Mortality after subsequent breast cancer

Source: Late Effects of Treatment for Childhood Cancer (PDQ®)–Health Professional Version, National Cancer Institute.

Source updated: April 14, 2025 · Captured 2026-09-09.

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Context: Subsequent Neoplasms / Therapy-Related Solid SNs / Breast cancer

In a study of female participants in the CCSS who were subsequently diagnosed with breast cancer (n = 274) and matched to a control group of women (n = 1,095) with de novo breast cancer, the following was observed:[54]

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Survivors of childhood cancer were found to have elevated mortality rates (HR, 2.2; 95% CI, 1.7–3.0), even after adjusting for breast cancer treatment.

Survivors were five times more likely to die from other health-related causes, including other SMNs and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4–9.0).

The cumulative incidence of a second asynchronous breast cancer was elevated significantly compared with controls (at 5 years, 8.0% among childhood cancer survivors vs. 2.7% among controls; P < .001).

Although current evidence does not show a survival benefit from the initiation of breast cancer surveillance in women treated with radiation therapy to the chest for childhood cancer, interventions to promote detection of small and early-stage tumors may improve prognosis. Those with more limited treatment options because of previous exposure to radiation or anthracyclines may especially benefit.

In support of surveillance, SJLIFE investigators observed that breast cancers detected by imaging and/or prophylactic mastectomy were more likely to be in situ carcinomas, be smaller masses (3.3 cm mean tumor size detected by physical examination vs. 1.1 cm detected by imaging), have no lymph node involvement, and be treated without chemotherapy, compared with breast cancers detected by physical findings.[25]

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Investigators used data from the CCSS and two Cancer Intervention and Surveillance Modeling Network breast cancer simulation models to estimate the clinical benefits, harms, and cost-effectiveness of breast cancer screening among childhood cancer survivors who were previously treated with chest radiation.[55]

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Screening with mammography and MRI, as recommended in COG Long-Term Follow-Up guidelines, is projected to avert half of the expected breast cancer deaths among high-risk survivors.

On an annual schedule, a survivor will have an average of 4 to 5 false-positive screening results and 1 to 2 benign biopsy results over the course of their lifetime.

Because of the large survival benefits, the harm-benefit tradeoffs for survivors were found to be appropriate, resulting in more favorable harm-benefit ratios.

Another CCSS investigation quantified the association between temporal changes in cancer treatment over three decades and subsequent breast cancer risk.[36]

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The cumulative incidence of breast cancer was 8.1% (95% CI, 7.3%–9.0%) by age 45 years among 11,550 female survivors (median age, 34.2 years), representing a more than sixfold excess risk (SIR, 6.6; 95% CI, 6.1–7.2), compared with age-, sex-, and calendar year–matched controls.

Concurrent with changes in therapy by decade, including reduced rates of chest and pelvic radiation therapy and increased rates of anthracycline chemotherapy exposure, and adjusting for age and age at diagnosis, the invasive breast cancer rate decreased 18% for every 5 years of primary cancer diagnosis era (rate ratio, 0.82; 95% CI, 0.74–0.90). This finding was largely associated with the reduced rate of chest radiation therapy.

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