Get notified of page updates

Study: Potential genetic basis for breast cancer survivors who develop therapy-related leukemia

Printer Friendly Page Read the Original Article

Contents

At a glance In-depth
Findings     Limitations             
Questions for your doctor Resources     


STUDY AT A GLANCE

What is this study is about?

This study explores whether inherited mutations in genes that increase cancer risk are risk factors for developing leukemia after therapy. Therapy-related leukemia is a rare, late complication that develops in less than 1% of breast cancer patients who receive cytotoxic cancer therapies such as chemotherapy or radiation.

Why is this study important?

Although treatment-related leukemia is rare, the majority of people who develop the disease are breast cancer survivors. This is a rare complication, but the number of therapy-related leukemia cases will likely increase as more patients survive breast cancer. A greater understanding is needed of who is at risk for the development of therapy-related leukemia, so that better detection and prevention of this potentially lethal complication can be established. In a large study published in the Journal of Clinical Oncology in 2014, among 20,000 patients who had I to III breast cancers treated with various therapies, only 50 survivors developed leukemia after follow-up periods ranging from 6 months to 10 years (median follow-up was about 5 years).

What did this study find?  

Of the 47 breast cancer survivors who received cytotoxic therapy and developed therapy-related leukemia and had available for mutation testing, about 20% had a mutation in a cancer-risk increasing gene:

  • 3 patients had mutations in
  • 2 patients had mutations in
  • 3 patients had mutations in
  • 1 patient had a mutation in
  • 1 patient had a mutation in

Limitations:

This study is relatively small, so the researchers cannot see potential differences in therapy-related leukemia between people with mutations in different genes (for example, mutation carriers compared to mutation carriers). Because the group of patients studied was small, individuals with different types of breast cancers and different treatments were grouped together, making it harder to clearly identify groups at risk. 

What does this mean for me?

The data from this research indicates that a in a gene that increases cancer risk may lead to susceptibility to therapy-related leukemia, however, more work needs to be done to fully understand this finding. It is important to remember that treatment-related leukemias are rare. If you are a , , , , or mutation carrier, and you have received a cytotoxic therapy such as chemotherapy or radiation, you may wish to discuss this risk for treatment-related leukemia with your health care provider. If you are a breast cancer survivor who developed therapy-related leukemia and you are unsure if you are a carrier of a mutation that increases cancer risk, talk to your health care provider about the possibility of genetic counseling and/or genetic testing to see if you carry such a mutation. Although this research focused on breast cancer survivors, these findings may also be relevant for people with inherited mutations who have received chemotherapy for other types of cancers. 

Posted 1/26/15

References

Churpek JE, Marquez R, Neistadt B, et al. “Inherited Mutations in Cancer Susceptibility Genes are Common Among Survivors of Breast Cancer Who Develop Therapy-Related Leukemia.” Cancer. Published online first on December 7, 2015.  

Wolff AC, Blackford AL, Visvanathan K, et al. “Risk of Marrow Neoplasms After Breast Cancer Therapy: The National Comprehensive Cancer Network Experience.” Journal of Clinical Oncology (2015), 33(4): 340-348.  

This article is relevant for:

Breast cancer patients who have an inherited mutation and breast cancer patients who developed leukemia after treatment for breast cancer.

This article is also relevant for:

men with breast cancer

people with triple negative breast cancer

people with ER/PR + cancer

people with Her2-positive cancer

people with a genetic mutation linked to cancer risk

people with breast cancer

Be part of XRAY:

IN DEPTH REVIEW OF RESEARCH

Study background:

Chemotherapy and radiation can help patients defeat their cancers, but many complications can occur during and after treatment. Breast cancer survivors are a growing population in the United States, and while they have survived their disease, they often face long-term complications and side effects. One example is developing therapy-related leukemia, a rare but potentially lethal complication of some cancer treatments.

In December 2015, Jane E. Churpek and colleagues at the University of Chicago published a study in Cancer that looked to see if inherited genetic mutations are linked to the development of therapy-related leukemia. Researchers and clinicians believe that therapy-related leukemia develops from cytotoxic therapies such as chemotherapy and radiation that cause mutations in blood cell , but they do not understand why this happens to certain patients and not to others. Some breast cancer patients who are treated with surgery alone develop leukemia—this raises the possibility that some cancers that are identified as therapy-related leukemia are actually second primary cancers caused by inherited mutations in genes that are associated with increased cancer risk.

Currently, no study has looked at the possibility of increased risk for therapy-related leukemia in people who carry mutations in genes that increase cancer risk.

What researchers of this study wanted to know:

Are risk-increasing gene mutations involved in the development of therapy-related leukemia in breast cancer survivors?

Population(s) looked at in the study:

The study included 88 female breast cancer survivors who received cytotoxic therapy (chemotherapy and/or radiation) after their primary breast cancer diagnosis, and later developed therapy-related leukemia. Family history and/or samples for genetic testing were available for patients in the study, and genetic testing was done whenever possible.

Study findings: 

  1. Of the 47 breast cancer survivors who received cytotoxic therapy and developed therapy-related leukemia and had available for mutation testing, about 20% had a mutation in a cancer-risk increasing gene:
    • 3 patients had mutations in
    • 2 patients had mutations in
    • 3 patients had mutations in
    • 1 patient had a mutation in
    • 1 patient had a mutation in
  2. About 20% of the study population had an additional primary cancer and therapy-related leukemia.
  3. Of the 70 patients for whom researchers had family histories, about 60% had a close relative who had breast, ovarian, or pancreatic cancer.

Limitations:

This study is relatively small, so the researchers cannot see potential differences in therapy-related leukemia between people with mutations in different genes (for example, mutation carriers compared to mutation carriers). Because the group of patients studied was small, individuals with different types of breast cancers and different treatments were grouped together, making it harder to clearly identify groups at risk. Additionally, while this study shows that about 1 in 5 women who developed treatment-related leukemia after cytotoxic therapy for breast cancer had a mutation in a gene known to increase cancer risk, this group was not compared to mutation carriers who were treated with cytotoxic therapy but did not develop therapy-related leukemia; doing so would have provided additional information.

Conclusions:

This study uncovers a potential link between having a mutation in a gene that increases cancer risk and susceptibility to developing therapy-related leukemia after receiving cytotoxic therapy for breast cancer. More work needs to be done to fully understand this, and to learn how therapy-related leukemia develops in these women. In the meantime, breast cancer survivors with mutations in or other genes that increase cancer risk should keep in mind that treatment-related leukemia is relatively rare, occurring in fewer than 1% of breast cancer survivors. Notably, 3 of the 47 patients with treatment-associated leukemia had inherited mutations in , which is already associated with increased risk for leukemia. While this study raises the possibility of a link that should be explored further through larger studies, the results alone cannot conclude that mutation carriers are more likely to develop therapy-related leukemia than non-mutation carriers. People concerned about their risk of leukemia after treatment should discuss their risk with their health care provider.

Posted 1/26/15

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Should I have genetic testing for an ?
  • What are the long term risks of chemotherapy?
  • Are there any other treatment options that would be as effective as chemotherapy for treating my cancer?

Peer Support
Peer Support

FORCE offers many peer support programs for people with inherited mutations. 

Updated: 08/06/2022

Find Experts
Find Experts

The following resources can help you locate a genetics expert near you or via telehealth.

Finding genetics experts

  • The National Society of Genetic Counselors website has a search tool for finding a genetic counselor by specialty and location or via telehealth. 
  • InformedDNA is a network of board-certified genetic counselors providing this service by telephone. They can also help you find a qualified expert in your area for face-to-face genetic counseling if that is your preference. 
  • Gene-Screen is a third-party genetic counseling group that can help educate, support and order testing for patients and their families. 
  • JScreen is a national program from Emory University that provides low-cost at-home genetic counseling and testing with financial assistance available.
  • Grey Genetics provides access to genetic counselors who offer genetic counseling by telephone. 
  • The Genetic Support Foundation offers genetic counseling with board-certified genetic counselors. 

Related experts

Genetics clinics

Other ways to find experts

Updated: 07/21/2023

Who covered this study?

Latinos Health

Breast cancer survivors at risk of getting leukemia: study This article rates 3.0 out of 5 stars

How we rated the media

Back to XRAY Home