice in the vast majority of these patients. Chemotherapy may be considered as a reasonable alternative in patients for whom endocrine treatment is inappropriate including individuals presenting with acute visceral crisis and/or hormone-resistant tumors [2][3][4]. Up to now, there are limited data from clinical trials having directly compared chemotherapy and endocrinebased treatment in patients with MBC.…”

Increased Fracture Risk in Women Treated With Aromatase Inhibitors Versus Tamoxifen: Beneficial Effect of Bisphosphonates

“…One limitation of the study was that data of severity and grade of breast cancer were not accessible. However, TAM and AI monotherapies are recommended and mainly used for hormone receptor–positive early breast cancer . Likewise, available data could not distinguish between osteoporotic fracture and high‐energy impact fracture.…”

SLCs contribute to endocrine resistance in breast cancer: role of SLC7A5 (LAT1)

“…While tamoxifen and fulvestrant are effective endocrine therapies 3 , further research is needed to prevent or overcome the development of resistance. Endocrine therapy resistance, particularly in advanced disease, is a major clinical challenge for patients and their physicians.…”

“…Of the 253,000 newly diagnosed breast cancers each year, approximately 70% are estrogen receptor positive (ER+) 2 . Endocrine therapies, such as aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs), have extended life expectancy for patients with ER+ disease 3 . Unfortunately, resistance to these treatments is common 4,5 .…”