Episode 10: Meta analysis of ovarian function suppression in early luminal breast cancer
Presented by Dr Kevin Punie (GZA Hospitals) and Prof Evandro De Azambuja (Institut Jules Bordet)
At ASCO 2023, data were presented from a meta-analysis investigating ovarian function suppression (OFS) in early luminal breast cancer. Upon comprehensive analysis, the earlier findings from previous trials were substantiated: the addition of OFS to endocrine therapy effectively mitigates recurrence in patients with early-stage hormone-positive breast cancer. The selected trials juxtapose patients receiving endocrine therapy with or without OFS. Those subjected to OFS exhibited a decreased risk of relapse without a concomitant rise in mortality risk.
Upon subgroup analysis, discernible nuances emerge. All subgroups derive benefits from OFS, albeit to varying degrees. This nuanced approach mirrors current clinical practices. Particularly noteworthy is the impact of age, with patients under 45 years experiencing the most substantial benefit at 11%. Those aged 45-54 derive a 7.5% benefit, while older patients exhibit diminishing benefits. Consequently, the recommendation is to consider OFS primarily for women younger than 50, aligning with prevailing clinical practices.
An intriguing concern pertains to the potential long-term impact of OFS-induced premature menopause on non-breast cancer-related mortality. While current trials do not indicate an elevated risk of mortality from non-breast cancer causes, caution is warranted due to the trials’ limited long-term follow-up. Registration trials typically conclude at 10 years, precluding an assessment of excess mortality over a 20-year or longer horizon. Mortality in such protracted timelines is multifactorial, involving factors such as prior chemotherapy and endocrine therapy, as well as the natural ageing process.
Discussion surrounds the optimal duration of OFS, commonly set at five years in major trials, although shorter durations in smaller studies demonstrate significant benefits. The translatability of these findings to clinical practice prompts consideration: should the duration of OFS be predetermined or contingent on safety and quality of life during treatment? Although the clinical aim is a five-year treatment duration, the actual duration is subject to patient tolerance and preference.
In cases where a patient experiences intolerance during OFS with tamoxifen, cessation of OFS is an option. However, in cases where aromatase inhibitors are involved, a transition to tamoxifen precedes OFS discontinuation. Patient input is pivotal in such decisions, emphasizing the collaborative nature of treatment planning with the overarching goal of achieving a five-year treatment duration.
References:
Gray RG. et al. (2023) Effects of ovarian ablation or suppression on breast cancer recurrence and survival: Patient-level meta-analysis of 14,993 pre-menopausal women in 25 randomized trials. Journal of Clinical Oncology 41:16_suppl, 503.