Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT04488614 |
| Other study ID # |
155 |
| Secondary ID |
2010/19572011/21 |
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2011 |
| Est. completion date |
July 15, 2030 |
Study information
| Verified date |
July 2020 |
| Source |
Helse Stavanger HF |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Prospective Breast Cancer Biobanking study (PBCB) will apply advanced monitoring in liquid
biopsies of early staged breast cancer ration in order to facilitate A. Early detection of
systemic relapses B.Improve adherence and drug monitoring av tamoxifen treatment C. Tumour
microenvironment in breast cancer - adipose stromal immune infiltration and interaction with
tumour at the growth zone D.Monitor side effects, QoL, depression, fatigue and work life
participation
Description:
A. Early detection of systemic relapses in breast cancer.
WP 1. Analysis of primary tumor.
Analysis of primary tumor and metastases (Pathology group). In this work package both DNA and
RNA from the primary tumors of 125 high-risk (Luminal-B) patients will be analyzed by
next-generation sequencing (NGS). Furthermore, the investigators will also analyze DNA and
RNA from the available metastatic lesions (currently material available for 3/8) that have
appeared, and will appear during the study period.
MiRNA and mRNA will be profiled using PureLink™ miRNA Isolation Kit (Invitrogen), Dynabeads
mRNA direct micro kit (Ambion),) and Ion total RNA-seq kit V2 (Life Technologies) on our Ion
Proton NGS instrument. Bioinformatic analyses of paired mRNA and microRNA expression profiles
will be used to reveal differentially expressed microRNAs between patients with and without
recurrences under treatment. These data will be linked to our previous studies and used to
identify target candidates for microRNA analysis in exosomes and TEPs.
In addition, NGS will also be performed on DNA from the primary tumors and metastases to
verify DNA mutations especially in ER and other known oncogenes, including those examined in
WP3. The DNA sequencing will be performed using the Oncomine Comprehensive Assay. This is an
amplicon based approach analyzing hotspot SNVs, indels, and CNVs. These analyses will provide
us with a biological understanding and background knowledge for each of the individual tumor,
and these datasets can also be compared to the recently published data.
WP 2. Circulating tumor celles (CTC).
Circulating tumor cells (Oncology group) Circulating tumor cells are being enriched from
peripheral blood samples by density centrifugation and subsequent immunomagnetic depletion of
leucocytes. The oncology group has recently developed and published a new depletion method,
termed MINDEC (Multi- marker Immuno- magnetic Negative Depletion Enrichment of CTCs), which
has superior recovery and enrichment rates. RNA and DNA are isolated simultaneously from the
enriched fraction, to allow CTC detection by both RNA and DNA-based approaches. Specific mRNA
markers, with high levels in tumor cells and low levels in normal leukocytes, are being
pre-amplified and quantified by real-time PCR as surrogate markers for CTCs. Both
epithelial-specific markers and markers related to epithelial mesenchymal transition are part
of the marker panel. Until now, the investigatorshave analyzed 170 consecutive blood samples
from the larger PBCB cohort, enriched by the MINDEC procedure and found evidence for CTCs in
about 20% of the samples (from both low- and high-risk patients), a finding that encourages
us to continue this project. The investigators have also analyzed blood samples from 30
healthy female volunteers for comparison. All collected blood samples from 125 high-risk
patients will be analyzed (around 575 samples). The presence or level of CTCs in the analyzed
samples will later be compared to known prognostic factors, treatment effect and disease
outcome.
WP 3. circulating tumor DNA (ctDNA).
Tumor-specific mutations can be utilized as markers for ctDNA because they are not present in
normal cells and normal plasma DNA. The oncology group has recently demonstrated the clinical
relevance of ctDNA measurements in pancreatic cancer. The investigators will now measure
ctDNA levels in plasma samples from high-risk breast cancer patients by targeted
next-generation sequencing. The recently released "Oncomine breast cfDNA assay" (Thermo
Fisher) will be used to detect mutations in a panel of ten genes that are frequently mutated
in breast cancer. The assay is based on molecular barcoding of templates and allows
reproducible detection of mutations down to 0,1% control samples. Taking the low
concentration of cell free DNA (=cfDNA) in plasma into account (typically 10 ng per ml
blood), a sensitivity of 0,1% is considered sufficient. The sequencing will be performed on
our Ion Proton NGS instrument (Life Technologies). The pre-operative blood sample and yearly
follow-up samples from the 125 high-risk patients will be analyzed in this WP. Blood samples
from 30 healthy female volunteers have already been collected and will be analyzed for
comparison.
The presence and level of tumor-specific mutations will be analyzed in relation to treatment
effect and disease outcome. The mutational profile in the primary tumor biopsy and the plasma
samples will be compared in order to reveal potential heterogeneity. In addition,
longitudinal changes in the mutation profile of ctDNA will be compared with disease
development to potentially shed some light on the biological mechanisms causing treatment
resistance or late disease relapses.
WP 4. microRNA (miRNA)
Circulating microRNA from exosomes and TEPs (Pathology group) Total RNA will be isolated from
exosomes and TEPs from the blood samples taken before and during treatment. The investigators
have recently established methods for isolation of total RNA from exosomes (using exoRNeasy
serum Plasma kit (Qiagen) and miRCURY RNA isolation kit (Exiqon)) and TEPs. Using the
mentioned protocol, total RNA from exosomes has already been isolated from all the 125 high
risk patients first visit/before treatment, additionally from the last blood samples
collected will from these patients, total RNA will be isolated from both exosomes and TEPs.
Furthermore, microRNA profile will be performed on the isolated RNA using the pipeline and
platform already established for our Ion Proton instrument. These profiles will be compared
with the bioinformatic analysis of mRNA-miRNA profiles from the primary tumor (WP1) and the
samples taken before treatment. MicroRNA that are not present in the tissue sample and/or in
the blood sample before treatment, but do appear in blood right before a recurrence appears
can then be retrospectively traced in previous blood samples in order to see how sensitive
these microRNAs are in predicting treatment resistance. MicroRNA profile from TEPs will be
compared to the microRNA profile from exosomes and to the mRNA-miRNA profiles from the
primary tumor (WP1, to see if TEPs reflects the tumor and if they have the potential to
predict relapse.
WP 5. Metabolomics
Metabolomics is the study of small molecules comprising substrates, intermediates and end
products of cellular metabolism, such as amino acids, sugars and small organic acids. The
metabolic state of cancer cells is substantially altered compared to normal cells, a fact
that can be utilized for diagnostic purposes. Specific metabolic signatures from tumor tissue
provide additional information for determination of breast cancer subtypes and prediction of
outcome1. For example, increased tumor lactate and glycine levels are related to poor
prognosis in patients with estrogen receptor (ER) positive cancer. Metabolomic analyses of
primary tumors have also demonstrated predictive value in relation to neoadjuvant treatment
of patients with locally advanced disease.
Circulating metabolites have also been shown to provide prognostic information in operable
breast cancer and further stratify risk within existing genetically determined risk
categories. Importantly, metabolomic alterations may arise directly or indirectly from
micrometastatic disease, rather than primary tumor. Recently, the investigators have shown
that systemic lactate and pyruvate levels predict inferior outcome in patients with operable
ER-positive breast cancers. Tumor-adjacent tissue and immunological responses may also
contribute to an altered metabolomic profile. There is also evidence that metabolic profiling
can be used for patient monitoring in some cancers, although such evidence is still lacking
in breast cancer. Therefore, the investigators intend to investigate whether postoperative
monitoring by means of metabolic profiling in blood is useful for early detection of breast
cancer recurrence.
WP 6. Integrative molecular monitoring for recurrence detection
New technology has revolutionized the level of biological information that can be obtained
from clinical samples, represented by the new "omics" terms genomics, transcriptomics,
metabolomics, etc. The availability of such big datasets, even in the public domain, has
encouraged the development of integrative methods that can extract vital information from
multiple combined data sources. Surprising new connections between omics-datasets have been
revealed by such approaches, exemplified by a link between cell-free DNA fragmentation and
gene expression46. Accordingly, our knowledge about breast cancer has also been extended by
integrative approaches, resulting in a more comprehensive understanding of the disease. The
prognostic subclassification of breast cancers has for instance been refined and novel
tumor-specific antigens identified. Integrated molecular data have even been shown to have a
higher prognostic power than separate molecular levels in breast cancer. Thus, a combined
analysis of the genetic (ctDNA), transcriptomic (miRNA) and metabolomic data levels in
peripheral blood samples is therefore planned in the current project to maximize their joint
biomarker potential in operable breast cancer.
Sample size calculations.
The investigators performed sample size calculations using SPSS Sample Power software. These
calculations demonstrated that 125 high-risk patients should be sufficient to give a log rank
test power of 80%, when testing the prognostic value of ctDNA/CTC detection before surgery.
The sample size calculations were based on the qualified assumption that the average 5-year
survival rate in the high-risk group is 90%, whereas it is 75% and 95% in the ctDNA/CTC
positive and negative subgroups, respectively. Of the estimated 125 patients, 30 were assumed
positive for ctDNA/CTC and 95 negative.
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B. Improve drug monitoring of tamoxifen in breast cancer
About 75% of all breast cancer belong to the luminal subtypes, which express the hormonal
receptors Estrogen Receptor and Progesterone Receptor. These patients are treated with the
anti estrogenic drugs; tamoxifen and/or aromatase inhibitors. The two most active tamoxifen
metabolites are Z-4OHtam and Z-4OHNDtam (Z-endoxifen) have 30-100 times higher affinity for
ER than tamoxifen. These metabolites ultimately constitute the blocking effect at the
ER-level aiming to eradicate micro metastatic disease and are responsible for the improved
survival following the establishment of this adjuvant systemic treatment. Direct measurement
of these metabolites bypasses all disturbances from the diversity of CYP2D6 activity i.e.
alternative metabolic pathways, adherence to the drug and inhibiting drug interactions. Our
novel LC / MS-MS methodology takes into account all of the above-mentioned variables and
provides a functional read-out report of the serum level of the active tamoxifen metabolites
in the individual patient. This method can also distinguish between the inactive and active
isomers of Endoxifen and 4-OHtam, which are the most active ER-blocking metabolites of
tamoxifen. In collaboration with the Oslo Breast Cancer Research Group, the investigators
have recently shown in a retrospective observational study that patients with low serum
concentrations of Z-4OHtam < 3.26 nM or Z-Endoxifen < 9.00 nM (about 12% of all patients)
have significant worse breast cancer specific and total survival than patients with serum
concentrations above these thresholds(adjusted HR = 4.3; CI95 = 1.9-13.6) (red curves in
Figure 4). Patients with a very high level of these metabolites (approximately 12% of
patients) had no breast-specific endpoints Now, the investigators need to validate this
discovery in independent patient materials. If validated, this will be of direct clinical
benefit for 25% of ER + breast cancer patients planning adjuvant tamoxifen treatment. Such
therapeutic drug monitoring (TDM) could identify risk patients with inadequate levels of
active tamoxifen metabolites. This could lead to a dose increase or switch to an alternative
endocrine treatment form in these patients. Patients with very high metabolite levels can
continue on tamoxifen and do not need to switch to an aromatase inhibitor.
Thus, TDM may turn out to be a paradigmatic shift in endocrine tam treatment of ER-positive
breast cancer. Importantly, the distance from "bench to bed" in this study is very short due
to our recent findings, a feasible method and over 30 years of experience with tamoxifen in
the clinical setting.
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C. Tumour microenvironment in breast cancer - adipose stromal immune infiltration and
interaction with tumour at the growth zone
Background: Breast cancer is still the most common cancer type among women in the Western
World, Norway included. Yearly, around 3500 new Norwegian breast cancer patients are
diagnosed. During the last 50 years, the incidence of breast cancer in Norway has more than
doubled. Interestingly, during the same time frame over-weight and obesity have increased
alarmingly. Molecular subtyping of breast cancer tumours has improved the understanding of
its intrinsic biology. This has opened up for a more personalized treatment approach and
improved the outcome for breast cancer patients over the last 20 years .
In addition to the molecular subtyping, the diagnostics of breast cancer today consists of
staging (through the TNM-classification system) and microscopic examination by a pathologist.
There is increasing evidence for the prognostic value of evaluating tumour microenvironment
(e.g. tumour infiltrating lymphocytes (TILs)) as a part of diagnostics in breast cancer, but
as of yet this is not implemented in clinical practice. High numbers of TILs are strongly
associated with good prognosis in patients with triple-negative breast cancer, but have not
shown any such correlation in luminal breast cancer. Macrophages in breast adipose tissue
differentiate into two distinct phenotypes, often classified as M1 and M2 with an increase of
the latter in breast cancer. M1 attack and phagocytize cancer cells, while M2 have
anti-inflammatory properties and have been shown to have tumour-promoting functions.
The present project will increase our knowledge of the interaction between the primary breast
tumour and the immune cell infiltration in the juxta-tumoral adipose tissue. Our findings
will be correlated to molecular breast cancer subtypes, proximity to tumour, markers of
proliferation, and ultimately to clinical outcome The researcers reason that this knowledge
will provide novel predictive targets for immune-modulating adjuvant cancer therapy. This PhD
project has three interrelated work packages (WP) with the ultimate goal of identifying
markers of inflammation in juxta-tumoral adipose tissue that are relevant in clinical
assessment of adjuvant therapy of breast cancer. In WP 1 and 2, the phenotypical and genomic
landscape of juxta-tumoral adipose tissue will be characterized, and in WP 3 the researches
will investigate whether this knowledge can predict clinical outcome.
The project is based on a strong regional collaboration between the Haukeland University
Hospital (HUH) and Stavanger University Hospital (SUH). For the current project, the
researches have in a systematic manner collected adipose and tumour tissue from 30
consecutive breast cancer patients undergoing mastectomies at SUH. Surgical specimens of the
breast are without delay forwarded to the pathologist who, under morphological control,
sample relevant tissue from the invasive front and the core (0,5x1x1 cm) of the primary
tumour. Controls from normal breast tissue (2000 mg) from the distant contralateral quadrant
will also be collected and verified morphologically by the pathologist. The tissue is
collected in duplicates pairs. One of the samples is immediately snap-frozen in liquid
nitrogen for preservation, while the other half of each pair is preserved in formalin and
fixated in paraffin (FFPE). In addition, three pairs of samples of adipose tissue (each of
1x1x1 cm) with increasing distance from the tumour border will make up a gradient of adipose
tissue from the invasive front of the tumour area. The gradients collected are also
immediately snap-frozen in liquid nitrogen and one half of each pair stored as FFPE. The
researches have performed a pilot study confirming a sufficient RNA yield from the frozen
tissue samples for RNA sequencing.
The tissue is collected as part of the general research biobank, Prospective Breast Cancer
Biobank (PBCB) (REK# 2010/1957), an ongoing biobank-project.
The retrospective Stavanger cohort consist of all breast cancer patients diagnosed with first
onset invasive breast cancer at the department of Pathology, Stavanger University Hospital,
between 1993 - 2004. As SUH is the only hospital in the region this is a true population
based biobank, already included are clinicopathological data like: grading, stage, TNM,
treatment and proliferation markers (Ki-67, PPH3/MAI); last clinical follow-up took place in
2016.
The researches have four main hypotheses related to inflammation and immune cell infiltration
in breast cancer:
1. The juxta-tumoral adipose tissue close to the tumour border shows an increased level of
inflammation and immune cell infiltration.
2. The inflammation and immune cell infiltration attenuate with increased distance from the
tumour border.
3. There are differences in the inflammation and immune cell infiltration between different
subtypes of breast cancer (Luminal A, Luminal B and Basal like).
4. Increased inflammation and immune cell infiltration are correlated to adverse clinical
outcome (i.e. relapse of disease).
4.1 STUDY DESIGN, METHODS AND ANALYSES
The researches have four main hypotheses related to inflammation and immune cell infiltration
in breast cancer:
1. The juxta-tumoral adipose tissue close to the tumour border shows an increased level of
inflammation and immune cell infiltration.
2. The inflammation and immune cell infiltration attenuate with increased distance from the
tumour border.
3. There are differences in the inflammation and immune cell infiltration between different
subtypes of breast cancer (Luminal A, Luminal B and Basal like).
4. Increased inflammation and immune cell infiltration are correlated to adverse clinical
outcome (i.e. relapse of disease).
WP 1: MORPHOLOGIC AND GENOMIC MAPPING OF IMMUNE CELL INFILTRATION IN ADIPOSE TISSUE
SURROUNDING BREAST CANCER
Background: Inflammation is an important facilitator for tumour development (16). Adipose
tissue near breast cancer have been shown to have increased immune cell infiltration, but it
is not yet known how this relates to molecular subtypes and/or proximity to tumour. The
researches will use IHC and RNA-sequencing to evaluate the level of inflammation,
infiltration of immune cells and immune gene expression signatures in the adipose tissue
surrounding breast cancer.
Design: Prospective explorative study Patients, material and power calculation: Adipose
tissue is collected from the prospectively collected mastectomy specimens. Tissue samples are
collected from three different molecular subgroups (Luminal A, Luminal B and Basal like
breast cancer), 10 in each group. Core biopsies are collected in a gradient with increasing
distance from tumour border (fig. 1). The Norwegian Genomics Consortium (NGC) has confirmed
that the sample sizes that are based on the selection in specific breast cancer subtypes are
sufficient for statistical power.
Methods: Slides of formalin fixated tissue from tumour, invasive front and adipose tissue
(fig. 1) will be stained using IHC and antibodies against immune cells (total immune cells,
CD45; T cells, CD3, CD8, FoxP3; myeloid cells, CD68, HLA-DR). The slides will be evaluated by
microscopy and the results will be correlated to molecular subgroups of breast cancer,
localization in relation to tumour and proliferation markers (i.e. Ki67, PPH3 and MAI). In
parallel, the researches will perform RNA-sequencing on frozen tissue collected from the same
tissue samples as described above. Several analysis approaches will be used on the
RNAseq-data. Except for analysing the data exploratory, specific analysis algorithms
including deconvoluting immune cells (ABIS, CIBERSORTx) and more specifically looking at
tumour immune signatures (TIP analysis), among others.
Expected outcome: The researches expect to find increased inflammation and immune cell
infiltration in the juxta-tumoral adipose tissue and altered expression of inflammatory gene
signatures that the researches can further investigate in WP 2.
WP 2: ASSESSMENT OF INFLAMMATORY REACTION IN JUXTA-TUMOURAL ADIPOSE TISSUE IN BREAST CANCER
USING IMMUNOHISTOCHEMISTRY AND IMAGING MASS CYTOMETRY.
Background: Breast cancer cells interact with the surrounding tissue and causes inflammation
and immune cell infiltration in the tumour and the adipose tissue. Imaging mass cytometry has
shown that immune cell infiltration in tumours correlates with prognosis, but as of yet there
are no studies examining whether the adipose tissue surrounding the tumour also show
structural patterns of immune cell infiltration. Therefore, the researches will examine the
adipose tissue surrounding breast cancer tumours using Hyperion™ Imaging Mass Cytometry.
Design: Prospective explorative study Patients, material and power calculation: Tissue
samples are collected from 30 prospectively obtained mastectomy specimens with three
different molecular subgroups (Luminal A, Luminal B and Basal like breast cancer), 10 in each
group. Adipose tissue is collected in a gradient away from tumour and from the contralateral
quadrant as a control sample (fig. 2). A sample size of 30 patients is deemed to be
sufficient for an explorative study of this sort.
Methods: A Hyperion™ IMC panel of up to 50 unique antibodies will be developed based on an
already existing and validated panel available at the UoB core facility which the researches
have previously successfully used in other projects. The available panel will be further
extended based on findings from WP 1 and first validated on "non-essential" breast tissue
samples before used on the above-described study samples. Using Hyperion™ IMC the researches
intend to analyse the levels of inflammatory reaction in the juxta-tumoural adipose tissue.
IMC data will be analysed with histoCAT+, MAV and FlowJo (typically used for flow cytometry
data analysis but also highly suitable for high-parameter imaging anslysis). Furthermore, the
researches will be able to use gene expression data of known and novel factors, identified in
WP 1, and visualize whether the expression is generalized or compartmentalized in the adipose
tissue. Normal adipose breast tissue from the contralateral quadrant will be used as control.
In order to examine the influence of BC on the inflammation of juxta-tumoural adipose tissue
of the various molecular subtypes in more detail, the researches also intend to stain tissue
from three tissue segments extending from the tumour in order to determine whether the levels
depend on the distance from tumour or the molecular subtype (Fig. 1). The inflammation in the
juxta-tumoural adipose tissue will also be assessed morphologically by using IHC. This will
allow us to select regions of interest to investigate using IMC.
Expected outcome: The researches expect to find increased inflammation and immune cell
infiltration in the adipose tissue near the tumour and to identify novel biomarkers in the
adipose tissue allowing for investigation of the clinical significance in WP 3.
WP 3: INFLAMMATORY REACTION IN JUXTA-TUMOURAL ADIPOSE TISSUE IN BREAST CANCER AND CLINICAL
OUTCOME.
Background:
Immunohistochemistry is a cornerstone in breast cancer diagnostics and serves as the main
modality for identifying molecular subgroups of breast cancer and proliferation markers such
as Ki-67. This is essential in determining what treatment regimen is best suited for the
particular patient. Heterogeneity in the tumour tissue (both tumour cells and infiltrating
immune cells) have been linked to difference in clinical outcome , but it is not yet known if
the same applies for the adipose tissue surrounding the tumour. Thus, the researches will
examine juxta-tumoral adipose tissue for inflammation and immune cell infiltration and
correlate this with clinical outcome in breast cancer patients.
Design: Clinical observational study
Patients and Methods: A number of 3500 breast cancer patients are accrued in a biobank with a
median follow-up time of 15 years. A large selection of tissue samples from these patients
will be assessed with respect to immune cells in the adipose tissue and biomarkers discovered
in WP 1 and 2 using IHC. The samples will be stratified into three groups according to
molecular subgroups (i.e. Luminal A, Luminal B and Basal like breast cancer). The tissue
slides will be analysed and the results correlated with clinical outcome from the patient
journals (access to journals is already approved by REK). Using Cox proportional hazard ratio
and log-rank test, the researches will evaluate the effect increased inflammation in adipose
tissue has on patient survivability.
Power calculation: The researches estimated the test power of the difference in recurrence
free survival between patients positive and negative for juxta tumoral inflammation as
assessed by IHC and IMC. The effect measure is the hazard rate (HR) as calculated by the Cox
regression method. For example: 1000 patients with a recurrence rate of 15% will have created
at least 150 endpoints. If the inflammation rate is 20% the researches will have an 80% power
to detect a survival difference with a hazard ratio (HR) of 1.80 or greater.
Expected outcome: This last work package is designed to give proof of principle that it is
feasible to incorporate histological examination of juxta-tumoural adipose tissue as a part
of breast cancer diagnostics. In the longer perspective the researches aim to identify new
specific biomarkers of immune infiltration in adipose tissue that correlate to adverse
outcome in breast cancer patients. Such biomarkers may serve as predictive tools for
identifying patients eligible for adjuvant anti-inflammatory or immune-modulating treatment.
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D.Monitor side effects, QoL, depression, fatigue and work life participation Background
Treatment of breast cancer employs all surgery, chemotherapy, radiation therapy and various
targeted therapy options like antiestrogen and anti HER-2 therapy.These treatment options
create bothersome side effects both in a short term and long term perspective. Importantly,
more complex relationships between oncological therapy modalities and subjective health
complaints in breast cancer patients are recently discovered. Fatigue, anxiety and depression
scores are probably functional read outs of the total treatment burden. The anti cancer
treatment has also a substantial impact on Quality of Life and social aspects for the cancer
survivors which extends to work life participation. Sick leave (SL) five years after the
breast cancer diagnosis is more dependent on social factors than on illness (2). Hence,
breast cancer hits the women twice; first the disease burden then the sosio-economic worries.
Breast cancer survivors have almost 3 x higher risk of receiving disability pension (DP)
compared to cancer -free patients in a retrospective register based study (3). However, this
study was based on mostly abandoned oncological treatment regimens.
Aims
The aim of this study is to identify risk factors for becoming a long term SL, WAA or DP
receiver by an in-depth qualitative analysis and mixed-method approach by triangulating PROM
data, clinical/biological data and the NAV-data. Use of NAV-data as endpoints will provide
valuable information to clinicians and general practitioners who may optimize the follow-up
also in regards to work-life participation. Hence, the investigators have a robust study
design to identy fisk factors for high SL, WAA and DP rates. Ultimately, the investigators
aim to lower the financial expenses breast cancer generates to society.
Study design / material & methods.
The study design is an observational study where the investigators will in the present study
map the rates of and denty fisk factors for high SL, WAA and DP among breast cancer survivors
with the up-to date treatment schedules. The investigators will follow a 4-step translational
approach:
1. The investigators will first conduct an exploratory qualitative study using document
analysis of health and work life policy in the Norwegian context, combined with
empirical data from semi- structured interviews and focus group with 20 high risk
patients) to be analyzed thematically. The theoretical framework for this qualitative
project is derived from symbolic interactionism in which uncovering and understanding
meaning in specific contexts is a goal. Since meaningful social and professional
interactions are important for psychosocial rehabilitation of breast cancer individuals
symbolic interactionism is an appropriate methodological framework. This qualitative
approach will create the bases of the approach in the PROM based and NAV-database
oriented studies below.
2. NAV- data
The investigators currently collaborate with vice director Anneline Christine Teigen and
senior consultant Günter Olsborg in NAV-Rogaland and the Mikrodata section at Statistics
Norway (SSB). The aim for this collaboration is gain more knowledge about the use of
social security services among breast cancer patients together with the NAV- Rogaland
experts and together with SSB use the FD-trygd database to obtain reliable prospective
sociodemographic data on SLs (both short & long term), Work Assessment Allowance (WAA)
(Arbeidsavklaringspenger) and DPs (both time limited
& life long) for each patients in the present PerMoBreCan study.
3. Patient reported outcome measure (PROM) data is obtained at baseline and thereafter
yearly from all PerMoBreCan patients. The PROM data consists of 1.HRQoL instruments
(EORTC QLQ-C30,EORTC QLQ-BR23 and FACT B), 2.Hospital Anxiety and Depression Scale, HAD,
3. Fatigue instruments Fatique Impact Scale, FIS; Fatugue Severity Scale (FSS) and
VAS-fatigue, 4.Side effects questionnaires, 5. Joint- pain questionnaire, 6. The Mishel
Uncertainty in Illness Scale, MUIS; and 7. Food habits questionnaire and the 8.ROMA III
questionnaire of bowel complaints (IBD and IBS).
4. Biomarker identification.
All patients attending this study will be screened on circulating biomarkers releated to
fatigue. These biomarkers are on the protein level, genetic expression level and also on the
epigenetic level. Our long-established pleasant cooperation with prof. Roald Omdal at
Stavanger University Hospital, who is a clinical immuologist and transaltional fatigue
researcher, is committed to conduct these analyses in his research lab.
