Ten-Year Survival Results of a Randomized Trial of Irradiation of Internal Mammary Nodes After Mastectomy
01 Aug 2013-International Journal of Radiation Oncology Biology Physics (Elsevier)-Vol. 86, Iss: 5, pp 860-866
TL;DR: No benefit of IMN irradiation on the overall survival could be demonstrated and this study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population of breast cancer patients after mastectomy.
Abstract: Purpose To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. Methods and Patients This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age Results T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group ( P =.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival. Conclusions In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population.
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TL;DR: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given.
1,533 citations
Radboud University Nijmegen1, European Organisation for Research and Treatment of Cancer2, Université catholique de Louvain3, Katholieke Universiteit Leuven4, Charité5, Utrecht University6, PSL Research University7, François Rabelais University8, Institut Gustave Roussy9, University of Tübingen10, University of Amsterdam11, University of Zurich12, Rambam Health Care Campus13
TL;DR: In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival, disease-free survival and distant disease- free survival were improved, and breast-cancer mortality was reduced.
Abstract: BACKGROUND The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown. METHODS We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer. RESULTS Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P = 0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P = 0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P = 0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P = 0.02). Acute side effects of regional nodal irradiation were modest. CONCLUSIONS In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.)
810 citations
TL;DR: IMNI increased overall survival in patients with early-stage node-positive breast cancer and was more pronounced in patients at high risk of internal mammary node metastasis.
Abstract: PurposeIt is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer.Patients and MethodsIn this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat.ResultsA total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a medi...
334 citations
TL;DR: The diagnosis and management of breast cancer are undergoing a paradigm shift from a one-size-fits-all approach to an era of personalized medicine, including molecular imaging and genomic expression profiles.
Abstract: The diagnosis and management of breast cancer are undergoing a paradigm shift from a one-size-fits-all approach to an era of personalized medicine. Sophisticated diagnostics, including molecular imaging and genomic expression profiles, enable improved tumor characterization. These diagnostics, combined with newer surgical techniques and radiation therapies, result in a collaborative multidisciplinary approach to minimizing recurrence and reducing treatment-associated morbidity. This article reviews the diagnosis and treatment of breast cancer, including screening, staging, and multidisciplinary management.
295 citations
TL;DR: A focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT) is developed, finding available evidence shows that PMRT reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes.
Abstract: PurposeA joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT).MethodsA recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data.RecommendationsThe panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the d...
239 citations
References
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TL;DR: It is found that variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality, and that avoidance of a local recurrence in the conserved breast is recommended.
4,743 citations
"Ten-Year Survival Results of a Rand..." refers background or methods in this paper
...In the EBCCTCG meta-analysis (4), in node-positive patients after mastectomy, the difference in survival in favor of postoperative RTwas 4....
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...analysis (4) published 15 years after the design of this study and showing an improvement of 5% in overall survival after postmastectomy irradiation, it seems that our hypothesis was too optimistic....
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...Mean age (y) <50 y 241 (36) 224 (33) >50 y 421 (64) 448 (67) Side Left 346 (52) 330 (49) Right 292 (44) 311 (46) Missing 24 (4) 31 (5) Tumor location: Lateral 236 (36) 232 (35) Medial/internal 426 (64) 440 (65) Tumor size (mm) 20 215 (32) 229 (34) 21-50 348 (53) 347 (52) >50 62 (9) 54 (8) Unknown 37 (6) 42 (6) No....
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TL;DR: Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade.
Abstract: Background Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). Methods A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. Results The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The ...
2,413 citations
"Ten-Year Survival Results of a Rand..." refers background in this paper
...Some randomized trials have demonstrated that postoperative radiation therapy (RT) increased survival after mastectomy (1-3)....
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TL;DR: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.
Abstract: Background Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began t...
1,644 citations
TL;DR: Postoperative radiotherapy decreased the risk of locoregional recurrence and was associated with improved survival in high-risk postmenopausal breast-cancer patients after mastectomy and limited axillary dissection, with 1 year of adjuvant tamoxifen treatment.
1,482 citations
TL;DR: In this paper, the authors investigated the long-term hazards of radiotherapy for early breast cancer in the general US population from routine cancer-registry and death-certificate data.
Abstract: Summary Background Radiotherapy for early breast cancer can decrease breast cancer mortality but increase other mortality, mainly from heart disease and lung cancer. The mean cardiac dose from irradiation of a left-sided breast cancer can be two or three times that for a right-sided breast cancer. The mean ipsilateral (ie, on the same side as the breast cancer) lung dose can also be two or three times the mean contralateral lung dose. Particularly during the 1970s, when typical heart and lung exposures were greater than now, the laterality of an irradiated breast cancer could measurably affect cardiac mortality and mortality from cancer of the right or the left lung decades later. This study aimed to assess the hazards in the general US population from routine cancer-registry and death-certificate data. Methods We analysed data for 308 861 US women with early breast cancer of known laterality (left-sided or right-sided) who were registered in the US Surveillance Epidemiology and End Results (SEER) cancer registries during 1973–2001 and followed prospectively for cause-specific mortality until Jan 1, 2002. Findings 115 165 (37%) received radiotherapy. Among those who did not, tumour laterality was of little relevance to subsequent mortality. For women diagnosed during 1973–82 and irradiated, the cardiac mortality ratio (left versus right tumour laterality) was 1·20 (95% CI 1·04–1·38) less than 10 years afterwards, 1·42 (1·11–1·82) 10–14 years afterwards, and 1·58 (1·29–1·95) after 15 years or more (trend: 2p=0·03). For women diagnosed during 1983–92 and irradiated, the cardiac mortality ratio was 1·04 (0·91–1·18) less than 10 years afterwards and 1·27 (0·99–1·63) 10 or more years afterwards. For women diagnosed during 1993–2001 and irradiated the cardiac mortality ratio was 0·96 (0·82–1·12), with none yet followed for 10 years. Among women irradiated for breast cancer who subsequently developed an ipsilateral or contralateral lung cancer, the lung cancer mortality ratio (ipsilateral versus contralateral) for women diagnosed during 1973–82 and irradiated was 1·17 (0·62–2·19), 2·00 (1·00–4·00), and 2·71 (1·65–4·48), respectively, less than 10 years, 10–14 years, and 15 or more years afterwards (trend: 2p=0·04). For women irradiated after 1982 there is, as yet, little information on lung cancer risks more than 10 years afterwards. Interpretation US breast cancer radiotherapy regimens of the 1970s and early 1980s appreciably increased mortality from heart disease and lung cancer 10–20 years afterwards with, as yet, little direct evidence on the hazards after more than 20 years. Since the early 1980s, improvements in radiotherapy planning should have reduced such risks, but the long-term hazards in the general populations of various countries still need to be monitored directly.
905 citations