A Cardiologist Highlights the Interwoven Elements of CVD and Breast Cancer

Patients with more advanced breast cancer at diagnosis are more likely to have prevalent cardiovascular disease (CVD), and additional data suggest that further drilling down into specific variables including type of heart disease, newer as well as traditional risk factors, and treatments for CVD are critical next steps in teasing out the association between the two conditions, according to Amy M. Ahnert, MD.

When investigators utilized a propensity score–matched, multivariable-adjusted model they found that patients who had locally advanced or metastatic breast cancer at diagnosis had statistically significantly increased odds of experiencing prevalent CVD (OR, 1.10; 95% CI, 1.03-1.17; P = .007); this included those with hormone receptor (HR)–positive disease (OR, 1.11; 95% CI, 1.03-1.19; P = .006) but not HR-negative disease (OR, 1.02; 95% CI, 0.86-1.21; P = .83).1

“This is opening up my mind to say maybe it’s a 2-way street. It may not be just linear that breast cancer treatments increase [the] risk of CVD, but maybe CVD also influences breast cancer and breast cancer outcomes. We’re going to need more definitive studies to fully understand [this], but [there] is proof of concept that the diseases are related,” Ahnert said. “One of the most significant parts of this [study] is it shows us the importance of having a multidisciplinary, comprehensive approach when we’re looking at patients and trying to understand their illnesses/diseases [as well as] how to treat them and how to prevent [the diseases].”

Furthermore, when examining patients with all receptor subtypes, data revealed that the ORs were directionally consistent among those with locally advanced (OR, 1.09; 95% CI, 1.02-1.17; P = .02) and metastatic (OR, 1.20; 95% CI, 0.94-1.54; P = .15) disease.

In the interview, Ahnert detailed the significance of findings from the study on the link between CVD and breast cancer as well as needed next steps to further define the connection. Ahnert is the director of the Women’s Heart Program at Morristown Medical Center and a cardiologist at Atlantic Health System in New Jersey.

OncLive: What emerging evidence suggests that CVD may play a direct causal role in the etiology and progression of breast cancer?

Ahnert: This study is very eye opening and gives us yet another study to demonstrate the links and the interconnectedness between CVD and cancer, breast cancer in particular. For a long time, we’ve known about the shared risk factors between CVD and breast cancer, but we haven’t been able to go the next step to say whether one is causing the other or vice versa. If you find a patient who has CVD and they happen to be a smoker, they’re going to be more likely to have breast cancer because that risk factor is something that increases their risk for both diseases. I always have the shared risk factors in my mind; there’s a Venn diagram where 1 circle has cardiovascular risks and the other circle has breast cancer risks, and the 2 circles intersect in the middle.

Interestingly, [previous] mouse models and animal models have started to suggest that it’s not just [a] relationship, but that CVD may increase the development or the worsening of cancer, breast cancer being one type.

This study [looking at individuals] is very intriguing and hypothesis generating, [but] it’s not confirmative. There is the suggestion that not only is there a link, but CVD may worsen a woman’s breast cancer and having a more advanced type of breast cancer. Part of the reason that we can’t say whether this is a confirmatory study is because of its design. It’s a great study and a large one, but it’s a case control study which relies upon retrospectively pulling data from a database. Anytime we do a study like that and go back retrospectively, there’s potential for flaws. There are potential confounders such as smoking status [or] whether patients had hormone replacement therapy. There are still questions [so] we can’t yet make that leap and say that we know for sure that CVD [can] cause breast cancer, but it’s another study and a well-designed, large study, supporting that we need more information.

How are the study findings that individuals with more advanced breast cancer at diagnosis are more likely to have prevalent CVD significant?

What’s most significant is it’s a study that undoubtedly demonstrates the interrelatedness and interconnectedness [between CVD and breast cancer]. In my practice—I’m the director of a woman’s heart program and have spent my career focused on heart disease in women—one of the biggest mistakes that the health care industry and healthcare providers make is trying to treat patients in a vacuum. Our healthcare industry is very siloed—you see your cardiologist, then endocrinologist, breast health surgeon, and OBGYN, and we need to think bigger. We have to cast a wider net, and we have to look at the whole patient; that’s the way I approach patients. I want to make sure I’m understanding all the different facets of their history, risk factors, illnesses, and family history.

We have known for a long time that cancer treatments—in particular radiation, chemotherapy, and other types of newer immune modulator therapy—can increase the risk of CVD and that has spawned this whole field of cardio-oncology. The good news is that we’re starting to understand that these specialties need to interact, [because] we’ve thought that [this relationship] probably [trends] in one direction, that it’s cancer treatments [that] may then cause toxicity to the heart.

The study found that the association between having locally advanced or metastatic breast cancer at diagnosis and increased odds of prevalent CVD was statistically significant in those with HR-positive disease but not in patients with HR-negative disease. Why might that be?

That is a big question mark; even when you read the study, the authors are left with a question mark and qualify that finding by saying that their study was underpowered to look for statistically significant differences in HR positivity and HR negativity. [Findings showed] that there is a signal that there may be subtypes of breast cancer that are more prone to [have prevalent CVD]. We have to take a bit of pause and have caution when we’re interpreting that because anytime you design a study, before you ask the question you have to make sure that the study is powered to be able to differentiate whether it’s truly significant from a statistical standpoint.

However, there are some theories that even the authors allude to. How does this connection even happen? Why would CVD increase the risk of breast cancer or worsening of breast cancer? One of the theories that they talk about is whether having CVD leads to an immune deficiency state, and that then the immune system’s reaction may, in some way, dysregulate and increase the risk of breast cancer and worsening of breast cancer. I don’t know that we fully understand if this is true, and if it is true, what the exact correlation is, but that’s where future studies will be important in terms of understanding whether CVD truly increases the risk of breast cancer and specific types of breast cancer. Then, more importantly, how does that translate into how we may have earlier detection screening and/or treatments for these patients? We’re left with uncertainty.

What are important next steps for this research on the link between CVD and breast cancer?

Research starts with laboratory type proof of concept [work], and then goes to large population studies, but ultimately the proof needs to be in prospective trials. Having well-designed trials [is key]. The other [limitation with this] study, because it was a database study, is there are questions [remaining]. What was the type of CVD? CVD is a big umbrella, it’s a very large encompassing term, and there are many different types of CVD—there’s congestive heart failure, coronary artery disease, arrhythmias, [and] valvular heart disease. When we lump it all [together] in one bucket, that’s a little challenging for me to say, ‘Is it all types? Is it one specific type? Is it CVD that’s been more severe? Is it CVD that’s been more acute, more recent?’

Being able to track those very specific variables of what type of heart disease it is and looking at the different variables that the patient may have in terms of risk factors and treatments of CVD [is crucial]. How do the treatments of CVD relate to this possible cause of breast cancer? Just like how breast cancer treatments can worsen CVD, what about the treatments for CVD, is it the disease itself or is it the treatments for the disease that affect outcomes? Do the treatments for the disease help or hurt? There are some theories saying some of the treatments for CVD [such as] statins may improve outcomes in patients with breast cancer.

Designing a clear trial where we can better prove cause and effect would be one [important future action], and also making sure that the trial is inclusive. The other limitation of the study was that it predominantly included White women. We want to make sure we have a more inclusive patient population, so that we can feel comfortable with potentially extrapolating this type of information, not only to White women, but [to all] women. That’s the next step and where we’re headed; that’s going to then give us the final chapter in the book of being able to better understand the links between heart disease and breast cancer, the cause, the 2-way street, and what to do about it.

Reference

1. Angelov I, Haas AM, Brock E, et al. Cardiovascular disease and breast cancer stage at diagnosis. JAMA Netw Open. 2025;8(1):e2452890. doi:10.1001/jamanetworkopen.2024.52890