BIO 241(T47)

Advanced Physiology

MS BIOLOGY I

“ ENDOCRINOLOGY “

Presented by: Fortune Joyce C. Baldonado

 Hypothyroidism and
hyperthyroidism and
breast cancer risk: a
nationwide cohort study
Mette Søgaard1, Do´ ra Ko¨ rmendine´ Farkas1, Vera Ehrenstein1,
Jens Otto Lunde Jørgensen2, Olaf M Dekkers1,3 and Henrik Toft
Sørensen1
Departments of 1Clinical Epidemiology, 2Endocrinology and Internal Medicine (MEA), Aarhus University
Hospital,
Olof Palmes Alle´ 43-45, DK-8200 Aarhus N, Denmark and 3Departments of Endocrinology and Clinical
Epidemiology,
Leiden University Medical Center, Leiden, The Netherlands
INTRODUCTION
 INTRODUCTION
Objective of the Study: To examine the association between
hypothyroidism, hyperthyroidism and breast cancer risk
INTRODUCTION
 SUBJECTS and METHODS
Study Setting
Location: Denmark

• The data was taken from January 1,1978 to November

31,2013

• Health service utilization is tracked by several nationwide

registries, linkable using each resident’s universal identifier,
assigned to all Danish residents at birth or upon immigration
since 1968

Source Population: 4 177 429 women

 SUBJECTS and METHODS
Hypothyroidism and Hyperthyroidism
• Danish National Patient Registry (DNPR) contains
information on all inpatient hospitalizations at Danish non-
psychiatric hospitals since 1977 and outpatient and
emergency department visits since 1995.

• Each hospital visit were recorded by physicians with one

primary diagnosis and one or more secondary diagnoses
classified according to the International Classification of
Diseases, 8th edition until the end of 1993.

• DNPR was used to identify all women with a first time

diagnosis of hyperthyroidism or hyperthyroidism from 1978
through 2013.
 SUBJECTS and METHODS
Hypothyroidism and Hyperthyroidism

Excluded: Women diagnosed of hypothyroidism and

hyperthyroidism on the same date

Women with hyperthyroidism who subsequently

developed hypothyroidism or vice versa were censored on the
date of the new diagnosis.
 SUBJECTS and METHODS
Breast Cancer
• The cohorts of women with a diagnosis of hypothyroidism or
hyperthyroidism were linked to the Danish Cancer Registry
(DCR).

• Through the DCR, data on breast cancer stage at diagnosis

were also obtained

• A linkage to the Danish Pathology Registry to retrieve data

on estrogen receptor ER status at breast cancer diagnosis
starting 1997 were also performed.

Excluded: Women with a breast cancer diagnosis prior to the

diagnosis of hypothyroidism or hyperthyroidism
 SUBJECTS and METHODS
Comorbid diseases
• Charlson Comorbidity Index (CCI) scores were computed for
each patient based on all available DNPR inpatient
hospitalization records preceding the date of diagnosis of
hypothyroidism and hyperthyroidism.

• The severity of comorbidities were categorized as low (CCI

score = 0), medium (CCI score = 1-2) or high (CCI score ≥ 3),
excluding breast cancer diagnoses from the CCI score
calculation.

• DNPR was also used to access information on clinical

diagnosis of obesity and alcohol-related disease.
 SUBJECTS and METHODS
Statistical Analysis
COMPUTATION

• Expected number of breast cancer using rates by age & year

of diagnosis

• Standardized Incidence Ratios (SIRs) for breast cancer as

the ratio of observed to expected cancers

• Confidence Intervals (CIs) for the SIRs

• Absolute risk of breast cancer with death as a competing risk

 SUBJECTS and METHODS
Statistical Analysis
EXCLUDED

• Breast cancer diagnosis in the first 12 months following

diagnosis of thyroid disease

• Patient’s with Grave’s disease is excluded in sensitivity

analysis in order to reduce potential confounding by smoking.
R
E
S
U
L
T
S
R
E
S
U
L
T
S
 DISCUSSION
• The higher incidence of hyperthyroidism compared with
hypothyroidism is in agreement with previous studies, as is the
increased incidence of thyroid disease overtime.

• Researchers limitations of their study was the lack of

laboratory data because they were unable to distinguish
between clinical and subclinical thyroid disease, as they were
also unable to link the hormone levels at time of diagnosis to
breast cancer risk

• Analyses were stratified by hospital diagnoses of obesity &

alcohol-related illness, however these diagnoses are likely to
capture only the most severe cases.
 DISCUSSION
• The observed association between hyperthyroidism and
breast cancer risk may have been underestimated due to
incompletely ascertained lifestyle risk factors for breast
cancer, such as obesity & alcohol consumption, both of which
are associated with a reduced risk of hyperthyroidism but
increased risk of hyperthyroidism.

• Smoking has been associated with an increased risk of

Grave’s disease but has no consistent association with breast
cancer.

• Hormonal treatment role was not addressed by the

researchers in the observed association.
 CONCLUSION
The researchers found an increased risk of breast
cancer in women with hyperthyroidism and a slightly
decreased risk in women with hypothyroidism suggesting an
association between the thyroid function level and breast
cancer risk.