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Title: Local-Regional Recurrence With and Without Radiation Therapy After Neoadjuvant Chemotherapy and Mastectomy for Clinically Staged T3N0 Breast Cancer

Abstract

Purpose: The purpose of this study was to determine local-regional recurrence (LRR) risk according to whether postmastectomy radiation therapy (PMRT) was used to treat breast cancer patients with clinical T3N0 disease who received neoadjuvant chemotherapy (NAC) and mastectomy. Methodsand Materials: Clinicopathology data from 162 patients with clinical T3N0 breast cancer who received NAC and underwent mastectomy were retrospectively reviewed. A total of 119 patients received PMRT, and 43 patients did not. The median number of axillary lymph nodes (LNs) dissected was 15. Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: At a median follow-up of 75 months, 15 of 162 patients developed LRR. For all patients, the 5-year LRR rate was 9% (95% confidence interval [CI], 4%-14%). The 5-year LRR rate for those who received PMRT was 4% (95% CI, 1%-9%) vs. 24% (95% CI, 10%-39%) for those who did not receive PMRT (p <0.001). A significantly higher proportion of irradiated patients had pathology involved LNs and were {<=}40 years old. Among patients who had pathology involved LNs, the LRR rate was lower in those who received PMRT (p <0.001). A similar trend was observed for those who did not have pathology involvedmore » LN disease. Among nonirradiated patients, the appearance of pathologic LN disease after NAC was the only clinicopathologic factor examined that significantly correlated with the risk of LRR. Conclusions: Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy but without PMRT had a significant risk of LRR, even when there was no pathologic evidence of LN involvement present after NAC. PMRT was effective in reducing the LRR rate. We suggest PMRT should be considered for patients with clinical T3N0 disease.« less

Authors:
 [1];  [2]; ; ; ; ;  [1];  [3];  [2];  [1];  [1]
  1. Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)
  2. Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)
  3. Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)
Publication Date:
OSTI Identifier:
21590453
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 81; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2010.06.027; PII: S0360-3016(10)00876-X; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; HAZARDS; LYMPH NODES; MAMMARY GLANDS; NEOPLASMS; PATHOLOGY; RADIOTHERAPY; BODY; DISEASES; GLANDS; LYMPHATIC SYSTEM; MEDICINE; NUCLEAR MEDICINE; ORGANS; RADIOLOGY; THERAPY

Citation Formats

Nagar, Himanshu, Mittendorf, Elizabeth A., Strom, Eric A., Perkins, George H., Oh, Julia L., Tereffe, Welela, Woodward, Wendy A., Gonzalez-Angulo, Ana M., Hunt, Kelly K., Buchholz, Thomas A., and Yu, Tse-Kuan, E-mail: tkyu@mdanderson.org. Local-Regional Recurrence With and Without Radiation Therapy After Neoadjuvant Chemotherapy and Mastectomy for Clinically Staged T3N0 Breast Cancer. United States: N. p., 2011. Web. doi:10.1016/j.ijrobp.2010.06.027.
Nagar, Himanshu, Mittendorf, Elizabeth A., Strom, Eric A., Perkins, George H., Oh, Julia L., Tereffe, Welela, Woodward, Wendy A., Gonzalez-Angulo, Ana M., Hunt, Kelly K., Buchholz, Thomas A., & Yu, Tse-Kuan, E-mail: tkyu@mdanderson.org. Local-Regional Recurrence With and Without Radiation Therapy After Neoadjuvant Chemotherapy and Mastectomy for Clinically Staged T3N0 Breast Cancer. United States. doi:10.1016/j.ijrobp.2010.06.027.
Nagar, Himanshu, Mittendorf, Elizabeth A., Strom, Eric A., Perkins, George H., Oh, Julia L., Tereffe, Welela, Woodward, Wendy A., Gonzalez-Angulo, Ana M., Hunt, Kelly K., Buchholz, Thomas A., and Yu, Tse-Kuan, E-mail: tkyu@mdanderson.org. 2011. "Local-Regional Recurrence With and Without Radiation Therapy After Neoadjuvant Chemotherapy and Mastectomy for Clinically Staged T3N0 Breast Cancer". United States. doi:10.1016/j.ijrobp.2010.06.027.
@article{osti_21590453,
title = {Local-Regional Recurrence With and Without Radiation Therapy After Neoadjuvant Chemotherapy and Mastectomy for Clinically Staged T3N0 Breast Cancer},
author = {Nagar, Himanshu and Mittendorf, Elizabeth A. and Strom, Eric A. and Perkins, George H. and Oh, Julia L. and Tereffe, Welela and Woodward, Wendy A. and Gonzalez-Angulo, Ana M. and Hunt, Kelly K. and Buchholz, Thomas A. and Yu, Tse-Kuan, E-mail: tkyu@mdanderson.org},
abstractNote = {Purpose: The purpose of this study was to determine local-regional recurrence (LRR) risk according to whether postmastectomy radiation therapy (PMRT) was used to treat breast cancer patients with clinical T3N0 disease who received neoadjuvant chemotherapy (NAC) and mastectomy. Methodsand Materials: Clinicopathology data from 162 patients with clinical T3N0 breast cancer who received NAC and underwent mastectomy were retrospectively reviewed. A total of 119 patients received PMRT, and 43 patients did not. The median number of axillary lymph nodes (LNs) dissected was 15. Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: At a median follow-up of 75 months, 15 of 162 patients developed LRR. For all patients, the 5-year LRR rate was 9% (95% confidence interval [CI], 4%-14%). The 5-year LRR rate for those who received PMRT was 4% (95% CI, 1%-9%) vs. 24% (95% CI, 10%-39%) for those who did not receive PMRT (p <0.001). A significantly higher proportion of irradiated patients had pathology involved LNs and were {<=}40 years old. Among patients who had pathology involved LNs, the LRR rate was lower in those who received PMRT (p <0.001). A similar trend was observed for those who did not have pathology involved LN disease. Among nonirradiated patients, the appearance of pathologic LN disease after NAC was the only clinicopathologic factor examined that significantly correlated with the risk of LRR. Conclusions: Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy but without PMRT had a significant risk of LRR, even when there was no pathologic evidence of LN involvement present after NAC. PMRT was effective in reducing the LRR rate. We suggest PMRT should be considered for patients with clinical T3N0 disease.},
doi = {10.1016/j.ijrobp.2010.06.027},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 81,
place = {United States},
year = 2011,
month =
}
  • Purpose: We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. Methods and Materials: We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascularmore » invasion, pathologic size >2 cm, and multifocal residual disease. Results: The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p = 0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p = 0.009). Conclusions: This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation.« less
  • Purpose: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. Methods and Materials: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. Results: The medianmore » follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close ({<=}2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. Conclusions: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small.« less
  • Purpose: To develop clinical prediction models for local regional recurrence (Lr) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status. Methods and Materials: Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy formed the database of the training and testing of clinical prognostic and prediction models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from which these models were built. To generate a prognostic index model, 15 clinical variables were examined for their impact on LRR. Patients were stratifiedmore » by lymph node involvement (<4 vs. {>=}4) and local regional status (recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients). Results: With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk group, there is no influence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both LR control and metastasis-free and overall survival. Conclusion: The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT. These models provide additional information criteria for selection of patients for PMRT, compared with the traditional selection criteria of nodal status and tumor size.« less
  • The purpose of this work was to determine the risk of local-regional failure following post-mastectomy radiotherapy and the incidence of complications associated with such treatment. The authors retrospectively analyzed the results in 309 patients with Stage I--III invasive breast cancer treated with post-mastectomy radiation therapy between 1975 and 1985. The median radiotherapy dose was 45 Gy in 1.8 to 2.25 Gy fractions. One hundred forty-seven (48%) of the patients received adjuvant systemic chemotherapy with 115 (78%) of these receiving a CMF-based or doxorubicin-containing regime. The median follow-up time of surviving patients was 130 months (range, 28 to 191 months) aftermore » mastectomy. Seventeen patients (6%) developed a local-regional failure at an interval of 4 to 87 months after radiotherapy. Moderate or severe complications related to radiotherapy and requiring treatment were uncommon. Symptomatic radiation pneumonitis occurred in four patients (1.3%), arm edema in 18 (5.8%), and brachial plexopathy in 2 (0.6%). The authors conclude that post-operative radiotherapy is a safe and effective means of reducing local-regional failure following mastectomy. The efficacy of post-mastectomy radiotherapy in improving survival should be addressed in new large randomized controlled studies. 33 refs., 1 fig., 3 tabs.« less
  • Purpose: The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. Methods and Materials: We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log–rank test and Coxmore » proportional regression analysis. Results: Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. Conclusions: PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.« less