Clinical investigation: breast
Sarcoma as a second malignancy after treatment for breast cancer

Presented in part at the American Society of Clinical Oncology meeting in Atlanta, Georgia, May, 1999.
https://doi.org/10.1016/S0360-3016(01)02799-7Get rights and content

Abstract

Background: Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer.

Methods: Cases with primary invasive breast cancer (n = 274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973–1997). The database was then queried to determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method.

Results: The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis, respectively (p = 0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast cancer (27–35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer.

Conclusions: Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is small. Angiosarcoma is significantly more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. The small difference in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy does not supersede the benefit of radiotherapy.

Introduction

Radiotherapy (RT) is considered a risk factor in breast cancer patients for the development of soft-tissue and bone sarcomas 1, 2, 3, 4, 5. Because of the low incidence of sarcomas, the absolute level of risk is not known with certainty. Prior studies examining radiation-associated sarcoma in breast cancer patients have been based on relatively small numbers of cases. Nonetheless, with new indications for RT and increased screening, more and younger patients are having multimodality treatment (including radiotherapy) for breast cancer (6). Using Surveillance, Epidemiology and End Result (SEER) data (7), we attempted to better define risk levels and the impact of radiation therapy on the development of sarcoma in women previously diagnosed as having breast cancer. Of major interest were the histologies encountered, the cumulative incidence rates, and the latency periods for sarcomas occurring with or without radiotherapy given as part of breast cancer treatment.

Section snippets

Methods and materials

Women having a diagnosis of invasive breast cancer were identified (n = 274,572) in the SEER Cancer Incidence Public-Use Database, 1973–1996 (7). Excluded from the analysis were cases initially identified based on autopsy reports or death certificates, cases for which breast cancer was diagnosed as a subsequent malignant neoplasm, and male breast cancers. Mixed mullerian tumor and carcinosarcoma were excluded from our classification as secondary sarcomas. The database was then queried to

Results

The characteristics of primary breast cancer cases studied are shown in Table 1. Of the 274,572 cases of invasive breast cancer identified in the SEER database 1973–1997, 82,296 (30%) received radiation therapy, and 192,276 (70%) did not receive radiation therapy. In 5,232 cases, it was unknown whether patients received radiation therapy; these were excluded from analysis. Few breast cancers were diagnosed in patients under the age of 20 (n = 23), and only about 7% of patients were aged 20–39

Discussion

Ionizing radiation is known to be a potent carcinogen (12); malignancy induced by radiation may result from natural sources or a radiation accident, or it may be a side effect of cancer therapy (13). Solid cancers associated with exposure to ionizing radiation may have latency periods of up to 40 years (13). Approximately 6.7% of new cancers represent second primary cancers in cancer survivors (14), and breast cancer survivors constitute up to 25% of all cancer survivors 15, 16. In addition to

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