Long-term cardiovascular mortality after radiotherapy for breast cancer.

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.

Long-term mortality in a cohort study of 6,800 French breast cancer patients treated between 1954 and 1983.

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.

Cyclical mastalgia and breast cancer risk: results of a French cohort study.

Cyclical mastalgia is a common complaint, with a potentially important relationship to breast cancer risk. In the last decade, case-control studies have reported that cyclical mastalgia could be considered as an independent risk factor for breast cancer. The subjectivity of a retrospectively collected symptom questioned the validity of this finding. We have examined the association between cyclical mastalgia and breast cancer risk in the French cohort study of women with benign breast disease diagnosed in two breast clinics between 1976 and 1979 and followed-up until 1997. The present study was restricted to the women free of any hormonal treatment (n = 247). The mean follow-up was 16 +/- 5 years, and a total of 22 breast cancers occurred during the follow-up. Using a Cox model with duration of cyclical mastalgia as a time-varying variable, the adjusted relative risk of breast cancer increased with the duration of cyclical mastalgia (P = 0.006). The corresponding relative risk for 37 months of cyclical mastalgia was 5.31 (95% confidence interval, 1.92-14.72). We show here that the conclusion still holds when the symptom cyclical mastalgia was collected prospectively in a cohort study, bringing additional evidence that cyclical mastalgia may represent an independent and useful clinical marker of increased breast cancer risk. It might be a confounding factor when assessing the effects of hormonal treatments on breast cancer risk such as hormonal replacement therapy or oral contraceptives.

Twenty-five years of follow-up in patients with operable breast carcinoma: correlation between clinicopathologic factors and the risk of death in each 5-year period.

BACKGROUND: Some investigators have suggested a decreased prognostic value for conventional prognostic factors over time in patients with breast carcinoma. The objective of this study was to assess the effect of prognostic factors on the risk of death in patients with breast carcinoma over a long follow-up. METHODS: The authors assessed clinicopathologic prognostic factors in patients with early-stage breast carcinoma over a follow-up > 25 years and analyzed the variation of their effect on death in consecutive 5-year follow-up intervals. The study included 2410 women who primarily underwent complete surgical resection. Time-dependent variables were analyzed by using different multivariate models. RESULTS: Four factors were related strongly to the risk of death in the first 5 years: tumor size, histologic grade, the number of involved axillary lymph nodes, and age at diagnosis. After 10-15 years of follow-up, only age at diagnosis was related to the risk of death. The effect of powerful prognostic factors, except age at diagnosis, on the risk of death was time limited, and no effects or very small effects were detectable after 10 years of follow-up. CONCLUSIONS: Conventional and widely accepted prognostic factors may explain a significant portion of early deaths among patients with early-stage breast carcinoma, but they were of limited value to explain late mortality, that also may be influenced by late events, such as new primary malignancies and treatment complications. Cancer 2006. (c) 2006 American Cancer Society.

Are risk factors for breast cancer similar in women with inflammatory breast cancer and in those with non-inflammatory breast cancer?

PURPOSE: The aim of the study was to compare reproductive factors in patients with inflammatory breast cancer (IBC), and with non-inflammatory breast cancer (non-IBC). The study was performed in two centers: one French including 49 IBC patients and 140 non-IBC and another Tunisian including 97 IBC and 139 non-IBC. Unconditional logistic regression was used for the analyses. PATIENTS AND METHODS: The French IBC patients had a lower educational level, a higher body mass index and a longer cumulative duration of breast-feeding, and they included a greater proportion of non-European women, than the non-IBC patients. In the multivariate analysis, only breast-feeding duration remained associated with the IBC status (P=10(-3)). These results could not be verified in the Tunisian series, because the duration of breast-feeding was unavailable in this center. RESULTS: This study suggests that the etiology of IBC might be different of that of non-IBC.

Dermal lymphatic emboli in inflammatory and noninflammatory breast cancer: a French-Tunisian joint study in 337 patients.

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.

Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment.

BACKGROUND: To quantify the risk of soft tissue and bone sarcomas after breast cancer according to the doses and technical modalities of irradiation. METHODS: We followed a cohort of 6597 breast-cancer patients for 8.3 years on average. The number of soft tissue and bone sarcomas was compared to the expected number based on the incidence rates in the general French population. We also estimated the risk of sarcoma according to the radiation dose received at site of the sarcoma in a nested case control study of 14 breast-cancer patients who subsequently developed a sarcoma and 98 controls matched for age at diagnosis of breast cancer, period of initial treatment and length of follow-up. RESULTS: In the cohort-study, 12 women who had initially received radiotherapy treatment developed a bone or soft tissue sarcoma during the follow-up period. The expected number of cases during this period was 1.7 (SIR = 7.0, 95% CI: 3.7-11.7) and the mean annual excess incidence during the same period was 21 per 100,000 person-years. The 15-year cumulative incidence of sarcoma was 0.28% (95% CI: 0.10-0.45%). In the case-control study, all the 14 cases had received at least 11.8 Gray at the site of the sarcoma, which was always located in the irradiated field or in the upper ipsilateral extremity of the arm. A dose-effect relationship was observed (p < 0.001). The best fit was obtained for a quadratic dose-response relationship, without a negative exponential term for cell killing at high doses. The risk of sarcoma was 30.6 higher for doses of more than 44 Gray than for doses of less than 15 Gray. CONCLUSIONS: High doses of radiation strongly increase the risk of bone and soft tissue sarcoma.

Choroid metastases: clinical features and treatments in 123 patients.

BACKGROUND: The current study was performed to analyze the effects of radiotherapy and chemotherapy on visual improvement in patients with choroid metastases (CM), and to determine the clinical factors potentially related to the risk of death. METHODS: One hundred twenty-three consecutive patients were diagnosed with CM at the Institut Gustave-Roussy between 1966 and 1992. Treatment failure was defined as the absence of tumor regression or choroid tumor progression documented at the time of last ophthalmologic examination. The Cox proportional hazards model was used to estimate the risk of treatment failure associated with analyzed covariates. RESULTS: Approximately 81% of the patients were women. The most frequent primary tumors were breast carcinoma (71%) and lung carcinoma (9%). Bilateral CM were found in 25% of patients. Sequential vinca alkaloid-based chemoradiotherapy was reported to be significantly associated with a decreased rate of treatment failure compared with radiotherapy alone (relative risk [RR] = 0.3; 95% confidence interval [95% CI], 0.03-2.2). However, when considered separately, each type of treatment also decreased the risk of treatment failure (RR = 0.5 [95% CI, 0.3-0.8] for radiotherapy and RR = 0.4 [95% CI, 0.3-0.7] for chemotherapy). The total dose of radiotherapy (< 30 grays [Gy] vs. > or = 30 Gy) was not found to modify treatment results. The 2-year overall survival rate was 25% (95% CI, 17-34%). The risk of death was found to be correlated with the presence of metastases in the liver (P = 0.02) or lung pleura (P = 0.04) at the time of the diagnosis of CM. CONCLUSIONS: Sequential combination radiotherapy and vinca alkaloid-based chemotherapy appear to be the most beneficial treatment modality. However, because treatments were not prescribed randomly, the results of the current study should be interpreted with caution.

The risk of multiple primary breast and thyroid carcinomas.

BACKGROUND: Some studies have suggested that there is an association between breast carcinoma and thyroid carcinoma. Because ionizing radiation is a well known risk factor for breast and thyroid carcinomas, the authors studied the effect of the radiation dose delivered for the treatment of each of these two malignancies on the risk of subsequently developing the other malignancy. METHODS: The risk of developing thyroid carcinoma subsequent to treatment for breast carcinoma was analyzed in 8 patients (cases) and 192 matched control patients (controls) nested in a cohort of 7711 women who were treated at Institut Gustave Roussy between 1954 and 1983. The risk of developing breast carcinoma after treatment for thyroid carcinoma was studied in a cohort of 2365 women who were treated in 3 French cancer centers between 1934 and 1995. RESULTS: Six of 8 patients with breast carcinoma (75%) who developed thyroid carcinoma and 71% of patients in the control group received radiation therapy during their treatment. The median dose to the thyroid was 6.6 grays (Gy) in the case group and 9.4 Gy in the control group. The overall relative risk of thyroid carcinoma associated with radiation therapy was 1.2 (95% confidence interval, 0.2-6.2). No relation was observed between the radiation dose and the risk of thyroid carcinoma (P = 0.8). Among 2365 women who were treated for thyroid carcinoma, 48 women developed a subsequent breast carcinoma. A significant excess of breast carcinoma was observed among women younger than 59 years at the time of diagnosis of breast carcinoma compared with women in the same age group in the general population. The mean absorbed dose delivered to the breasts by (131)I and external radiation therapy was 0.7 Gy. No relation was found between the radiation dose and the risk of breast carcinoma (P = 0.8). CONCLUSIONS: The previously reported excess incidence of breast carcinoma after thyroid carcinoma was not related to radiation treatment with (131)I and/or external radiation therapy. Radiation therapy for breast carcinoma did not increase the risk of subsequent thyroid carcinoma.

Prognostic factors for death after an isolated local recurrence in patients with early-stage breast carcinoma.

BACKGROUND: The authors analyzed the outcome of patients with early-stage breast carcinoma after an isolated local recurrence, taking into account initial tumor characteristics and the type of initial treatment and local salvage treatment. METHODS: One hundred five patients were studied who presented with a breast tumor measuring