Risk factors for locoregional recurrence after postmastectomy radiotherapy in breast cancer patients with four or more positive axillary lymph nodes

Background

We investigated risk factors for locoregional recurrence (lrr) in breast cancer patients with 4 or more positive axillary lymph nodes receiving postmastectomy radiotherapy (pmrt).

Methods

Medical records (1998–2007) were retrospectively reviewed for the population of interest. The Kaplan–Meier method was used to calculate the survival rate; Cox regression models were used for univariate and multivariate analysis of predictors of breast cancer lrr.

Results

The study enrolled 439 patients. Median duration of follow-up was 54 months. The 5-year rates of locoregional recurrence-free survival (lrrfs), distant metastasis–free survival (dmfs), and breast cancer–specific survival (bcss) were 87.8%, 59.5%, and 70.7% respectively. In patients with lrr and no concomitant metastasis, and in those without lrr, the 5-year rates of dmfs were 21.1% and 65.7% respectively (p < 0.001), and the 5-year rates of bcss were 34.5% and 76.4% respectively (p < 0.001).Univariate analysis showed that menopausal status (p = 0.041), pN stage (p = 0.006), and positivity for her2 [human epidermal growth factor receptor 2 (p = 0.003)] or the triple-negative disease subtype (p < 0.001) were determinants of lrrfs. Multivariate analysis showed that pN3 stage [hazard ratio (hr): 2.241; 95% confidence interval (ci): 1.270 to 3.957; p = 0.005], her2 positivity (hr: 2.705; 95% ci: 1.371 to 5.335; p = 0.004), and triple-negative disease subtype (hr: 4.617; 95% ci: 2.192 to 9.723; p < 0.001) were independent prognostic factors of lrrfs.

Conclusions

In breast cancer patients with 4 or more positive axillary lymph nodes who undergo pmrt for breast cancer, lrr significantly influences survival. Patients who developed lrr carried a high risk for distant metastasis and death. Pathologic stage (pN3), her2 positivity, and the triple-negative disease subtype are risk factors that significantly influence lrrfs.     

Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph nodes without adjuvant radiotherapy

PURPOSE: To analyze the incidence and risk factors for locoregional recurrence (LRR) in patients with breast cancer who had T1 or T2 primary tumor and 1-3 histologically involved axillary lymph nodes treated with modified radical mastectomy without adjuvant radiotherapy (RT). MATERIALS AND METHODS: Between April 1991 and December 1998, 125 patients with invasive breast cancer were treated with modified radical mastectomy and were found to have 1-3 positive axillary nodes. The median number of nodes examined was 17 (range 7-33). Of the 125 patients, 110, who had no adjuvant RT and had a minimum follow-up of 25 months, were included in this study. Sixty-nine patients received adjuvant chemotherapy and 84 received adjuvant hormonal therapy with tamoxifen. Patient-related characteristics (age, menopausal status, medial/lateral quadrant of tumor location, T stage, tumor size, estrogen/progesterone receptor protein status, nuclear grade, extracapsular extension, lymphovascular invasion, and number of involved axillary nodes) and treatment-related factors (chemotherapy and hormonal therapy) were analyzed for their impact on LRR. The median follow-up was 54 months. RESULTS: Of 110 patients without RT, 17 had LRR during follow-up. The 4-year LRR rate was 16.1% (95% confidence interval [CI] 9.1-23.1%). All but one LRR were isolated LRR without preceding or simultaneous distant metastasis. According to univariate analysis, age <40 years (p = 0.006), T2 classification (p = 0.04), tumor size >==3 cm (p = 0.002), negative estrogen receptor protein status (p = 0.02), presence of lymphovascular invasion (p = 0.02), and no tamoxifen therapy (p = 0.0006) were associated with a significantly higher rate of LRR. Tumor size (p = 0.006) was the only risk factor for LRR with statistical significance in the multivariate analysis. On the basis of the 4 patient-related factors (age <40 years, tumor >==3 cm, negative estrogen receptor protein, and lymphovascular invasion), the high-risk group (with 3 or 4 factors) had a 4-year LRR rate of 66.7% (95% CI 42.8-90.5%) compared with 7.8% (95% CI 2.2-13.3%) for the low-risk group (with 0-2 factors; p = 0.0001). For the 110 patients who received no adjuvant RT, LRR was associated with a 4-year distant metastasis rate of 49.0% (9 of 17, 95% CI 24.6-73.4%). For patients without LRR, it was 13.3% (15 of 93, 95% CI 6.3-20.3%; p = 0.0001). The 4-year survival rate for patients with and without LRR was 75.1% (95% CI 53.8-96.4%) and 88.7% (95% CI 82.1-95.4%; p = 0.049), respectively. LRR was independently associated with a higher risk of distant metastasis and worse survival in multivariate analysis. CONCLUSION: LRR after mastectomy is not only a substantial clinical problem, but has a significant impact on the outcome of patients with T1 or T2 primary tumor and 1-3 positive axillary nodes. Patients with risk factors for LRR may need adjuvant RT. Randomized trials are warranted to determine the potential benefit of postmastectomy RT on the survival of patients with a T1 or T2 primary tumor and 1-3 positive nodes.     

Effects of postmastectomy radiotherapy on prognosis in different tumor stages of breast cancer patients with positive axillary lymph nodes

Objective： To explore the effects of postmastectomy radiotherapy（PMRT） on the locoregional failure-free survival（LRFFS） and overall survival（OS） of breast cancer patients under different tumor stages and with one to three positive axillary lymph nodes（ALNs）. Methods： We conducted a retrospective review of 527 patients with one to three positive lymph nodes who underwent modified radical or partial mastectomy and axillary dissection from January 2000 to December 2002. The patients were divided into the T1-T2 N1 and T3-T4 N1 groups. The effects of PMRT on the LRFFS and OS of these two patient groups were analyzed using SPSS 19.0, Pearson＇s χ2-test, Kaplan-Meier method, and Cox proportional hazard model. Results： For T1-T2 N1 patients, no statistical significance was observed in the effects of PMRT on LRFFS [hazard ratio（HR）=0.726; 95% confidence interval（CI）： 0.233-2.265; P=0.582] and OS（HR=0.914; 95% CI： 0.478-1.745; P=0.784） of the general patients. Extracapsular extension（ECE） and high histological grade were the risk factors for LRFFS and OS with statistical significance in multivariate analysis. Stratification analysis showed that PMRT statistically improved the clinical outcomes in high-risk patients [ECE（＋）, LRFFS： P=0.026, OS： P=0.007; histological grade III, LRFFS： P〈0.001, OS： P=0.007] but not in low-risk patients [ECE（–）, LRFFS： P=0.987, OS： P=0.502; histological grade I-II, LRFFS： P=0.816, OS： P=0.296]. For T3-T4 N1 patients, PMRT effectively improved the local control（HR=0.089; 95% CI： 0.210-0.378; P=0.001） of the general patients, whereas no statistical effect was observed on OS（HR=1.251; 95% CI： 0.597-2.622; P=0.552）. Absence of estrogen receptors and progesterone receptors（ER/PR）（–） was an independent risk factor. Further stratification analysis indicated a statistical difference in LRFFS and OS between the high-risk patients with ER/PR（–） receiving PMRT and not receiving PMRT [ER/PR（–）, LRFF     

腋窝淋巴结1～3个转移的乳腺癌根治术后辅助放疗指征探讨

目的 回顾分析412例腋窝淋巴结1～3个转移的乳腺癌根治术后患者的预后因素,探讨术后辅助放疗的指征.方法 用Kaplan-Meier法计算生存率,用Logrank法和Cox模型分别进行单因素和多因素预后分析,分析影响局部复发和远处转移的预后因素.结果 随访率为98.7%.随访满5、10年者分别为215、41例.5、10年总生存率分别为90.0%、81.3%.无、有局部复发的5年总生存率分别为92.9%、69.9%(x2=20.79,P=0.000).5、10年局部复发±远处转移率分别为10.7%、18.6%.多因素分析显示T2期,≥2个腋窝淋巴结转移,雌、孕激素受体均阴性为影响局部复发的预后因素.含0～1、2～3个预后因素的10年局部复发率分别为3.9%、36.9%(x2=20.64,P=0.000).多因素分析显示局部复发、阳性淋巴结转移率＞25%为影响远处转移的预后因素,无、有局部复发的5年远处转移率分别为9.7%、36.6%(x2=16.34,P=0.000).结论 对腋窝淋巴结1～3个转移的乳腺癌根治术后患者且含2～3个影响局部复发的预后因素者建议行术后辅助放疗.     

术后放疗在伴有腋窝淋巴结1～3个转移的T1～T2期乳腺癌中的作用

目的分析T1-T2期伴有腋窝淋巴结1—3个转移的乳腺癌患者接受术后淋巴引流区放疗后的淋巴结复发率和胸壁复发率，并分析腋窝淋巴结转移率与复发率的相互关系。方法320例的中位年龄44岁（26—72岁），根治术或改良根治术清扫腋窝淋巴结中位数8个（1～24个），淋巴结转移率中位值为25％（5％-100％）。术后行同侧内乳和锁骨上淋巴引流区放疗，中位剂量50Gy分25次。结果中位随访期93个月（7—205个月）。5年总生存率为89．7％，无瘤生存率为83．4％。总5年淋巴结复发率和胸壁复发率分别为7．9％、5．7％。淋巴结转移率〈30％和〉t30％的5年淋巴结复发率分别为4．4％、14．2％（x^2=9．49，P=0．002）。淋巴结转移率〈30％和t〉30％的5年胸壁复发率分别为3．5％、9．6％（x^2=5．61，P=0．018）。淋巴结转移率t〉30％伴佗期的5年淋巴结复发率和胸壁复发率分别为15．8％和12．2％。淋巴结转移率≥30％伴年龄≤35岁的5年淋巴结复发率和胸壁复发率分别为40．0％和20．0％。多因素分析显示年龄和淋巴结转移率是总复发率的独立预后因素。胸壁复发率独立危险因素为淋巴结转移率。结论T1-T2期乳腺癌伴有腋窝淋巴结1—3个转移者中，淋巴结转移率t〉30％伴他期或年龄≤35岁者胸壁复发率较高，需考虑术后淋巴引流区域和胸壁放疗。     

Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy

PURPOSE: To define the individual factors and combinations of factors associated with increased risk of locoregional recurrence (LRR) that may justify postmastectomy radiotherapy (PMRT) in patients with T1-T2 breast cancer and one to three positive nodes. METHODS AND MATERIALS: The study cohort comprised 821 women referred to the British Columbia Cancer Agency between 1989 and 1997 with pathologic T1-T2 breast cancer and one to three positive nodes treated with mastectomy without adjuvant RT. The 10-year Kaplan-Meier estimates of isolated LRR and LRR with or without simultaneous distant recurrence (LRR +/- SDR) were analyzed according to age, histologic findings, tumor location, size, and grade, lymphovascular invasion status, estrogen receptor (ER) status, margin status, number of positive nodes, number of nodes removed, percentage of positive nodes, and systemic therapy use. Multivariate analyses were performed using Cox proportional hazards modeling. A risk classification model was developed using combinations of the statistically significant factors identified on multivariate analysis. RESULTS: The median follow-up was 7.7 years. Systemic therapy was used in 94% of patients. Overall, the 10-year Kaplan-Meier isolated LRR and LRR +/- SDR rate was 12.7% and 15.9%, respectively. Without PMRT, a 10-year LRR risk of >20% was identified in women with one to three positive nodes plus at least one of the following factors: age <45 years, Stage T2, histologic Grade 3, ER-negative disease, medial location, more than one positive node, or >25% of nodes positive (all p < 0.05 on univariate analysis). On multivariate analysis, age <45 years, >25% of nodes positive, medial tumor location, and ER-negative status were statistically significant predictors of isolated LRR and LRR +/- SDR. In the classification model, the first split was according to age (<45 years vs. >/=45 years), with 29.3% vs. 13.7% developing LRR +/- SDR (p < 0.0001). Of 123 women <45 years, the presence of >25% of nodes positive was associated with a risk of LRR +/- SDR of 58.0% compared with 23.8% for those with 45 years, the presence of >25% of nodes positive also conferred a greater LRR +/- SDR risk (26.7%) compared with women with 45 years with 25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT.     

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes

BACKGROUND: Adjuvant therapy for women with T1-T2 breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.     

T1～T2期伴1～3个腋窝淋巴结转移乳腺癌患者改良根治术后放疗的作用

目的 回顾性分析370例T1～T2期、腋窝淋巴结转移数为1～3个乳腺癌患者改良根治术后的治疗结果,探讨放疗的作用.方法 用Kaplan-Meier法计算生存率,分析放疗对生存率和复发率的影响,同时分析对未放疗患者复发率有影响的临床病理因素.结果 中位随访时间为50个月(9～91个月).全组患者的5年无局部区域复发率为91.0%,总生存率为85.4%.放疗显著提高5年无局部区域复发生存率(100%和89.5%;x2=5.17,P=0.023),对总生存率无影响.对319例未行放疗患者的单因素分析显示T分期、腋窝淋巴结阳性数、C-erbB-2和PR状态是预测无复发生存率的有意义因素.结论 T1～T2期且腋窝淋巴结转移数1～3个乳腺癌患者改良根治术后,放疗显著降低局部复发率,但对总生存率无影响.T分期、腋窝淋巴结阳性数、C-erbB-2和PR状态是预测元复发生存率的有意义因素.     

Predictors of positive axillary lymph nodes in breast cancer patients with metastatic sentinel lymph node

INTRODUCTION: Breast cancer with metastatic sentinel lymph nodes (SLN) may have clinico-pathologic factors associated with the presence of positive non-sentinel axillary nodes (NSLN). The aim of the present study was to determine factors that predict involvement of NSLN in breast cancer patients with positive SLN. MATERIAL AND METHODS: A prospective database search identified 80 patients who underwent SLN biopsy for invasive breast cancer between January 1999 and August 2002. Clinico-pathologic data was analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: A total of 23 patients had positive SLN and underwent conventional axillary lymph node dissection. Statistical analysis revealed that lympho-vascular invasion (p~0.00000), SLN metastasis >2 mm (p=0.002), and the presence of extra-nodal involvement (p=0.002), were positive predictors of the metastatic involvement of NSLN. CONCLUSIONS: The likelihood of positive NSLN correlates with pathologic parameters such as the presence of lympho-vascular invasion, size of the SLN metastasis, and extra-nodal involvement. These data may be helpful with the regard to the decision to undertake axillary dissection in breast cancer patients with metastatic sentinel lymph nodes.     

Minimal impact of postmastectomy radiation therapy on locoregional recurrence for breast cancer patients with 1 to 3 positive lymph nodes in the modern treatment era

Introduction

Given modern treatment strategies, controversy remains regarding whether postmastectomy radiation therapy (PMRT) is necessary for breast cancer patients with 1–3 positive axillary lymph nodes (ALN). Our aim was to assess the significance of PMRT in the modern treatment era for these patients.

放疗对乳腺癌全乳切除术后腋窝淋巴结1~3个转移患者的意义

乳腺癌是危害女性健康的主要恶性肿瘤之一。随着乳腺癌综合治疗的深入研究和广泛应用,放疗在治疗中的作用越来越不容忽视。国际上对于腋窝1～3个转移淋巴结患者术后是否需要放疗一直尚未达成共识,影响这类患者预后的高危因素有哪些仍是各国学者讨论的热点。本文就放疗对乳腺癌全乳切除术后腋窝淋巴结1～3个转移患者的意义作一综述。     

Minimal risk of macrometastases in the non-sentinel axillary lymph nodes in breast cancer patients with micrometastatic sentinel lymph nodes and preoperatively ultrasonically uninvolved axillary lymph nodes

Micrometastases in the sentinel lymph node (SLN) carry a considerable risk of macrometastases in the non-sentinel lymph nodes (NSLN), resulting in axillary lymph node dissection (ALND). Preoperative ultrasound (US) examination of the axillary lymph nodes combined with a fine-needle aspiration biopsy (FNAB) has been proved to discover metastases in the axillary lymph nodes. The aim of our study was to assess the risk of macrometastases in NSLN in patients with micrometastatic SLN after a preoperative US examination of the axillary lymph nodes. The study included 36 patients in whom, after preoperative axillary US, micrometastases in the SLN were revealed and ALND was subsequently performed. At final histopathology, no macrometastases were discovered in the NSLN. In four patients, additional micrometastases were discovered in the NSLN. In conclusion, the risk of macrometastases in the NSLN in patients with preoperatively ultrasonically uninvolved axillary lymph nodes is minimal.     

临床腋窝淋巴结阳性乳腺癌患者内乳区前哨淋巴结活检术研究*

目的：评估临床腋窝淋巴结阳性乳腺癌患者行内乳区前哨淋巴结活检术（IM-SLNB）的临床意义。方法：2013年6 月至2014年10月对山东省肿瘤医院乳腺病中心就诊的64例临床腋窝淋巴结阳性的原发性乳腺癌患者行前瞻性单臂入组研究,采取腋窝淋巴结清扫术,同时均应用新的核素注射技术进行IM-SLNB。结果：64例患者中内乳区前哨淋巴结（IM-SLN）显像为38例,显像率为59.4%（38/ 64）。 38例IM-SLN 显像患者中IM-SLNB 成功率为100%（38/ 38）,并发症发生率为7.9%（3/ 38）,IM-SLN 转移率为21.1%（8/ 38）。 肿瘤位于内上象限和腋窝淋巴结转移数目较多的患者,其IM-SLN 转移率较高（P < 0.001 和P = 0.017）。 患者临床获益率为59.4%（38/ 64）,其中12.5%（8/ 64）另接受了内乳区放疗、46.9%（30/ 64）避免了不必要的内乳区放疗。结论：临床腋窝淋巴结阳性的乳腺癌应进行IM-SLNB,尤其对于肿瘤位于内上象限及怀疑存在较多腋窝淋巴结转移数目的患者,以获得内乳区淋巴结的转移状态,指导乳腺癌患者内乳区放疗。     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.     

1至3个腋窝淋巴结转移乳腺癌根治术后放疗的应用

Nowadays the decision whether to offer early breast cancer patients with 1～3 positive axillary nodes adjuvant radiotherapy is a heated controversy. Results of several randomized trials have shown that post-mastectomy radiotherapy including the whole chest wall and regional lymph node-bearing areas can improve the Iocoregional control and survival rate of patients with 1～3 positive axillary nodes. Tumor size and stage, number of dissected nodes, positive lymph node ratio, extracapsular extension and lymphovascular invasion may determine whether post-mastectomy radiotherapy is needed or not for these patients. The best radiotherapy approach and patients selections should be verified by further prospective randomized control clinical trials.