Investigation of Genetic and Clinical Risk Factors for the Prediction of Early Endocrine Therapy Side Effects..
Abstract
Breast cancer is the most common women's cancer worldwide. Prevention trials show
that endocrine therapy can significantly reduce the incidence of breast cancer, though
benefits must be weighed against side effects. Concerns about side effects are cited
as a major reason behind poor uptake and adherence to endocrine therapy. However,
research focussed on the risk factors of side effects or their impact on long-term breast
cancer outcomes is limited. Hypotheses of this thesis are that there are multiple diverse
risk factors for side effects; that risk factors can be used to predict side effect incidence;
and that early reported side effects are a sign of endocrine therapy efficacy.
Hypotheses were tested through studies of clinical baseline factors, genetic risk factors
and sex hormones to explore associations with side effects in women from the IBIS-I
and IBIS-II trials. Statistical algorithms combining risk factors were subsequently used
to develop side effect prediction models and risk scores. Lastly, a study assessed the
effect of reporting side effects on breast cancer incidence during long-term follow-up of
IBIS-I and IBIS-II.
Markers including menopausal status, BMI, age, reproductive factors, and sex hormones
were found to affect the risk of side effects. However, no significant genetic
markers were identified. Prediction of side effects using a side effect risk score derived
from a logistic regression model, containing clinical and sex hormone factors was possible,
but performance was poor. Further investigation of risk factors is required before
accurate prediction is possible. Contrary to the initial hypothesis, reporting hot ushes
in women randomised to tamoxifen and reporting arthralgia in women randomised to
anastrozole was associated with increased risk of breast cancer, particularly oestrogen
receptor-positive breast cancer in postmenopausal women.
Overall, risk factors were identified that impact a woman's risk of side effects. The
negative impact of side effects on breast cancer outcomes was also established.
Authors
Hale., Michael James.Collections
- Theses [4203]