Herceptin (chemical name: trastuzumab) is a targeted therapy used to treat HER2-positive breast cancer. Heart problems, including heart muscle damage and heart failure, are possible serious side effects of Herceptin.
Most of the studies done on heart problems caused by Herceptin have been done in women age 65 and older. Still, most women diagnosed with breast cancer are younger than 65. So a group of researchers wanted to know if younger women treated with Herceptin also had a higher risk of heart problems.
Their study suggests that any woman treated with Herceptin -- no matter how old she is -- has a higher risk of heart problems and should be monitored.
The study was published online on April 18, 2016 by the Journal of Clinical Oncology. Read the abstract of “Breast Cancer Therapy-Related Cardiac Dysfunction in Adult Women Treated in Routine Clinical Practice: A Population-Based Cohort Study.”
HER2-positive breast cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive and harder to treat than HER2-negative breast cancers.
Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals. Herceptin, which is given intravenously, is approved by the U.S. Food and Drug Administration (FDA) to:
- treat advanced-stage, HER2-positive breast cancers
- lower the risk of recurrence (the cancer coming back) of early-stage, HER2-positive breast cancers with a high risk of recurrence
A newer form of Herceptin, Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk), can be given as an injection.
Herceptin is often given at the same time as or right after chemotherapy. In many cases, the chemotherapy regimen may include an anthracycline.
Anthracycline chemotherapy medicines are:
- Adriamycin (chemical name: doxorubicin)
- Ellence (chemical name: epirubicin)
- Doxil (chemical name: liposomal doxorubicin)
- daunorubicin (brand names: Cerubidine, DaunoXome)
- mitoxantrone (brand name: Novantrone)
Anthracyclines work by damaging cancer cells’ genes and interfering with their reproduction. Anthracyclines also can cause heart problems.
To do the study, the researchers identified women diagnosed with stage I to stage III HER2-positive breast cancer in Ontario, Canada, who received Herceptin and chemotherapy within 1 year of diagnosis between 2007 and 2012. Of the 18,540 women in the study, 79% were younger than 65.
"Breast cancer is the most common type of cancer in Canadian women, and treatments for early-stage breast cancer have proven highly effective," said the study's lead author Dr. Dinesh Thavendiranathan, of the Ted Rogers Centre for Heart Research. "Unfortunately, some of the drugs used for the treatment of breast cancer are associated with injury to the heart and heart dysfunction. If you look at the clinical trials which were used to approve these drugs, the risk of heart dysfunction was not very high. But when these drugs are used in clinical practice, they're used on a broader cohort of patients, and some of these patients had a higher risk of heart dysfunction."
The researchers grouped the women according to the type of treatment they received:
- 54.8% had anthracycline chemotherapy without Herceptin (10,160 women)
- 4.5% had Herceptin with non-anthracycline chemotherapy (832 women)
- 17.5% had anthracycline chemotherapy followed by Herceptin, called sequential therapy (3,250 women)
- 23.2% had non-anthracycline chemotherapy without Herceptin, called other chemotherapy (4,298 women)
Also, 78.5% of the women received radiation therapy after surgery.
The researchers then looked to see if any women had a major cardiac event during the approximately 3 years of follow-up. Major cardiac events include heart attacks and strokes or dying from congestive heart failure.
The researchers also compared the rate of heart problems in the treatment groups with the rate of heart problems of a control group of 92,700 women of similar ages who hadn’t been diagnosed with breast cancer.
In general, women who were treated with anthracycline chemotherapy without Herceptin or sequential therapy:
- were younger
- had cancer that was a higher stage
- had fewer cardiovascular risk factors
- were less likely to have been diagnosed with heart disease before starting breast cancer treatment
After 3 years of follow-up:
- 3.08% of women diagnosed with breast cancer had had a major cardiac event
- 0.96% of women in the control group had had a major cardiac event
After 5 years of follow-up, rates of major cardiac events were:
- 4.13% for women diagnosed with breast cancer
- 1.68% for women in the control group
Women who were younger than 65 were less likely to have a major cardiac event than older women.
Rates of major cardiac events by treatment group were:
- 6.6% for sequential therapy
- 5.1% for Herceptin with non-anthracycline chemotherapy
- 2.0% for anthracycline chemotherapy without Herceptin
- 3.2% for other chemotherapy
Compared to women treated with other chemotherapy, women treated with sequential therapy were nearly 4 times more likely to have heart problems.
"Trastuzumab regimens for breast cancer have greatly improved survival of breast cancer patients," said Dr. Douglas Lee, of the Cardiovascular Research Program at the Institute for Clinical Evaluative Sciences and the other paper author. "Although the absolute risk was higher in older patients, younger patients were also at significant risk of major cardiac events with cancer treatment regimens. These results suggest the need for equal consideration of surveillance for breast cancer therapy-related cardiac dysfunction in younger patients who have until now been considered at lower risk for cardiotoxicity from these drugs."
If you’ve been diagnosed with early-stage, HER2-positive breast cancer, you may want to talk to your doctor about this study if Herceptin and/or anthracycline chemotherapy will be part of your treatment plan. No matter how old you are, it’s a good idea to ask your doctor about your personal risk of treatment-related heart problems and whether or not visiting a cardiologist before treatment starts is a good idea for you. The cardiologist can evaluate your heart function and decide if you’re at risk of developing heart disease or heart failure from breast cancer treatment. You also may want to ask your oncologist how your heart function will be monitored during treatment.
Together, you can decide on the best treatment plan for your unique situation.
Editor’s Note: This article was updated with information about Herceptin Hylecta, which the FDA approved on Feb. 28, 2019.
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