Uncontrolled local disease after salvage treatment for ipsilateral breast tumour recurrence.

AIM: Uncontrolled local disease (ULD) following breast conservation constitutes a clinical problem with a major impact on quality of life. The current study analysed the outcome following treatment of ipsilateral breast tumour recurrence (IBTR) and the risk for ULD with the aim to identify risk factors for ULD. METHODS: In a cohort of 5502 patients treated for invasive breast cancer Stage I-II with breast-conserving surgery 1976-1998 in Stockholm, 307 patients with subsequent IBTR were identified. The majority (n = 219) had received postoperative radiotherapy. Twenty-six per cent of the patients received adjuvant tamoxifen, for 2 or 5 years, and 9% received adjuvant polychemotherapy. Median follow-up time was 11(2-23) years. 50/307 patients developed ULD, defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated within 3 months of detection. Multivariate linear logistic regression was used in the statistical analysis to identify prognostic factors for ULD. RESULTS: Five years following the diagnosis of IBTR the cumulative incidence of ULD was 13%. Five independent risk factors for ULD were identified; non-surgical treatment of IBTR, disseminated disease concurrent with IBTR, axillary lymph node metastases (at primary breast conservation), time < 3 years between breast conservation and IBTR, no adjuvant endocrine therapy. Eighty-eight per cent of the patients were treated with salvage mastectomy (n = 207) or re-excision (n = 62). The cumulative incidence at 5 years of ULD following salvage mastectomy and salvage re-excision were 10% and 16% respectively compared to 32% among patients treated non-surgically. Following IBTR, the 5-year overall survival among patients with local control was 78% in contrast to 21% among patients with ULD. CONCLUSION: Uncontrolled local disease is an infrequent but important outcome following breast-conserving surgery. Primary postoperative radiotherapy reduces the risk for IBTR and is therefore recommended as part of the primary treatment to avoid both IBTR and ULD. In addition to radiotherapy, adjuvant therapy reduces the risk for IBTR and thereby the risk for subsequent ULD. Patients with IBTR, independent of concurrent distant metastases, should when feasible be recommended for salvage surgery as it provides superior local control compared to salvage systemic therapy alone.     

Classification of ipsilateral breast tumor recurrence after breast-conserving therapy: New primary cancer allows a good prognosis

PURPOSE: To classify and assess ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy. METHODS: Between 1986 and 2001, 2,137 patients who had breast cancer underwent breast-conserving surgery with or without radiotherapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Of these patients, 83 (3.9%) had an IBTR. We classified the IBTR as a new primary cancer (NP) if the primary tumor had completely negative margins at first operation by detailed pathological examination and if the IBTR had an intraductal component. All other IBTRs were judged true local recurrence (TR). RESULTS: Of the 83 patients, 42 patients were classified as TR (29 had no radiotherapy) and 41 as NP (40 had no radiotherapy). Mean time to disease recurrence was 37 months for TR (52% were within 2 years) versus 55 months for NP (19% were within 2 years) (p=0.031). Six patients (14%) with TR did not receive re-operation, and 67% received salvage mastectomy and 19% re-lumpectomy. All cases of NP were operable, 78% underwent salvage mastectomy and 22% underwent re-lumpectomy. Distant metastases were observed in 33% of patients with TR and 5% of patients with NP, and cause-specific death occurred in 6 cases with TR and in one with NP. The patients with NP had improved 5-year rates of overall survival (NP 91% vs. TR 76%, P=0.0627) and distant disease-free survival (NP 93% vs. TR 61%, P=0.0028). Patients with NP more often developed contralateral breast cancer (NP 37% vs. TR 12%, P=0.018) CONCLUSIONS: Patients with NP had better survival rates than those with TR. Distinguishing new primary breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies.     

Ipsilateral breast tumor recurrence after breast conservation therapy: outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation

PURPOSE: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. METHODS AND MATERIALS: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size < 3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with < or = 3 positive nodes. RESULTS: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n = 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. CONCLUSIONS: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is discussed.     

Repeat breast-conserving therapy for ipsilateral breast cancer recurrence: A systematic review

The standard of care for patients with an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) is a salvage mastectomy. However, there is growing interest in the feasibility of repeat BCT for these patients. This systematic review contains the latest insights on BCT options for patients with an IBTR after initial BCT.A PubMed literature search was performed for articles on BCT options for IBTR after primary lumpectomy followed by radiotherapy. Weighted estimates were calculated for 5- and 10-year local control, distant metastasis-free and overall survival rates. Secondary outcomes were toxicity, cosmesis and quality of life.In total, 34 studies were eligible for analysis, of which 5 reported on repeat breast-conserving surgery (BCS) alone, 10 with mixed populations (BCS ± RT and/or mastectomy), 18 on repeat BCS followed by re-irradiation (whole-breast or partial) and one on quality of life. The weighted estimates for 5-year overall survival for repeat BCS and repeat BCS followed by reirradiation were 77% and 87%, respectively. Five-year local control was 76% for repeat BCS alone and 89% for repeat BCS followed by re-irradiation. Grade III-IV toxicity rates after re-irradiation varied from 0 to 21%, whereas the cosmesis was excellent-good in 29–100% of patients and unacceptable in 0–18%.Repeat BCS followed by re-irradiation, with either whole breast or partial breast re-irradiation, seems a feasible alternative to mastectomy in case of IBTR, in selected patients. Toxicity rates are low and the cosmetic outcome is good, but the size and follow-up of the published patient series is limited.     

Analysis of ipsilateral breast tumor recurrences after breast-conserving treatment based on the classification of true recurrences and new primary tumors

BACKGROUND: Ipsilateral breast tumor recurrences (IBTR) after breast-conserving treatment include two different entities: true recurrence (TR) thought to occur when residual cancer cells grow gradually to detectable size and new primary (NP) thought to be de novo cancer independently arising in the preserved breast. The patients with ipsilateral breast tumor recurrence (IBTR) are potentially at high risk for subsequent distant metastasis, but many studies do not distinguish between these types of recurrence. The aim of this study is to clarify the biological difference between TR and NP, and to show the clinical significance of classifying IBTR into these two types of recurrence. PATIENTS AND METHODS: A total of 172 patients with IBTR after breast-conserving therapy from the cohort of a long-term large scale study (Research of cancer treatment from the Ministry of Health, Labor and Welfare of Japan (no.13-9)) were analyzed. We classified IBTRs as TR or NP based on tumor location and pathological findings. The characteristics of the primary tumors of TR and NP were compared. Survival rates and risk factors of each type of IBTR were examined by the Kaplan-Meier method. The results of salvage surgery were also analyzed. RESULTS: Of the 172 patients, 135 patients were classified as TR and 26 as NP. Eleven cases could not be categorized. The primary tumor of TR was characterized by a high rate of lymph node metastasis (37.8%) and short disease-free interval (mean DFI; 46.6 months) while that of NP showed a rather low lymph node positivity (8.7%) and longer DFI (62.1 months). The risk factors for TR were young age, positive surgical margin, omission of irradiation and positive lymph node metastasis. Those for NP were young age, omission of irradiation and contralateral breast cancer after the primary operation. The 5-year survival rates after IBTR were 71.0% in TR and 94.7% in NP (p=0.022). Salvage operation was performed in 136 IBTRs. Eighty-one patients underwent salvage mastectomy and 55 patients underwent repeat lumpectomy. Five-year survival rates after salvage operation were 75.7% for mastectomy and 84.2% for lumpectomy (N.S.). Twenty percent of patients who underwent repeat lumpectomy developed secondary local relapse within 5 years after salvage treatment. The risk factors for secondary local relapse were analyzed. Limited to cases of IBTR which received radiation therapy after the primary operation, NP was the only factor influencing secondary local relapse by univariate analysis. CONCLUSIONS: TR and NP show clinically quite different features; time to occurrence, characteristics of the original tumor, prognosis and risk factor profile for IBTR were all different. Classifying IBTR as TR or NP can provide clinically significant data for the management of IBTR.     

Multifocality in ipsilateral breast tumor recurrence - A study in ablative specimens

BackgroundThe incidence and clinical significance of multifocality in ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) are unclear. With growing interest in repeat BCT, this information has become of importance. This study aimed to gain insight in the incidence of multifocality in IBTR, to identify patient- and tumor-related predicting factors and to investigate the prognostic significance of multifocality.MethodsTwo hundred and fifteen patients were included in this analysis. All had an IBTR after BCT and were treated by salvage mastectomy and appropriate adjuvant therapy. Predictive tumor- and patient-related factors for multifocality in IBTR were identified using X2 test and univariate logistic regression analyses. Prognostic outcomes were calculated using Kaplan Meier analysis and compared using the log rank test.ResultsMultifocality was present in 50 (22.9%) of IBTR mastectomy specimens. Axillary positivity in IBTR was significantly associated with multifocality in IBTR. Chest wall re-recurrences occurred more often after multifocal IBTR (14% versus 7% after unifocal IBTR, p = 0.120). Regional re-recurrences did not differ significantly between unifocal and multifocal IBTR (8% vs. 6%, p = 0.773). Distant metastasis after salvage surgery occurred more frequently after multifocal IBTR (15% vs. 24%, p = 0.122). Overall survival was 132 months after unifocal IBTR and 112 months after multifocal IBTR (p = 0.197).ConclusionThe prevalence of multifocality in IBTR is higher than in primary breast cancer. Axillary positivity in IBTR was associated with a multifocal IBTR. Chest wall re-recurrences and distant metastasis were, although not statistically significant, more prevalent after multifocal IBTR.     

Ipsilateral breast tumor reappearance in patients treated with conservative surgery after primary chemotherapy. The role of surgical margins on outcome

BACKGROUND AND OBJECTIVES: To evaluate the ipsilateral breast tumor reappearance (IBTR) rate after breast conservative surgery (BCS) following primary chemotherapy (PC) and to assess whether positive margins affects IBTR rate and overall survival (OS). METHODS: Three hundred nine women candidates for mastectomy received PC before surgery. One hundred ninety-five patients (63.1%) underwent BCS and 114 patients (36.9%) a modified radical mastectomy. RESULTS: After a median follow-up of 41 months (range 7-90), 13 patients of the 195 treated with BCS had an IBTR (6.7%), 6 patients had a regional relapse (3.1%), 28 women had distant metastases (14.4%). Twenty-three patients died of breast cancer (11.8%). Twenty-four patients treated with BCS had positive margins (12.3%). At 3 years, the crude cumulative incidence of local recurrence was 4.7% in women with negative margins, and 13.3% in women with positive margins (P=0.05). Cumulative incidence of distant metastases was similar in patients with positive and negative margins (P=0.16) and there was no significant difference in terms of OS according to the margin status (P=0.577). CONCLUSIONS: BCS after PC has an acceptable rate of IBTR. After a short follow-up, the presence of positive margins does not affect OS.     

The Salzburg concept of intraoperative radiotherapy for breast cancer: results and considerations

Aim of this study is to show that ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery can be reduced by proper surgery and modern radiotherapy techniques. Three hundred and seventy eight women with stage I or II breast cancer had breast conserving surgery and received 51-56.1 Gy of postoperative radiation to the whole breast in 1.7 Gy fractions, but patients received different boost strategies. Group 1 (n = 188) received electron boost radiation of 12 Gy subsequent to the irradiation to the whole breast, group 2 (n = 190) received intraoperative electron boost radiation of 9 Gy directly to the tumor bed, followed by whole breast irradiation. After a median follow up period of 81.0 months in group 1 and a median follow up period of 51.1 months in group 2, 12 IBTRs (6.4%) could be observed in group 1 and no IBTR could be observed in group 2 (0.0%). The 5-year actuarial rates of IBTR were 4.3% (95% CI, 1.9-8.3%) and 0.0% (95% CI, 0.0-1.9%), respectively (p = 0.0018). The 5-year actuarial rates of distant recurrence were 8.6% (95% CI, 4.9-13.5%) and 4.2% (95% CI, 1.8-8.2%), respectively (p = 0.08). The 5 year disease-free survival rates were 90.9% (95% CI, 85.8-94.7%) in group 1 and 95.8% (95% CI, 91.8-98.2%) in group 2 (p = 0.064). Immediate IORT-boost and whole breast irradiation yields excellent local control at 5 years, and was associated with a statistically significant decreased rate of IBTR compared with a similar cohort of patients treated with whole breast irradiation and conventional electron boost.     

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. MATERIALS AND METHODS: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). RESULTS: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. CONCLUSIONS: After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.     

Classifying local disease recurrences after breast conservation therapy based on location and histology: new primary tumors have more favorable outcomes than true local disease recurrences

BACKGROUND: To distinguish true local recurrences (TR) from new primary tumors (NP) and to assess whether this distinction has prognostic value in patients who develop ipsilateral breast tumor recurrences (IBTR) after breast-conserving surgery and radiotherapy. METHODS: Between 1970 and 1994, 1339 patients underwent breast-conserving surgery at The University of Texas M. D. Anderson Cancer Center for ductal carcinoma in situ or invasive carcinoma. Of these patients, 139 (10.4%) had an IBTR as the first site of failure. For the 126 patients with clinical data available for retrospective review, we classified the IBTR as a TR if it was located within 3 cm of the primary tumor bed and was of the same histologic subtype. All other IBTRs were designated NP. RESULTS: Of the 126 patients, 48 (38%) patients were classified as NP and 78 (62%) as TR. Mean time to disease recurrence was 7.3 years for NP versus 5.6 years for TR (P = 0.0669). The patients with NP had improved 10-year rates of overall survival (NP 77% vs. TR 46%, P = 0.0002), cause-specific survival (NP 83% vs. TR 49%, P = 0.0001), and distant disease-free survival (NP 77% vs. TR 26%, P < 0.0001). Patients with NP more often developed contralateral breast carcinoma (10-year rate: NP 29% vs. TR 8%, P = 0.0043), but were less likely to develop a second local recurrence after salvage treatment of the first IBTR (NP 2% vs. TR 18%, P = 0.008). CONCLUSIONS: Patients with NP had significantly better survival rates than those with TR, but were more likely to develop contralateral breast carcinoma. Distinguishing new breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies. This is because patients with new carcinomas had significantly lower rates of metastasis than those with local disease recurrence, but were more likely to develop contralateral breast carcinomas.     

Independent Prognostic Factors for Overall Survival after Salvage Operation for Ipsilateral Breast Tumor Recurrence Following Breast-Conserving Surgery

Purpose

Few studies address independent prognostic factors after ipsilateral breast tumor recurrence (IBTR) following breast-conserving surgery (BCS). Locoregional recurrence is associated with distant metastases and increased mortality rates. Therefore anticipating prognoses after IBTR and evaluating risk factors for overall survival following a second salvage operation are important. We evaluated independent prognostic factors affecting overall survival after a second operation for IBTR.

Methods

We retrospectively identified 11,073 patients who underwent breast cancer surgery between November 1995 and December 2011. Locoregional recurrence occurred in 787 patients. Among them, IBTR developed in 165 patients selected for analysis. Excluding eight patients who refused further treatment, we analyzed 157 patients who underwent a second operation (partial mastectomy, 28 [17.8%]; total mastectomy, 129 [82.2%]) for IBTR. Excluding 26 patients with incomplete data, we evaluated the clinicopathol-ogical features influencing overall survival at the first and the second operation in the 131 patients who underwent a second operation.

Results

The median age of patients at the first operation was 43.6 years (range, 27-69 years). The median duration from the first to the second operation was 45.0 months (range, 2.5-164.6 months). The 5-year overall survival rate after IBTR was 87.1%. In the multivariable analyses, duration from the first to the second operation, histopathology, lymph node status, and adjuvant chemotherapy, radiotherapy, and endocrine therapy at the first operation were independent prognostic factors for overall survival. Positive estrogen receptor status and endocrine therapy at the second operation were also associated with increased overall survival following salvage operations for IBTR.

Conclusion

The time interval to IBTR following BCS is related to overall survival after salvage operation for IBTR and it is important to undergo optimal adjuvant treatments according to risk factors after the first operation because those risk factors affect overall survival for IBTR following BCS.     

The Italian Association of Radiotherapy and Oncology Recommendation for Breast Tumor Recurrence: Grades of Recommendation,Assessment, Development and Evaluation Criteria

Salvage mastectomy is currently considered the standard of care for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and postoperative radiotherapy (RT). Alternative treatment options for these patients, such as a second BCS followed by repeated RT, have been suggested.The panel of the Italian Association of Radiotherapy and Clinical Oncology developed clinical recommendations for second BCS followed by re-irradiation over mastectomy alone for women with IBTR using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the evidence to decision framework. The following outcomes were identified by the panel: locoregional control, metastasis-free survival, overall survival, and cancer-specific survival; acute and late toxicity, specific late toxicity, second locoregional tumor, and death related to treatment.An Embase and PubMed literature search was performed by two independent authors. Five retrospective observational studies were eligible for inclusion in the present analysis.According to the reports in the literature and our analysis, the advantages of second quadrantectomy and re-irradiation (re-QUART) outweigh its side effects, with overall good rates of survival and adequate toxicity without increasing costs.Given the very low level of evidence, the panel stated that a second BCS plus re-irradiation can be considered as an alternative to salvage mastectomy for selected patients with IBTR.     

Outcome After Ipsilateral Breast Tumor Recurrence in Patients With Early-Stage Breast Cancer Treated With Accelerated Partial Breast Irradiation

PurposeLimited outcomes exist in patients who develop an ipsilateral breast tumor recurrence (IBTR) after accelerated partial breast irradiation (APBI). The purpose of this study was to evaluate these outcomes and patterns of failure in our cohort of patients undergoing APBI.Methods and MaterialsA total of 534 patients with early-stage breast cancer were treated with APBI between 1993 and 2010. Clinical, pathologic, and treatment-related variables were analyzed. Clinical outcomes, including further IBTR, regional recurrence, disease-free survival, cause-specific survival, and overall survival were analyzed.ResultsEighteen (3.3%) patients developed an IBTR, for a 5-year actuarial rate of 2.0%; 14 (77.8%) of the recurrences were thought to represent new primary cancers. After IBTR, 13 (72.2%) patients were managed with salvage mastectomy and 4 (22.2%) patients with a second attempt at breast-conserving therapy. Five-year rates of disease-free survival, cause-specific survival, and overall survival after salvage mastectomy for IBTR were 81%, 100%, and 100%, respectively. In the 4 patients treated with a second attempt at breast-conserving therapy, no IBTR, axillary failure, regional recurrence, or distant metastases were noted at 5 years.ConclusionsIBTRs that developed after APBI resulted in excellent clinical outcomes comparable with those observed after whole-breast irradiation.     

Local treatment options for ipsilateral breast tumour recurrence

Purpose

In case of ipsilateral breast tumour recurrence (IBTR), radical mastectomy represents the treatment option frequently proposed. A second conservative treatment (2ndCT) has been proposed using either lumpectomy alone or associated with a re-irradiation of the tumor bed. However, in both clinical situations, the proof level of such therapeutic approaches remains low, based on cased-series or retrospective studies (level C).

Material and methods

In order to assess the different strategies of local treatment proposed in case of IBTR, a PubMed literature review was performed using the following keywords: breast cancer, ipsilateral recurrence, mastectomy, radiation therapy, brachytherapy. Four different salvage options were analyzed: (a) salvage mastectomy alone; (b) salvage mastectomy with postoperative re-irradiation; (c) 2ndCT with surgery alone; (d) 2ndCT with re-irradiation.

Results

The rate of second local recurrence is about 10% [3–32%], about 25% [7–36%] and about 10% [2–26%], after salvage mastectomy, salvage lumpectomy alone or combined with a re-irradiation of the tumor bed respectively.However, the 5-year overall survival rates after salvage mastectomy and 2ndCT seem to be equivalent (≈75%) mainly influenced by distant metastatic progression.

Conclusion

In terms of Evidence Based Medicine, different options can be discussed such as Phase III or II randomized trials comparing salvage mastectomy versus 2ndCT, retrospective studies based on a matched-pair analysis or observatory studies. Those study designs need to be carefully analyzed to be able to propose new treatment options for women who experience an IBCR.     

放射治疗在早期乳腺癌保乳术中的价值

目的：进一步证实放射治疗在早期乳腺癌保乳术中的重要性。方法：1994年12月～2001年12月本院共收治237例早期乳腺癌。其中83例做保乳手术。154例做改良根治术。保乳术后全部患者接受放疗。放疗的范围根据肿块的大小、部位、腋淋巴结是否受累而定。胸壁切线剂量予8MV—X线5000cGy。肿瘤瘤床加电子线1500cGy。改良根治术后仅3例作放疗。结果：保乳组和改良组局部复发各1人。保乳组区域淋巴结复发1例。改良组无区域淋巴结复发，有肝转移、肺转移各1人。两组各死亡1人。保乳组五年生存率96．49％，改良组98．61％。保乳组双侧乳房外形基本一致，柔软，有弹性。结论：早期乳腺癌保乳术加放射治疗，效果与改良根治术相似，并伴良好美容效果。     

The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

PURPOSE: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. METHODS AND MATERIALS: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. RESULTS: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p=0.04). On multivariate analysis, positive margin (p<0.01), positive/no reexcision (p=0.04), and presence of LCIS (p=0.02) remained independently associated with IBTR; positive margin (p<0.01) and LCIS (p=0.04) were also associated with TR/MM failure. When examining only cases with negative final margins, the presence of LCIS remained associated with higher IBTR and TR/MM rates (p<0.01). CONCLUSION: The presence of LCIS was independently associated with higher rate of IBTR and TR/MM after BCT for invasive breast cancer. LCIS may have significant premalignant potential and progress to an invasive IBTR at the site of index lesion. The adequacy of excision of LCIS associated with invasive carcinoma should be considered in patients undergoing BCT.     

Repeat lumpectomy for patients with ipsilateral breast tumor recurrence after breast-conserving surgery. Preliminary results

In this study, we assessed the appropriateness of conducting repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) based on the characteristics of recurrence after primary breast conserving surgery (BCS). Of 41 patients who had developed IBTR from October 1986 to June 2000 at our institute, 11 underwent mastectomy of the remaining breast and 30 underwent repeat lumpectomy. The 5-year overall survival rate at a median follow-up of 43 months after salvage surgery was 90.9% for the mastectomy group and 90.0% for the lumpectomy group. The 5-year distant disease-free survival rate was 70.1% for the mastectomy group and 83.0% for the lumpectomy group. The survival rates were remarkably high in both treatment groups, with no significant difference between them. IBTRs in the majority of our patients were small lesions less than 1 cm in diameter. They did not feature lymphatic invasion and had low histological grade. Compared with that of primary lesions, the malignancy of recurrent tumors was not increased in many patients. In contrast to these preferable features, 9 of 30 patients who underwent repeat lumpectomy developed second local relapse within 3 years after salvage operation. Young age (相似文献   

Primary chemotherapy for operable breast cancer: incidence and prognostic significance of ipsilateral breast tumor recurrence after breast-conserving surgery.

PURPOSE: To determine the incidence and the prognostic value of ipsilateral breast tumor recurrence (IBTR) in patients treated with primary chemotherapy and breast-conserving surgery. PATIENTS AND METHODS: Between January 1985 and December 1994, 257 patients with invasive T1 to T3 breast carcinoma were treated with primary chemotherapy, lumpectomy, and radiation therapy. The median follow-up time was 93 months. To evaluate the role of IBTR in metastase-free survival, a Cox regression multivariate analysis was performed using IBTR as a time-dependent covariate. RESULTS: The IBTR rates were 16% (+/- 2.4%) at 5 years and 21.5% (+/- 3.2%) at 10 years. Multivariate analysis showed that the probability of local control was decreased by the following independent factors: age < or = 40 years, excision margin < or = 2 mm, S-phase fraction more than 4%, and clinical tumor size more than 2 cm at the time of surgery. In patients with excision margins of more than 2 mm, the IBTR rates were 12.7% at 5 years and 17% at 10 years. Nodal status, age < or = 40 years, and negative estrogen receptor status were predictors of distant disease in the Cox multivariate model with fixed covariates. The contribution of IBTR was highly significant (relative risk = 5.34) when added to the model, whereas age < or = 40 years was no longer significant. After IBTR, 31.4% (+/- 7.0%) of patients developed metastases at 2 years and 59.7% (+/- 8.1%) at 5 years. Skin involvement, size at initial surgery, and estrogen receptor status were predictors of metastases after IBTR. CONCLUSION: IBTR is a strong predictor for distant metastases. There are implications for conservative surgery after downstaging of the tumor and therapy at the time of IBTR.     

Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy

Purpose: The association between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) after conservative surgery and radiation is controversial. The width of the resection margin that minimizes the risk of IBTR is unknown. While adjuvant systemic therapy may decrease the risk of an IBTR in all patients, its impact on patients with positive or close margins is largely unknown. This study examines the interaction between margin status, margin width, and adjuvant systemic therapy on the 5- and 10-year risk of IBTR after conservative surgery and radiation.

Methods and Materials: A series of 1,262 patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery, axillary node dissection, and radiation between March 1979 and December 1992. The median follow-up was 6.3 years (range 0.1–15.6). The median age was 55 years (range 24–89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent of patients were node-negative. Only 5% of patients had tumors that were EIC-positive. Forty-one percent had a single excision, and 59% had a reexcision. The final margins were negative in 77%, positive in 12%, and close (≤ 2 mm) in 11%. The median total dose to the tumor bed was 60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with positive margins. Chemotherapy ± tamoxifen was used in 28%, tamoxifen alone in 20%, and no adjuvant systemic therapy in 52%.

Results: The 5-year cumulative incidence (CI) of IBTR was not significantly different between patients with negative (4%), positive (5%), or close (7%) margins. However, by 10 years, a significant difference in IBTR became apparent (negative 7%, positive 12%, close 14%, p = 0.04). There was no significant difference in IBTR when a close or positive margin was involved by invasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years if the final margin was negative; however, the highest risk was observed in patients with persistently positive (13%) or close (21%) (p = 0.02) margins. The median interval to failure was 3.7 years after no adjuvant systemic therapy, 5.0 years after chemotherapy ± tamoxifen, and 6.7 years after tamoxifen alone. This delay to IBTR was observed in patients with close or positive margins, with little impact on the time to failure in patients with negative margins. The 5-year CI of IBTR in patients with close or positive margins was 1% with adjuvant systemic therapy and 13% with no adjuvant therapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to more late failures in the patients who received adjuvant systemic therapy.

Conclusion: A negative margin (> 2 mm) identifies patients with a very low risk of IBTR (7% at 10 years) after conservative surgery and radiation. Patients with a close margin (≤ 2 mm) are at an equal or greater risk of IBTR as with a positive margin, especially following a reexcision. A margin involved by DCIS or invasive tumor has the same increased risk of IBTR. A reexcision of an initially close or positive margin that results in a negative final margin reduces the risk of IBTR to that of an initially negative margin. A close or positive margin is associated with an increased risk of IBTR even in patients who are EIC-negative or receiving higher boost doses of radiation. The median time to IBTR is delayed; however, the CI is not significantly decreased by adjuvant systemic therapy in patients with close or positive margins—the 5 year results in these patients underestimate their ultimate risk of recurrence.     

乳腺癌保乳治疗的现状和展望

本文介绍早期乳腺癌保乳治疗的现状和进展,主要从乳腺癌病理生理特点、保乳治疗与根治性手术的等效性、保乳手术的技术要求、前哨淋巴结活检、局部复发的相关风险因素和术后放疗等几个方面加以探讨。随着乳腺癌早期发现比例的逐渐提高和医患观念的更新,乳腺癌保乳治疗的应用前景将更加广阔。