Endocrine Treatment-Related Symptoms and Patient Outcomes in Breast Cancer: A Meta-Analysis

Abstract

PurposeAn association between endocrine treatment-related symptoms and breast cancer recurrence has been suggested previously; however, conflicting results have been reported. We performed a meta-analysis of published studies to clarify this relationship.MethodsWe systematically searched PubMed, Embase, Scopus, and the Cochrane database for studies investigating the association between endocrine treatment-related symptoms and patient survival. Random-effects meta-analysis was conducted with recurrence rate as the primary outcome.ResultsOut of 7,713 retrieved articles, six studies were included. In patients who received endocrine treatment, the presence of any endocrine treatment-related symptom was found to be associated with a lower recurrence rate in comparison to an absence of any symptoms (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.66–0.87). This relationship persisted in patients presenting with only vasomotor or only musculoskeletal symptoms (HR, 0.74, 95% CI, 0.63–0.87; HR, 0.69, 95% CI, 0.55–0.86, respectively). At both time-points of symptom evaluation (3 months and 12 months), patients with endocrine treatment-related symptoms had a lower recurrence rate (HR, 0.74, 95% CI, 0.66–0.84; HR, 0.79, 95% CI, 0.69–0.90, respectively). This association was also significant in pooled studies including patients with and without baseline symptoms (HR, 0.73, 95% CI, 0.54–0.99; HR, 0.76, 95% CI, 0.69–0.85, respectively).ConclusionEndocrine treatment-related symptoms are significantly predictive of lower recurrence rate in breast cancer patients, regardless of the type of symptoms, time-point of evaluation, or inclusion of baseline symptoms. These symptoms could be biomarkers for the prediction of long-term responses to endocrine treatment in patients with breast cancer.

Association of single nucleotide polymorphisms of cytochrome P450 enzymes with experience of vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients: a systematic review

“…Vaginal atrophy, vasomotor symptoms such as hot flashes [6][7][8] and musculoskeletal symptoms including joint pain and stiffness [9] are commonly reported adverse effects of adjuvant endocrine therapies with tamoxifen and/or AIs. Consistent with this, a recent metaanalysis showed that the occurrence of vasomotor and musculoskeletal symptoms is associated with a lower rate of breast cancer recurrence, an outcome associated with the administration of adjuvant endocrine therapies [10]. It therefore follows that the development of the above symptoms can be attributed to the active metabolites of the drugs used in adjuvant endocrine therapies (tamoxifen and AIs).…”

“…In support of this finding, Lee et al [15] recently demonstrated that a dose reduction in tamoxifen treatment could reduce endoxifen levels and in turn result in patients' perceived alleviation of hot flashes. Moreover, as indicated above, a recent meta-analysis [10] also established the relationship between the occurrence of vasomotor or musculoskeletal symptoms and breast cancer recurrence, an outcome that may be influenced by CYP's metabolising activity [16][17][18], among patients who undergo endocrine therapy. Together, these findings suggest that CYP's activities may be linked to the occurrence and/or severity of these therapy-induced symptoms.…”

Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management

“…While this association has not been consistently observed in all trials ( 49 , 69 ), there has been speculation regarding this observation. It has been suggested that patients reporting adverse effects are more adherent to therapy ( 70 ) or alternatively that patients with AIMSS are benefiting from greater reductions in estrogen levels with enhanced efficacy against HR+ breast cancer ( 71 ).…”

Tamoxifen related side effects and their impact on breast cancer incidence: A retrospective analysis of the randomised IBIS-I trial

“…However, they may play an important indirect role in breast cancer prevention. Studies in the adjuvant setting have shown that endocrine therapy related side effects are associated with a reduction in breast cancer recurrence [ [25] , [26] , [27] , [28] , [29] ], which suggests that side effects might be a marker for predicting therapy benefit [ 30 ].…”