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Objectives: This study sought to investigate long-term cardiovascular mortality and its relationship to the use of radiotherapy for breast cancer., Background: Cardiovascular diseases are among the main long-term complications of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, <20 years of follow-up., Methods: A total of 4,456 women who survived at least 5 years after treatment of a breast cancer at the Institut Gustave Roussy between 1954 and 1984 were followed up for mortality until the end of 2003, for over 28 years on average., Results: A total of 421 deaths due to cardiovascular diseases were observed, of which 236 were due to cardiac disease. Women who had received radiotherapy had a 1.76-fold (95% confidence interval [CI]: 1.34 to 2.31) higher risk of dying of cardiac disease and a 1.33-fold (95% CI: 0.99 to 1.80) higher risk of dying of vascular disease than those who had not received radiotherapy. Among women who had received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27 to 1.90) higher risk of dying of cardiac disease than those treated for a right-sided breast cancer. This relative risk increased with time since the breast cancer diagnosis (p = 0.05)., Conclusions: This study confirmed that radiotherapy, as delivered until the mid-1980s, increased the long-term risk of dying of cardiovascular diseases. The long-term risk of dying of cardiac disease is a particular concern for women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the impact of initial tumour characteristics and loco-regional radiotherapy on long-term survival following breast cancer diagnosis., Methods and Materials: This study was conducted among 6,800 French women from a cohort of 7 711 subjects diagnosed at the IGR with breast cancer between 1954 and 1983 and followed-up until January 2004. Overall mortality in the cohort was compared with that in the French general population using Standardized Mortality Ratios (SMR) and the Absolute Excess Risk (AER) estimated by Poisson regression., Results: During the 1954-2004 follow-up period, 5,436 women died. Mortality was 3.15-fold higher in the cohort than in the general female population in France. It decreased from 6.86 to 1.26 during the first 30 years of follow-up then rose again to 1.60. Both SMRs and AERs were more than 2-fold higher in women who had received radiotherapy during initial treatment than in those who had not, this difference being higher for women treated before 1976 than afterwards (p < 0.0001). They (SMRs and AERs) were also higher for subjects who had stage II, III or IV lesions than for those with less advanced tumours., Conclusion: The results of this study suggest that the excess deaths observed during the first two decades are closely linked to the initial clinical characteristics of the tumour and to radiotherapy. The late increase in mortality may be partially due to deleterious late effects of radiotherapy.

Background: We studied whether dermal lymphatic emboli (DLE) add independent prognostic information to the clinical definition of inflammatory breast cancer (IBC)., Patients and Methods: The study was performed in 2 centers, one each in France and Tunisia. For every patient with IBC, 1-3 patients with noninflammatory breast cancer (non-IBC) were included. All patients were to have a surgical tumor biopsy, including a sample of the skin surrounding the tumor. The endpoint was the risk of a relapse at 2 years, which was estimated using univariate and multivariate Cox models., Results: Three hundred thirty-seven patients were included (150 in France and 187 in Tunisia). The IBC status was divided into 2 clinical categories according to the extent of inflammation in the breast (localized IBC, which was defined as clinical inflammation in the tumor area, vs. diffuse IBC, which was defined as inflammation of at least two thirds of the breast). In total, 57 patients presented with localized IBC, 71 with diffuse IBC, and 209 with non-IBC. Dermal lymphatic emboli were found in 7% of non-IBC cases, in 25% of localized IBC cases, and in 45% of diffuse IBC cases. We found a significant interaction between the presence of DLE and diffuse IBC (P = 0.01). In patients with diffuse IBC, the presence of DLE increased the risk of relapse 3-fold. Conversely, DLE were not associated with the risk of relapse in patients with non-IBC, nor in patients with localized IBC. In patients with diffuse IBC and no DLE, the risk of relapse was similar to that of patients with localized IBC., Conclusion: A DLE status might be a useful prognostic indicator exclusively in patients with diffuse IBC. However, because all patients with localized and diffuse IBC generally receive similar types of treatment, additional information on the presence or absence of DLE will not have an impact on treatment practice.

Background: We studied the effect of adjuvant anthracycline-based chemotherapy in postmenopausal patients with resected early breast cancer treated with adjuvant tamoxifen., Patients and Methods: The trial included 835 patients with either axillary lymph node involvement, or tumors with histological grade II or III. They were randomized after local surgery to receive either tamoxifen (TAM group) or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5-fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the TAM group., Results: The 5-year disease-free survival (DFS) rates were 73% in the TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local recurrence rates were 6% and 4%, respectively (P = 0.23). There were no significant differences for contralateral breast cancer or other new primary malignancies. Chemotherapy tended to be more effective for patients who had tumors without estrogen receptors (trend test, P = 0.05)., Conclusions: Anthracycline-based chemotherapy administered to postmenopausal patients receiving adjuvant tamoxifen gave a borderline significant benefit on overall and DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six courses of chemotherapy did not affect local control after up to 10 years of follow-up.

Ninety-nine patients presenting with non-metastatic inflammatory breast cancer were treated with an alternating protocol of radiotherapy and chemotherapy. The alternating schedule consisted of 8 courses of combined chemotherapy, including doxorubicin, vincristine, cyclophosphamide, methotrexate and 5-Fluorouracil, and 3 series of loco-regional radiotherapy delivering a total dose of 65 to 75 Gy to the breast tumor, 65 Gy to the axilla, and 50 Gy to the supraclavicular and internal mammary chain lymph nodes. Radiotherapy was started after the third course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy-five percent of patients were in complete remission at the end of this induction treatment. The 3-year local control was 72% and the 3-year overall survival rate was 70%. An isolated local recurrence was observed in only 4% of patients. Approximately one-half of patients developed distant metastases. These results show that alternating radiotherapy and chemotherapy schedules deserve further investigation in locally advanced breast cancer.

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

We report the largest series of induction chemotherapy for inflammatory breast carcinoma (IBC). Results of two chemotherapy protocols with radiation therapy (RT) (170 patients) are compared with results with radiation alone (60 patients) in the treatment of this disease. From 1973 to 1975, 60 patients (control, group C) received RT (45 Gy and 20 to 30 Gy boost) and hormonal manipulation. From 1976 to 1980, 91 patients (group A) were treated with induction chemotherapy: Adriamycin (Adria Laboratories, Columbus, Ohio), vincristine, and methotrexate (AVM) and RT on a cyclical schedule; and maintenance chemotherapy: vincristine, cyclophosphamide, and 5-fluorouracil (5-FU) (VCF). From 1980 to 1982, 79 patients (group B) received induction chemotherapy, Adriamycin, vincristine, cyclophosphamide, methotrexate, and 5-FU (AVCMF) and RT on a cyclical schedule and VCF maintenance. Hormonal manipulation was performed in all groups. Disease-free survival at 4 years was 15% for group C, 32% for group A, and 54% for group B (P less than .005 group C v group A, less than .00001 group C v group B, and less than .01 group A v group B). Total survival at 4 years was 42% for group C, 53% for group A, and 74% for group B (P = .17 group C v group A, less than .00001 group C v group B, and less than .001 group A v group B). Clinical assessment of tumor aggressiveness, nodal status, type of chemotherapy administered, and early response to chemotherapy (by third course) were all prognostic factors. There is an important, highly statistically significant benefit in terms of both disease-free survival and total survival observed in patients treated with the addition of chemotherapy compared with radiation alone in IBC.

Twenty-five cases of presumed radiation-induced brachial plexopathy were identified out of a population treated at the Institut Gustave-Roussy, in 3 different ways, during the period 1967-1980. The incidence of this complication is given for each group, and the radiation dosage and natural history is described, with results of neurolysis when it was possible. The absence of successful treatment methods makes prevention of this complication crucial. The use of fraction sizes no greater than 2.5 Gy, and the avoidance of radiation treatment to the completely dissected axilla, are advocated.