For the one in eight women who will be diagnosed with breast cancer in their lifetime, advancements in early diagnosis and personalized therapies are a light at the end of the tunnel.
But despite remarkable advances in cancer therapeutics, many patients will still face a secondary health scare related to their cancer diagnosis – the threat that certain treatments for breast cancer, such as chemotherapy and radiation therapy, may cause damage to the heart.
“Cancer therapies have the potential to cause damage to the heart, which we term as cardiotoxicity,” says Bonnie Ky, MD, assistant professor of Medicine and Epidemiology at Penn and an expert in cardio-oncology, a field that focuses on how cancer and its associated therapies can impact the heart. “In certain cases, as a result of cancer therapy, the heart muscle is weakened and unable to pump enough blood to supply the body with essential oxygen and nutrients. Furthermore, cancer patients, even prior to therapy, can have a number of cardiovascular diseases that compound treatment for each issue.”
She says that cardiotoxicity associated with cancer therapy is a growing problem, magnified by the lack of ability to identify patients at increased risk for cardiotoxicity, both before and early in therapy.
To help prevent lasting damage to the heart, doctors and researchers have been working at developing newer chemotherapeutic agents that may cause less damage to heart tissue. In addition to this area of research, doctors at Penn Medicine are also involved in research that aims to pinpoint certain biomarkers and other diagnostic measures, such as the use of echocardiograms, which may allow doctors to detect cardiotoxicity in breast cancer patients early on in their treatment.
"In patients with breast cancer treated with the specific chemotherapeutic agents anthracyclines, taxanes and trastuzumab, measuring a combination of blood biomarkers early after treatment may help to identify subsequent cardiac dysfunction," says Dr. Ky. “This combination of agents has been highly successful in improving survival in patients with HER2-positive breast cancer. Unfortunately, some data suggest that patients treated with this combination of agents have up to a seven fold increased risk of heart failure or cardiomyopathy as a result of their treatment.”
Ky and colleagues at Massachusetts General Hospital and Harvard Medical School, MD Anderson, and McGill University recently published a study that measured eight potentially relevant biomarkers for cardiotoxity in patients treated for HER2-positive breast cancer.
They measured the markers in 78 patients undergoing chemotherapy with two specific agents -- doxorubicin and trastuzumab -- and assessed cardiotoxicity every three months for up to 15 months.
A number of biomarkers showed an increase from baseline to three months, but cardiotoxicity was associated only with changes in ultrasensitive troponin I (a protein that is released when the heart muscle has been damaged) and myeloperoxidase (an inflammatory and oxidant stress enzyme).
Dr. Ky and her colleagues also found that in patients with the largest changes in both the biomarkers, the risk of cardiotoxicity was as high as 46 percent. Overall, the results suggest that early interval changes in individual and multiple biomarkers may be helpful in predicting adverse cardiovascular outcomes with doxorubicin and trastuzumab.
The results still need validation before widespread application in the clinical setting. To that end, Dr. Ky has been recently been awarded a five year multi-million dollar grant from the National Heart, Lung, and Blood Institute ( NHLBI) to study the mechanisms and predictors of doxorubicin and trastuzumab cardiotoxicity. She is also involved with colleagues from the National Cancer Institute (NCI) to study these and other diagnostic measures in additional cancer patient groups.
Dr. Ky notes that the field of cardio-oncology is still growing as cardiotoxicity is quite broad, especially with the growth and development of new cancer drugs. “This creates a critical need for specialists in both oncology and cardiology to come together in the care of patients receiving cancer therapy to improve upon the overall oncologic and cardiovascular health of each individual patient.”
To address this need, Penn Medicine has a specialized program in cardio-oncology that combines the expertise of Dr. Ky and Joseph Carver, MD, clinical professor of Medicine in Cardiology and chief of staff at the Abramson Cancer Center (ACC). Together, Dr. Ky and Dr. Carver team with clinicians at the ACC to help patients explore the full range of treatment options for their cardiac and cancer care.