Clinical trial NCT04007861: Exploring the Link Between Cancer Genetics and PPSP
Official title: Exploring the Link Between Cancer Genetics and Persistent Post-surgical Pain (PPSP) Following Breast Cancer Treatment
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cancer-related Pain
Chronic Post Cancer Surgery Pain
Breast Cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Although two groups of patients will be identified retrospectively:

1. The first group will be patients who have been referred to the pain management team for persistent-post surgical pain following breast cancer treatment.
2. The second group, will consist of patients who have been matched for age, procedure and time-lapsed since operation. These patients will not have persistent post-surgical pain.

Ultimately, archived paraffin-embedded tissue samples, that have previously been taken from these patients, will be requested. Samples accessed will be from patients who have previously provided consent for their samples to be used for research purposes.

Brief summary: Pain is common in cancer, affecting between 40 and 60% of patients depending on tumour type and stage of disease, and represents a major area of unmet need in cancer survivors. Despite advances in treatment, there has been no significant reduction in those who experience pain. Breast cancer is common. It represents 10% of newly diagnosed cancers globally and is often associated with pain.

Exact physiological mechanisms for cancer pain are not yet fully established. There is a complex relationship between a malignant lesion and its micro-environment; a tumour does not exist in isolation but has a dynamic relationship with host cells. There is a growing interest in delineating the relationship between tumour manifestations and pain.

By retrospectively identifying individuals who have been referred to specialist pain clinics at a cancer centre and matching them to controls, the investigators can identify two groups of patients (those who experienced significant problems with pain and those who did not). Accessing paraffin-embedded tissue samples from those that have had surgical resections, will allow the investigators to compare tissue samples, in particular the metabolic and genetic differences, between the two groups.

No new tissue samples will be required for this study.

Pain is a major area of unmet need in cancer survivors. The investigators propose that this project would provide valuable knowledge and pilot data regarding the link between pain and tumour genetics. It has the potential to identify tumour genes or mutations that are associated with greater incidences of pain and ultimately potentially guide targeted interventions to help reduce the frequency and impact of pain on patients living with and beyond cancer.

Detailed description: This study will be a retrospective, case-control study. There will be two groups of patients identified retrospectively:

The first group will be patients who have been referred to the pain management team for persistent-post surgical pain following breast cancer treatment.

The second group, will consist of patients who have been matched for age, procedure and time-lapsed since operation. These patients will not have persistent post-surgical pain.

Archived paraffin-embedded tissue samples, that have previously been taken from these patients, will be required. Samples accessed will be from patients who have previously provided consent for their samples to be used for research purposes. Once appropriate samples have been identified by the tissue banks, all data will be pseudonymised. This will include details that patients have consented to providing for research purposes via the Pain Management Database, which has Trust (CCR 442) and Research Ethics Committee (REC 16/LO/1989) approval.

Laboratory studies will then be conducted to A) investigate the underlying variations of the PIK3CA gene of tumours within the two cohorts of patients, B) investigate other genetic variations between these two groups and C) establish the key genetic and signalling pathway alterations between these two groups.

The methods by which these investigations will be conducted will be by performing PIK3CA genomics, genetic profiling, next generation sequencing and finally immunohistochemistry for activation of signalling pathways.

This study will analyse archived paraffin embedded tissue samples in a laboratory only.

The anticipated time-scale for this project would be approximately one year.

Eligibility criteria: Inclusion Criteria:

* Patients receiving treatment at the Royal Marsden Hospital.
* Patients with a diagnosis of primary breast cancer.
* Patients who have had surgical resection of their breast tumour.
* Paraffin-embedded tissue samples available from Royal Marsden Tissue Banks.

Exclusion Criteria:

* Under 18 years of age.
* Lack of adequate tissue sample available from the Tissue Bank.

Primary outcomes:
measure: The difference in the proportion of mutations of the PIK3CA gene.
timeFrame: Within 6-8months
Secondary outcomes:
measure: Proportion of individual gene mutations in pain group compared with the no pain group.
timeFrame: Within 6-8months
measure: Difference in mean gene expression in those with pain compared with those without pain.
timeFrame: Within 6-8months
measure: Proportion of individual DNA copy number changes (either amplification/gain or loss) in those with pain compared with those without pain.
timeFrame: Within 6-8months
measure: Frequency of changes to DNA copy number (either amplification/gain or loss) in those with pain compared with those without pain.
timeFrame: Within 6-8months
measure: Difference in median of magnitude of activation status of signalling pathways between those with pain and those without pain.
timeFrame: Within 6-8months
Other outcomes:
Locations:
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Matt Brown, MBBS
role: PRINCIPAL_INVESTIGATOR
References: