Thyroid function and breast cancer. Risk and clinical outcome in relation to thyroid hormones (free T3/T4), TSH, TPO-Antibodies and genetic variants.

Thyroid hormone level has been positively associated
with breast cancer cell proliferation and
tumour growth in experimental studies. However,
previous observational studies have been contradictory
on the relationship between thyroid
function and breast cancer. Age is a known risk
factor for breast cancer but its role as a prognostic
factor is less clear. The present thesis therefore
aimed to examine the contradictory relation between
thyroid function and breast cancer risk,
progression and survival. Also, age at breast cancer
diagnosis was evaluated as a prognostic factor.
The first paper was a baseline study on the
influence of age at diagnosis on breast cancer
mortality in different diagnostic periods (follow-up
until 2001). The study was conducted
on 4,453 women diagnosed with breast cancer.
We found that women under 40 years of age had
a poor prognosis, and this association seemed
to be strongest among young women with axillary
lymph node negative breast cancer. Furthermore,
an age of 80 years or more was a prognostic
factor for poor survival, independent of stage
at diagnosis and diagnostic period.
The second paper evaluated pre-diagnostic
levels of free triiodothyronine (free T3), free
thyroxine (free T4), thyroid-stimulating hormone
(TSH), and thyroid peroxidase antibodies
(TPO-Ab) in relation to breast cancer subgroups
and aggressiveness. The cohort used was
the Malmö Diet and Cancer Study, which is a
population based cohort of 17,035 women recruited
between 1991 and 1996. Our results
indicated that high pre-diagnostic free T4 levels
and low pre-diagnostic TPO-Ab levels were
associated with an increased risk of breast cancer.
This increase was mainly limited to a higher
incidence rate of less aggressive forms of breast
cancer.
In the third paper we examined if the effect of
thyroid function on breast cancer subgroups also
influenced breast cancer survival. We displayed
a positive association between free T4 levels and
an improved breast cancer survival.
The possible effect of genetic markers for free
T4 and TPO-Ab on breast cancer risk was assessed
in the fourth paper. We identified five
markers that influenced the risk of breast cancer,
of which rs2235544 (D101 gene) was the most
interesting. This was the first study to suggest
an association between thyroid-related genetic
variants and breast cancer risk.
The potential association between thyroid
function and breast cancer is complex, as it exerts
its effect through several pathways. This thesis
has contributed to our understanding of how
thyroid function influences breast cancer risk
and breast cancer mortality. In addition, it has
enlightened the importance of age at diagnosis
as a prognostic factor.