The further along women are from a diagnosis of breast cancer, the more likely they are to die from noncancer-related causes — most commonly heart disease, report US researchers.
The findings come from a population-based study of more than 750,000 US women diagnosed with breast cancer in the 15 years since the turn of the century.
The proportion of deaths attributable to noncancer causes rose from about 28% in the first year after diagnosis to just over 60% in women who survived for more than 10 years.
Notably, women who survived that long had a significantly increased risk of both heart disease and Alzheimer's disease compared with the general population.
The team says the findings "provide important insight into how breast cancer survivors should be counselled regarding future health risks."
The research, published online in the journal Cancer on December 16, was led by Mohamad Bassam Sonbol, MD, an oncologist from the Mayo Clinic in Phoenix, Arizona.
Speaking to Medscape Medical News, Sonbol said the risk of noncancer-related causes of death "is something we've been suspecting before…but now we're showing it objectively".
Explaining the findings, he said that some of the women who died of noncancer-related causes may have been cured of their disease whereas, for others, the breast cancer may have been converted into something like a chronic disease.
"For example, if it's a metastatic hormone positive breast cancer," he said, "some of the women are living for years and their cancer is under control with their systematic therapy, so that's when other causes are contributing to death."
Sonbol added that the high rates of death from heart diseases are likely related to chemotherapy- and radiotherapy-related toxicity.
"We know some chemotherapies such as anthracyclines and other chemotherapies that are more targeted therapy — so, the HER2-directed therapies — can affect the heart function and women can have problems in the long run," he said.
He added that many women, especially those who have a breast cancer diagnosis in the left breast, "can have long-term problems related to coronary artery disease and heart problems…when they get radiation as part of curative therapy".
All this means that survivorship clinics will have to work closely with primary care physicians for long-term follow-up and address issues other than breast cancer that may arise.
Sonbol said: "I do think that future follow-up will take our data into consideration to be vigilant about primary prevention and secondary prevention as well."
Although breast cancer remains the most common primary malignancy in women, and the second most common cause of cancer-related mortality, there have been dramatic improvements in survival rates over the last four decades.
This, the authors argue, means that women may live long enough after being diagnosed with breast cancer that noncancer-related causes may significantly affect their overall survival.
To investigate further, they used data from the Surveillance, Epidemiology, and End Results (SEER) program to conduct the largest population-based, long-term analysis of noncancer causes of death.
In all, they were able to access 18 SEER registers, covering approximately 28% of the US population diagnosed with breast cancer between 2000 and 2015. The women were followed up until death or until the end of 2015.
A total of 754,270 were included (37.5% aged 50-64 years; 38.6% aged over 64 years; 81% white; 54.8% married). Localized breast cancer was the most common diagnosis, in 61.2%.
During follow-up, 24.3% of the women died, at a mean age of 72.6 years. The largest proportion (46.2%) of deaths occurred within 1 to 5 years of the breast cancer diagnosis.
A further 16.3% occurred within 1 year of diagnosis, 27.6% occurred within 5 to 10 years of diagnosis, and 10% occurred after 10 years.
For the deaths within a year of diagnosis, 65.4% were from breast cancer, 6.7% from other cancers, and 27.9% from noncancer causes.
The most common noncancer causes of death were heart diseases (10%), followed by cerebrovascular diseases (2.4%), and chronic obstructive pulmonary disease (COPD) in 2%.
Compared with the general population, women with breast cancer had a significantly higher risk of death from septicemia, and from other infectious and parasitic diseases, in the first year after diagnosis, at standardized mortality ratios (SMRs) of 1.21 and 1.49, respectively.
For deaths 1 to 5 years after diagnosis, 58.6% of the women died from breast cancer, 8.9% from other cancers, and 32.4% from noncancer causes.
Heart disease was again the most common noncancer cause of death, in 11.2%, followed by cerebrovascular deaths in 2.7%, COPD in 3%, and Alzheimer's disease in 1.6%.
In women who died 5 to 10 years after breast cancer diagnosis, breast cancer was the cause of death in 38.2%, followed by other cancers in 13.4%, and noncancer causes in 48.4%.
Heart diseases were the most common noncancer cause of death (15.7%), followed by cerebrovascular diseases and COPD (both 3.9%), and Alzheimer's disease (3.4%).
Compared with the general population, women with breast cancer were significantly more likely to die from chronic liver diseases and cirrhosis within 5 to 10 years of diagnosis, at an SMR 1.23, and from in situ or benign neoplasms, at an SMR of 1.33.
Finally, 23.6% of women who died more than 10 years after breast cancer diagnosis died of the disease, while 15.5% died from other cancers, and 60.9% died from noncancer causes.
As in the other groups, heart disease was the most common noncancer cause of death (19.3%), followed by Alzheimer's disease (5.3%), cerebrovascular diseases (5.2%), and COPD (4.9%).
Women who died more than 10 years after a breast cancer diagnosis were significantly more likely to die of Alzheimer's disease than the general population, at an SMR of 1.21, and heart diseases, at an SMR of 1.06.
The team also notes that, among women diagnosed with breast cancer at age 50 to 64 years, the risk of death from suicide was significantly higher compared with the general population more than 10 years after diagnosis, at an SMR of 1.70.
No specific funding was disclosed. The authors have disclosed no relevant financial relationships.
Cancer. Published online December 16, 2019. Abstract
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Cite this: Heart Disease Biggest Killer Among Breast Cancer Survivors - Medscape - Dec 23, 2019.