Evaluation of Prognostic Factors: From Breast Cancer to Bone Metastases (BC-BOMET)

February 6, 2024 updated by: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
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.

Study Overview

Detailed 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.

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The population consists of 30 subjects who underwent surgery for bone metastases from breast cancer disease. Within the waste material collected during surgery intervention, it is expected to have 24 samples with an adequate content of metastatic tissue. For 12 of these patients it will be possible to retrieve the sample of the primary breast cancer, and then insert it into the study design. The control group will consist of 12 breast cancer samples that have not shown metastatic development after long follow up and will instead be found in commerce.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Breast cancer metastatic to bone
No direct intervention(s) will be administer to the patients. We will use the sample (slides) recovered from the surgery on primary tumor (breast cancer responsible for metastatic disease).
Patients will be assisted in the recovery of samples (slides) related to surgery on primary tumor (breast cancer responsible for metastatic disease).
Bone metastasis
No direct intervention(s) will be administer to the patients. Waste material will be analysed for the expression of specific proteins
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SENP1 expression
Time Frame: 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of new predictive molecular markers of breast cancer progression towards an aggressive metastatic state.
Time Frame: 18 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2020

Primary Completion (Estimated)

September 12, 2024

Study Completion (Estimated)

November 12, 2024

Study Registration Dates

First Submitted

November 15, 2019

First Submitted That Met QC Criteria

November 15, 2019

First Posted (Actual)

November 19, 2019

Study Record Updates

Last Update Posted (Estimated)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 6, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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