Breast Cancer Res: How to predict the risk of coronary heart disease in breast cancer survivors?

In 2018, there were approximately 2.
1 million new female breast cancer cases worldwide , accounting for 25% of female cancer cases
.
In the past 30 years, with the advancement of cancer treatment, women's long-term survival conditions have improved, and mortality from other causes has become more important

.

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Given that the current balance of survival benefits and future cardiotoxicity harms has led to an increase in the burden of cardiovascular disease for breast cancer survivors, risk stratification may help solve this clinical dilemma
.
This study is the first to assess the relationship between coronary artery disease-specific polygenic risk scores and coronary events in female breast cancer survivors

.

The study group covered 12413 participants
.
The average age at diagnosis was 54.

6 years, the median time from diagnosis to entry into the study was 1.

The genotyping characteristics of CAD patients observed during the diagnosis follow-up

After adjusting for age, the association of each variable with event CAD survival rate was studied (Table 2)

.

After adjusting for age, the association of each variable with event CAD survival rate was studied (Table 2)

The sample size of the multivariate model is 8946 with a total of 432 events (Figure 1)

.

The sample size of the multivariate model is 8946 with a total of 432 events (Figure 1)

The interaction between PRS and cardiovascular disease risk factors, log (BMI) and smoking is added to an array containing genotypes, 8 genetic pcs, log (BMI), smoking, education level, alcohol consumption, parity, hormone replacement In the model of therapy (Table 4)

.

The interaction between PRS and cardiovascular disease risk factors, log (BMI) and smoking is added to an array containing genotypes, 8 genetic pcs, log (BMI), smoking, education level, alcohol consumption, parity, hormone replacement In the model of therapy (Table 4)

Interaction between PRS and tumor therapy: In a model containing genotype sequences, 8 gene PCs, log (BMI), and genetic factors, the HRs of the interaction items between PRS and radiotherapy, PRS and chemotherapy, and PRS and antihormonal therapy were 1.
15 (0.
92,1.
43), 0.
93(0.
74,1.
16), 1.
15(0.
90,1.
46)
.

Interaction between PRS and tumor therapy: In a model containing genotype sequences, 8 gene PCs, log (BMI), and genetic factors, the HRs of the interaction items between PRS and radiotherapy, PRS and chemotherapy, and PRS and antihormonal therapy were 1.
15 (0.
92,1.
43), 0.
93(0.
74,1.
16), 1.
15(0.
90,1.
46)
.

The ability of PRS to stratify the risk of coronary heart disease in breast cancer survivors: The cumulative incidence of women in the lowest one-fifth of the risk reached 5% at the age of 15.
1, while the cumulative incidence of women in the highest one-fifth was 8.
9 years
.

The ability of PRS to stratify the risk of coronary heart disease in breast cancer survivors: The cumulative incidence of women in the lowest one-fifth of the risk reached 5% at the age of 15.
1, while the cumulative incidence of women in the highest one-fifth was 8.
9 years
.

The discrimination of PRS measured only by the c index is slightly lower than that of the combined model of BMI and smoking (0.
73 vs.
0.
74, P=0.
048) (Figure 3)
.
Adding PRS has little practical improvement in models including genotype sequence, 8 genetic pcs, BMI, smoking status, education level, drinking, IMD, age at menarche, parity, hormone replacement therapy, and thyroid disease (0.
757 vs.
0.
764, P=0.
052)
.
The total proportions of selected CAD and non-CAD cases were 22% and 11%, respectively
.

The discrimination of PRS measured only by the c index is slightly lower than that of the combined model of BMI and smoking (0.
73 vs.
0.
74, P=0.
048) (Figure 3)
.
Adding PRS has little practical improvement in models including genotype sequence, 8 genetic pcs, BMI, smoking status, education level, drinking, IMD, age at menarche, parity, hormone replacement therapy, and thyroid disease (0.
757 vs.
0.
764, P=0.
052)
.
The total proportions of selected CAD and non-CAD cases were 22% and 11%, respectively
.

The results of this cohort study based on a large number of breast cancer women in the UK showed that the CAD polygenic risk score developed for the general population can be extended to breast cancer patients.
It is estimated that every additional SD of PRS will increase the risk of CAD by 33% (HR= 1.
33, 95% CI 1.
20, 1.
47)
.
This is independent of established cardiovascular risk factors (age, smoking, BMI), tumor treatment and other variables related to cardiovascular risk (education level)
.
PRS can improve the risk identification of breast cancer survivors.
For example, when we compared individuals at the top and bottom 1/5 of the risk score distribution, we found that the HR of coronary heart disease was more than doubled
.
In addition, when considering the risk of coronary heart disease 10 years after breast cancer diagnosis, we found that after adding PRS to the baseline model, 5.
6% of low-risk participants who did not record coronary heart disease events were reclassified as high-risk groups
.

The results of this cohort study based on a large number of breast cancer women in the UK showed that the CAD polygenic risk score developed for the general population can be extended to breast cancer patients.
It is estimated that every additional SD of PRS will increase the risk of CAD by 33% (HR= 1.
33, 95% CI 1.
20, 1.
47)
.
This is independent of established cardiovascular risk factors (age, smoking, BMI), tumor treatment and other variables related to cardiovascular risk (education level)
.
PRS can improve the risk identification of breast cancer survivors.
For example, when we compared individuals at the top and bottom 1/5 of the risk score distribution, we found that the HR of coronary heart disease was more than doubled
.
In addition, when considering the risk of coronary heart disease 10 years after breast cancer diagnosis, we found that after adding PRS to the baseline model, 5.
6% of low-risk participants who did not record coronary heart disease events were reclassified as high-risk groups
.

In summary, cardiovascular disease is an important long-term risk in breast cancer survivors, and this risk is increased by some breast cancer therapies
.
A comprehensive risk model of cardiovascular disease may help clinically manage this risk and may improve the long-term outcomes of these women
.

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Original source:

Liou et al.
Genomic risk prediction of coronary artery disease in women with breast cancer:a prospective cohort study.
Breast Cancer Res (2021) 23:94
https://doi.
org/10.
1186/s13058-021-01465-0

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