The Journal of Clinical Oncology has featured an analysis of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial which had originally compared the long-term effects of exemestane monotherapy with sequential treatment (tamoxifen followed by exemestane) in postmenopausal women (median age 64 years, range 35-96) with hormone-receptor-positive breast cancer.
This analysis investigated the relationship between survival outcomes and specific AEs experienced in the first year of treatment, including vasomotor symptoms (VMSs), musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in 9,325 patients. The efficacy end points of the present investigation were DFS, OS, and distant metastases (DM), starting as of the second year of therapy.
Researchers reported that patients with specific AEs (vs nonspecific or no AEs) had better DFS and OS:
• Multivariate hazard ratio [HR] for DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866, p<0.001]; MSAEs, 0.826 [0.694 to 0.982, p=0.030]; VVSs, 0.769 [0.585 to 1.01, p=0.058];
• Multivariate HR for OS: VMSs, 0.583 [95% CI, 0.424 to 0.803, p=0.001]; MSAEs, 0.811 [0.654 to 1.005, p=0.055]; VVSs, 0.570 [0.391 to 0.831, p=0.003])
Fewer DM were noted (VMSs, 0.813 [95% CI, 0.664 to 0.996, p=0.046]; MSAEs, 0.749 [0.601 to 0.934, p=0.010]; VVSs, 0.687 [0.436 to 1.085, p=0.107]) than patients not reporting these symptoms. Increasing numbers of specific AEs were also associated with better survival outcomes. Outcomes were unrelated to treatment allocation.
Because of the unplanned nature of these analyses, pre-existing symptoms were not recorded, and this analysis only included patients who reported symptoms in the first year of endocrine therapy. The effect observed may therefore be larger when the occurrence of specific AEs over the entire follow-up period is considered. Additionally, it may be worth considering that reporting of AEs may not be uniform across study centres, and therefore it is conceivable that results may be influenced by reporting bias.
All AEs were patient-reported AEs, and no standardised symptom checklist was used. Cultural differences between countries may therefore also reflect differences in reporting of AEs. A symptom checklist that actively inquires about a patient’s symptoms and severity thereof will undoubtedly lead to a more accurate assessment and potentially observe a stronger relationship between specific AEs, severity, and improved outcomes.
Nonetheless, the researchers concluded that even after adjusting for possible confounders, the correlation between specific AEs and superior outcomes was still present, and although these results must be considered hypothesis generating, they show an association between specific adverse effects caused by endocrine therapy and positive outcomes and may thus potentially be a valuable predictor and biomarker of treatment efficacy. Future prospective studies therefore, are warranted to advance the personalisation of treatment strategies for patients with breast cancer.
NICE, in their clinical guideline on the management of early and locally advanced breast cancer state that postmenopausal women with oestrogen receptor (ER)-positive early invasive breast cancer who are not considered to be at low risk should be offered an aromatase inhibitor, either anastrozole or letrozole, as their initial adjuvant therapy. Tamoxifen should be offered if an aromatase inhibitor is not tolerated or contraindicated.
Additionally, in their guideline on the management of advanced breast cancer, they recommend an aromatase inhibitor (either non-steroidal or steroidal) to:
• postmenopausal women with ER-positive breast cancer and no prior history of endocrine therapy, or
• postmenopausal women with ER-positive breast cancer previously treated with tamoxifen.