Identifying subgroups with High cArdiovascular Risk in Breast cancer survivORs (HARBOR)

Breast cancer (BC) incidence is increasing, while mortality from BC is
decreasing. Since the life expectancy of BC patients is improving, the
evaluation of treatment-associated cardiovascular disease (CVD) in BC survivors
is becoming increasingly important. An excess risk of CVD, mainly due to
coronary heart disease (CHD), has been observed after radiotherapy (RT) as
administered in the 1960s-1980s. Anthracycline-containing CT and trastuzumab
are known to induce acute cardiotoxicity, especially congestive heart failure
(CHF). However, the long-term risks of CVD after anthracycline-containing CT,
trastuzumab, hormonal therapy (HT) and contemporary RT techniques have hardly
been examined. Furthermore, the potential interaction of these treatment
modalities has not been well addressed, and there is limited knowledge about
the contribution of classic cardiovascular risk factors and the metabolic
syndrome to risk and severity of treatment-associated CVD in BC survivors.

- to evaluate the prevalence of (sub)clinical CVD, cardiovascular risk factors
and metabolic abnormalities among BC survivors treated with and without
anthracyclines in two groups at (a) 5-7 years and (b) 10-12 years after
diagnosis;
- to prospectively evaluate changes in prevalence of (sub)clinical CVD,
cardiovascular risk factors and metabolic abnormalities after two years in the
same patients.
Secondary objectives are to evaluate the predictive role of newly developed
markers for CVD and to evaluate the effects of other BC treatment modalities
(radiotherapy, immunotherapy, hormonal therapy), psychosocial outcomes
(depression, fatigue, quality of life), endocrine function, menopausal status
induced by breast cancer treatment and cellular senescence on the risk of
developing (sub)clinical CVD. Examining cognitive functioning in the different
groups is also a secondary objective.

Multicenter (AVL and UMCG) cross-sectional cohort study with prospective
monitoring of the same cohort.
Eligible study candidates will receive an invitation letter through their
(former) treating physician. Candidates willing to participate are asked to
provide their informed consent and fill in an online questionnaire. After
receiving the informed consent participants are scheduled for their first visit
at the outpatient clinic. At the study visit blood will be drawn at the
laboratory and additional information on medical history, current medication
and current status is obtained by the research physician. A full physical
examination will be performed, including skin autofluorescence. Furthermore an
echocardiography and echography of the carotid and femoral artery are planned
and the participant is asked to provide us with a urine sample. At the end of
the program, participants will again meet with the research physician. Besides,
the participant will be asked to make online cognitive tests and fill in a
questionnaire about cognitive functioning at home, using the Amsterdam
Cognition Scan tool.
The format of the second study visit, two years after the first visit has the
same format. The participant will receive an invitation letter for the second
visit at the outpatient clinic and a request to fill in an online
questionnaire. Participants unwilling to participate in the second study visit
can decline by contacting the study coordinator, this is explained in the
invitation letter. At the outpatient blood will be drawn, urine collected and
the same tests will be performed.

The burden of participation comes from the two visits at the outpatient clinic.
Patients will fill in questionnaires, make cognitive tests, undergo physical
examination and cardiovascular assessment. ECG, echocardiography, echography of
the carotis and femoralis and skin autofluorescence are non-invasive tests. A
maximum of 110ml blood is drawn per visit. Cardiovascular risk assessment could
be beneficial for the participant, since CVD and cardiovascular risk factors
will be treated if necessary.