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First Breast Cancer – Then Diabetes Type 2
Posted on 08.03.2023
Breast cancer is the most common cancer in the world. Fortunately, due to earlier diagnosis and improved treatment, breast cancer survivors are a growing group. Today, over 90% of women with breast cancer survive for more than five years after their diagnosis. However, most women suffer from side effects from both chemotherapy and anti-oestrogen treatment. Most are not aware of the risks of increased weight, blood sugar, cholesterol and metabolic diseases including type 2 diabetes in postmenopausal women diagnosed with breast cancer.
Therefore, formerly DDA-Funded Assistant Professor Linn Gillberg is working on a project titled ‘Healthy Living after Breast Cancer’ led by Professor Peter Schwarz, Department of Endocrinology, Rigshospitalet. Linn Gillberg and her MSc students collaborate with colleagues at Rigshospitalet where they follow women with postmenopausal breast cancer before – and during five years after their chemotherapy treatment, with a focus on their metabolic, endocrine, and inflammatory health.
Linn Gillberg’s work aims to determine why women with postmenopausal breast cancer develop metabolic side effects. The study shows that, in general, women with breast cancer have increased blood lipids and insulin levels compared to age-matched healthy women. This is seen already at diagnosis, and these conditions worsen after chemotherapy.
First Breast Cancer – Then Metabolic Diseases
Thus far, Linn Gillberg and a group of MSc students have analysed pro-inflammatory cytokines and metabolic hormones in blood samples from the women before and during the first two years after chemotherapy treatment.
– Chemotherapy clearly increase pre-inflammatory cytokines (e.g. IL-6 and TNF-α) in the blood, but the changes reverse between 6 and 12 months after ended chemotherapy treatment. Metabolic hormones, on the other hand, are different in women with breast cancer and age- and BMI-matched controls already before initiation of chemotherapy treatment, says Linn Gillberg. In fact, women with breast cancer have a generally worsened metabolic profile compared to women without breast cancer. Indeed, type 2 diabetes and postmenopausal breast cancer share the risk factors obesity and hyperinsulinemia.
Linn Gillberg and her team also have some very exciting preliminary data showing that mitochondrial respiration in skeletal muscle is impaired in breast cancer patients after chemotherapy compared to healthy controls. Mitochondrial dysfunction of skeletal muscle has previously been associated with impaired fat metabolism, lipid storage in muscle cells and insulin resistance. Thus, their findings indicate that mitochondrial dysfunction of skeletal muscle might contribute to the increased risk of metabolic disease, including type 2 diabetes, in breast cancer survivors.
Lifestyle Changes May Prevent Metabolic Diseases
Fortunately, metabolic diseases can be partly prevented by lifestyle changes such as diet and physical activity. Therefore, identification of women who have an increased risk of developing metabolic diseases due to e.g. obesity or high fasting blood glucose levels may prevent them from developing metabolic diseases such as diabetes type 2 secondary to breast cancer.
In the long term, Linn Gillberg therefore hopes that her study will bring new insight and awareness about treatment related side effects and contribute to a closer follow-up of breast cancer survivors about their metabolic health.
– However, we still need to understand the underlying causes. Is the increased risk primarily attributed to a worsened metabolic health at diagnosis? Or is it rather the chemotherapy and/or anti-oestrogen therapy that affect cells and tissues involved in metabolic disease development?, says Linn Gillberg.
Research in Women’s Health is Underfunded and Understudied
Women make up half of the population, but research in women’s health is still underfunded and understudied.
– Naturally, studying men and women is of equal importance, but we have a lot to catch up on when it comes to studying women’s diseases. In turn, this means that there is also great potential for new solutions and innovations that make a difference for women. This has also influenced my choice of focus and my drive to make a difference for breast cancer survivors in my current project, says Linn Gillberg.
Important Questions Yet to be Answered
Currently, the study ‘Healthy Living after Breast Cancer’ has almost 100 patients included. Linn Gillberg is excited to continue the analysis of samples that they continuously collect from women with breast cancer.
– I am working on several articles that will be submitted soon. Furthermore, I have recently initiated analyses on how chemotherapy affects epigenetics – modifications on the DNA that control gene expression – in our patient samples, says Linn Gillberg.
Epigenetics can change gene expression and thereby disease development. Unlike DNA bases, epigenetic modifications may change with aging, lifestyle, or disease. How chemotherapy impacts epigenetics and gene expression of key metabolic tissues from breast cancer patients has not yet been studied.
– I am eager to continue the epigenetic and further molecular characterization of blood and tissue samples from breast cancer patients and controls when we receive more funding to the project, says Linn Gillberg.
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