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JACC Adv
JACC Adv
JACC: Advances
2772-963X
Elsevier

S2772-963X(24)00440-X
10.1016/j.jacadv.2024.101209
101209
Editorial Comment
Under Pressure to Optimize the Cardiac Care of Breast Cancer Survivors
Akhter Nausheen MD n-akhter@northwestern.edu
a∗
Hibler Elizabeth A. PhD b
a Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
b Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
∗ Address for correspondence: Dr Nausheen Akhter, Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 600, Chicago, Illinois 60611, USA. n-akhter@northwestern.edu
14 8 2024
9 2024
14 8 2024
3 9 101209© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Corresponding Author

Key words

breast cancer
heart disease
hypertension
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pmcHypertension is recognized as one of the most prevalent, modifiable, and targetable risk factors to affect adverse cardiovascular (CV) outcomes in breast cancer survivors.1,2 The American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guidelines emphasize health promotion in breast cancer survivors without specific recommendations for blood pressure targets.3 According to the European Society of Cardiology (ESC) Cardio-Oncology Guidelines, treatment for asymptomatic hypertension should be based on different patient scenarios depending on stage of disease and prognosis.4 The ESC guidelines specify that initiation of blood pressure treatment for cancer survivors should be considered for systolic blood pressure (SBP) at 135 to 140 mm Hg. Is this an optimal blood pressure target? Or should we be lowering blood pressure goals for cancer survivors to a similar range as patients without cancer? Should high-risk cancer survivors exposed to cardiotoxic treatment be managed differently? Unfortunately, major clinical trials that targeted SBP, such as SPRINT (Systolic Blood Pressure Intervention Trial), excluded patients with active cancer, and it is not clear how many patients with a history of cancer were enrolled.5 As the breast cancer survivor population ages, CV disease becomes the primary driver of morbidity and mortality. We must better understand the contribution of hypertension to increased CV disease in breast cancer survivors and optimal blood pressure goals for these patients.

In this issue of JACC: Advances, Leedy et al present the results of The Pathways Heart Study,6 which sought to address these questions by examining the associations between blood pressure and three CV outcomes (ischemic heart disease [IHD], stroke, and incident heart failure/cardiomyopathy) in female breast cancer survivors. In this large prospective cohort study with a median follow-up of 9.6 years, female breast cancer survivors were matched 5:1 to controls on age, race, and ethnicity. They measured time-averaged SBP and diastolic blood pressure (DBP) from cancer diagnosis until the first incident CV outcome. Blood pressure groups were divided into continuous and categorical variables by 10-unit increments from 100 to 160 mm Hg for SBP and <60 to 90 mm Hg for DBP. They found a positive association between SBP and IHD and stroke, a J-shaped association between DBP and IHD and stroke, and a U-shaped association between SBP and DBP and incident heart failure/cardiomyopathy. There were no differences between these blood pressure associations when female breast cancer survivors were compared to controls.

These complex associations between blood pressure and CV outcomes draw attention to the extremes of high and low blood pressure and individualizing blood pressure to CV outcomes. Elevated SBP and elevated/low DBP are associated with risk of IHD and stroke. Elevated/low SBP and DBP are associated with risk of heart failure/cardiomyopathy. This U-shaped blood pressure relationship for heart failure/cardiomyopathy has been previously reported in patients without cancer in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).7 These results should be considered in the design of future prospective studies of hypertension.

Should these blood pressure targets also be extended beyond breast cancer survivors to patients with active cancer? Notably, the ESC guidelines recommend more lenient hypertension treatment targets for patients during treatment with either curable cancer or metastatic disease. Arguably, metastatic HER2+ breast cancer patients should be treated like breast cancer “survivors” due to good prognosis and increased survival from the success of targeted anti-HER2 therapies. However, further research is needed regarding optimal blood pressure for all breast cancer patients, including those with metastatic disease or undergoing active cancer treatment, to reduce potential late-effects of cancer treatment related to elevated hypertension. Elevated blood pressure during breast cancer therapy has been associated with decreased left ventricular ejection fraction and global longitudinal strain, which increase the risk of CV late effects of cancer treatment.8 Optimizing blood pressure control during active breast cancer therapies can also lead to better long-term tolerability of cancer therapies and thus potentially improved treatment outcomes.

Another reason to control blood pressure in breast cancer survivors is the research demonstrating a relationship between hypertension and the development of breast cancer. Several observational studies have demonstrated an association between hypertension with risk of breast cancer in postmenopausal women. A large meta-analysis demonstrated a 15% higher risk of breast cancer in adults with hypertension.9 While the mechanisms driving associations between hypertension and breast cancer risk are not well established, it is plausible that hypertension may also increase risk of breast cancer recurrence. A study by Lorona et al10 found that women with hypertension treated with specific antihypertensive medications were at increased risk of breast cancer recurrence. Additional prospective studies are needed to understand the relationship between hypertension as well as cardiac comorbidities such as obesity and diabetes among breast cancer survivors and risk of cancer outcomes.

Although promotion of cardiac health and prevention of cardiotoxicity are emphasized in the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Guidelines, the primary focus is on lifestyle modifications such as weight management and exercise. Often clinicians are biased in lenient management of blood pressure in patients with cancer. However, as cancer survivors are living longer, guidelines for prevention of chronic diseases in this population must also adapt and change. Prospective research should be ongoing to determine whether optimal blood pressure targets vary for breast cancer patients along the cancer care continuum exposed to additional clinical risk factors such as left-sided radiation and new/specific anticancer therapies. Patients with cancer and a history of cancer should not be excluded from randomized clinical trials for hypertension. Education of patients, primary care physicians, oncologists, and cardiologists on the importance of optimizing blood pressure in cancer survivors is essential. Let us ensure that emphasizing a healthy lifestyle in breast cancer survivors incorporates optimal targets for blood pressure.

Funding support and author disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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