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Title: pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

Abstract

Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examined outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RRmore » events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal locoregional management for women with pN0(i+) breast cancer.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [1];  [1];  [2];  [1];  [2]
  1. Radiation Therapy Program, Vancouver Island and Vancouver Centre, British Columbia Cancer Agency, University of British Columbia, Victoria, BC (Canada)
  2. (Canada)
  3. University of Victoria, Victoria, BC (Canada)
Publication Date:
OSTI Identifier:
22267943
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 87; Journal Issue: 4; Other Information: Copyright (c) 2013 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; MAMMARY GLANDS; NEOPLASMS; PATIENTS; RADIOTHERAPY; TUMOR CELLS

Citation Formats

Karam, Irene, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Lesperance, Maria F., Berrang, Tanya, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Speers, Caroline, Tyldesley, Scott, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca, and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes. United States: N. p., 2013. Web. doi:10.1016/J.IJROBP.2013.07.028.
Karam, Irene, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Lesperance, Maria F., Berrang, Tanya, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Speers, Caroline, Tyldesley, Scott, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca, & Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes. United States. doi:10.1016/J.IJROBP.2013.07.028.
Karam, Irene, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Lesperance, Maria F., Berrang, Tanya, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Speers, Caroline, Tyldesley, Scott, Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC, Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca, and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC. Fri . "pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes". United States. doi:10.1016/J.IJROBP.2013.07.028.
@article{osti_22267943,
title = {pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes},
author = {Karam, Irene and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC and Lesperance, Maria F. and Berrang, Tanya and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC and Speers, Caroline and Tyldesley, Scott and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC and Truong, Pauline T., E-mail: ptruong@bccancer.bc.ca and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC},
abstractNote = {Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examined outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal locoregional management for women with pN0(i+) breast cancer.},
doi = {10.1016/J.IJROBP.2013.07.028},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 87,
place = {United States},
year = {Fri Nov 15 00:00:00 EST 2013},
month = {Fri Nov 15 00:00:00 EST 2013}
}
  • 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: 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
  • Purpose: Locoregional control is associated with breast cancer-specific and overall survival in select women with breast cancer. Although several patient, tumor, and treatment characteristics have been shown to contribute to locoregional recurrence (LRR), studies evaluating factors related to radiotherapy (XRT) technique have been limited. We investigated the relationship between LRR location and XRT fields and dose delivered to the primary breast cancer in women experiencing subsequent locoregional relapse. Methods and Materials: We identified 21 women who were previously treated definitively with surgery and XRT for breast cancer. All patients developed biopsy-result proven LRR and presented to Emory University Hospital betweenmore » 2004 and 2010 for treatment. Computed tomography (CT) simulation scans with XRT dose files for the initial breast cancer were fused with {sup 18}F-labeled fluorodeoxyglucose positron emission tomography (FDG PET)/CT images in DICOM (Digital Imaging and Communications in Medicine) format identifying the LRR. Each LRR was categorized as in-field, defined as {>=}95% of the LRR volume receiving {>=}95% of the prescribed whole-breast dose; marginal, defined as LRR at the field edge and/or not receiving {>=}95% of the prescribed dose to {>=}95% of the volume; or out-of-field, that is, LRR intentionally not treated with the original XRT plan. Results: Of the 24 identified LRRs (3 patients experienced two LRRs), 3 were in-field, 9 were marginal, and 12 were out-of-field. Two of the 3 in-field LRRs were marginal misses of the additional boost XRT dose. Out-of-field LRRs consisted of six supraclavicular and six internal mammary nodal recurrences. Conclusions: Most LRRs in our study occurred in areas not fully covered by the prescribed XRT dose or were purposely excluded from the original XRT fields. Our data suggest that XRT technique, field design, and dose play a critical role in preventing LRR in women with breast cancer.« less
  • Purpose: To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. Methods and Materials: The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. Results: On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and beingmore » ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Conclusion: Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.« less
  • Evidence is presented compatible with the hypothesis that the inevitable tissue injury to the breast engendered by mastectomy or primary radiotherapy may in itself be a factor facilitating recurrence through a variety of local, regional, and systemic tumor-promoting mechanisms. The potential for tumor enhancement appears to be commensurate with the extent of injury and concerns both local and systemic recurrence. The hypothesis lends itself well to experimental testing. If confirmed, it will point to the importance of minimizing any form of tissue injury in the process of treating primary breast cancer, be it by operation or irradiation and curtailing themore » extent or intensity of both.« less