Radiation May Cause Secondary Cancer in Some Breast Cancers

Author(s):

Ashley Chan

Fact checked by:

Darlene Dobkowski, MA

Key Takeaways

Patients with TP53 germline variants have an increased risk of secondary sarcoma post-radiation therapy.
The 15-year risk of sarcoma for TP53 pathogenic variant carriers is 8.8%, higher than the general population.
Longer-term follow-up and larger cohorts are needed to refine risk estimates for radiation-associated sarcoma.
Radiation therapy is a significant risk factor for soft tissue sarcoma in breast cancer survivors.

Receiving radiation therapy for breast cancers harboring TP53 germline variants may cause secondary cancers, but risk estimates are unconfirmed.

Patients with breast cancer who carry TP53 germline variants may develop secondary cancer associated with radiation therapy, according to study findings.

Patients with breast cancer who carry TP53 germline variants may be at a higher risk for developing secondary cancer associated with radiation therapy.

In a research letter published in JAMA Oncology, researchers have established that patients with breast cancer carrying TP53 germline variants who underwent radiation therapy may be more susceptible to developing sarcoma. However, they noted that risk estimates are still currently unknown.

According to Johns Hopkins Medicine, sarcoma is a rare cancer that develops in the bones or soft tissues, although it is categorized based on where it develops in the body.

In the research letter, the researchers evaluated 91 patients with breast cancer who carried the TP53 germline variant. Outcomes after radiation therapy were compared among patients with TP53 germline variants and those without this variant, according to the study.

Glossary

Axillary lymph nodes: lymph nodes located in the armpit region that drain lymph from the breast.

Pathogenic variant: a DNA sequence change that may lead to higher susceptibility to developing certain diseases, such as cancer.

Patients had their TP53 germline variants classified as either pathogenic or of unknown significance. Among the total patients, 40 underwent radiation therapy and 51 did not. Of note, patients who had undergone radiation therapy had higher tumor stages and a higher number of involved axillary lymph nodes compared with patients who did not undergo radiation.

“To our knowledge, this is the largest analysis of radiation therapy-associated cancer risk among patients with breast cancer harboring TP53 germline variants,” the researchers wrote. “We estimate the longitudinal risk of radiation therapy-associated sarcoma among carriers of TP53 pathogenic to be 8.8% at 15 years — significantly increased compared with that of the general population.”

Of the 28 patients who were TP53 pathogenic variant carriers and underwent radiation therapy, three developed secondary sarcoma, researchers stated. This is compared with no events related to a sarcoma diagnosis in patients who did not have any variant. The 10-year likelihood of developing any secondary cancer after radiation therapy was not significantly different in patients with TP53 pathogenic variant carriers treated with radiation and in those who did not receive radiation therapy.

The median age among noncarriers was 38 years old at diagnosis, 35 years old in patients with a TP53 pathogenic variant and 41 years old in patients with TP53 variant of unknown significance, researchers established. The median follow-up times were 11 years, 14 years and 8.5 years for patients with the respective TP53 germline variant statuses.

“Our results highlight that TP53 [pathogenic variant] carriers face substantial overall risk of any secondary cancers, most of which develop unrelated to radiation therapy and must be interpreted in the context of the study design,” the researchers wrote. “Longer-term follow-up with larger cohorts may further refine relevant risk estimates.”

In a similar retrospective study published in The Lancet Oncology in 2022, researchers found that radiation therapy was “the strongest risk factor” for soft tissue sarcoma in the chest area in breast cancer survivors.

At a median follow-up of 9.3 years, 19 eligible breast cancer survivors of 15,940 had developed soft tissue sarcoma in the chest region, the study showed. In 18 of 19 survivors, the soft tissue sarcoma occurred after having received radiation therapy for breast cancer.

Researchers noted that radiation therapy was associated with a significantly increased risk of developing soft tissue sarcoma in the chest area.

“This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance,” the researchers wrote.

References:

“Radiation-Associated Secondary Cancer in Patients With Breast Cancer Harboring TP53 Germline Variants” by Dr. Gustav Y. Cederquist, et al., JAMA Oncology.

“Treatment-related thoracic soft tissue sarcomas in US breast cancer survivors: a retrospective cohort study” by Dr. Lene H.S. Veiga, et al. The Lancet Oncology.

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