Vav1 downmodulates Akt in different breast cancer subtypes: a new promising chance to improve breast cancer outcome

11557 Background: Obesity at breast cancer (BC) diagnosis is associated with poor outcome, although the magnitude of effect in different BC subtypes is uncertain. Here we report on the association of obesity at BC diagnosis with disease-free (DFS) and overall survival (OS) in the following subtypes: (i) hormone receptor (ER/PgR) +ve, HER2-ve, (ii) HER2+ve, any ER/PgR and (iii) triple negative (TN). Methods: We searched MEDLINE, EMBASE and COCHRANE databases to December 31, 2018 and meeting presentations (past 5 years) using predefined search terms. Study eligibility, data abstraction were performed independently by two authors; those reporting hazard ratios (HR) for obesity and DFS/OS in BC subtypes were included. Using Review Manager pooled HRs were computed and weighted using generic inverse variance in fixed and random effects models (results were similar, random effects are presented). Results: Of 10,702 titles, 26 studies (108,793 patients) were included. Pooled HR for DFS for obese vs non-obese were (i) ER/PgR+ve HER2-ve 1.21 (95% Confidence interval, CI; 1.12-1.31, p < 0.00001), (ii) HER2+ve, any ER/PgR 1.16 (95%CI, 1.06-1.26; p = 0.0006) and (iii) TN, 1.13 (95%CI; 1.05-1.22 p = 0.002). Pooled HRs for OS were (i) ER/PgR+ve, HER2-ve 1.45 (95%CI; 1.30-1.62 p < 0.00001), (ii) HER2+ve any ER/PgR 1.21 (95%CI; 1.10-1.34 p = 0.0001) and (iii) TN 1.13 (95%CI, 1.04-1.23, p = 0.003).PooledHR for OS (but not DFS) were somewhat higher in observational vs interventional studies in (i) ER/PgR+ve, HER2-ve 1.57 vs 1.36, HER2+ve any ER/PgR (ii) 1.37 vs 1.09 but not (iii) TN 1.12 vs 1.22 (p = 0.21, 0.03 and 0.48, respectively). Conclusions: Obesity was associated with a worse outcome in all BC subtypes. Higher HR for OS in observational studies in (i) ER/PgR+ve, HER2- and (ii) HER2+ve any ER/PgR BC may reflect selection of healthier patients for intervention trials.

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Association of Obesity with Breast Cancer Outcome in Relation to Cancer Subtypes: A Meta-Analysis

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djab023 ◽

2021 ◽

Author(s):

Ana Elisa Lohmann ◽

Sara V Soldera ◽

Isabel Pimentel ◽

Domen Ribnikar ◽

Marguerite Ennis ◽

...

Keyword(s):

Breast Cancer ◽

Meta Analysis ◽

Obese Women ◽

Her2 Positive ◽

Random Effects Models ◽

Cancer Subtypes ◽

Hormone Receptor Positive ◽

Hazard Ratios ◽

Breast Cancer Outcome ◽

Cancer Outcome

Abstract Background Obesity at breast cancer (BC) diagnosis has been associated with poor outcome, although the magnitude of effect in different BC subtypes is uncertain. We report on the association of obesity/overweight at diagnosis of non-metastatic BC with disease-free (DFS) and overall survival (OS) in the following defined subtypes: hormone receptor positive/HER2 negative (HR+HER2-), HER2 positive (HER2+), and triple negative (TNBC). Methods We searched MEDLINE, EMBASE and COCHRANE databases until January 1, 2019. Study eligibility were performed independently by two authors. Studies reporting hazard ratios (HR) of OS and/or DFS for obesity/overweight in BC subtypes were included. Pooled HR were computed and weighted using generic inverse variance and random effects models. Results 27 studies were included. Obese, compared to non-obese, women, had worse DFS in all subtypes: the hazard ratios were 1.26 (95% confidence interval [CI] = 1.13 to 1.41, P < .001) for HR+HER2-BC, 1.16 (95%CI = 1.06 to 1.26, P < .001) for HER2+ BC, and 1.17 (95%CI = 1.06 to 1.29, P = .001) for TNBC. OS was also worse in obese vs non-obese women (HR+HER2-BC HR = 1.39, 95%CI = 1.20 to 1.62, P < .001; HER2+BC HR = 1.18, 95%CI = 1.05 to 1.33, P = .006 and TNBC HR = 1.32, 95%CI = 1.13 to 1.53, P < .001). As opposed to obesity, overweight was not associated with either DFS or OS in HER2+BC (HR = 1.02, 95%CI = 0.81 to 1.28, P = .85; and HR = 0.96, 95%CI = 0.76 to 1.21, P = .99, respectively) or TNBC (HR = 1.04, 95%CI = 0.93 to 1.18, P = .49; and HR = 1.08, 95%CI = 0.81 to 1.44, P = .17), respectively. In HR+HER2-BC, being overweight was associated with worse OS (HR = 1.14, 95%CI = 1.07 to 1.22, P < .001). Conclusions Obesity was associated with modestly worse DFS and OS in all BC subtypes.

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Identification of new therapeutic leads for triple negative breast cancer subtypes

Planta Medica ◽

10.1055/s-0035-1556254 ◽

2015 ◽

Vol 81 (11) ◽

Author(s):

AJ Robles ◽

L Du ◽

S Cai ◽

RH Cichewicz ◽

SL Mooberry

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Therapeutic Leads

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Faculty Opinions recommendation of Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13405017.14775138 ◽

2011 ◽

Author(s):

Thomas Egelhoff

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Targeted Therapies ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Preclinical Models ◽

Cancer Subtypes ◽

Selection Of

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Comprehensive landscape of epigenetic-dysregulated lncRNAs reveals a profound role of enhancers in carcinogenesis in breast cancer subtypes

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2020.12.024 ◽

2021 ◽

Author(s):

Hongying Zhao ◽

Xiaoqin Liu ◽

Lei Yu ◽

Shihua Lin ◽

Caiyu Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Subtypes ◽

Cancer Subtypes

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Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽

10.3390/cancers13010002 ◽

2020 ◽

Vol 13 (1) ◽

pp. 2

Author(s):

Lee D. Gibbs ◽

Kelsey Mansheim ◽

Sayantan Maji ◽

Rajesh Nandy ◽

Cheryl M. Lewis ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Significance ◽

Cell Lines ◽

Breast Cancer Subtypes ◽

Enzyme Linked Immunosorbent Assay ◽

Breast Cancer Patients ◽

Serum Samples ◽

Cancer Subtypes ◽

Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

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