Postmastectomy radiotherapy: patterns of recurrence and long-term disease control using electrons

PURPOSE: To determine the patterns of failure and prognostic factors for locoregional recurrence after postmastectomy radiotherapy (RT), using a specific electron beam technique. METHODS AND MATERIALS: A uniform electron beam was used in 323 patients with invasive breast cancer at the University of Florida Health Science Center. The patterns of disease recurrence, prognostic factors, and overall outcome were studied. RESULTS: At 10 years, the freedom from locoregional recurrence, disease-free survival, and absolute survival rate was 90%, 62%, and 55%, respectively. The 10-year disease-free survival rate for patients with 0, 1-3, and >3 positive lymph nodes was 73%, 75%, and 47%, respectively. On multivariate analysis, the three factors significantly associated with locoregional recurrence were T stage, number of involved nodes, and RT fields. Full axillary fields appeared to be beneficial (p = 0.02). Patients with positive surgical margins appeared to benefit from a mastectomy incision boost to >/=65 Gy. Finally, patients with T2N0 disease had a substantial risk of chest wall recurrence without chest wall RT. CONCLUSION: Findings include a low rate of clinically detectable locoregional recurrence. The data suggest benefits for the addition of full axillary RT in node-positive patients and chest wall RT in patients with T2N0 disease.     

乳腺癌改良根治术后T1-2N1期患者局部区域复发的部位分析

目的 分析乳腺癌改良根治术后T1-2N1患者的局部区域复发(LRR)部位分布,探讨放疗的照射范围。方法 1997年9月至2015年4月中国医学科学院肿瘤医院收治2472例改良根治术后T1-2N1女性乳腺癌患者,均未行新辅助治疗。1898例未行术后放疗的患者纳入本研究,分析患者的局部和区域复发部位。采用Kaplan-Meier法进行局部复发率和区域复发率计算,采用Log-Rank法对影响患者局部复发和区域复发的各因素分别进行单因素分析,纳入单因素分析P值小于0.05的因素进行Cox回归法多因素分析。结果 中位随访时间71.3个月,164例(8.6%)患者发生局部和(或)区域复发。其中复发在锁骨上106例(65%),胸壁69例(42%),腋窝39例(24%),内乳19例(12%)。多因素分析显示年龄(>45岁/≤45岁)、肿瘤位置(其他象限/内象限)、T分期(T1/T2)、腋窝阳性淋巴结数(1个/2~3个)、激素受体(阳性/阴性)是局部复发和区域复发共同的影响因素。结论 乳腺癌改良根治术后T1-2N1期患者的LRR部位主要是锁骨上,其次是胸壁,腋窝和内乳少见。影响局部和区域复发的高危因素基本相似,放疗患者建议照射锁骨上区和胸壁。     

乳腺癌改良根治术后T1-2N1期患者局部区域复发的部位分析

目的 分析乳腺癌改良根治术后T1-2N1患者的局部区域复发(LRR)部位分布,探讨放疗的照射范围。方法 1997年9月至2015年4月中国医学科学院肿瘤医院收治2472例改良根治术后T1-2N1女性乳腺癌患者,均未行新辅助治疗。1898例未行术后放疗的患者纳入本研究,分析患者的局部和区域复发部位。采用Kaplan-Meier法进行局部复发率和区域复发率计算,采用Log-Rank法对影响患者局部复发和区域复发的各因素分别进行单因素分析,纳入单因素分析P值小于0.05的因素进行Cox回归法多因素分析。结果 中位随访时间71.3个月,164例(8.6%)患者发生局部和(或)区域复发。其中复发在锁骨上106例(65%),胸壁69例(42%),腋窝39例(24%),内乳19例(12%)。多因素分析显示年龄(>45岁/≤45岁)、肿瘤位置(其他象限/内象限)、T分期(T1/T2)、腋窝阳性淋巴结数(1个/2~3个)、激素受体(阳性/阴性)是局部复发和区域复发共同的影响因素。结论 乳腺癌改良根治术后T1-2N1期患者的LRR部位主要是锁骨上,其次是胸壁,腋窝和内乳少见。影响局部和区域复发的高危因素基本相似,放疗患者建议照射锁骨上区和胸壁。     

Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report

BackgroundRates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT).Patients and methodsLocal, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years.ResultsTen-year cumulative incidence for chest wall recurrence of >15% was seen in patients aged <40 years (16.1%), with ≥4 positive nodes (16.5%) or 0–7 uninvolved nodes (15.1%); for supraclavicular failures >10%: ≥4 positive nodes (10.2%); for axillary failures of >5%: aged <40 years (5.1%), unknown primary tumor size (5.2%), 0–7 uninvolved nodes (5.2%). In patients with 1–3 positive nodes, 10-year cumulative incidence for chest wall recurrence of >15% were age <40, peritumoral vessel invasion or 0–7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site.ConclusionPMRT to the chest wall and supraclavicular fossa is supported in patients with ≥4 positive nodes. With 1–3 positive nodes, chest wall PMRT may be considered in patients aged <40 years, with 0–7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.     

改良根治术后pT1-2N1期乳腺癌的局部区域复发部位——12个中心 5442例患者的联合分析

目的 分析改良根治术后pT1-2N1期乳腺癌患者的局部区域复发(LRR)部位及放疗对复发的影响。方法 收集中国12家医院符合条件的 5442例乳腺癌患者资料,分析放疗和未放疗患者的LRR部位及不同部位放疗对复发的影响。采用Kaplan-Meier法计算LRR率并log-rank法检验。结果 全组中位随访63.8个月,395例患者出现LRR。无论辅助放疗与否和不同分子分型,胸壁和锁骨上区均为最常见的LRR部位。全组胸壁照射和未照射患者的 5年胸壁复发率分别为2.5%和3.8%(P=0.003);锁骨上区照射和未照射患者的 5年锁骨上淋巴结复发率分别为1.3%和4.1%(P<0.001);腋窝照射和未照射患者的 5年无腋窝复发率分别为0.8%和1.5%(HR=0.31,95%CI为 0.04~2.23,P=0.219);内乳照射和未照射患者的 5年无内乳复发率分别为0.8%和1.5%(HR=0.45,95%CI为 0.11~1.90,P=0.268)。结论 改良根治术后pT1-2N1期乳腺癌患者的主要LRR部位是胸壁和锁骨上区,不受辅助放疗与否和分子分型的影响。胸壁和锁骨上区放疗显著降低相应部位的复发风险,而腋窝和内乳放疗未降低相应部位的复发风险。     

Post-mastectomy radiotherapy in pT3N0M0 breast cancer: is it needed?

BACKGROUND AND PURPOSE: It is not been established whether breast cancer patients who have a primary tumor 5 cm or larger but no axillary nodal or distant metastases at the time of the diagnosis (pT3N0M0) benefit from post-operative radiation therapy after mastectomy. MATERIAL AND METHODS: We identified 81 patients with T3N0M0 breast cancer out of the total of 4190 breast cancer patients treated in one university radiotherapy department from 1987 to 1994 from the department patient registry, and examined the clinical records and histopathological slides. RESULTS: Only 38 of the 81 patients had true pT3N0M0 breast cancer after the review (0.9% of the 4190 new breast cancer patients registered in the department from 1987 to 1994). Three (60%) of the five patients who were not treated with post-operative radiation therapy developed locoregional recurrence of breast cancer as compared with only three (9%) of the 33 patients who were given post-operative radiotherapy during a median follow-up of 58 months (P = 0.0003). Patients who were given post-operative radiotherapy had a better distant disease-free survival rate (P = 0.04) and overall survival rate (P = 0.03) than the ones who were not treated with radiation therapy after surgery. Of the 29 patients who had chest wall irradiation only, one had in-field recurrence at the surgical scar, one both at the scar and the unirradiated axilla, and only one (3%) solely in the axilla. CONCLUSIONS: Patients with true pT3N0M0 breast cancer are rare. The results suggest that women with pT3N0M0 breast cancer benefit from post-operative radiotherapy, but the value of irradiating the dissected ipsilateral axilla remains unsettled.     

Survival following locoregional recurrence of breast cancer: univariate and multivariate analysis.

Although prognostic variables for locoregional recurrence of breast cancer have been evaluated by univariate analysis, multifactorial analysis has not been previously performed. In the present study, survival following chest wall and/or regional lymphatic recurrence was determined in 230 patients with locoregionally recurrent breast cancer without evidence of distant metastases treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology and affiliated hospitals. Multifactorial analysis demonstrated that the site of recurrences correlated most strongly with overall survival (p = 0.001). The 5-year actuarial overall survival was 44-49% for patients with isolated chest wall, axillary, and internal mammary lymph node recurrence. Patients with either supraclavicular, multiple lymphatic, or concomitant chest wall and lymphatic recurrence had an 21-24% 5-year overall survival. The 5-year disease-free survival was 28-37% for patients with chest wall, axillary, or internal mammary recurrences compared to 4-13% for those with supraclavicular, chest wall and lymphatic, or those with multiple sites of lymphatic recurrence. Disease-free interval from mastectomy to recurrence was also found to be a significant prognostic factor for overall survival (p = 0.005). Fifty percent of patients with a disease-free interval of at least 2 years survived 5 years following locoregional relapse, compared to 35% for those with disease-free interval of less than 2 years. In the subset of patients with small chest wall recurrences (excised or less than 3 cm) and a disease-free interval of at least 2 years, the 5-year overall and disease-free survivals were 67% and 54%, respectively. These results suggest that subsets of patients with locoregional recurrence of breast cancer can survive for long periods of time. The conventional wisdom that chest wall and/or regional nodal recurrence following mastectomy uniformly confers a dismal prognosis is not necessarily true.     

Significance of axillary lymph node extranodal soft tissue extension and indications for postmastectomy irradiation.

BACKGROUND: Extranodal soft tissue extension of axillary lymph node metastases (ETE) has been considered an indication for postmastectomy radiotherapy, including the axilla. However, it is unclear whether patients with ETE are at an increased risk of axillary recurrence. METHODS: From a single institutional database of 2362 patients with breast carcinoma treated between 1974-1994, a total of 487 patients who underwent mastectomy for lymph node positive, infiltrating (T1-T3) breast carcinoma was found. All the patients had pathologically confirmed axillary lymph node metastases and negative surgical margins; none had received postoperative irradiation. Of these patients, 50 had histologically documented axillary ETE. Forty-three patients had a minimum follow-up of at least 1 year and comprise the study population. The median follow-up time of surviving ETE positive patients was 79 months. Twenty-five patients (58.1%) received adjuvant systemic therapy. Sites of first failure were local or distant. Local failure was categorized further as chest wall failure, axillary failure, supraclavicular lymph node failure, or internal mammary lymph node failure. RESULTS: For the 43 patients with ETE, the median patient age was 59.5 years (range, 38-81 years) and the median tumor size was 3.6 cm (range, 0.5-12.0 cm). The median number of positive axillary lymph nodes was 6 (range, 1-36 lymph nodes) versus 2 (range, 1-30 lymph nodes) for all T1-T3 ETE positive patients compared with ETE negative patients (P < 0. 001). The risk of ETE increased significantly with increasing numbers of axillary lymph node metastases (P < 0.001). Of the patients with ETE, 16 (37.2%) developed recurrent disease. ETE positive patients with disease recurrence had significantly greater numbers of positive axillary lymph nodes (median, 10 lymph nodes) than those patients who were recurrence free (median, 4 lymph nodes) (P = 0.02). The site of first failure was local in 7 patients (16. 3%) and distant in 9 patients (20.9%). All patients with local recurrence had chest wall failures; there were no isolated lymph node recurrences. The only simultaneous local and distant failure was in one patient presenting with supraclavicular and intraabdominal metastases. CONCLUSIONS: The risk of axillary recurrence, either as an isolated event or as part of simultaneous failure, is extremely low, even in patients with ETE. These data suggest that patients with ETE frequently have higher numbers of positive axillary lymph nodes and on that basis are at risk for local recurrence and as a rule would be considered for postmastectomy irradiation. However, these data suggest that the presence of ETE is not an indication for routine postmastectomy axillary lymph node irradiation.     

Outcome of postmastectomy radiotherapy after primary systemic treatment in patients with clinical T1-2N1 breast cancer

Purpose

The role of postmastectomy radiotherapy following primary systemic treatment in patients with clinical T1-2N1 breast cancer remains a controversial issue. The purpose of this study was to evaluate the benefit of postmastectomy radiotherapy following primary systemic treatment.

Breast cancer in very young women

Aims

The purpose was to analyse the characteristics, treatment, recurrences and survival of very young women with breast cancer.

Methods

212 female breast cancer patients ≤35 years old were treated during 1997-2007. The median follow-up time was 78 months.

Results

117 patients had lymph node metastases and 14 distant metastases at diagnosis. 81 (38%) tumours were hormone receptor negative and 130 (65%) grade 3. HER2 positivity was seen in 47 (34%) and triple negativity in 35 (26%) of the 137 tumours with known HER2 status. 140 women were treated with mastectomy and 68 with breast conserving surgery. 163 patients received postoperative radiotherapy, 175 adjuvant chemotherapy, 95 endocrine therapy and 18 trastuzumab. 63 patients experienced a recurrence, of which 20 had only a locoregional recurrence. 10 (15%) of the women with breast conserving surgery experienced ipsilateral breast tumour recurrence while ipsilateral thoracic wall recurrence was seen in 8 patients (6%) after mastectomy. Seven of these eight patients did not receive postmastectomy radiotherapy. DFI was shorter in patients with hormone receptor positive tumours. At the end of follow-up 44 women had died. The 5-year OS was 80%.

Conclusions

The 5-year OS for young women has become better but is still lower than for all breast cancer patients. DFI was shorter in patients with hormone receptor positive disease. Locoregional recurrences were seen more often after breast conserving surgery.     

A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer

OBJECTIVE: Postoperative radiotherapy is frequently employed among breast cancer patients with positive surgical margins after mastectomy but there is little evidence to support this practice. This study examined relapse and survival among women with node-negative breast cancer and positive surgical margins after mastectomy. METHODS: Among 2570 women diagnosed between 1989 and 1998 and referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0 invasive breast cancer treated with mastectomy, 94 had positive surgical margins and formed the study cohort. Women with more established indications for postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease were excluded. Demographic, tumor, and treatment factors; relapse patterns; and Kaplan-Meier 8-year locoregional relapse-free, breast cancer-specific, and overall survival rates were compared between women who were treated with (n = 41) and without (n = 53) PMRT. RESULTS: Median follow-up time was 7.7 years. The distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen receptor status, and number of axillary nodes removed were similar between the two treatment groups. Six local chest wall recurrences (6.4%), 4 regional recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local relapse rates were 2.4% vs. 9.4% (p = 0.23), and regional relapse rates were 2.4% vs. 5.7% (p = 0.63), with and without PMRT, respectively. Trends for higher cumulative locoregional relapse (LRR) rates without PMRT were identified in the presence of age <==50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%). Statistical significance was not demonstrated in these differences (p > 0.10), possibly because of the small number of events. In patients with age >50 years, T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse occurred even with positive margins. PMRT did not improve distant relapse, 8-year breast cancer-specific and overall survival rates. CONCLUSION: This study suggests that not all patients with node-negative breast cancer with positive margins after mastectomy require radiotherapy. Locoregional failure rates approximating 20% were observed in women with positive margins plus at least one of the following factors: age <==50 years, T2 tumor size, grade III histology, or LVI. The absolute and relative improvements in locoregional control with radiotherapy in these situations support the judicious, but not routine, use of PMRT for positive margins after mastectomy in patients with node-negative breast cancer.     

Status of postmastectomy radiotherapy in the United States: a patterns of care study

PURPOSE: The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer. METHODS AND MATERIALS: A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used. RESULTS: A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields. CONCLUSION: This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results.     

Multivariate analyses of locoregional recurrences and skin complications after postmastectomy radiotherapy using electrons or photons

PURPOSE: We retrospectively analyzed factors of locoregional (LR) recurrence and skin complications in patients after postmastectomy radiotherapy (PMRT). METHODS AND MATERIALS: From January 1988 to December 1999, a total of 246 women with Stage II and III breast cancer received PMRT. Doses of 46 to 52.2 Gy/23 to 29 fractions were delivered to the chest wall (CW) and peripheral lymphatic drainage with 12 to 15 MeV single-portal electrons or 6MV photons. Of the patients, 84 patients received an additional 6 to 20 Gy boost to the surgical scar using 9 MeV electrons. We used the Cox regression model for multivariate analyses of CW, supraclavicular nodes (SCN), and LR recurrence. RESULTS: N3 stage (positive nodes >9) (p = 0.003) and diabetes (p = 0.004) were independent factors of CW recurrence. Analysis of ipsilateral SCN recurrence showed that N3 stage (p < 0.001) and electrons (p = 0.006) were independent factors. For LR recurrence, N3 (p < 0.001), T3 to T4 (p = 0.033) and electrons (p = 0.003) were significant factors. Analysis of skin telangiectasia revealed that electrons (p < 0.001) and surgical scar boost (p = 0.003) were independent factors. CONCLUSIONS: Photons are superior to single-portal electrons in patients receiving postmastectomy radiotherapy because of better locoregional control and less skin telangiectasia. In patients in whom the number of positive axillary nodes is >9, more aggressive treatment may be considered for better locoregional control.     

乳腺癌改良根治术后复发高危患者的放疗结果和预后因素分析

目的 总结本院高危乳腺癌患者改良根治术后的治疗结果,探讨放疗的作用和照射野的选择,并对生存预后因素进行分析.方法 回顾性分析381例T_3～T_4期和(或)腋窝淋巴结转移数≥4个的改良根治术后乳腺癌患者临床资料.用Kaplan-Meier法计算生存率,并Logrank法检验.单因素分析临床病理和治疗因素对生存率的影响,多因素分析用Cox回归模型.结果 中位随访时间为48个月.总5年无局部区域复发率为89.7%、总生存率为76.8%.放疗显著提高5年无局部区域复发生存率(93.4%:77.1%,χ~2=19.95,P=0.000)和总生存率(80.9%:62.3%,χ~2=15.47,P=0.001).胸壁和锁骨上区域照射能提高患者的5年无胸壁复发生存率(96.8%:86.2%;χ~2=12.66,P=0.001)和无锁骨上淋巴结复发生存率(97.7%:90.7%,χ~2=9.98,P=0.002),腋窝照射对5年无腋窝复发生存率无影响(98.4%:96.1%,χ~2=0.74,P=0.389).多因素分析显示未放疗(χ~2=14.42,P=0.000)、腋窝淋巴结阳性数≥10个(χ~2=21.60,P=0.000)和T_4期(χ~2=10.79,P=0.001)是总生存率的独立不良预后因素.结论 T_3～T_4期和(或)腋窝淋巴结转移数≥4个乳腺癌患者改良根治术后放疗显著降低局部复发率和提高总生存率,照射部位可选择同侧胸壁和锁骨上淋巴结引流区.     

Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer

PURPOSE: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. METHODS AND MATERIALS: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. RESULTS: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p=0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p=0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p=0.54). CONCLUSION: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients.     

乳腺癌改良根治术后大分割放疗的研究

目的:探讨乳腺癌改良根治术后大分割放疗的疗效及不良反应。方法:2011年-2012年陕西省人民医院收治高危乳腺癌患者85例,行同侧胸壁和锁骨上下区照射,其中41例行大分割放疗（大分割组）,DT 42.56Gy／16f,总疗程22-24天;44例行常规分割放疗（常规组）,DT 50Gy／25f,总疗程33-35天。观察肿瘤的局部控制率、远处转移率及急性放疗反应的发生率。结果:中位随访时间为15个月,随访率为100％。全组2年生存率均为100％,无照射野内复发。大分割组和常规组远处转移率分别为12.2％、11.4％（χ2=0.039,P=0.843）。大分割组和常规组1级白细胞减少、2级放射性皮炎、2级放射性肺炎发生率分别为24.4％与27.3％（χ2=0.092,P=0.762 ）、17.1％与13.6％(χ2=0.194,P＝0.660)、 4.9％与6.8％(χ2=0.144,P=0.704)。结论:乳腺癌改良根治术后大分割放疗的近期疗效与常规分割相似,急性毒副反应可以接受。     

Management of locoregional recurrence of breast cancer

The locoregional recurrence of breast cancer is not a sign of distant metastases, and a substantial proportion of cases are cured by salvage therapy. Patients with locoregional recurrence should not be treated with palliative intent as if they have visceral metastases. The recommended treatment for ipsilateral breast recurrence after breast conservative therapy is a mastectomy. For patients who suffer from isolated chest wall recurrence after mastectomy, a surgical approach is recommended. Neoadjuvant chemotherapy is considered for patients with unresectable disease in order to render the disease resectable. For patients with isolated chest wall recurrence who have received no prior radiotherapy, postoperative radiotherapy involving the chest wall and regional lymph nodes is recommended. Patients with isolated axillary lymph node recurrence should be treated with axillary dissection or resection. Although the effectiveness of systemic therapy for patients with locoregional recurrence is unclear, there is a trend toward treating patients with supraclavicular lymph node recurrence with radiotherapy plus systemic therapy. Pain relief and the eradication of other distressing symptoms resulting from inoperable disease are achieved in two-thirds to three-quarters of patients by radiotherapy with or without systemic therapy. New anti-cancer agents and molecular target therapies should be evaluated with the objective of improving the treatment outcome of patients with locoregional recurrence. A combination of approaches is required for treatment of patients with locoregional recurrence, and a multidisciplinary tumor board should be organized at each institute.     

Her2/neu-positive disease does not increase risk of locoregional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiotherapy

PURPOSE: Preclinical data suggest that overexpression of Her2/neu confers cellular radioresistance. We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer. METHODS AND MATERIALS: Data from 337 patients treated in four institutional prospective clinical trials neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT were reviewed. The trials were conducted between 1989 and 2000. Of the 337 patients, 108 (32%) had tumors that were tested for Her2/neu, with positivity defined by 3+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. RT was delivered to the chest wall and draining lymphatics (median dose, 50 Gy) followed by a chest wall boost (median dose, 10 Gy). RESULTS: Thirty-two patients had Her2/neu-positive disease and 76 patients had Her2/neu-negative disease. The Her2/neu-positive tumors were associated with a greater rate of estrogen receptor-negative disease (p = 0.03), the presence of supraclavicular disease at diagnosis (p = 0.027), and a greater number of positive lymph nodes after chemotherapy (p = 0.026). Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2/neu-positive tumors vs. those with Her2/neu-negative tumors (5-year rate 17.5% vs. 13.9%, respectively; 10-year rate 17.5% vs. 18.9%, respectively; p = 0.757). On Cox regression analysis of LRR adjusted for N stage and estrogen receptor status, the hazard ratio for Her2/neu positivity was 0.89 (95% confidence interval, 0.31-2.59; p = 0.83). CONCLUSION: Her2/neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT.     

T4期乳腺癌患者改良根治术后胸壁放疗加量的疗效及预后分析

目的分析T4期乳腺癌患者改良根治术后胸壁放疗加量的疗效。方法回顾分析2000-2016年收治的148例T4期、改良根治术后放疗的乳腺癌患者资料,胸壁放疗加量组57例,不加量组91例。放疗采用常规+胸壁电子线、三维适形+胸壁电子线、调强放疗+胸壁电子线照射,加量组EQD2>50Gy。全组患者均接受新辅助化疗。Kaplan-Meier法生存分析并Logrank检验差异,Cox模型多因素预后分析。结果中位随访时间67.2个月,5年胸壁复发(CWR)、局部区域复发(LRR)、无瘤生存(DFS)、总生存(OS)率分别为9.9%、16.2%、58.0%、71.4%。胸壁放疗加量和不加量的5年CWR、LRR、DFS、OS率分别为14%和7%、18%和15%、57%和58%、82%和65%(P>0.05)。多因素分析显示胸壁加量与否对预后无显著影响(P>0.05)。45例复发高危组患者中放疗加量组似乎有较高的OS率(P=0.058)、DFS率(P=0.084)和较低的LRR率(P=0.059)。结论T4期乳腺癌患者异质性较强,胸壁放疗加量对全组患者无明显获益。对于有脉管瘤栓阳性、pN2-N3、激素受体阴性中2~3个高危因素患者胸壁放疗加量有改善疗效趋势。     

A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger

Introduction: Indications for postmastectomy radiation include primary tumor size ≥5 cm and/or ≥4 positive axillary nodes. In clinical practice, patients with a close or positive margin after mastectomy are also often treated with postmastectomy radiation. However, there is little data regarding the risk of a chest wall recurrence in patients with close or positive margins who otherwise would be considered low risk (tumor size <5 cm and/or 0–3 positive nodes). To address this issue, we assessed the risk of a chest wall recurrence in women with Stage I–II breast cancer who underwent mastectomy and were found to have primary tumor size <5 cm and 0–3 positive nodes with a close or positive deep margin.Methods and Materials: The pathologic reports from 789 patients treated by mastectomy between 1985 and 1994 at our institution were retrospectively reviewed. Of these, 136 (17%) had tumor within 1 cm of the deep resection margin. The study population consists of 34 of these patients with close or positive margins whose primary tumor size was <5 cm with 0–3 positive axillary nodes and who received no postoperative radiation. The median age was 43 years (range 29–76). Of these, 44% had T1 tumors and 56% T2 tumors. Pathologic axillary nodal status was negative in 65% and positive in 35%. The median number of positive nodes was 1. The deep margin was positive in 2 patients, ≤2 mm in 17 patients, 2.1–4 mm in 7 patients and 4.1–6 mm in 8 patients. Of the 34 patients, 67% received adjuvant chemotherapy ± tamoxifen and 21% received tamoxifen alone. The median follow-up was 59 months (range 7–143).Results: There were 5 chest wall recurrences at a median interval of 26 months (range 7–127). One was an isolated first failure, one occurred concurrent with an axillary recurrence, and three were associated with distant metastases. The 5- and 8-year cumulative incidences of a chest wall recurrence were 9% and 18%. Patient age correlated with the cumulative incidence of chest wall recurrence at 8 years; age ≤50 years had a rate of 28% vs. 0% for age >50 (p = 0.04). There was no correlation with chest wall failure and number of positive nodes, ER status, lymphovascular invasion, location of primary, grade, family history, or type of tumor close to the margin. Of 5 chest wall failures, 4 were in patients who had received adjuvant systemic chemotherapy ± tamoxifen. Chest wall failures occurred in 1 patient with a positive deep margin, 3 patients with margins within 2 mm, and 1 patient with a margin of 5 mm. The estimated cumulative incidence probability of chest wall recurrence at 8 years by margin proximity was 24% ≤ 2 mm vs. 7% 2.1–6 mm (p = 0.36), and by clinical size 24% for T2 tumors vs. 7% for T1 (p = 0.98).Conclusions: A close or positive margin is uncommon (≤5%) after mastectomy in patients with tumor size <5 cm and 0–3 positive axillary nodes but, when present, it appears to be in a younger patient population. The subgroup of patients aged 50 or younger with clinical T1–T2 tumor size and 0–3 positive nodes who have a close (≤5 mm) or positive mastectomy margin are at high risk (28% at 8 years) for chest wall recurrence regardless of adjuvant systemic therapy and, therefore, should be considered for postmastectomy radiation.