Evaluation of Prognostic Factors: From Breast Cancer to Bone Metastases

Bone Metastases Clinical Trial

— BC-BOMET  

Official title:

Evaluation of Prognostic Factors: From Breast Cancer to Bone Metastases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04167605
• Other study ID #: BC-BOMET
• Status: Recruiting
• Start date: January 13, 2020
• Est. completion date: November 12, 2024

Study information

• Verified date: February 2024
• Source: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
• Contact: Paola Maroni, PhD
• Phone: +39 026621
• Email: paola.maroni[@]grupposandonato.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Bone metastases represent a frequent complication of some solid tumours, particularly prostate, breast and lung carcinomas. Bone metastases can cause pain and give rise to the so-called "Skeletal-related Events" (SRE) such as pathological fractures and nerve compression. Despite advances in cancer treatment in general, treatment options for bone metastases remain inadequate and generally palliative. It is therefore necessary to identify patients at "high risk" of developing metastases at an early stage of neoplastic disease in order to counteract it. Therefore, the identification of changes in the expression of proteins that could be variously involved in the progression of breast cancer is of primary importance since they could act as prognostic factors and therefore address the therapeutic strategy. The aim of the investigators is to clarify the role of de-regulation of post-translational events (such as SUMOylation) in the progression of breast cancer.

Description:

The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites, often distant from the primary site of growth. Bone is a breeding ground for many types of cancer, especially those derived from breast, prostate and lung. Despite the enormous progress in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival, being often responsible for the outcome of the disease. To improve the outcome of patients with poor prognosis, a deep knowledge of the mechanisms underlying dissemination, colonization and progression of cancer cells in the bone is necessary.

The investigators therefore intend to clarify some pathogenic mechanisms involved in the growth of bone metastases, and to uncover predictive signs that underlie the spread of breast cancer cells to bone.

Primary aim of the investigators is to deepen the role of the de-regulation of post-translational events, such as Small Ubiquitin-like Modifier- (SUMO) SUMO-ylation in the progression of breast cancer. The expression of SENP1 (a member of the SUMO-specific protease family) in bone metastatic and non-metastatic mammary carcinomas will be evaluated. The evaluation of the expression of SENP1 in bone metastases will be finalised to define a possible use as a therapeutic target. SENP1 could be a potential prognostic indicator of the neoplastic progression of breast cancer and a potential therapeutic target, but data on its participation in the process of metastasis to bone are still scarce. Moreover, the investigators try to deepen the knowledge of the interaction between tumour cells and bone microenvironment and the role of immunosurveillance as an important part of the immune response against to neoplastic cells. Finally, the investigators will analyze the role of autophagy and apoptosis in the dissemination and growth of metastases due to the capacity of autophagy to provide energy, nutrients and resistance to anoikis, and to promote the dissemination of cancer cells and metastatic growth.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 12, 2024
• Est. primary completion date: September 12, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult women (= 18 years) candidates for excisional surgery and bone consolidation due to osteolytic bone metastases from breast cancer.

• Female

• Ability to understand the experimental study and willingness to sign the written consent

Exclusion Criteria:

• Retraction of written consent

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastases
• Bone Neoplasms
• Breast Cancer Metastatic
• Breast Neoplasms
• Neoplasm Metastasis

Intervention

Other:
• Bone metastasis
Collection of waste tissue samples during surgery and immediate immersion of the same in 10% Neutral buffered formalin. The samples will be send to the laboratory where they will be processed (decalcification, inclusion in paraffin, sectioning etc.) for subsequent analyzes.
• Breast cancer metastatic to bone
Patients will be assisted in the recovery of samples (slides) related to surgery on primary tumor (breast cancer responsible for metastatic disease).

Locations

Country	Name	City	State
Italy	IRCCS Istituto Ortopedico Galeazzi	Milan

Sponsors (1)

Lead Sponsor	Collaborator
I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Feng Y, Yao Z, Klionsky DJ. How to control self-digestion: transcriptional, post-transcriptional, and post-translational regulation of autophagy. Trends Cell Biol. 2015 Jun;25(6):354-63. doi: 10.1016/j.tcb.2015.02.002. Epub 2015 Mar 8. — View Citation

Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C, Dipaola RS, Karantza-Wadsworth V, White E. Autophagy suppresses tumorigenesis through elimination of p62. Cell. 2009 Jun 12;137(6):1062-75. doi: 10.1016/j.cell.2009.03.048. Erratum In: Cell. 2011 Apr 15;145(2):322. — View Citation

Moscat J, Diaz-Meco MT. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell. 2009 Jun 12;137(6):1001-4. doi: 10.1016/j.cell.2009.05.023. — View Citation

Sowder ME, Johnson RW. Bone as a Preferential Site for Metastasis. JBMR Plus. 2019 Jan 15;3(3):e10126. doi: 10.1002/jbm4.10126. eCollection 2019 Mar. — View Citation

Wang Z, Jin J, Zhang J, Wang L, Cao J. Depletion of SENP1 suppresses the proliferation and invasion of triple-negative breast cancer cells. Oncol Rep. 2016 Oct;36(4):2071-8. doi: 10.3892/or.2016.5036. Epub 2016 Aug 24. — View Citation

Yeh ET. SUMOylation and De-SUMOylation: wrestling with life's processes. J Biol Chem. 2009 Mar 27;284(13):8223-7. doi: 10.1074/jbc.R800050200. Epub 2008 Nov 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SENP1 expression	The expression of SENP1 in bone metastatic mammary carcinomas will be studied. The evaluation of the expression of SENP1 in bone metastases will be finalized to define a possible use as a therapeutic target. The expression of SENP1 in bone metastatic breast carcinoma samples will be compared with the expression of SENP1 in non-metastatic breast cancer (commercial source).	6 months
Secondary	Identification of new predictive molecular markers of breast cancer progression towards an aggressive metastatic state.	Analysis of the expression of proteins involved in the interaction between tumour cells and bone microenvironment, in the immunosurveillance and in the autophagic process in sample of mammary carcinomas that gave rise to bone metastases and in sample of breast cancer without history of bone metastasis.	18 months