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Title: Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer

Abstract

Purpose: Data have suggested that the molecular features of breast cancer are important determinants of outcome; however, few studies have correlated these features with locoregional recurrence (LRR). In the present study, we evaluated estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as predictors of LRR in patients with lymph node-negative disease and tumors {<=}1 cm, because these patients often do not receive adjuvant chemotherapy or trastuzumab. Methods and Materials: The data from 911 patients with stage T1a,bN0 breast cancer who had received definitive treatment at our institution between 1997 and 2002 were retrospectively reviewed. We prospectively analyzed ER/PR/HER2 expression from the archival tissue blocks of 756 patients. These 756 patients represented the cohort for the present study. Results: With a median follow-up of 6.0 years, the 5- and 8-year Kaplan-Meier LRR rate was 1.6% and 5.9%, respectively, with no difference noted in those who underwent breast conservation therapy vs. mastectomy (p = .347). The 8-year LRR rates were greater in the patients with ER-negative (10.6% vs. 4.2%, p = .016), PR-negative (9.0% vs. 4.2%, p = .009), or HER2-positive (17.5% vs. 3.9%, p = 0.009) tumors. On multivariate analysis, ER-negative and PR-negative disease (hazardmore » ratio, 2.37; p = .046) and HER2-positive disease (hazard ratio, 3.13, p = .016) independently predicted for LRR. Conclusion: Patients with ER/PR-negative or HER2-positive T1a,bN0 breast cancer had a greater risk of LRR. Therapeutic strategies, such as the use of chemotherapy and/or anti-HER2 therapies, should be considered for future clinical trials for these patients.« less

Authors:
 [1];  [2]; ;  [3]
  1. Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
  2. Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
  3. Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
Publication Date:
OSTI Identifier:
21436101
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 77; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2009.12.011; PII: S0360-3016(09)03675-X; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ESTROGENS; MAMMARY GLANDS; NEOPLASMS; PROGESTERONE; RECEPTORS; BODY; DISEASES; GLANDS; HORMONES; KETONES; MEMBRANE PROTEINS; ORGANIC COMPOUNDS; ORGANS; PREGNANES; PROTEINS; STEROID HORMONES; STEROIDS

Citation Formats

Albert, Jeffrey M., Gonzalez-Angulo, Ana M., Guray, Merih, and Sahin, Aysegul. Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer. United States: N. p., 2010. Web. doi:10.1016/j.ijrobp.2009.12.011.
Albert, Jeffrey M., Gonzalez-Angulo, Ana M., Guray, Merih, & Sahin, Aysegul. Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer. United States. doi:10.1016/j.ijrobp.2009.12.011.
Albert, Jeffrey M., Gonzalez-Angulo, Ana M., Guray, Merih, and Sahin, Aysegul. 2010. "Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer". United States. doi:10.1016/j.ijrobp.2009.12.011.
@article{osti_21436101,
title = {Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer},
author = {Albert, Jeffrey M. and Gonzalez-Angulo, Ana M. and Guray, Merih and Sahin, Aysegul},
abstractNote = {Purpose: Data have suggested that the molecular features of breast cancer are important determinants of outcome; however, few studies have correlated these features with locoregional recurrence (LRR). In the present study, we evaluated estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as predictors of LRR in patients with lymph node-negative disease and tumors {<=}1 cm, because these patients often do not receive adjuvant chemotherapy or trastuzumab. Methods and Materials: The data from 911 patients with stage T1a,bN0 breast cancer who had received definitive treatment at our institution between 1997 and 2002 were retrospectively reviewed. We prospectively analyzed ER/PR/HER2 expression from the archival tissue blocks of 756 patients. These 756 patients represented the cohort for the present study. Results: With a median follow-up of 6.0 years, the 5- and 8-year Kaplan-Meier LRR rate was 1.6% and 5.9%, respectively, with no difference noted in those who underwent breast conservation therapy vs. mastectomy (p = .347). The 8-year LRR rates were greater in the patients with ER-negative (10.6% vs. 4.2%, p = .016), PR-negative (9.0% vs. 4.2%, p = .009), or HER2-positive (17.5% vs. 3.9%, p = 0.009) tumors. On multivariate analysis, ER-negative and PR-negative disease (hazard ratio, 2.37; p = .046) and HER2-positive disease (hazard ratio, 3.13, p = .016) independently predicted for LRR. Conclusion: Patients with ER/PR-negative or HER2-positive T1a,bN0 breast cancer had a greater risk of LRR. Therapeutic strategies, such as the use of chemotherapy and/or anti-HER2 therapies, should be considered for future clinical trials for these patients.},
doi = {10.1016/j.ijrobp.2009.12.011},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 77,
place = {United States},
year = 2010,
month = 8
}
  • Purpose: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). Methods and Materials: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. Results: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) ofmore » 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. Conclusion: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.« less
  • Purpose: To evaluate the prognostic value of determining estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression in node-positive breast cancer patients treated with mastectomy. Methods and Materials: The records of 835 node-positive breast cancer patients who had undergone mastectomy between January 2000 and December 2004 were analyzed retrospectively. Of these, 764 patients (91.5%) received chemotherapy; 68 of 398 patients (20.9%) with T1-2N1 disease and 352 of 437 patients (80.5%) with T3-4 or N2-3 disease received postoperative radiotherapy. Patients were classified into four subgroups according to hormone receptor (Rec+ or Rec-) and HER2 expression profiles:more » Rec-/HER2- (triple negative; n = 141), Rec-/HER2+ (n = 99), Rec+/HER2+ (n = 157), and Rec+/HER2- (n = 438). The endpoints were the duration of locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival. Results: Patients with triple-negative, Rec-/HER2+, and Rec+/HER2+ expression profiles had a significantly lower 5-year locoregional recurrence-free survival than those with Rec+/HER2- profiles (86.5% vs. 93.6%, p = 0.002). Compared with those with Rec+/HER2+ and Rec+/HER2- profiles, patients with Rec-/HER2- and Rec-/HER2+ profiles had significantly lower 5-year distant metastasis-free survival (69.1% vs. 78.5%, p = 0.000), lower disease-free survival (66.6% vs. 75.6%, p = 0.000), and lower overall survival (71.4% vs. 84.2%, p = 0.000). Triple-negative or Rec-/HER2+ breast cancers had an increased likelihood of relapse and death within the first 3 years after treatment. Conclusions: Triple-negative and HER2-positive profiles are useful markers of prognosis for locoregional recurrence and survival in node-positive breast cancer patients treated with mastectomy.« less
  • Purpose: Breast conservation surgery (BCS) and radiotherapy (RT) following neoadjuvant chemotherapy (NCT) have been linked with high locoregional recurrence (LRR) rates and ipsilateral breast tumor recurrence (IBTR) rates. The purpose of this study was to analyze clinical outcomes in patients who exhibited LRR and IBTR after being treated by BCS and RT following NCT. Methods and Materials: In total, 251 breast cancer patients treated with BCS and RT following NCT between 2001 and 2006 were included. All patients had been shown to be clinically node-positive. Clinical stage at diagnosis (2003 AJCC) was II in 68% of patients and III inmore » 32% of patients. Of those, 50%, 35%, and 15% of patients received anthracycline-based, taxane-based, and combined anthracycline-taxane NCT, respectively. All patients received RT. Results: During follow-up (median, 55 months), 26 (10%) patients had LRR, 19 of these patients had IBTR. Five-year actuarial rates of IBTR-free and LRR-free survival were 91% and 89%, respectively. In multivariate analyses, lack of hormone suppression therapy was found to increase both LRR and IBTR rates. Hazard ratios were 7.99 (p < 0.0001) and 4.22 (p = 0.004), respectively. Additionally, pathology stage N2 to N3 increased LRR rate (hazard ratio, 4.22; p = 0.004), and clinical AJCC stage III IBTR rate (hazard ratio, 9.05; p = 0.034). Achievement of pathological complete response and presence of multifocal tumors did not affect LRR or IBTR. Conclusions: In patients with locally advanced disease, who were clinically node-positive at presentation, BCS after NCT resulted in acceptably low rates of IBTR and LRR. Mastectomy should be considered as an option in patients who present with clinical stage III tumors or who are not treated with adjuvant hormone suppression therapy, because they exhibit high IBTR rates after NCT and BCS.« less
  • Purpose: To examine the power of the nodal ratio (NR) of positive/excised nodes in predicting postmastectomy locoregional recurrence (LRR) in patients with 1-3 positive nodes (N+) and in identifying cohorts at similar risk across independent data sets. Methods and Materials: Data from 82 patients with 1-3 N+ treated without postmastectomy radiotherapy (PMRT) in the British Columbia (BC) randomized trial were compared with data from 462 patients treated without PMRT in prospective chemotherapy trials at the M. D. Anderson Cancer Center (MDACC). Kaplan-Meier LRR curves were compared between centers using the absolute number of N+ and nodal ratios. Results: The medianmore » number of excised nodes was 10 in BC and 16 in MDACC (p < 0.001). Examining LRR by number of N+, the 10-year LRR rate for patients with 1-3 N+ was higher in BC compared with MDACC (21.5% vs. 12.6%; p = 0.02). However, when examining LRR using NR, no differences were found between institutions. In patients with NR {<=} 0.20, the 10-year LRR rate was 17.7% BC vs. 10.9% MDACC (p = 0.27). In patients with NR {>=} 0.20, the 10-year LRR rate was 28.7% BC vs. 22.7% MDACC (p = 0.32). On Cox regression analysis, NR was a stronger prognostic factor compared with number of N +. Conclusions: In patients with 1-3 N+, evaluating nodal positivity using NR reduced inter-institutional differences in LRR estimates that may exist due to variations in numbers of nodes excised. Nodal ratio >0.20 was associated with LRR >20%, warranting PMRT consideration. Nodal ratio may be useful for extrapolating data from prospective trials to clinical practices in which axillary staging extent vary.« less
  • Purpose: Postmastectomy radiation therapy (PMRT) can reduce locoregional recurrences (LRR) in high-risk patients, but its role in the treatment of lymph node negative (LN-) breast cancer remains unclear. The aim of this study was to identify a subgroup of T1-T2 breast cancer patients with LN- who might benefit from PMRT. Methods and Materials: We retrospectively reviewed 1,136 node-negative T1-T2 breast cancer cases treated with mastectomy without PMRT at the Massachusetts General Hospital between 1980 and 2004. We estimated cumulative incidence rates for LRR overall and in specific subgroups, and used Cox proportional hazards models to identify potential risk factors. Results:more » Median follow-up was 9 years. The 10-year cumulative incidence of LRR was 5.2% (95% CI: 3.9-6.7%). Chest wall was the most common (73%) site of LRR. Tumor size, margin, patient age, systemic therapy, and lymphovascular invasion (LVI) were significantly associated with LRR on multivariate analysis. These five variables were subsequently used as risk factors for stratified analysis. The 10-year cumulative incidence of LRR for patients with no risk factors was 2.0% (95% CI: 0.5-5.2%), whereas the incidence for patients with three or more risk factors was 19.7% (95% CI: 12.2-28.6%). Conclusion: It has been suggested that patients with T1-T2N0 breast cancer who undergo mastectomy represent a favorable group for which PMRT renders little benefit. However, this study suggests that select patients with multiple risk factors including LVI, tumor size {>=}2 cm, close or positive margin, age {<=}50, and no systemic therapy are at higher risk of LRR and may benefit from PMRT.« less