Abstract
Abstract
Objectives: Breast cancer (BC) still remains the leading cause of mortality in women worldwide despite substantial developments in diagnosis and therapeutic interventions. Several factors, i.e. different molecular subtypes, biological behaviors, and risk profiles still pose a challenge for prognostication and clinical management. Traditional prognostic and treatment options for BC patients are largely based on careful histological analysis of tumor size, tumor grade, lymph node metastasis and tumor subtypes. Molecular mechanisms play critical roles in developing tumors as well as early and late stage tumor progression of metastatic disease. It is not surprising that many genes are shared amongst the various gene signatures and may have a similar performance in survival risk assessment of the BC patients. Given the production of Shh and IL-6 in the breast tumor microenvironment, we hypothesized that Shh and IL-6 might be detectable in the general circulation. If positive, then it would be clinically useful to identify whether robust expression of serum Shh and IL-6 is correlated with BC prognosis, distant metastasis, lymph node positivity, multidrug resistance as well as self-renewal and maintenance of BC stem cells. We evaluated relative clinical outcome of Shh and IL-6 in the serum from a cohort of patients with untreated early operable and progressive metastatic BC.
Patients and Methods: One hundred and ten breast cancer patients and 30 healthy female volunteers, enrolled in this study and, were evaluated for serum levels of Shh and IL-6 using human ShhN and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS).
Results: Overall outcome analysis was based on serum Shh and IL-6 levels from 45 early operable and 65 progressive metastatic BC patients. In patients with progressive metastatic BC, serum Shh was elevated in 44% (29 of 65) and IL-6 in 63% (41 of 65). Serum Shh (p=0.0001) and IL-6 (p=0.0001) levels were significantly elevated in BC patients compared to low levels in healthy volunteers, and tended to increase with metastatic progression and lymph node positivity. High serum Shh and IL-6 levels were associated with inferior EFS and OS opposite to negative or lower levels of serum Shh and IL-6. Elevated levels of both serum Shh and IL-6 were mainly observed in hormone refractory BC patients, who had a significantly higher risk of early recurrence, bone metastasis and death.
Conclusion: Elevated levels of serum Shh and IL-6 are associated with increased risk of recurrence and a worse survival for patients with progressive metastatic BC. Further studies are warranted for validating these biomarkers as prognostic and predictive therapeutic tools in a larger patients cohort.
Citation Format: Sonam Akther, Abu Shadat M. Noman, Junayed Nayeem, Zaheer Raihan, Irfanur Rashid, Lutfur Rahman, David Barua, Afrin Sultana, Afsana Shirin, Jannatul Ferdous, Rashed Parag, Mizanur Rahman, Reaz Mahmud, Chandsultana Jerin, Nusrat Jahan, Ayesha Siddiqua, Emran Sabur, Sabrina Alam, Sunanda Baidya, Saiful M. Islam, Syed S. Islam. Serum Sonic hedgehog (Shh) and interleukin-(IL-6) as dual prognostic biomarkers in progressive metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5722. doi:10.1158/1538-7445.AM2017-5722