scholarly journals Association of body mass and systemic immune-inflammation indices with endocrine therapy resistance in luminal breast cancers

2019 ◽  
Vol 47 (5) ◽  
pp. 1936-1947 ◽  
Author(s):  
Qing-xia Li ◽  
Dong-jian Shi ◽  
Li-xia Zhang ◽  
Dong-miao Wang ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Disease Free Survival ◽  
Therapy Resistance ◽  
Luminal Breast Cancer ◽  
Endocrine Therapy Resistance ◽  
Free Survival ◽  
Resistance Rates ◽  
High Bmi

Objective To explore correlations between body mass index (BMI), preoperative systemic immune-inflammation index (SII) and endocrine therapy resistance, and evaluate BMI and SII as predictors of resistance, in patients with luminal breast cancer. Methods This retrospective study included patients with luminal breast cancer who underwent endocrine therapy at Hebei General Hospital. Relationships between BMI and SII subgroups, and clinicopathological parameters were analysed using χ2-tests. Disease-free survival was assessed using Log-rank statistics. Multivariate analysis of factors related to disease progression were analysed using Cox proportional hazards model. Results Out of 161 patients, those with normal BMI and low SII had significantly lower endocrine resistance rates versus those with high BMI and SII, and BMI was significantly positively correlated with SII. High BMI or SII was associated with significantly lower disease-free survival rates. Hazard ratios for disease progression risk were 6.036, 3.508 and 1.733, for SII, BMI and TNM stage, respectively. Conclusion In patients with luminal breast cancer, high BMI (>23 kg/m2) and SII (>518 × 109/L) levels may predict high endocrine resistance rates. BMI, SII and TNM stage were independent prognostic factors for endocrine therapy resistance.

scholarly journals Candidate methylation sites associated with endocrine therapy resistance in ER+/HER2- breast cancer

2020 ◽  
Author(s):  
Maryam Soleimani ◽  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Pernette J. Verschure ◽  
Stefan Wiemann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Endocrine Therapy ◽  
Proportional Hazards ◽  
Endocrine Resistance ◽  
Therapy Resistance ◽  
Cox Proportional Hazards ◽  
Endocrine Treatment ◽  
Endocrine Therapy Resistance ◽  
Cox Proportional Hazards Models

Abstract Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods: We used genome-wide DNA methylation profiles of primary ER+/HER2- tumours from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AI or TAM) that patients received (N=210 and N=172, respectively). We also identified multivariable methylation signatures associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results: We identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of tumour stage, age, AI treatment, and luminal status. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Also at the gene set level, several sets related to endocrine therapy and resistance were identified in both survival and T47D signatures. Conclusions: We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours prior to endocrine treatment are associated with development of endocrine resistance.

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

scholarly journals Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1424 ◽  
Author(s):  
Toshihiko Takeiwa ◽  
Kazuhiro Ikeda ◽  
Yuichi Mitobe ◽  
Kuniko Horie-Inoue ◽  
Satoshi Inoue
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Therapy Resistance ◽  
Long Noncoding Rnas ◽  
Endocrine Therapy Resistance ◽  
New Biomarkers

Long noncoding RNAs (lncRNAs) are defined as RNAs longer than 200 nucleotides that do not encode proteins. Recent studies have demonstrated that numerous lncRNAs are expressed in humans and play key roles in the development of various types of cancers. Intriguingly, some lncRNAs have been demonstrated to be involved in endocrine therapy resistance for breast cancer through their own mechanisms, suggesting that lncRNAs could be promising new biomarkers and therapeutic targets of breast cancer. Here, we summarize the functions and mechanisms of lncRNAs related to the endocrine therapy resistance of breast cancer.

scholarly journals 48P Association of a genomic index of sensitivity to endocrine therapy with disease-free survival in breast cancer

2020 ◽  
Vol 31 ◽  
pp. S32
Author(s):  
P. Singh ◽  
I. Bedrosian ◽  
M.J. Ha ◽  
Y. Shen ◽  
L. Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000937
Author(s):  
Annalisa Petrelli ◽  
Sara Erika Bellomo ◽  
Ivana Sarotto ◽  
Franziska Kubatzki ◽  
Paola Sgandurra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Endocrine Therapy ◽  
Molecular Subtype ◽  
Molecular Taxonomy ◽  
Endocrine Resistance ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Luminal Breast Cancer ◽  
Luminal A

PurposeOverexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer.MethodsmiR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype.ResultsBaseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype.ConclusionsOur findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer.

scholarly journals Loss of MutL Disrupts CHK2-Dependent Cell-Cycle Control through CDK4/6 to Promote Intrinsic Endocrine Therapy Resistance in Primary Breast Cancer

2017 ◽  
Vol 7 (10) ◽  
pp. 1168-1183 ◽  
Author(s):  
Svasti Haricharan ◽  
Nindo Punturi ◽  
Purba Singh ◽  
Kimberly R. Holloway ◽  
Meenakshi Anurag ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Endocrine Therapy ◽  
Primary Breast Cancer ◽  
Cell Cycle Control ◽  
Therapy Resistance ◽  
Endocrine Therapy Resistance ◽  
Dependent Cell

Clinical response at 4 months to neoadjuvant letrozole predicts distant disease free survival in postmenopausal women with stage II-III ER/PgR-positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10531-10531 ◽  
Author(s):  
V. Guillem ◽  
A. Llombart-Cussac ◽  
J. Lopez Guerrero ◽  
A. Guerrero ◽  
C. Fuster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Prognostic Indicators ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (<5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p < 0.02), cT3/4 (p < 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p < 0.05), cN (p < 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.

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