Breast cancer is the most common type of cancer among women. Treatment and survival have advanced significantly in recent years. Understanding the long-term risks associated with breast cancer has therefore become even more crucial. A new study shows that women still have an increased risk of developing leukaemia despite the improved treatment. Whether this increased risk results from the treatment of breast cancer itself or a generally increased risk of cancer among women is uncertain.
Recent advancements in treating people with breast cancer have improved the survival rate. Diagnostic techniques and radiation therapy technologies have become more precise, molecular diagnostics have enabled the characteristics of individual tumours to be identified, and new therapies and immunotherapies have revolutionised the treatment itself. These advancements have increased survival, with 90% of those with breast cancer still alive 5 years after diagnosis.
“Specifically, women who survive breast cancer have previously been shown to have an increased risk of developing new types of cancer. In our new study, we wanted to investigate whether new treatment approaches had changed this situation, but the numbers suggest that the risk is still increased, especially for acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). Long-term attention to these diseases is therefore still needed, whether they result from the treatment itself or because breast cancer and leukaemia have common causes,” explains lead author Cathrine Fonnesbech Hjorth, Postdoctoral Fellow at the Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University.
Tripling with chemotherapy
The study analysed data from Denmark’s health registries, collecting a nationwide cohort of more than 100,000 women diagnosed with non-metastatic breast cancer between 1980 and 2017. The women who had survived were compared with the general population to assess their risk of developing leukaemia types such as AML, ALL and CLL.
“The results revealed several important aspects contributing to understanding the possible associations. One key finding was that the risk of AML, CML and ALL is still significantly increased among women who have survived breast cancer. The study showed that these women had a 65% higher risk of developing AML than the general population, and the risk for ALL and CML was doubled,” says Cathrine Fonnesbech Hjorth.
The risk was especially high among women who had received chemotherapy as part of their breast cancer treatment. For this group, the risk of AML was more than tripled compared with the general population and the risk of CML was more than doubled.
“This finding underscores the potential role of chemotherapy in developing secondary types of cancer. So even though chemotherapy is an essential and effective treatment for breast cancer, it can also increase the risk of developing other types of cancer later in life. Note that women who had not undergone chemotherapy as part of breast cancer treatment also had an increased risk of AML,” explains Cathrine Fonnesbech Hjorth. “This suggests that there may be some shared risk factors with breast cancer.”
Importance of medical attention
This does not mean that all breast cancer survivors have a high risk of developing these types of leukaemia. Many factors can affect a person’s risk of developing cancer, and chemotherapy is just one.
“In contrast to the increased risks for AML and ALL, we initially found that breast cancer survivors had a reduced risk of CLL,” says Cathrine Fonnesbech Hjorth.
However, when the researchers further examined the numbers, they discovered a tripling of the risk of developing CLL within the first 6 months after the breast cancer diagnosis.
“This observation is likely attributable to surveillance bias, meaning that the intensified diagnostic investigations during the diagnosis and treatment of breast cancer lead to earlier detection of CLL. Because this type of leukaemia is detected so early, the long-term risk for breast cancer survivors is reduced,” explains Cathrine Fonnesbech Hjorth.
Cathrine Fonnesbech Hjorth highlights the importance of medical attention as a key conclusion:
“After someone has breast cancer, healthcare professionals should be aware of the risk of recurrence in the years that follow. Although this will fortunately only affect a few women, healthcare professionals should also be mindful of the risk of developing other types of cancer,” continues Cathrine Fonnesbech Hjorth.
Possible shared risk factors
Despite the new important knowledge about the long-term effects of breast cancer treatment, this study also highlights the need for continued research to identify the increased risk factors for leukaemia and thus minimise the future risk of secondary types of cancer such as AML.
“Other studies show that certain chemotherapy agents, such as cyclophosphamide, are particularly associated with an increased risk of AML 5–7 years after the breast cancer diagnosis, which aligns with the time periods we found in our study. However, further research is needed to understand the underlying mechanisms and improve care for breast cancer survivors,” explains Cathrine Fonnesbech Hjorth.
The researchers cannot conclusively determine from the study what proportion of the increased risk to attribute to chemotherapy versus other mechanisms.
“Further research is necessary to elucidate the complex interaction between breast cancer, treatment and the development of various types of leukaemia,” concludes Cathrine Fonnesbech Hjorth.
