Long-term outcome after postmastectomy radiation therapy for breast cancer patients at high risk for local-regional recurrence

PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.     

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant tamoxifen alone: patterns of recurrence

Purpose: To determine the patterns, incidence and risk factors for local-regional recurrence in patients with Stage II and III breast cancer treated with adjuvant tamoxifen alone, without adjuvant radiation.Material and Methods: The records of patients referred to the London Regional Cancer Centre with a diagnosis of breast cancer between 1980–1989 were reviewed. During this time period, it was the policy of the institution to omit local-regional radiation to patients receiving adjuvant systemic therapy. One hundred and fifty axillary node-positive Stage II and III breast cancer patients received adjuvant tamoxifen alone without postoperative local-regional radiation; these patients form the basis of this report.Results: Median follow-up was 67 months for the entire patient group and 85 months for the living patients. During this time, 42% of patients developed a recurrence, 22% first recurred in local-regional sites. The total incidence of local-regional recurrence (including those patients who first relapsed with systemic metastases) was 30%. Of the segmental mastectomy patients, 13% had recurrences in the intact breast. Of the modified radical mastectomy patients, 10% developed chest wall recurrences. Five percent of recurrences were first in the axilla and 6% in the supraclavicular nodes. Five-year actuarial survival for the entire patient group was 79% and disease-free survival was 60%, with a median disease-free survival time of 87 months. Five-year local-regional relapse-free survival was 76%. Five-year local-regional relapse-free survival was < 76% for those patients with 4 or more positive axillary nodes, regardless of tumor size. On univariable analysis, positive resection margins, number of positive axillary nodes, menopausal status, and negative estrogen and progesterone receptors were significant for isolated local-regional recurrence. On multivariable analysis, only positive resection margins and negative receptors remained significant. In terms of regional recurrence specifically, negative estrogen and progesterone-receptor status and positive resection margins were, again, prognostically significant.Conclusions: Postmenopausal women receiving adjuvant tamoxifen who have positive resection margins, ≥ 4 positive axillary nodes and/or negative estrogen and progesterone receptors, are at higher risk of local and regional recurrence and should, therefore, receive local-regional radiation.     

Radiotherapy for the prevention of local-regional recurrence in high risk patients post mastectomy receiving adjuvant chemotherapy

From 1977 to 1986, 63 patients at high risk for isolated local-regional recurrence following mastectomy and adjuvant chemotherapy received post-operative radiotherapy. All patients had operable primary tumors (T_1–3a.). For entire group the mean and median number of positive nodes were 10 and 8, respectively. Radiotherapy consisted of 4500 to 5000 rad to the chest wall and regional nodes. Chemotherapy consisted of CMF ± prednisone (45 patients), CAF (16 patients), and other variable regimens (2 patients). Relapse occurred in 23 patients with only two patients experiencing an isolated local-regional recurrence. In 3 patients local-regional recurrence appeared simultaneously with or following distant metastases and in 18 patients the pattern of failure was distant metastases alone. With a median follow-up of 28 months (range 9–87 mo.), 40 patients are alive without disease, 9 are alive with disease, and 14 have died with disease. The 4-year actuarial overall survival is 67% and the 4year actuarial disease-free survival is 47%. The 4-year actuarial probability of an isolated local-regional recurrence is 5%. Complications related to the radiation included a 9% incidence of moderate to severe arm edema. This study demonstrates the ability of radiation to reduce the incidence of local-regional recurrence in a previously identified high risk group of patients and has produced encouraging survival results with minimal morbidity.     

Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant

PURPOSE: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. METHODS AND MATERIALS: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. RESULTS: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p = 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. CONCLUSIONS: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment.     

Prognostic significance of isolated local recurrences in breast cancer following mastectomy and axillary node excision. Apropos of 77 recurrences in 2362 patients

During the years 1958-1984, 2 362 patients presenting with breast carcinoma were treated at the Fondation Bergonié by modified radical mastectomy and followed or not by radiotherapy or adjuvant chemotherapy. A retrospective analysis of this series showed that 77 patients (3.3%) presented an isolated locoregional recurrence as the first sign of treatment failure. A chest wall recurrence alone was noted in 47 patients, while 30 presented an involvement of the lymph nodes, sometimes associated with chest wall disease. The prognosis' factors of isolated locoregional recurrence, studied by multidimensional analysis by Cox's model are by decreasing order the disease free interval and the Scarf and Bloom's histologic grade. The median survival is 29 months after isolated locoregional recurrence and the survival curve is very similar to that of patients with isolated bone metastatic recurrences (median survival of 26 months) and slightly better than the median survival of patients with non osseous metastasis (median survival of 16 months).     

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。     

Local-regional recurrence in breast cancer after mastectomy and adriamycin-based adjuvant chemotherapy: evaluation of the role of postoperative radiotherapy

In an attempt to determine whether patients treated for breast cancer with radical or modified radical mastectomy and adjuvant chemotherapy benefit from postoperative radiotherapy, 400 women with Stages II-III breast cancer who received adjuvant chemotherapy based on the combination of Adriamycin and Cytoxan were analyzed retrospectively. Prognostic features which predicted a high risk of isolated local-regional relapse were identified. Thirty-eight percent of these patients were also treated with postoperative radiation in addition to adjuvant chemotherapy and were compared to those patients treated only with adjuvant chemotherapy. With a median follow-up of 60 months, 15% of the patients reviewed developed local-regional disease as the first site of relapse without concommitant systemic relapse. When examined univariately, stage of disease, tumor size, nodal status, and estrogen receptor status were strong prognostic variables. Age, cell type, location of tumor within the breast, menstrual status, radiation dose, and type of treatment were not significantly related to isolated local-regional relapse. However, patients who received postoperative radiation were significantly more advanced in their disease condition. When the factors were examined multivariately, the type of treatment along with stage of disease were found to be statistically significant prognostic indicators. About half of the patients were tested for estrogen receptor status. Multivariate analysis performed on this subset of patients showed that estrogen receptor status, type of treatment, and axillary nodal status were significant predictors of the risk of isolated local-regional relapse. This study suggests that patients treated with mastectomy and Adriamycin and Cytoxan-based adjuvant chemotherapy may benefit from postoperative radiation in reducing the risk of isolated local-regional recurrence.     

乳腺癌根治术后区域淋巴结复发放射治疗疗效分析

目的：探讨乳腺癌根治术后区域淋巴结复发患者放射治疗和其他综合治疗手段的合理联用以及影响局部控制率和生存率的预后因素。方法：回顾性分析了1994～2003年期间在我院放疗科收治的77例乳腺癌根治术后区域淋巴结复发作为术后第一次治疗失败的患者，其中45例为锁骨上淋巴结，16例腋下淋巴结，6例内乳淋巴结，10例同时有2个淋巴结区累及。中位随访时间为34．4个月。所有患者均接受放射治疗。12例在放疗前接受复发灶手术切除。照射剂量范围为50-74Gy，中位剂量为60Gy。结果：本组患者中位生存期为4．67年，二年、五年和八年生存率分别为77．8％、47．4％和31．5％。无病间期、激素受体状态为影响生存率的独立的预后因素。总计有30例(39％)发生再次局部和(或)区域性复发，其中4例发生在原复发部位，26例发生在其他部位，胸壁是发生率最高的二次复发部位，总计有18例(23％)患者发生的再次复发部位中包括胸壁。首次术后病理腋淋巴结转移数目是影响局部控制率的预后因素。结论：放射治疗是乳腺癌术后区域淋巴结复发的有效治疗手段。23％的患者治疗后发生后续的胸壁复发，建议对患侧胸壁作预防性照射。首次术后病理腋淋巴结转移数目4个及以上的患者作胸壁预防的意义更大。无病间期2年及以上，激素受体阳性的患者是相对预后较好的患者群。全身治疗在改善生存率方面的意义尚不明确。     

The importance of local-regional radiotherapy with conventional or high-dose chemotherapy in the management of breast cancer patients with > or = 10 positive axillary nodes

PURPOSE: To assess the effect of local-regional radiotherapy (RT) on the outcome of breast cancer patients with > or = 10 positive axillary lymph nodes who have received modern conventional or high-dose systemic therapy. METHODS AND MATERIALS: A total of 55 women with local-regionally confined breast cancer involving 10 or more axillary nodes were treated between October 1983 and January 1996. Local-regional therapy consisted of modified radical mastectomy in 39 and breast-conserving surgery in 16. Postoperative radiotherapy was given to 44 of the 55 patients. Radiotherapy consisted of tangential fields to the chest wall or intact breast to a median dose of 50.40 Gy. A total of 86% (38 of 44) received regional nodal irradiation as follows: 35 patients received RT to the supraclavicular (SC) region and axillary midplane to a median dose of 50.40 Gy and 46.20 Gy, respectively; 3 patients received RT to the SC region without inclusion of the axilla to a median dose of 50. 40 Gy. All patients received adjuvant standard-dose systemic chemotherapy, 9 of whom received additional intensification chemotherapy followed by autologous bone-marrow transplant (ABMT) or peripheral blood stem-cell transplant (PBSC). Twenty-five patients received adjuvant tamoxifen.Results: With a median follow-up of 30 months, the crude overall survival (OS) and disease-free survival (DFS) for the entire group were 67% and 53%, respectively. On univariate analysis of various clinical, pathological, and therapy-related features, radiotherapy emerged as the most important factor influencing the relapse rate. The addition of RT was significantly associated with an improved DFS (p = 0.003), specifically by prolonging the time to disease progression. The median time to failure was 61 months and 12.5 months with and without RT, respectively. Patients receiving RT also appeared to survive longer; however, the groups were not statistically different (p = 0.10). Analysis of the patterns of failure showed local-regional recurrence (LRR) as the first site of failure in 12 (22%) of 55 and distant failure in 20 (36%) of 55. Univariate results revealed both radiotherapy and tamoxifen to be significantly associated with decreased LRR rates (p = 0.0001 and p = 0.03, respectively); only RT remained independently significant on multivariate analysis.Conclusion: Local-regional radiotherapy is an essential component of the management of breast cancer patients with extensive nodal involvement, despite the use of contemporary adjuvant chemotherapy including high-dose regimens with autologous rescue. In addition to the expected improvement in LRR, radiotherapy is also associated with significantly prolonged DFS and a trend for improvement in OS.     

Survival and Pattern of Failure Following Locoregional Recurrence of Breast Cancer

This study analyzed prognostic factors at primary diagnosis and at first recurrence for impact on survival after isolated locoregional failure. The aims were: (1) assessment of prognostic factors for time to second locoregional failure, distant failure, and survival in isolated locoregional recurrence of breast cancer after mastectomy; and (2) investigation of the impact of a second locoregional failure on dissemination and survival.Between 1983 and 1985, 99 patients who had undergone mastectomy and then developed isolated local and/or regional recurrences, were treated with radical excision and radiotherapy; none of these patients had distant metastases. Survival and the times to second local failure and distant metastasis were analyzed according to potential prognostic factors.The median follow-up was 123 months; 38 patients were still alive. Median survival was 89 months and the 10-year survival rate was 38%, with no difference between local and regional recurrences. A total of 43 patients developed a second locoregional recurrence after a median of 73 months; primary tumour size and initial node status were significant independent prognostic factors. The annual hazard rates for recurrence were similar for patients developing local failure or systemic recurrence. The 10-year rate of dissemination was 49% for patients with locoregional control, compared with 51% for patients who had a second locoregional recurrence. The prognostic factors for survival were node status at mastectomy and haemoglobin level at first recurrence.The development of a second locoregional recurrence was not associated with an increased risk of dissemination or reduced survival. Differences in prognostic factors for locoregional control and distant metastases suggest that these recurrences represent different biological entities that require different treatment strategies. However, as the achievement of locoregional control had no influence on prognosis, the use of systemic adjuvant therapy may be warranted in a subset of these patients.     

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.     

Radiotherapy for postmastectomy local-regional recurrent breast cancer

From 1980 to 1989, 70 women with postmastectomy local-regional recurrent breast cancer and no clinical or radiographic evidence of distant metastasis were treated with radiotherapy with or without systemic therapy. The interval from mastectomy to local-regional recurrence ranged from 5 to 240 months (median, 34 months). The chest wall alone was involved in 37 patients, the supraclavicular area in 12 patients, the internal mammary node area in 3 patients, the infraclavicular area in 2, and the axilla in 1. Fifteen patients had multiple areas of involvement. The complete response rate was 87%. Further local-regional recurrence developed in at least 21 patients, and distant metastasis developed in at least 41 patients. Twenty-five patients (36%) survived at least 5 years and 15 patients (21%) survived at least 10 years. An initial negative node status and long disease-free interval from mastectomy to recurrence were associated with an improved postrecurrence survival. Patients with local-regional recurrence postmastectomy who do not have clinical or radiographic evidence of distant metastasis should be treated aggressively with radiotherapy with or without systemic therapy. Distant metastasis will develop in most such patients, but the majority will remain free of further local-regional recurrence.     

Adjuvant endocrine therapy compared with no systemic therapy for elderly women with early breast cancer: 21-year results of International Breast Cancer Study Group Trial IV.

PURPOSE: Increasing numbers of older women are affected by early breast cancer, because of prolonged life expectancy and the increasing incidence of breast cancer with age. The role of adjuvant therapy for this population is still a matter of debate. We reviewed the long-term outcome of a mature trial comparing endocrine treatment versus no adjuvant therapy in older women with node-positive breast cancer. PATIENTS AND METHODS: From 1978 to 1981, 349 women 66 to 80 years of age with pathologically involved lymph nodes after total mastectomy and axillary clearance were randomly assigned to receive 12 months of adjuvant tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred twenty patients were eligible. RESULTS: At 21 years' median follow-up, 1 year of p+T significantly prolonged disease-free survival (DFS; P =.003) and overall survival (P =.05; 15-year DFS, 10% +/- 3% v 19% +/- 3%; hazard ratio, 0.71; 95% CI, 0.58 to 0.86). When comparing competing causes of failure (breast cancer recurrence and deaths before breast cancer recurrence), p+T was far superior in controlling breast cancer recurrence (P =.0003), but the improvement was seen mainly in soft tissue sites. Conversely, patients in the p+T group were more likely to die before a breast cancer recurrence (P =.03). CONCLUSION: This trial demonstrates that significant treatment benefits continue to be observed in older patients treated for 1 year with p+T. Despite issues relating to competing causes of failure, older breast cancer patients can benefit from treatment and should be considered for trials of adjuvant systemic therapy.     

Do surgical oncologists achieve lower rates of local‐regional recurrence in node positive breast cancer treated with mastectomy alone?

BACKGROUND AND OBJECTIVE: Adjuvant radiotherapy for node positive breast cancer postmastectomy has been recommended by two previously published randomized controlled trials (RCT). The local-regional recurrence rates in the control arms, however, were considered by some critics to be excessive (> 25% at 10 years). Inadequate surgery, as evidenced by the low number of axillary nodes reported, may have resulted in the high local-regional recurrence rates, allowing for the benefits seen with radiotherapy. Fellowship trained surgical oncologists might provide "better quality" surgery, resulting in lower recurrence rates and thus making adjuvant radiotherapy unnecessary. Our objective was to establish the local-regional control rate postmastectomy in node positive breast cancer patients operated on by surgical oncologists, and to determine if treatment recommendations from previous RCTs are generalizable. METHODS: Node positive stage IIb and IIIa breast cancer patients treated with mastectomy at the Medical College of Virginia Hospitals by surgical oncologists, without adjuvant radiotherapy, and entered into adjuvant chemotherapy trials between 1978 and 1993 were identified retrospectively. Pathology and follow-up records were reviewed. RESULTS: One hundred and thirty-seven patients were identified. A median of 18 axillary nodes was reported with a median of 4 positive nodes. The locoregional recurrence at 10-years was 27% (95% confidence interval, 19-35%). CONCLUSION: Despite some evidence of "better quality" surgery, there was no clinically significant difference in the local-regional recurrence rate in this case series compared to controls in two previous RCTs. Recommendations for postmastectomy radiotherapy should be considered for node positive breast cancers, even if operated upon by surgical oncologists.     

Electron arc irradiation of the postmastectomy chest wall in locally recurrent and metastatic breast cancer

The purpose of this study was to evaluate local-regional control and overall survival in women with locally recurrent and metastatic breast cancer (MBC) treated with postmastectomy electron arc therapy. Postmastectomy electron arc irradiation was used to treat 39 women with isolated local-regional recurrence of breast cancer following mastectomy, and 14 patients with MBC who had, or who were at high risk of, local-regional recurrence. After computed tomography treatment planning, patients were treated with electron arc radiotherapy to a median dose of 59.3 Gy. The median follow-up for alive patients was 45.4 months. For patients with local-regional recurrence, the 5-year local-regional control and overall survival rates were 74% and 43%, respectively. The 2-year overall survival was greater for those patients with a disease-free interval greater than 24 months when compared to patients with a disease-free interval less than 24 months (83% vs. 60%, respectively); however, the median survival was not significantly different (57.6 and 58.6 months, respectively). Patients with a solitary nodule at recurrence had an improved 5-year overall survival of 58% compared with 40% for patients with multiple lesions. For patients with metastatic disease, the 5-year local-regional control and overall survival rates were 76% and 31%, respectively. Local-regional control can be achieved in the majority of patients with local-regionally recurrent breast cancer (74%) or MBC (76%) who had, or who were, at high risk of local-regional recurrence treated with postmastectomy electron arc irradiation.     

The effect of systemic therapy on local-regional control in locally advanced breast cancer.

One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival.     

Influence of radiotherapy on the dose of adjuvant chemotherapy in early breast cancer

399 patients with early breast cancer were randomly allocated to treatment by either modified radical mastectomy or lumpectomy and radiotherapy. 169 had histologically involved axillary nodes and were randomised to receive either adjuvant cytotoxic chemotherapy (76 patients) or no systemic adjuvant treatment (93 patients). Chemotherapy comprised a combination of oral cyclophosphamide and intravenous methotrexate and 5-fluorouracil (CMF) for 12 cycles over one year. Patients in the mastectomy group received a significantly higher percentage of the planned chemotherapy dose compared with those in the radiotherapy group (median 85% v. 71% p less than 0.05). Patients treated with radiotherapy were more frequently nauseated and developed more severe alopecia, but these differences were not statistically significant. At median follow-up of 37 months the relapse-rate and pattern of relapse were similar in both groups of patients receiving CMF.     

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.     

Analysis of 6 Cases of Stromal Sarcoma of the Breast

OBJECTIVE To investigate the clinical and pathological characteristics,diagnosis and treatment of stromal sarcoma of the breast(SSB).Methods:The clinical and pathological data of 6 patients with SSB treated between 1954 and 2007 were retrospectively analyzed.METHODS The clinical and pathological data of 6 patients with SSB treated between 1954 and 2007 were retrospectively analyzed.RESULtS Atl patients were female and one was menopausal.The median age of the patients was 39 years old(range,20-55).All cases had a history of a palpable mass.The tumor rapidly augmented in a short time period in 3 patients.One patient had discontinuous pain and 3 patients had masses located in the upper outer quadrant of the breast.The median tumor radius was 6.0 cm(range,3-15 cm).According to the AJCC breast cancer staging standard(6th edition),1 case was of stage ⅡA,2 cases were of stage ⅡB,2 cases were of stage ⅢB and one case couldn't be staged.Four patients were initially treated by excising the tumor and then undergoing mastectomy or modified radical mastectomy after recurrence.Radical mastectomy was suitable for those with pectoralis major muscle involvement.Two patients received simple mastectomy, 2 patients underwent radical mastectomy and another 2 patients received modified radical mastectomy,After surgery,all patients were identified as SSB through pathology,with focal ossification in one case and mucinous degeneration in another one case.Four patients who underwent axillary Iymph node dissection did not have lymph node metastases.Three patients received chemotherapy after surgery. After a median follow-up time of 36.5 months(8-204 months),4 patients had recurrence after local excision and 3 patients had recurrence more than 2 times with a median time to recurrence of 2.5 months(1to 4 months) after surgery.One patient had lung metastases at 7months after the initial surgery and the other 5 patients were alive without disease at the end of the follow-up period.CONCLUSION SSB is difficult to diagnose preoperatively and is characterized by its tendency to recur locally.To obtain negative margins,wide local excision or mastectomy must be performed.Axillary lymph node dissection is not mandatory.The roles of adjuvant chemotherapy and radiotherapy have still been controversial.