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Genetic factors, body constitution, and tumor characteristics in relation to breast cancer prognosis

Markkula, Andrea LU (2015) In Lund University Faculty of Medicine Doctoral Dissertation Series 2015:127.
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Professor Thune, Inger, The Cancer Centre, Oslo University Hospital, Norway
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2015:127
pages
151 pages
publisher
Division of Oncology and Pathology, Clinical Sciences, Lund University
defense location
Lecture Hall in Strålbehandlingshuset, Klinikgatan 5, Lund
defense date
2015-12-03 09:00:00
ISSN
1652-8220
ISBN
978-91-7619-207-8
language
English
LU publication?
yes
id
c644aa1d-f44b-41f3-a27d-e5f0581e6091 (old id 8230265)
date added to LUP
2016-04-01 14:13:31
date last changed
2019-05-22 05:31:49
@phdthesis{c644aa1d-f44b-41f3-a27d-e5f0581e6091,
  abstract     = {{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. <br/><br>
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.<br/><br>
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.}},
  author       = {{Markkula, Andrea}},
  isbn         = {{978-91-7619-207-8}},
  issn         = {{1652-8220}},
  language     = {{eng}},
  publisher    = {{Division of Oncology and Pathology, Clinical Sciences, Lund University}},
  school       = {{Lund University}},
  series       = {{Lund University Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Genetic factors, body constitution, and tumor characteristics in relation to breast cancer prognosis}},
  volume       = {{2015:127}},
  year         = {{2015}},
}