Feature

Mortality risk after breast cancer greater among those who survived childhood cancers

Photo of Chaya Moskowitz 2018
Chaya S. Moskowitz

Female childhood cancer survivors who developed breast cancer later in life appeared more than twice as likely to die of any cause than women with breast cancer who never had a childhood malignancy, according to study results.

“Breast cancer is one of the most frequent subsequent malignant neoplasms among female childhood cancer survivors, and there have been many studies that have characterized and evaluated the risk for breast cancer in this patient population,” study author Chaya S. Moskowitz, PhD, associate attending biostatistician at Memorial Sloan Kettering Cancer Center, told HemOnc Today.

In contrast, much less is known about health outcomes for childhood cancer survivors after they are diagnosed with breast cancer.

Moskowitz and colleagues estimated risks for all-cause and breast cancer-specific mortality among 274 5-year childhood cancer survivors with invasive or in situ breast cancer. Median age at first breast cancer diagnosis was 38 years (range, 20-58) and median follow-up after diagnosis was 8 years.

Researchers matched survivors 1:5 with a control group of individuals with breast cancer based on race, sex, disease stage, age and calendar year of diagnosis.

Ninety-two (33.5%) of the childhood survivors died, including 49 (17.8%) who died of breast cancer.

Childhood cancer survivors demonstrated higher 10-year cumulative incidence of all-cause mortality (33% vs. 16%) and breast cancer-specific mortality (20% vs. 13%).

Childhood cancer survivors demonstrated greater risk for death of any cause after breast cancer diagnosis than controls (HR = 2.2; 95% CI, 1.7-3). The mortality risk for this group remained higher after adjustments for breast cancer treatment with radiation therapy (HR = 2.2; 95% CI, 1.7-3.1), chemotherapy (HR = 2.3; 95% CI, 1.8-3.2) or both (HR = 2.4; 95% CI, 1.7-3.2).

Risk for death after diagnosis of early-stage breast cancer — defined as stage 0, I or II — also was higher among childhood cancer survivors (HR = 2.6; 95% CI, 1.9-3.7). However, breast cancer-specific mortality was not significantly higher among childhood cancer survivors than controls (HR = 1.4; 95% CI, 0.9-2).

The most common causes of death other than breast cancer among childhood cancer survivors included subsequent neoplasms (44%) and cardiovascular disease (26%).

HemOnc Today spoke with Moskowitz about the study, why the mortality risk after breast cancer diagnosis is so much higher for women who survived childhood cancer, and the potential benefit of more intense screening or other strategies to reduce mortality among this group.

 

Question: Why are female childhood cancer survivors at elevated risk for breast cancer later in life?

Answer: There are multiple risk factors for breast cancer among female childhood cancer survivors; however, treatment with chest radiotherapy is one of the most notable. Women treated with chest radiotherapy for childhood cancer have one of the highest risks for breast cancer among any population. To a lesser degree, breast cancer also is elevated among survivors of leukemia or sarcoma who are not treated with chest radiation. There are multiple treatment exposures and potential genetic factors that contribute to the risk.

 

Q: How did you conduct the study?

A: We used data from an existing cohort. We studied women with breast cancer included in the Childhood Cancer Survivor Study. We compared these women with other women in the general population who were diagnosed with breast cancer and did not have a previous history of cancer. We gathered this information from the SEER database.

 

Q: What did you find?

A: Childhood cancer survivors had a significantly elevated risk for dying after a breast cancer diagnosis than women with de novo breast cancer. Their risk for dying was double, even among childhood cancer survivors diagnosed with early-stage breast cancer.

We then looked at the causes of death. The risk for dying of breast cancer was slightly elevated among childhood cancer survivors, but the risk for dying of causes other than breast cancer was markedly different. Childhood cancer survivors had a more than fivefold increased risk for dying of other health-related causes after breast cancer, and this difference persisted when we looked at women diagnosed with early-stage breast cancer. Childhood cancer survivors diagnosed with early-stage disease had a more than sixfold increased risk for dying of health-related causes other than breast cancer compared with women diagnosed with early-stage de novo breast cancer. The difference was even higher when we looked at women diagnosed with breast cancer at age 40 years or older. We estimated that these childhood cancer survivors had a sevenfold increased risk for dying of other health-related causes. We also found a significantly elevated risk for a second breast cancer diagnosis among childhood cancer survivors.

Q: Why is the mortality risk after a breast cancer diagnosis so much higher for those who had childhood cancer?

A: A key contributing factor is that childhood cancer therapies are associated with multiple late effects, including breast cancer. Other cancers, cardiovascular disease and pulmonary complications are other late effects that childhood cancer survivors experience. In fact, these were some of the other causes of death that we observed.

 

Q: What are the implications of these findings?

A: A key take-home message is that childhood cancer survivors who are diagnosed with breast cancer need to be evaluated and followed closely for cardiac problems, for second cancers and for pulmonary complications. Oncologists who are treating women with breast cancer after a childhood cancer need to be aware of these elevated risks. Even when childhood cancer survivors are diagnosed with early-stage breast cancer, they still have an elevated risk for death.

 

Q: What must be addressed in future research?

A: Further work is needed to determine if some of the elevated mortality is due to limited therapeutic options available to childhood cancer survivors or whether it is possible to implement strategies at the time of the breast cancer diagnosis that will reduce the mortality risk from other causes.

 

Q: How important is intense screening for childhood cancer survivors? Could more risk-reducing strategies be implemented at the time of breast cancer diagnosis to try to reduce mortality?

A: If they are not already being actively followed by clinicians who are familiar with their unique risks, then a breast cancer diagnosis may be an opportunity to get such clinicians involved. Similarly, if a childhood cancer survivor is not already actively engaged in routine cardiac surveillance, the breast cancer diagnosis presents an opportunity to change this. Guidelines recommend routine cardiac surveillance for childhood cancer survivors at risk for cardiac complications, but we do not know if the childhood cancer survivors we studied here were actively engaged in this type of screening. It also is possible that a breast cancer diagnosis presents an opportunity to counsel women about adopting healthier lifestyles. There are several possibilities that may help and are worth further study. – by Jennifer Southall

 

Reference:

Moskowitz, CS. Abstract 10511. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

 

For more information:

Chaya S. Moskowitz, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: moskowc1@mskcc.org.

Disclosure: Moskowitz reports no relevant financial disclosures.

Photo of Chaya Moskowitz 2018
Chaya S. Moskowitz

Female childhood cancer survivors who developed breast cancer later in life appeared more than twice as likely to die of any cause than women with breast cancer who never had a childhood malignancy, according to study results.

“Breast cancer is one of the most frequent subsequent malignant neoplasms among female childhood cancer survivors, and there have been many studies that have characterized and evaluated the risk for breast cancer in this patient population,” study author Chaya S. Moskowitz, PhD, associate attending biostatistician at Memorial Sloan Kettering Cancer Center, told HemOnc Today.

In contrast, much less is known about health outcomes for childhood cancer survivors after they are diagnosed with breast cancer.

Moskowitz and colleagues estimated risks for all-cause and breast cancer-specific mortality among 274 5-year childhood cancer survivors with invasive or in situ breast cancer. Median age at first breast cancer diagnosis was 38 years (range, 20-58) and median follow-up after diagnosis was 8 years.

Researchers matched survivors 1:5 with a control group of individuals with breast cancer based on race, sex, disease stage, age and calendar year of diagnosis.

Ninety-two (33.5%) of the childhood survivors died, including 49 (17.8%) who died of breast cancer.

Childhood cancer survivors demonstrated higher 10-year cumulative incidence of all-cause mortality (33% vs. 16%) and breast cancer-specific mortality (20% vs. 13%).

Childhood cancer survivors demonstrated greater risk for death of any cause after breast cancer diagnosis than controls (HR = 2.2; 95% CI, 1.7-3). The mortality risk for this group remained higher after adjustments for breast cancer treatment with radiation therapy (HR = 2.2; 95% CI, 1.7-3.1), chemotherapy (HR = 2.3; 95% CI, 1.8-3.2) or both (HR = 2.4; 95% CI, 1.7-3.2).

Risk for death after diagnosis of early-stage breast cancer — defined as stage 0, I or II — also was higher among childhood cancer survivors (HR = 2.6; 95% CI, 1.9-3.7). However, breast cancer-specific mortality was not significantly higher among childhood cancer survivors than controls (HR = 1.4; 95% CI, 0.9-2).

The most common causes of death other than breast cancer among childhood cancer survivors included subsequent neoplasms (44%) and cardiovascular disease (26%).

HemOnc Today spoke with Moskowitz about the study, why the mortality risk after breast cancer diagnosis is so much higher for women who survived childhood cancer, and the potential benefit of more intense screening or other strategies to reduce mortality among this group.

 

Question: Why are female childhood cancer survivors at elevated risk for breast cancer later in life?

Answer: There are multiple risk factors for breast cancer among female childhood cancer survivors; however, treatment with chest radiotherapy is one of the most notable. Women treated with chest radiotherapy for childhood cancer have one of the highest risks for breast cancer among any population. To a lesser degree, breast cancer also is elevated among survivors of leukemia or sarcoma who are not treated with chest radiation. There are multiple treatment exposures and potential genetic factors that contribute to the risk.

 

Q: How did you conduct the study?

A: We used data from an existing cohort. We studied women with breast cancer included in the Childhood Cancer Survivor Study. We compared these women with other women in the general population who were diagnosed with breast cancer and did not have a previous history of cancer. We gathered this information from the SEER database.

 

Q: What did you find?

A: Childhood cancer survivors had a significantly elevated risk for dying after a breast cancer diagnosis than women with de novo breast cancer. Their risk for dying was double, even among childhood cancer survivors diagnosed with early-stage breast cancer.

We then looked at the causes of death. The risk for dying of breast cancer was slightly elevated among childhood cancer survivors, but the risk for dying of causes other than breast cancer was markedly different. Childhood cancer survivors had a more than fivefold increased risk for dying of other health-related causes after breast cancer, and this difference persisted when we looked at women diagnosed with early-stage breast cancer. Childhood cancer survivors diagnosed with early-stage disease had a more than sixfold increased risk for dying of health-related causes other than breast cancer compared with women diagnosed with early-stage de novo breast cancer. The difference was even higher when we looked at women diagnosed with breast cancer at age 40 years or older. We estimated that these childhood cancer survivors had a sevenfold increased risk for dying of other health-related causes. We also found a significantly elevated risk for a second breast cancer diagnosis among childhood cancer survivors.

 

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Q: Why is the mortality risk after a breast cancer diagnosis so much higher for those who had childhood cancer?

A: A key contributing factor is that childhood cancer therapies are associated with multiple late effects, including breast cancer. Other cancers, cardiovascular disease and pulmonary complications are other late effects that childhood cancer survivors experience. In fact, these were some of the other causes of death that we observed.

 

Q: What are the implications of these findings?

A: A key take-home message is that childhood cancer survivors who are diagnosed with breast cancer need to be evaluated and followed closely for cardiac problems, for second cancers and for pulmonary complications. Oncologists who are treating women with breast cancer after a childhood cancer need to be aware of these elevated risks. Even when childhood cancer survivors are diagnosed with early-stage breast cancer, they still have an elevated risk for death.

 

Q: What must be addressed in future research?

A: Further work is needed to determine if some of the elevated mortality is due to limited therapeutic options available to childhood cancer survivors or whether it is possible to implement strategies at the time of the breast cancer diagnosis that will reduce the mortality risk from other causes.

 

Q: How important is intense screening for childhood cancer survivors? Could more risk-reducing strategies be implemented at the time of breast cancer diagnosis to try to reduce mortality?

A: If they are not already being actively followed by clinicians who are familiar with their unique risks, then a breast cancer diagnosis may be an opportunity to get such clinicians involved. Similarly, if a childhood cancer survivor is not already actively engaged in routine cardiac surveillance, the breast cancer diagnosis presents an opportunity to change this. Guidelines recommend routine cardiac surveillance for childhood cancer survivors at risk for cardiac complications, but we do not know if the childhood cancer survivors we studied here were actively engaged in this type of screening. It also is possible that a breast cancer diagnosis presents an opportunity to counsel women about adopting healthier lifestyles. There are several possibilities that may help and are worth further study. – by Jennifer Southall

 

Reference:

Moskowitz, CS. Abstract 10511. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

 

For more information:

Chaya S. Moskowitz, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: moskowc1@mskcc.org.

Disclosure: Moskowitz reports no relevant financial disclosures.