Malignant breast tumors after radiotherapy for a first cancer during childhood.

PURPOSE: To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors. PATIENTS AND METHODS: In a cohort of 1,814 3-year female survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean). RESULTS: Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (< 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin's disease (relative risk, 7.0; 95% CI, 1.4 to 30.9). CONCLUSION: The reported high risk of BC after childhood Hodgkin's disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.

Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood.

Soft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3-year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case-control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow-up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34-89)). The SIR was 113 (95% CI: 62-185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2-125) after chemotherapy alone (1 STS) and 19 (95%CI: 3-60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case-control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended.

Radiation dose, chemotherapy and risk of lung cancer after breast cancer treatment.

It is of particular concern to evaluate the risk of lung cancer occurrence after breast cancer treatment as women with breast cancer quite often undergo radiation therapy as part of their initial treatment and their life expectancy remains long. From a roster of 7711 women initially treated for breast cancer between 1954 and 1984, a cohort-study was performed among 4171 1-year survivors followed during the period 1975-1995. The relationship between the radiation dose received by the lung and the risk of lung cancer was then evaluated in a nested case-control study of 11 breast-cancer patients who developed lung cancer and 22 controls matched for age at diagnosis of breast cancer, period of initial treatment and length of follow-up. Among the 4171 women, six developed lung cancer during the entire follow-up as compared to 5.4 cases expected (SIR = 1.1, 95% CI: 0.4-2.3). When considering only the women initially treated by radiotherapy with or without adjunction of chemotherapy and excluding the 10 first years of follow-up, the SIR was significantly increased (SIR = 3.2, 95%CI: 1.0-7.4). In the case-control study, nine of the 11 lung cancers occurred in the ipsilateral lung and two in the trachea. The overall odds ratio (OR) of lung cancer associated with initial radiotherapy was 1.4 (95% CI: 0.2-11.1) and an excess in the OR of 7% (90% CI: ? to 41%, p = 0.10) per gray delivered to the site of lung cancer was evidenced. Our results agree with previous studies in favor of an increased risk of lung cancer after radiation therapy for breast cancer.