Risk factors for local recurrence after breast-conserving therapy

Background. Breast-conserving therapy has been widely accepted as a standard treatment for early breast cancer both in Western countries and in Japan. In Western countries, many studies have investigated the risk factors for local recurrence after breast-conserving therapy (BCT), but few such studies have been done in Japan. Methods. To determine the risk factors for local recurrence in 399 breast cancer patients (stage I and II, n = 396; stage III, n = 3) who had undergone BCT with or without postoperative radiation therapy, we evaluated their clinicopathological features by univariate and multivariate analyses. The patients were treated at Osaka National Hospital between February 1988 and December 1997. Results. Univariate analysis showed that a young age (≤45 years; P = 0.0005) was a significant risk factor for local recurrence, while radiation therapy (P = 0.0058) and adjuvant endocrine therapy (P = 0.0041) significantly reduced the risk of local recurrence. In patients with BCT, without radiation therapy a positive surgical margin significantly increased the risk of local recurrence (P = 0.0470). Multivariate analysis showed that a young age (P = 0.0285) was a significant independent risk factor for local recurrence, while radiation therapy (P = 0.0457) significantly decreased recurrence. In patients with a negative surgical margin, radiation therapy (P = 0.0158) and adjuvant endocrine therapy (P = 0.0421) significantly reduced the relative risk of local recurrence, to 0.160 and 0.366, respectively. In patients with a positive surgical margin, radiation therapy marginally significantly (P = 0.0756) reduced the relative risk of local recurrence, to 0.181, and adjuvant endocrine therapy significantly (P = 0.0119) reduced the risk, to 0.076. Conclusions. Young age and lack of radiation therapy or adjuvant endocrine therapy were risk factors for local recurrence in breast cancer patients treated with breast-conserving therapy, with surgical margin status also being a possible risk factor. Received: November 9, 1998 / Accepted: March 11, 1999     

The prognostic significance of late local recurrence after breast-conserving therapy

Of 178 local recurrences occurring in 1593 patients with clinical Stages I-II breast cancer treated by conservative surgery and megavoltage radiotherapy, 71 were diagnosed after the 5th year. Compared with recurrences occurring prior to 60 months, late recurrences were less frequently inoperable (1/71, 1.4%, versus 18/107, 17%, p less than 0.001), were more often located at a distance from the initial primary tumor (23/71, 32%, versus 15/106, 14%, p less than 0.005), and had a more favorable prognosis (5-year survival 84% versus 61% for late and early operable recurrences, respectively, p = 0.05). Five-year metastasis-free survival after late failure depended mainly on the anatomic extent of the recurrence (87% for recurrences apparently confined to the breast versus 34% for relapses involving the axilla, p less than 0.002). Prognosis of late recurrence appeared to be unaffected both by location of the recurrence within the breast and by the type of salvage operation used (mastectomy versus wide excision). Local-regional control after salvage surgery was satisfactory (89% at 5 years). Whereas recurrence in the breast prior to 5 years profoundly affected survival after initial diagnosis, patients with late failure had identical 15-year survival as other 5-year survivors who never failed locally. Late recurrences were more frequent in patients younger than 40 at initial treatment, and in patients who had inadequate radiotherapy. We conclude that late local recurrences after breast conservation do not represent a serious management problem.     

Family history of breast cancer and local recurrence after breast-conserving therapy

The impact of a family history of breast cancer on the local recurrence (LR) risk after breast-conserving therapy (BCT) was performed within the framework of a large, multicentre matched case–control study of risk factors for LR after BCT (BORST study). Family history was assessed for 218 breast cancer patients with LR (cases) and 480 patients without LR (controls). Detailed histological tumour features were determined by review of the primary tumour. The risk of LR for patients with a positive family history was similar to or less than that of non-familial patients (unadjusted odds ratio (OR_unadj) 0.66 (95% confidence interval (CI) 0.40–1.08)). Familial patients were older than non-familial patients (P=0.07) and their tumours had a lower histological grade (P=0.07). A second primary tumour occurred significantly more often in familial patients (P=0.02). Adjustment for these factors did not essentially alter the results (OR_adj 0.71 (0.38–1.32)). Separate analyses according to age at onset (younger and older than 50 years) and time to LR/site of LR produced similar results. The sole presence of a positive family history of breast cancer does not appear to be a risk factor for local recurrence after BCT. Whilst this might be different for genetically predisposed patients, a positive family history does not appear to be a contra-indication for BCT.     

Correlation between clinical features and prognosis of local recurrence after breast-conserving therapy

Background. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled. Methods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients. Results. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy. Conclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery. Received: May 13, 1999 / Accepted: September 22, 1999     

Ipsilateral breast tumor recurrence after breast-conserving therapy

In the modern era of breast-conserving therapy for early-stage breast cancer, ipsilateral breast tumor recurrence (IBTR) represents an increasingly common clinical dilemma. Two kinds of IBTRs have been described: true recurrences, which represent regrowth of uneradicated initial disease, and new primaries, which may be distinct from the index lesion in histology and location. Whether these two entities have different biologies and survival prognoses remains unclear. This article will examine contemporary clinical and pathologic methods to distinguish true recurrence from new primary tumors, focusing on available published data from prospective and retrospective studies. Current challenges and future avenues are discussed for developing a standardized, reproducible classification system for different types of IBTR that may be used in the clinical setting to prognosticate and individualize treatment for patients following in-breast recurrences.     

广泛导管内成分与保乳术后局部复发风险评估

保乳手术已成为早期乳腺癌的主要治疗手段,评估其局部复发的首选指标为广泛导管内成分(EIC).许多研究证实,EIC阳性者局部复发率较高,但远期生存率并不明显低于阴性者.除了病理检查之外,钼靶X线对检出EIC也有较高的参考作用.从分子生物学角度看,EIC与染色体1q21-23区域的等位基因缺失、cerbB-2过表达等因素正相关,而与p53的过度表达、细胞凋亡没有明显关系.EIC的检测对于早期乳腺癌的综合治疗方案选择具有重要指导意义.     

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.     

An assessment of extensive intraductal component as a risk factor for local recurrence after breast-conserving therapy

The influence of extensive intraductal component (EIC) on local recurrence risk was studied for 496 patients with stage I-II infiltrating ductal cancers treated by conservative surgery and irradiation. EIC was diagnosed in 65 of 231 (28%) premenopausal and 41 of 265 (15.5%) post-menopausal patients. Local recurrence risk was markedly increased in EIC+ patients (5-year actuarial risk 18% versus 8% without EIC, P less than 0.001), but this effect appeared limited to premenopausal patients. Local recurrence risk increased with increasing degree of EIC. EIC with more than 50% intraductal carcinoma was more prevalent in patients younger than 40, perhaps accounting to some degree for the higher local recurrence rates observed in younger patients. The presence of EIC had no influence on overall survival, on median time to local recurrence, or on short-term survival after local failure. The usefulness of EIC as a risk factor for local recurrence is discussed.     

Gene expression profiles of primary breast carcinomas from patients at high risk for local recurrence after breast-conserving therapy.

PURPOSE: Several risk factors for local recurrence of breast cancer after breast-conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also in improving understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence. EXPERIMENTAL DESIGN: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients, 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9 of 19 patients, the local recurrence was also available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences. RESULTS: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from nonrecurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences. CONCLUSIONS: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after BCT were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy.     

Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin

Breast Cancer Research and Treatment - Invasive lobular carcinoma (ILC) typically presents at a later stage than invasive ductal carcinoma (IDC) and poses unique radiographic and surgical...     

乳腺癌保留乳房手术后局部复发的相关因素分析

虽然近年来中国保留乳房手术率不断上升,保留乳房手术已逐渐成为早期乳腺癌患者的主要手术方式之一,但与欧美发达国家相比,中国的保留乳房手术率仍较低。患者担心乳腺癌保留乳房手术后局部复发是影响保留乳房手术率提高的重要原因之一。大量文献对乳腺癌保留乳房手术后局部复发的相关因素进行了报道,笔者对近年来相关文献进行分析并综述。     

The risk of local recurrence after breast-conserving surgery for breast cancer

Recently, the rates of early stage breast cancers involving breast-conserving therapy have increased due to use of mammography screening. Morever, a patient's desire to keep the breast is now considered to be a factor which determines the surgery tactics. However, there has been so far no consensus on optimal extent of surgery capable of preventing local recurrence. In order to precisely estimate such risk it is essential to take into account factors such as tumor size, surgical margin status and age. Besides, correlations between certain subtypes of breast cancer and various associated risks of local recurrence are to be established. Another important factor is to devise the necessary subsequent radiotherapy.     

Factors increasing local recurrence in breast-conserving surgery

From 20-year follow-up results of two pioneering randomized controlled trials demonstrating equal survival after mastectomy and breast-conservation therapy, recent high-quality, evidence-based clinical practice recommendations have been made. Breast-conservation therapy undoubtedly represents substantial progress for a better quality of life for women with early-stage breast cancer. However, lumpectomy is associated with a substantial proportion, approximately 10–20%, of local recurrence in long-term follow-up studies even after accounting for postoperative radiotherapy. Risk factors for local failure include margin status, young age and an extensive intraductal component. Young age and family history strongly suggest the need for genetic testing before initiation of treatment. Women with BRCA1 or BRCA2 mutations should be informed about the increased risk of contralateral breast cancer and ipsilateral failure after breast-conservation therapy. Bilateral mastectomy should also be offered as a treatment option. There is controversy over whether current effective adjuvant treatment, including chemotherapy and endocrine therapy, beyond appropriate local treatment as surgery and radiotherapy, can improve local control. Instead of debate over whether an ipsilateral tumor after breast-conservation therapy is local recurrence or a new primary cancer by analyzing conflicting data lacking strong evidence, efforts should be focused on reducing this risk irrespective of origin. Selecting women for breast-conservation therapy and achieving margin control can reduce ipsilateral failures.     

Factors increasing local recurrence in breast-conserving surgery

From 20-year follow-up results of two pioneering randomized controlled trials demonstrating equal survival after mastectomy and breast-conservation therapy, recent high-quality, evidence-based clinical practice recommendations have been made. Breast-conservation therapy undoubtedly represents substantial progress for a better quality of life for women with early-stage breast cancer. However, lumpectomy is associated with a substantial proportion, approximately 10-20%, of local recurrence in long-term follow-up studies even after accounting for postoperative radiotherapy. Risk factors for local failure include margin status, young age and an extensive intraductal component. Young age and family history strongly suggest the need for genetic testing before initiation of treatment. Women with BRCA1 or BRCA2 mutations should be informed about the increased risk of contralateral breast cancer and ipsilateral failure after breast-conservation therapy. Bilateral mastectomy should also be offered as a treatment option. There is controversy over whether current effective adjuvant treatment, including chemotherapy and endocrine therapy, beyond appropriate local treatment as surgery and radiotherapy, can improve local control. Instead of debate over whether an ipsilateral tumor after breast-conservation therapy is local recurrence or a new primary cancer by analyzing conflicting data lacking strong evidence, efforts should be focused on reducing this risk irrespective of origin. Selecting women for breast-conservation therapy and achieving margin control can reduce ipsilateral failures.     

Risk factors for local recurrence after breast-conserving therapy for invasive carcinomas: a case-control study of histological factors and alterations in oncogene expression.

PURPOSE: Many studies have focused on histological risk factors for local recurrence (LR) after breast-conserving therapy (BCT). In addition to histological factors, we studied alterations in the expression of various proteins in relation to LR using a case-control approach. METHODS AND MATERIALS: Ninety-nine LR occurred in a patient cohort of 1,481 tumors treated with BCT. These patients were randomly matched, each with two controls. Matching was performed for age group (< or = 50 and > 50 years), pN stage, and follow-up time. Histology slides were reviewed. Immunohistochemical staining was performed for the following proteins: bcl-2, CD31, cyclin D1, E-cadherin, EGF receptor, ER, PR, Ki-67, c-erbB2/neu, and p53. Statistical analyses were performed using conditional logistic regression. RESULTS: Sixty-six cases and 139 controls with invasive carcinoma remained for analysis. The following variables were significant risk factors for LR: young age (p = 0.006), high nuclear grade (p = 0.04), high mitotic count (p = 0.03), extensive DCIS around the tumor (p = 0.02) but not within the tumor, poorly differentiated type of DCIS (p = 0.03), > 20% ki-67 positive cells (p = 0.006), and PR negativity (p = 0.03). When the analysis was performed for patients < or = and > 50 years, these risk factors were found in the older patients, but not in the younger patients. CONCLUSION: High mitotic count and Ki-67 positivity are risk factors for LR. EDCIS surrounding the invasive tumor is a risk factor for LR, especially when of poorly differentiated type. Age is an important risk factor for LR independent of other risk factors, including alterations in oncogene expression.