Prior Treatment Time Affects Survival Outcomes in Metastatic Breast Cancer

Rocque, Gabrielle Betty; Gilbert, Aidan; Williams, Courtney; Kenzik, Kelly; Nakhmani, Arie; Kandhare, Pravinkumar G.; Bhatia, Smita; Burkard, Mark E.; Azuero, Andres

doi:10.1200/cci.20.00008

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…[15][16][17] The early disease may be the most adequate setting to evaluate the real impact of beta-blockers on patients with breast cancer, since patient outcomes in this scenario are not influenced by potential subsequent lines of treatment, as it occurs in those with advanced disease. 18,19 In this regard, we carried out a systematic review and meta-analysis to assess the impact of beta-blockers on the outcomes of patients with early-stage breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Beta-blockers in early-stage breast cancer: a systematic review and meta-analysis

et al. 2021

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Background: Preclinical and retrospective studies suggest that beta-blockers are active against breast cancer. We carried out a systematic review and meta-analysis to assess the impact of beta-blockers on the outcomes of patients with earlystage breast cancer. Methods: A systematic literature search was performed to identify studies comparing outcomes of patients with earlystage breast cancer according to beta-blocker use (yes versus no). The primary endpoint was recurrence-free survival (RFS), defined as the occurrence of breast cancer recurrence or death. Secondary objectives were pathologic complete response (pCR), breast cancer recurrence, breast cancer-specific mortality and overall survival (OS). Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from each study and a pooled analysis with the random-effect model was conducted. The Higgins' I-squared test was used to quantify heterogeneity. Egger's test was applied to assess publication bias. All P values were two-sided and considered significant if 0.05. Results: Overall, 13 studies were included as follows: RFS (6), pCR (2), breast cancer recurrence (6), breast cancerspecific mortality (7) and OS (5). The use of beta-blockers was associated with a significant RFS improvement in the overall population (N ¼ 21 570; HR 0.73; 95% CI, 0.56-0.96; P ¼ 0.025) and in patients with triple-negative disease (N ¼ 1212; HR 0.53; 95% CI, 0.35-0.81; P ¼ 0.003). No significant differences in terms of pCR (N ¼ 1554; OR 0.77; 95% CI, 0.44-1.36; P ¼ 0.371), breast cancer recurrence (N ¼ 37 957; OR 0.66; 95% CI, 0.42-1.03; P ¼ 0.065), breast cancer-specific mortality (N ¼ 64 830; HR 0.77; 95% CI, 0.56-1.08; P ¼ 0.130) or OS (N ¼ 103 065; HR 1.03; 95% CI, 0.87-1.23; P ¼ 0.692) were observed according to beta-blocker use. Discussion: In this meta-analysis, beta-blocker use was associated with a longer RFS in patients with early-stage breast cancer, with a more pronounced effect observed in those with triple-negative disease. Beta-blockers arise as an interesting option to be explored in prospective studies for patients with early-stage breast cancer.

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Section: Introductionmentioning

confidence: 99%

Beta-blockers in early-stage breast cancer: a systematic review and meta-analysis

et al. 2021

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“…A study evaluating patients receiving Palbociclib and Letrozole demonstrated that patients without prior cancer treatments who received this regimen had a two-fold PFS benefit compared to those with prior endocrine therapy or chemotherapy [ 14 ]. Similarly, an analysis of patients with MBC receiving paclitaxel, where patients experienced an increased hazard of death of 71% with one line of treatment before paclitaxel, a 30% increase with two prior treatments, and a 123% increase with three or more prior treatments compared to those with no prior treatments before paclitaxel [ 15 ]. Together these studies emphasize the importance of considering both duration and type of prior therapy when interpreting clinical trials results.…”

Section: Discussionmentioning

confidence: 99%

“…Given the challenge in capturing these higher dimensional data for different treatment sequences and their metadata, we employed our visualization algorithm to help create a topological representation of such heterogeneity [ 15 , 18 ]. The features of the resultant treatment sequence graph can inform us about sequence frequency, median survival, overall average prior lines, and performance of any specific agent on disease behavior and outcome within the large sequence landscape of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Effect of prior treatments on post-CDK 4/6 inhibitor survival in hormone receptor-positive breast cancer

Franks

Caston

Elkhanany

et al. 2022

Breast Cancer Res Treat

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Purpose Multiple treatment options exist for patients with metastatic breast cancer (MBC). However, limited information is available on the impact of prior treatment duration and class on survival outcome for novel therapies, such as cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ HER2−) MBC. Methods This study used a nationwide, de-identified electronic health record-derived database to identify women with HR+ HER2− MBC who received at least one CDK 4/6i between 2011 and 2020. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for the association between prior duration and class of cancer treatment (both early-stage and metastatic) and prior CDK 4/6i survival as well as for those with multiple CDK 4/6i. Results Of 5363 patients, the median survival from first CDK 4/6 inhibitor administration was 3.3 years. When compared to patients with no prior treatments, patients with < 1 year of prior treatment duration had a 30% increased hazard of death (HR, 1.30; 95% CI 1.15–1.46), those with 1 to < 3 years a 68% increased hazard of death (HR 1.68; 95% CI 1.49–1.88), and those with 3 or more years a 55% increased hazard of death (HR 1.55; 95% CI 1.36, 1.76). Patients who received prior therapy (endocrine or chemotherapy) before their CDK 4/6i had worse outcomes than those who received no prior therapy. Similar results were seen when comparing patients in the metastatic setting alone. Finally, patients who received a different CDK 4/6i after their first saw a lower hazard of death compared to patients who received subsequent endocrine or chemotherapy after their first CDK 4/6i. Conclusion Prior treatment duration and class are associated with a decreased overall survival after CDK 4/6 inhibitor administration. This highlights the importance for clinicians to consider prior treatment and duration in treatment decision-making and for trialists to stratify by these factors when randomizing patients or reporting results of future studies.

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“… 6 Metastasis and tumor recurrence, which significantly impair treatment, are the major causes of poor outcome. 7 Therefore, identifying novel and effective treatment strategies for preventing and treating breast cancer is an active area of research.…”

Section: Introductionmentioning

confidence: 99%

LINC00504 Promotes the Malignant Biological Behavior of Breast Cancer Cells by Upregulating HMGB3 via Decoying MicroRNA-876-3p

Dong²,

Wang

et al. 2021

CMAR

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Purpose Long intergenic non-protein coding RNA 504 (LINC00504) is a long non-coding RNA that has an important regulatory role in a variety of human cancers. In this study, LINC00504 expression in breast cancer tissues and cell lines was detected. Studies were also conducted to determine the impact of LINC00504 on the tumor behavior of breast cancer cells. The potential mechanisms underlying the oncogenic role of LINC00504 in breast cancer cells were elucidated in detail. Methods Expression of LINC00504 in breast cancer was analyzed by quantitative real-time polymerase chain reaction. The effects of LINC00504 on proliferation, apoptosis, in vitro migration and invasion, and in vivo tumor growth were elucidated using Cell Counting Kit-8 assay, flow cytometry, Transwell assays, and tumor xenograft models, respectively. Bioinformatics analyses in conjunction with RNA immunoprecipitation, luciferase reporter assays, and rescue experiments were conducted to investigate the underlying molecular mechanisms. Results LINC00504 was upregulated in breast cancer tissues and cell lines. Knocking down LINC00504 suppressed breast cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro. In addition, tumor growth in vivo was significantly inhibited by LINC00504 depletion. Regarding the underlying mechanism, LIN00504 could function as a competing endogenous RNA in breast cancer by sponging microRNA-876-3p (miR-876-3p), resulting in the upregulation of high mobility group box 3 (HMGB3). Rescue experiments further revealed that miR-876-3p downregulation or HMGB3 upregulation effectively reversed the inhibitory effects of LIN00504 deficiency on breast cancer cells. Conclusion The LIN00504-miR-876-3p-HMGB3 axis shows carcinogenic effects in modulating the biological behavior of breast cancer cells. This pathway may represent an effective target for CRC diagnosis and anticancer therapy.

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Prior Treatment Time Affects Survival Outcomes in Metastatic Breast Cancer

Cited by 7 publications

References 27 publications

Beta-blockers in early-stage breast cancer: a systematic review and meta-analysis

Beta-blockers in early-stage breast cancer: a systematic review and meta-analysis

Effect of prior treatments on post-CDK 4/6 inhibitor survival in hormone receptor-positive breast cancer

LINC00504 Promotes the Malignant Biological Behavior of Breast Cancer Cells by Upregulating HMGB3 via Decoying MicroRNA-876-3p

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