Genetic factors, body constitution, and tumor characteristics in relation to breast cancer prognosis
Author
Summary, in English
Prior advancements in research on biomarkers and prognostic host factors have made it increasingly clear that breast cancer is an immensely heterogeneous disease. It remains difficult to predict which patients will benefit from different breast cancer treatments. Hence, interest in personalized medicine is internationally wide-spread and growing.
In paper I, we found that tumor detection mode, as well as several tumor- and preoperative patient characteristics were associated with nonadherence to adjuvant endocrine treatment. Furthermore, two clinical profiles were strongly associated with nonadherence to adjuvant endocrine breast cancer therapy at both the 1- and the 2-year follow-up visits. In paper II, we found that waist-to-hip ratio (WHR), waist circumference, as well as breast volume were associated with disease-free survival. Breast cancer patients with ER positive tumors and a breast volume ≥850 mL had a significantly shorter disease-free survival, regardless of age, WHR, waist circumference, and BMI. In paper III, a strong interaction between having any COX2 rs5277 C-allele and ER status on disease-free survival was found. The effect was further modified by breast volume. Two subgroups of patients were identified: GG carriers with a large breast volume who responded poorly to chemotherapy regardless of ER status and C-allele carriers with ER positive tumors and a large breast volume who responded poorly to endocrine treatment but responded well to chemotherapy. In paper IV, the IL6 rs1800795 Any C genotype was strongly associated with early events among patients with ER negative tumors, particularly among radiotherapy-treated patients, and among chemotherapy-treated patients regardless of ER status.
In conclusion, taking a more holistic view of the patient may prove beneficial both in and outside the clinic, ultimately paving the way for more personalized breast cancer treatment.
In paper I, we found that tumor detection mode, as well as several tumor- and preoperative patient characteristics were associated with nonadherence to adjuvant endocrine treatment. Furthermore, two clinical profiles were strongly associated with nonadherence to adjuvant endocrine breast cancer therapy at both the 1- and the 2-year follow-up visits. In paper II, we found that waist-to-hip ratio (WHR), waist circumference, as well as breast volume were associated with disease-free survival. Breast cancer patients with ER positive tumors and a breast volume ≥850 mL had a significantly shorter disease-free survival, regardless of age, WHR, waist circumference, and BMI. In paper III, a strong interaction between having any COX2 rs5277 C-allele and ER status on disease-free survival was found. The effect was further modified by breast volume. Two subgroups of patients were identified: GG carriers with a large breast volume who responded poorly to chemotherapy regardless of ER status and C-allele carriers with ER positive tumors and a large breast volume who responded poorly to endocrine treatment but responded well to chemotherapy. In paper IV, the IL6 rs1800795 Any C genotype was strongly associated with early events among patients with ER negative tumors, particularly among radiotherapy-treated patients, and among chemotherapy-treated patients regardless of ER status.
In conclusion, taking a more holistic view of the patient may prove beneficial both in and outside the clinic, ultimately paving the way for more personalized breast cancer treatment.
Department/s
- Tumor microenvironment
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2015
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2015:127
Document type
Dissertation
Publisher
Division of Oncology and Pathology, Clinical Sciences, Lund University
Topic
- Cancer and Oncology
Status
Published
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-207-8
Defence date
3 December 2015
Defence time
09:00
Defence place
Lecture Hall in Strålbehandlingshuset, Klinikgatan 5, Lund
Opponent
- Inger Thune (Professor)