Cohort profile: The Clinical and Multi-omic (CAMO) cohort, part of the Norwegian Women and Cancer (NOWAC) study

Abstract

Introduction: Breast cancer is the most common cancer worldwide and the leading cause of cancer related deaths among women. The high incidence and mortality of breast cancer calls for improved prevention, diagnostics, and treatment, including identification of new prognostic and predictive biomarkers for use in precision medicine.

Material and methods: With the aim of compiling a cohort amenable to integrative study designs, we collected detailed epidemiological and clinical data, blood samples, and tumor tissue from a subset of participants from the prospective, population-based Norwegian Women and Cancer (NOWAC) study. These study participants were diagnosed with invasive breast cancer in North Norway before 2013 according to the Cancer Registry of Norway and constitute the Clinical and Multi-omic (CAMO) cohort. Prospectively collected questionnaire data on lifestyle and reproductive factors and blood samples were extracted from the NOWAC study, clinical and histopathological data were manually curated from medical records, and archived tumor tissue collected.

Results: The lifestyle and reproductive characteristics of the study participants in the CAMO cohort (n = 388) were largely similar to those of the breast cancer patients in NOWAC (n = 10 356). The majority of the cancers in the CAMO cohort were tumor grade 2 and of the luminal A subtype. Approx. 80% were estrogen receptor positive, 13% were HER2 positive, and 12% were triple negative breast cancers. Lymph node metastases were present in 31% at diagnosis. The epidemiological dataset in the CAMO cohort is complemented by mRNA, miRNA, and metabolomics analyses in plasma, as well as miRNA profiling in tumor tissue. Additionally, histological analyses at the level of proteins and miRNAs in tumor tissue are currently ongoing.

Conclusion: The CAMO cohort provides data suitable for epidemiological, clinical, molecular, and multi-omics investigations, thereby enabling a systems epidemiology approach to translational breast cancer research.

Fig 1. Study population.

Venn diagram showing size and overlap of study populations in the Norwegian Women and Cancer (NOWAC) study, the NOWAC Post-genome cohort and the Clinical and Multi-omic (CAMO) cohort.

Fig 2. Timeline of the study period.

Timeline of the study period showing year of breast cancer diagnosis of the study participants (dots), as well as notable changes in screening, diagnostic, and treatment regimes in Norway (vertical lines). Line A denotes the introduction of the national breast cancer (BC) screening program, line B the introduction of chemotherapy regimens AC and FEC in the Norwegian national guidelines for BC treatment, line C the introduction of HER2 analysis in BC diagnostics, line D the use of paclitaxel and docetaxel, aromatase inhibitor, and adjuvant trastuzumab in BC treatment, and line E the introduction of Ki67 analysis and change of ER cutoff to 1% in BC diagnostics. The time periods of data collection in the NOWAC study are shown as colored, horizontal bars. Abbreviations: AC = doxorubicin (also known as Adriamycin) and cyclophosphamide; ER = estrogen receptor; FEC = 5-fluorouracil, epirubicin and cyclophosphamide.

Fig 3. Overview of sample sizes, data sources, and data types.

The Clinical and Multi-omic (CAMO) cohort, nested within the Norwegian Women and Cancer (NOWAC) study, provides multiple types of data from a wide range of sources, thereby enabling a systems epidemiology approach to breast cancer. These multimodal data may be combined in various ways to create complex study designs that can be used to investigate hypotheses related to breast cancer prevention, diagnostics, treatment, and survival.