Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

PURPOSE: To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. METHODS AND MATERIALS: Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. RESULTS: With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p=0.017) and in Cox proportional hazards analysis (p=0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. CONCLUSIONS: This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy.     

癌蛋白c—erbB2在乳腺肿瘤患者中过度表达的免疫组化研究

目的检测ｃ－ｅｒｂＢ２蛋白过度表达与乳腺肿瘤患者预后的关系,探讨其作为预后指标的可行性。方法共８５例原发乳腺肿瘤的石蜡切片标本,采用免疫组化方法。结果７例良性病变无１例过度表达;７８例乳腺癌２３例过度表达,表达率为２９．４％;８０％的无淋巴结转移病例未检测到ｃ－ｅｒｂＢ２的过度表达。ｃ－ｅｒｂＢ２蛋白的过度表达在临床Ⅲ期病例中占７１％。ｃ－ｅｒｂＢ２与雌激素受体（ＥＲ）表达呈相反关系的占６７％。该蛋白过度表达与腋淋巴结转移情况未发现相关性（Ｐ＞０．０５）,与临床分期呈显著的正相关（Ｐ＜０．００５）,与ＥＲ呈显著的负相关（Ｐ＜０．００５）。结论ｃ－ｅｒｂＢ２过度表达者预后不良。它可以作为判断乳腺肿瘤患者预后的有效指标,用于临床,辅助判断患者预后,可能具有重要意义。     

Long-term prognosis of patients with local recurrence of breast cancer

From 1985 to 2002, 22 patients with local recurrence after radical mastectomy have been treated in our hospital. Resection was possible in 9 patients. We evaluated long-term prognosis of the 9 patients. The observation interval from first recurrence was 17-207 months (median 91.5 months). Five of the 9 experienced recurrence again. Opposite axillary lymph node metastasis was observed in 2, bone metastasis in 1, liver metastasis in 1, and lung metastasis in 1. Disease free interval (DFI) until the first recurrence of patients with a second recurrence was 69-100 months (median 90 months). The interval from first recurrence to second recurrence was 46-108 months (median 60 months). Each second recurrence occurred within double the DFI until the first recurrence. For all of the patients in which a second recurrence was not observed, the observed interval was shorter than the DFI until first recurrence. Local recurrence should be considered systemic disease. Many of the patients who underwent resection of the local recurrence experienced a second recurrence after longer observation. We believe that patients with local recurrence should be observed for a period of about double the DFI.     

Phase II study of homoharringtonine in patients with recurrent primary malignant central nervous system tumors

A phase 11 trial of Homoharringtonine (HHT) was performed in 15 patients with recurrent or progressive malignant glioma. The drug was administered at a initial dose of 4 mg/m²/day by continuous 5 day intravenous infusion (3 mg/m²/day x 5 days for heavily pretreated patients). Courses were repeated every 3–4 weeks upon recovery from toxicity. No objective antitumor regressions occurred. Two patients had no change in their CT brain scans for 2–3 months and one patient had stable disease for 6 months. Toxicity was tolerable and included myelosuppression and occasionally mild hypotension. Chemosensitivity testing with HHT and several other chemotherapy drugs was performed in glioma cell lines, including cell lines derived from these patients. The results suggest that HHT is an inactive drug in malignant glioma using this dose schedule.     

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer

BackgroundIpsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed.MethodsWe retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and re-interventions.ResultsInvasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%–96%) and disease free survival was 78% (95% CI: 69%–85%).ConclusionsImmediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome.     

Clinicopathologic factors of the recurrent tumor predict outcome in patients with ipsilateral breast tumor recurrence

BACKGROUND:

The role of clinicopathologic characteristics of the recurrent tumor in determining survival in a cohort of patients with ipsilateral breast tumor recurrence (IBTR) was investigated.

METHODS:

Among 6020 women with pT1‐T2, pN0‐1, M0 treated with breast‐conserving surgery from 1989 to 1999, 269 developed isolated IBTR. Ten‐year Kaplan‐Meier breast cancer‐specific survival (BCSS) and overall survival (OS), calculated from date of IBTR, were analyzed according to clinicopathologic characteristics.

RESULTS:

Factors that were associated with diminished OS and BCSS on univariate analysis were: time to IBTR ≤48 months, lymphovascular invasion positive status, estrogen receptor (ER) negative status, high grade, clinical IBTR detection, biopsy alone, and close/positive margins (all P < .05). On multivariate analysis, time to IBTR ≤48 months (hazard ratio [HR], 1.87, P = .012), lymphovascular invasion positive status (HR, 2.46; P < .001), ER negative status (HR, 2.08; P = .013), high‐grade recurrent disease (HR, 1.88; P = .013), and close/positive margins after surgery for IBTR (HR, 1.94; P = .013) retained significance for prediction of diminished OS. When stratified according to number of adverse prognostic features, 10‐year OS was 70.4% in patients with 1 factor, 35.8% with 2 factors, and 19.9% with 3 or more factors (P < .001).

CONCLUSIONS:

Time to recurrence ≤48 months, lymphovascular invasion positive status, ER negative status, high‐grade histology, and close/positive margins in association with the recurrent tumor are independent prognostic factors for survival after IBTR. The presence of 2 or more of these features at recurrence is significantly associated with poor OS. These criteria can be used to prognosticate and guide clinical decisions after recurrence. Cancer 2011. © 2010 American Cancer Society.     

Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors

Background: Pathologists can distinguish benign phyllodes tumors, which very rarely metastasize, from malignant phyllodes tumors, which metastasize in approximately one fourth of patients. However, whether these same histologic criteria can be used to predict the likelihood that a phyllodes tumor will locally recur after breast conserving therapy remains controversial.Study Design: Since few patients with malignant phyllodes tumors have been treated with breast conserving surgery in any individual series, the literature was reviewed using a Medline search.Results: After local excision, 21 (111/540), 46 (18/39), and 65 (26/40) of patients with benign, borderline, and malignant phyllodes tumors, respectively, recurred in the breast. Following wide local excision, 8 (17/212), 29 (20/68), and 36 (16/45) of patients with benign, borderline, and malignant phyllodes tumors recurred in the breast.Conclusions: Malignant phyllodes tumors are much more likely than benign phyllodes tumors to recur in the breast after breast conserving surgery. This high rate of local recurrence of borderline and malignant phyllodes tumors suggests that wide local excision is less than optimal therapy, and challenges us to look for methods to improve local tumor control.     

Pleomorphic adenoma of the human breast with local recurrence

Pleomorphic adenoma of the human breast is a rare, benign tumor for which the literature is sparse. A local recurrence has been reported only once before. The diagnostic challenge of this cancer-imitating lesion is emphasized in this report. Although local excision of the tumor is the treatment of choice, almost 50% of the patients reported have undergone fairly extensive surgery, i.e., simple or radical mastectomy. A paraffin secretion of the excised tumor is mandatory to confirm the benign nature of the lesion to avoid an unnecessary mastectomy for a benign condition.     

Immunohistochemical study of bone GLA protein in primary bone tumors.

METHODS. The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex. RESULTS. As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed. CONCLUSION. These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.     

DNA ploidy of primary breast cancer and local recurrence after breast-conserving therapy.

The value of DNA-flow cytometry and clinico-pathological prognostic factors for the prediction of local recurrences after breast-conserving therapy (BCT) were evaluated in a retrospective study. Thirty-one patients with a local recurrence were compared with 31 matched patients without a local recurrence. Morphology and DNA-indices of the local recurrences and their corresponding primary tumours were compared. Ductal carcinoma in situ was present significantly more often in the group with a primary recurring tumour, than in the matched group (P less than 0.001), and the same holds for lobular carcinoma (n = 5). Half of the tumours that recurred had macroscopically positive surgical margins compared to about one-fourth of the matched group. Fifty-six per cent of the DNA-aneuploid stemlines in cases with local recurrence were present in the corresponding primary tumour as well (confidence limits 45%-75%), an indication that the majority of local recurrences are true recurrences and not independently developed tumours. The lack of similarity of DNA stemlines between some primary DNA-aneuploid tumours and their local recurrences indicates that these tumours had developed independently. The percentage of DNA-aneuploid cases in the group with local recurrence (89%) did not differ significantly from that in the matched group (70%). However, the findings suggest a selective recurrence of DNA-diploid stemlines. This might indicate increased resistance of DNA-diploid tumour cells to radiotherapy as compared with the resistance level in DNA-aneuploid cells.     

Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patients. This study included a consecutive series of 536 patients ≤40 years of age at diagnosis with pathological T1N0-3M0 BC, treated between 1989 and 2005. A multistate survival model was used to evaluate the influences of local treatment and LRR on DMD, adjusted for potential prognostic factors. Patients were treated with mastectomy (N = 213) or BCT (N = 323). Median age at diagnosis was 36.3 years, with a median follow-up of 9.0 years. The 10-year actuarial cumulative incidence of DMD was 30.6 % after mastectomy and 26.3 % after BCT (P = 0.04). In total, 81 (15 %) LRRs were observed. After BCT, patients had a threefold higher risk of LRR than after mastectomy (HR 2.9; 95 % CI 1.6–5.3). Patients with LRR had a higher risk of DMD compared with patients without LRR (HR 5.5; 95 % CI 2.1–14.5). However, BCT was not negatively associated with DMD-after-LRR (HR 0.47; 95 % CI 0.2–1.1, BCT vs mastectomy). In conclusion, although LRR significantly affected DMD, the increased risk of LRR after BCT compared with mastectomy did not lead to a worse DMD outcome in BC patients ≤40 years of age.     

Margin status and the risk of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

We sought to assess whether a close surgical margin (>0 and <2 mm) after breast-conserving therapy (BCT) confers an increased risk of local recurrence (LR) compared with a widely negative margin (≥2 mm). We studied 906 women with early-stage invasive breast cancer treated with BCT between January 1998 and October 2006; 91 % received adjuvant systemic therapy. Margins were coded as: (1) widely negative (n = 729), (2) close (n = 85), or (3) close (n = 84)/positive (n = 8) but having no additional tissue to remove according to the surgeon. Cumulative incidence of LR and distant failure (DF) were calculated using the Kaplan–Meier method. Gray’s competing-risk regression assessed the effect of margin status on LR and Cox proportional hazards regression assessed the effect on DF, controlling for biologic subtype, age, and number of positive lymph nodes (LNs). Three hundred seventy-seven patients (41.6 %) underwent surgical re-excision, of which 63.5 % had no residual disease. With a median follow-up of 87.5 months, the 5-year cumulative incidence of LR was 2.5 %. The 5-year cumulative incidence of LR by margin status was 2.3 % (95 % CI 1.4–3.8 %) for widely negative, 0 % for close, and 6.4 % (95 % CI 2.7–14.6 %) for no additional tissue, p = 0.3. On multivariate analysis, margin status was not associated with LR; however, triple-negative subtype (AHR 3.7; 95 % CI 1.6–8.8; p = 0.003) and increasing number of positive LNs (AHR 1.6; 95 % CI 1.1–2.3; p = 0.025) were associated. In an era of routine adjuvant systemic therapy, close surgical margins and maximally resected close/positive margins were not associated with an increased risk of LR compared to widely negative margins. Additional studies are needed to confirm this finding.     

Metaplastic breast tumors with a dominant fibromatosis-like phenotype have a high risk of local recurrence.

BACKGROUND: In the current study the authors describe the clinicopathologic characteristics of a low grade variant of spindle cell metaplastic tumors of the breast. Previously these tumors have been considered within a larger group recognized as metaplastic carcinoma, including cases with higher grade features. METHODS: Breast tumors comprised predominantly of low grade spindle cells, with sparse low grade epithelial elements, were selected. Clinical features as well as macroscopic, microscopic, and immunohistochemical findings were reviewed with emphasis on the biologic behavior and the differential diagnosis from other spindle cell lesions. RESULTS: Of 30 tumors fulfilling strict criteria, 20 contained squamous or glandular elements associated with the spindle cells. Ten tumors were comprised entirely of low grade spindle cells with limited clustered epithelioid cells. At the periphery, all tumors showed a proliferation of bland spindle cells infiltrating the adjacent parenchyma and mimicking fibromatosis. The epithelioid cells and some spindle cells expressed both vimentin and one or more cytokeratins. Seven of eight patients treated by excisional biopsy developed local recurrence, whereas only one of ten patients treated with wide excisional biopsy developed a local recurrence. No distant or regional metastases occurred. CONCLUSIONS: The presence of limited clusters of epithelioid cells along with a dominant fibromatosis-like pattern may be unique in the breast. The biologic potential of the fibromatosis-like, spindle cell, metaplastic breast tumors most likely is defined by their major histologic phenotype; they are capable of local recurrence with no demonstrated distant spread or regional metastases, as in pure fibromatosis of the breast.     

Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy

Introduction

Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.

Methods

We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.

Results

Within the estrogen receptor-positive (ER⁺) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER^- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER⁺/ER^-).

Conclusion

A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.     

年龄对保乳术后局部复发风险的影响

目的:探讨与乳腺癌保乳术后局部复发相关的因素。方法:回顾性分析2000年1月—2007年12月接受保乳手术的548例乳腺癌患者的病历资料并进行随访。对与乳腺癌保乳术后局部复发相关的因素进行单因素和多因素分析。结果:548例患者中,局部复发22例(4.01%)。年龄(<45岁和≥45岁,P=0.041)、肿瘤大小(T1、T2和T3,P=0.014)和组织学分级(Ⅰ～Ⅱ级和Ⅲ级,P=0.003)与局部复发相关。多因素分析结果显示,年龄(<45岁和≥45岁,P=0.013)和组织学分级(Ⅰ～Ⅱ级和Ⅲ级,P=0.046)是影响乳腺癌保乳术后局部复发的独立因素。结论:青年乳腺癌患者(<45岁)保乳术后具有相对较高的局部复发风险,临床医师应当采取更为积极的治疗措施以预防局部复发。     

乳腺癌术后局部复发因素的临床分析

目的探讨乳腺癌术后局部复发的影响因素.方法自1997年1月至2001年1月我院共收治乳腺癌患者435例.观察肿瘤自身因素和治疗因素对术后复发的影响.结果 3年复发率6.4%,总复发率7.0%.肿瘤自身因素中,患者年龄和是否绝经、病理类型和激素受体情况、原发肿瘤大小和腋窝淋巴结转移数目对术后局部复发有显著影响,而患者性别和是否有肿瘤家族史对术后局部复发无显著影响.治疗因素中,术后辅助放疗对减少局部复发有一定作用,而保乳术后局部复发率高于根治术和改良根治术.结论早期诊断、早期治疗是减少乳腺癌复发转移的有效途径,加强辅助治疗可以减少和延缓术后局部复发.