Survival outcomes of beta-blocker usage in HER2-positive advanced breast cancer patients: a retrospective cohort study

Hsieh, Hui-Hsia; Wu, Tien-Yuan; Chen, Chi‐Hua; Kuo, Yu‐Hung; Hour, Mann‐Jen

doi:10.1177/20420986231181338

Cited by 3 publications

(8 citation statements)

References 31 publications

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“…In line with this, data extracted from retrospective studies in which some patients incidentally received betablockers revealed better outcomes after cancer surgery [64]. A few prospective studies also supported that beta-blockers reduced the incidence of recurrence and the risk of progressive disease [65,66]. By blocking stress hormones and thanks to their anxiolytic property, betablockers offer the opportunity to alleviate both glucocorticoid and psychological stress.…”

Section: Psychological Stressmentioning

confidence: 71%

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

Bezu,

Akçal Öksüz,

Bell

et al. 2024

Cancers

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Surgical excision of the primary tumor represents the most frequent and curative procedure for solid malignancies. Compelling evidence suggests that, despite its beneficial effects, surgery may impair immunosurveillance by triggering an immunosuppressive inflammatory stress response and favor recurrence by stimulating minimal residual disease. In addition, many factors interfere with the immune effectors before and after cancer procedures, such as malnutrition, anemia, or subsequent transfusion. Thus, the perioperative period plays a key role in determining oncological outcomes and represents a short phase to circumvent anesthetic and surgical deleterious factors by supporting the immune system through the use of synergistic pharmacological and non-pharmacological approaches. In line with this, accumulating studies indicate that anesthetic agents could drive both protumor or antitumor signaling pathways during or after cancer surgery. While preclinical investigations focusing on anesthetics’ impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive. Herein, we highlight the main factors occurring during the perioperative period of cancer surgery and their potential impact on immunomodulation and cancer progression. We also discuss patient management prior to and during surgery, taking into consideration the latest advances in the literature.

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Section: Psychological Stressmentioning

confidence: 71%

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

Bezu,

Akçal Öksüz,

Bell

et al. 2024

Cancers

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“…Thus, the study of Ramondetta et al . showed that patients with ovary cancer treated with propranolol had 55.5% complete response, 33.3% partial response, 5.6% stable response, and only 5.6% progressive disease 165 . In the randomized controlled trial by De Giorgi et al .…”

Section: Published Clinical Trialsmentioning

confidence: 99%

“…Only three trials failed to report prognostic effects of β-blockers 162–164 except a better response to pembrolizumab in the treatment of stage III melanoma. 162 Only one study reported negative effects of β-blockers in a cohort of HER2+ breast cancer patients treated with trastuzumab, where β-blocker appeared to decrease survival (PFS adjusted HR = 2.21, 95%[1.56–3.12]; p < 0.001 and OS adjusted HR = 2.46, 95%[1.69–3.57]; p < 0.001) 165 . However, the higher rate of mortality observed in this trial might involve cardiovascular mortality or immune toxicity.…”

Section: Published Clinical Trialsmentioning

confidence: 99%

“…Control of tumor growth ( p =0.001), tumor progression ( p =0.0001) and higher survival ( p =0.015). Strong correlation between β-blockers and survival ( p =0.049) Retrospective 150 Breast cancer (HER2+) Atenolol, bisoprolol, carvedilol, propranolol Trastuzumab PFS adjusted HR=2.21, 95%CI[1.56–3.12]; p <0.001 OS adjusted HR=2.46, 95% CI[1.69–3.57]; p <0.001 Retrospective 165 Breast cancer (HER2-) Atenolol, bisoprolol, metoprolol, propranolol Docetaxel and/or ramucirumab Improved PFS (15.5 vs 8.3 months); p =0.038 No significant difference in OS Retrospective 151 Breast cancer Atenolol, bisoprolol, propranolol, timolol NA Reduction in metastasis ( p =0.026), tumor recurrence ( p =0.001) and longer disease-free interval ( p =0.01). A 57% reduction in risk of metastasis (HR=0.430; 95%CI[0.200–0.926], p =0.031).…”

Section: Published Clinical Trialsmentioning

confidence: 99%

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Trial watch: beta-blockers in cancer therapy

Carnet Le Provost,

Kepp,

Kroemer

et al. 2023

OncoImmunology

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Compelling evidence supports the hypothesis that stress negatively impacts cancer development and prognosis. Irrespective of its physical, biological or psychological source, stress triggers a physiological response that is mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic adrenal medullary axis. The resulting release of glucocorticoids and catecholamines into the systemic circulation leads to neuroendocrine and metabolic adaptations that can affect immune homeostasis and immunosurveillance, thus impairing the detection and eradication of malignant cells. Moreover, catecholamines directly act on β-adrenoreceptors present on tumor cells, thereby stimulating survival, proliferation, and migration of nascent neoplasms. Numerous preclinical studies have shown that blocking adrenergic receptors slows tumor growth, suggesting potential clinical benefits of using β-blockers in cancer therapy. Much of these positive effects of β-blockade are mediated by improved immunosurveillance. The present trial watch summarizes current knowledge from preclinical and clinical studies investigating the anticancer effects of β-blockers either as standalone agents or in combination with conventional antineoplastic treatments or immunotherapy.

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“…In the meta-analyses published to date, some of the more recent observational studies have not been included [ 23 , 24 ]. Further, there have not been many meta-analyses that have examined potentially important effect modifiers of the association such as the presence of immortal time bias (ITB), the type of BB (selective vs non-selective), or the exposure period in which BBs were used (prediagnosis vs postdiagnosis).…”

Section: Introductionmentioning

confidence: 99%

Beta-blocker use and breast cancer outcomes: a meta-analysis

Scott,

TinTin,

Cavadino

et al. 2024

Breast Cancer Res Treat

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Purpose Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR). Methods Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I2 statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger’s regression tests. Results Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78–1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71–1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes. Conclusion In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.

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Survival outcomes of beta-blocker usage in HER2-positive advanced breast cancer patients: a retrospective cohort study

Cited by 3 publications

References 31 publications

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review

Trial watch: beta-blockers in cancer therapy

Beta-blocker use and breast cancer outcomes: a meta-analysis

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