Rationale: In addition to surgery, effective breast cancer (BC) treatment typically requires chemotherapy, radiotherapy, or both. However, it is still unclear whether patients with BC are at increased risk of long-term cardiac dysfunction due to the adverse effects of these therapies. In a cross-sectional study in primary care, a comparison on cardiac dysfunction between 350 BC survivors and 350 age- and general practitioner (GP)- matched controls without cancer was made. In that study, BC survivors were at increased risk of mild systolic cardiac dysfunction (left ventricle ejection fraction (LVEF)< 54%). By contrast, there was no significant difference in an LVEF < 50% or in diastolic dysfunction. To date it remains uncertain whether the mild or subclinical dysfunction we observed predicts further cardiac deterioration. Consequently, the translation of these results into guidelines for the daily practice of the GP is unclear.

Objective: The aim of the here proposed study is to clarify whether cardiac function in survivors of BC should be monitored by GPs, by assessing whether an unselected population of long-term BC survivors is at increased risk of developing cardiac dysfunction, whether in this group at-risk subgroups exists, and what factors are associated with the highest risk.

Study design: A new assessment of cardiac function among women included in the BLOC-I study. This produces a longitudinal matched cohort design consisting of two cohorts in primary care.

Study population: Survivors of BC, diagnosed ≥11 years ago who received chemotherapy and/or radiotherapy, and a matched reference population with no history of cancer. All participants participated in the Breast cancer Long-term Outcome of Cardiac function (BLOC-I) study.

Main study parameters/endpoints: Left ventricular systolic dysfunction. Systolic cardiac dysfunction is defined as a LVEF <54/50/45%.

Inclusion Criteria:

• Patients who previously took part in de BLOC-I study will be included. These criteria were:
• females diagnosed with stage I-III BC at least five years ago or local or locoregional recurrence of BC at least five years ago
• treatment with chemotherapy and/or radiotherapy.

Exclusion Criteria:

• Patients unfit to travel to the hospital due to severe mental or physical illness, based on assessment by their GP.

Exclusion criteria for the BC survivors in the BLOC-I study were:

• metastatic disease at the time of BC diagnosis;
• BC treatment after 80 years of age;
• history of treatment for other types of cancer.

BC survivors were matched with women of the same age (±1 year) who had the same GP, but who had no history of cancer or cancer treatment (chemotherapy or radiotherapy).

A longitudinal matched cohort design consisting of two cohorts in primary care: one with survivors of BC, diagnosed ≥11 years ago who received chemotherapy and/or radiotherapy, and one with a matched reference population with no history of cancer.