ABSTRACT
In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN > 3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.
Subject(s)
Breast Neoplasms/etiology , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/radiotherapy , Neoplasms, Second Primary/etiology , Adult , Aged , Carcinoma in Situ/etiology , Carcinoma, Ductal, Breast/etiology , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasms, Radiation-Induced/etiology , Retrospective Studies , Risk Factors , Survival Rate , Treatment OutcomeABSTRACT
Peripheral blood lymphocytes (PBL) of patients with Hodgkin's disease were studied for their capacity to produce interleukin 2 upon in vitro phytohemaglutinin stimulation in the presence or absence of either interleukin 1 or indomethacin (2 micrograms/ml); eight patients were studied at the discovery of their disease before receiving any therapy (onset HD; OHD). Seventeen patients were tested in long-term (greater than 3 yr) remission (remission HD; RHD); most RHD were treated with both chemotherapy and irradiation. Fourteen healthy individuals served as controls. PBL from OHD have a significant (P less than 0.01) defect in the production of PHA-induced IL-2. Indomethacin and IL-1 had no effect on IL-2 yield. PBL from RHD yield intermediate levels of IL-2, which are nevertheless significantly lower (P less than 0.02) than control values. RHD recover the capacity of normal PBL to increase their production of IL-2 in indomethacin-supplemented culture medium. Interestingly, PHA responsiveness was significantly decreased only in RHD, thus not explaining the low IL-2 yield obtained in supernatants. In addition, 4-day PHA-blasts from both HD patients and control individuals increase their thymidine incorporation in the presence of purified lectin-free IL-2 to a similar degree, suggesting that their IL-2 receptors are unimpaired. Finally, OHD sera significantly inhibit PHA-induced IL-2 yield of normal PBL, suggesting that a seric component(s) may play a role in some cases. We conclude that defective IL-2 production may play a role in the well-documented deficient cellular immunity seen in Hodgkin's disease.
