scholarly journals Liver Kinase B1—A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 149 ◽  
Author(s):  
Binafsha Manzoor Syed ◽  
Andrew R Green ◽  
David A L Morgan ◽  
Ian O Ellis ◽  
Kwok-Leung Cheung
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Clinical Outcome ◽  
Older Women ◽  
Therapeutic Target ◽  
Axillary Lymph Node ◽  
Tumour Size ◽  
Axillary Lymph ◽  
Liver Kinase B1

Background: The role of liver kinase B1 (LKB1), a serine/threonine kinase, has been described in the development of PeutzJagher’s syndrome, where a proportion (~45%) of patients have developed breast cancer in their lifetime. Cell line studies have linked LKB1 with oestrogen receptors (ER) and with the Adenosine monophosphate-activated protein kinase (AMPK) pathway for energy metabolism. However, limited studies have investigated protein expression of LKB1 in tumour tissues and its intracellular relationships. This study aimed to investigate the intracellular molecular relationships of LKB1 in older women with early operable primary breast cancer and its correlation with long-term clinical outcome. Methods: Between 1973 and 2010, a consecutive series of 1758 older (≥70 years) women with T0-2N0-1M0 breast carcinoma were managed in a dedicated facility. Of these, 813 patients underwent primary surgery, and 575 had good quality tumour samples available for tissue microarray construction. LKB1 was assessed in 407 cases by indirect immunohistochemistry (IHC). Tumours with 30% or more of cells with cytoplasmic LKB1 expression were considered positive. LKB1 expression was compared with tumour size, histological grade, axillary lymph node stage, ER, PgR, EGFR, HER2, HER3, HER4, BRCA1&2, p53, Ki67, Bcl2, Muc1, E-Cadherin, CD44, basal (CK5, CK5/6, CK14 and CK17) and luminal (CK7/8, CK18 and CK19) cytokeratins, MDM2 and MDM4, and correlated with long-term clinical outcome. Results: Positive LKB1 expression was seen in 318 (78.1%) patients, and was significantly associated with high tumour grade, high Ki67, over-expression of HER2, VEGF, HER4, BRCA2, MDM2 and negative expression of CD44 (p < 0.05). There was no significant correlation with tumour size, axillary lymph node status, ER, PgR, p53, basal or luminal cytokeratins, Bcl2, Muc1, EGFR, HER3, MDM4, E-cadherin and BRCA1. LKB1 did not show any significant influence on survival in the overall population; however, in those patients receiving adjuvant endocrine therapy for ER positive tumours, those with positive LKB1 had significantly better 5-year breast cancer specific survival when compared to those without such expression (93% versus 74%, p = 0.03). Conclusion: LKB1 expression has shown association with poor prognostic factors in older women with breast cancer. However, LKB1 expression appears to be associated with better survival outcome among those patients receiving adjuvant endocrine therapy. Further research is required to explore its potential role as a therapeutic target.

Relationship Between Age and Axillary Lymph Node Involvement in Women With Breast Cancer

2009 ◽  
Vol 27 (18) ◽  
pp. 2931-2937 ◽  
Author(s):  
Hans Wildiers ◽  
Ben Van Calster ◽  
Lonneke V. van de Poll-Franse ◽  
Wouter Hendrickx ◽  
Jo Røislien ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Older Women ◽  
Cancer Registry ◽  
Axillary Lymph Node ◽  
Immune Defense ◽  
Age At Diagnosis ◽  
Axillary Lymph ◽  
Independent Population ◽  
Effect Of Age

Purpose To study the relation between the presence of axillary lymph node (LN) involvement and age in breast cancer. Patients and Methods The breast cancer database of the University Hospitals Leuven contains complete data on 2,227 patients with early breast cancer consecutively treated between 2000 and 2005. A multivariate piecewise logistic regression model was used to analyze LN involvement in relation to age at diagnosis. A similar analysis was then performed on a large, independent, population-based database from the Eindhoven Cancer Registry to investigate whether the effects of the Leuven model could be replicated. Results We observed a piecewise effect of age. That is, women up to 70 years of age were less likely to have positive LNs with increasing age (odds ratio per 10-year increase, 0.87). In contrast, older women were more likely to have positive LNs with increasing age. However, for older women, the effect of age interacted with tumor size (P = .0044), suggesting that increasing age is associated with increased risk of LN involvement, mainly in small tumors. These findings were replicated in the Eindhoven Cancer Registry database. Conclusion Axillary LN involvement varies with age at diagnosis; its probability decreases with increasing age up to the age of approximately 70 years, but increases again thereafter. However, this increase is mainly seen in smaller tumors and suggests a different behavior of small breast cancers in older adult patients. We hypothesize that decreased immune defense mechanisms, related with aging, may play a role in earlier invasion into LNs.

scholarly journals Long-term Tracing of Carbon Nanoparticles for Axillary Lymph Node Dissection in Patients with Fusion Lymph Nodes before Neoadjuvant Chemotherapy

2019 ◽  
Author(s):  
Jian-Yi Li ◽  
Shi Jia ◽  
Yi-Tong Wang ◽  
Yang Zhang ◽  
Lin-Na Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Regression Model ◽  
Axillary Lymph Node ◽  
Carbon Nanoparticles ◽  
Lymphovascular Invasion ◽  
Axillary Lymph ◽  
Node Dissection

Abstract Background: The regression model of positive nodes in breast cancer after neoadjuvant chemotherapy (NAC) remains controversial. This study aimed to investigate this regression model by injecting and tracing carbon nanoparticles (CNs) into the fusion node prior to NAC in patients with breast cancer. Methods: Guided by ultrasound, 0.3 mL of CNs suspension was injected in a fusion node prior to NAC in 110 patients with local advanced breast cancer. Patients underwent breast surgery and total axillary lymph node dissection following 2-6 cycles of NAC. The distribution by intercostobrachial nerves (ICBN) of positive nodes, black-stained nodes and lymphovascular invasion was investigated by response to NAC. Results: When patients were ranked by response to NAC (from sensitive to resistance), the number of positive nodes increased, as did the proportion of lymphovascular invasion, the number of black-stained nodes decreased. A significantly negative relationship was found between the number of positive nodes and the number of black-stained nodes (p < 0.001). The positive nodes in patients with sensitive consequence followed the rule from under the ICBN to above the ICBN. However, there was counter-example (skip metastasis) in the patients with resistance result. Conclusion: The regression model of positive nodes follows the rule from upper to under, inner to outer in the patients with sensitive consequence to NAC. Long-term staining and tracing by CNs might provide an acceptable and feasible technique to investigate the regression model of positive nodes, and would be a potential method for NAC-treated patients by using of ICBN. Trial registration: NCT 03355261. Retrospectively registered on November 28, 2017.

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