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.     

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.     

Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer

Introduction: The aims of the study were to assess the outcome among patients with early breast cancer operated on with wide local excision who developed a subsequent ipsilateral breast tumor recurrence, and to identify risk factors for uncontrolled local disease. Uncontrolled local disease (ULD) was defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated with salvage treatment during the period of follow-up (2–18 years). Patients and methods: Eighty-five patients in a cohort of 759 patients, treated for invasive Stage I–II breast cancer with breast-conserving surgery 1976–1985 in Stockholm, with a subsequent ipsilateral breast tumor recurrence (IBTR) were reviewed retrospectively. The majority of the patients were premenopausal (58%), node negative (72%), and had received postoperative radiotherapy (79%). Median follow-up time following breast-conserving surgery was 13 (9–19) years. Multivariate Cox's hazard regression was used in the statistical analysis to identify prognostic factors for ULD. Results: The majority (n = 61) of the IBTR's were located in the original tumor quadrant and showed the same histopathological features as the primary tumor. Salvage mastectomy (n = 65) or reexcision (n = 14) were performed in 79 (93%) of the patients. Twenty-one patients developed ULD. Five years following the diagnosis of IBTR the disease-free survival was 59%, the cumulative incidence for ULD was 24%, and for death in breast cancer 34%. In the cohort of 759 patients, patients who received radiotherapy following the primary breast-conserving surgery had 1% cumulative incidence of ULD following the diagnosis of IBTR compared to 4% among patients that received no postoperative radiotherapy. The cumulative incidence at 5 years of ULD following salvage mastectomy was 12% compared to 33% after salvage reexcision. Patients operated on with breast-conserving surgery with an original tumor size < 15 mm, who were treated with salvage mastectomy for IBTR, had in multivariate analysis the lowest relative risk for ULD. Adjuvant chemotherapy following IBTR treatment did not seem to improve local tumor control. Following the diagnosis of IBTR, 78% (n = 21) of the patients with ULD and/or regional recurrence (n = 27), died of a disseminated breast cancer in contrast to 10% (n = 6) among the remaining 58 patients. Conclusion: Uncontrolled local disease is an important outcome measure following breast-conserving surgery. In this cohort, salvage mastectomy provided a superior local control rate compared to salvage reexcision. A higher although not statistically significant rate of ULD was also seen in patients who had not received postoperative radiotherapy as part of their primary treatment.This revised version was published online in October 2005 with corrections to the Cover Date.     

True recurrence vs. new primary ipsilateral breast tumor relapse: an analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management

Purpose: The purpose of this study was to classify all ipsilateral breast tumor relapses (IBTR) in patients treated with conservative surgery and radiation therapy (CS+RT) as either new primary tumors (NP) or true local recurrences (TR) and to assess the prognostic and therapeutic implications of this classification.

Methods and Materials: Of the 1152 patients who have been treated at Yale–New Haven Hospital before 1990, 136 patients have experienced IBTR as their primary site of failure. These relapses were classified as either NP or TR. Specifically, patients were classified as NP if the recurrence was distinctly different from the primary tumor with respect to the histologic subtype, the recurrence location was in a different location, or if the flow cytometry changed from aneuploid to diploid. This information was determined by a detailed review of each patient’s hospital and/or radiotherapy record, mammograms, and pathologic reports.

Results: As of 2/99, with a mean follow-up of 14.2 years, the overall ipsilateral breast relapse-free rate for all 1152 patients was 86% at 10 years. Using the classification scheme outlined above, 60 patient relapses were classified as TR, 70 were classified as NP and 6 were unable to be classified. NP patients had a longer mean time to breast relapse than TR patients (7.3 years vs. 3.7 years, p < 0.0001) and were significantly younger than TR patients (48.9 years vs. 54.5 years, p < 0.01). Patients developed both TR and NP at similar rates until approximately 8 years, when TR rates stabilized but NP rates continued to rise. By 15 years following original diagnosis, the TR rate was 6.8% compared to 13.1% for NP. Of the patients who had been previously tested for BRCA1/2 mutations, 17% (8/52) had deleterious mutations. It is noteworthy that all patients with deleterious mutations had new primary IBTR, while patients without deleterious mutations had both TR and NP (p = 0.06). Ploidy was evenly distributed between TR and NP but NP had a significantly lower S phase fraction (NP 13.1 vs. TR 22.0, p < 0.05). The overall survival following breast relapse was 64% at 10 years and 49% at 15 years. With a mean follow-up of 10.4 years following breast relapse, patients with NP had better 10-year overall survival (TR 55% vs. NP 75%, p < 0.0001), distant disease-free survival (TR 41% vs. NP 85%, p < 0.0001), and cause-specific survival (TR 55% vs. NP 90%, p < 0.0001).

Conclusion: It appears that a significant portion of patients who experience ipsilateral breast tumor relapse following conservative surgery and radiation therapy have new primary tumors as opposed to true local recurrences. True recurrence and new primary tumor ipsilateral breast tumor relapses have different natural histories, different prognoses, and, in turn, different implications for therapeutic management.     

Second invasive breast cancers in patients treated with breast-conserving therapy

ObjectiveSecond breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments.Methods168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis.ResultsWith median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly.ConclusionPatients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments.     

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.     

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.     

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.     

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.     

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 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.     

The use of molecular assays to establish definitively the clonality of ipsilateral breast tumor recurrences and patterns of in-breast failure in patients with early-stage breast cancer treated with breast-conserving therapy

BACKGROUND: Results from numerous trials have indicated that breast-conserving therapy (BCT) produces outcomes equivalent to those produced by mastectomy in terms of both locoregional control and survival. However, conservative treatment has resulted in the dilemma of how best to address recurrences when they appear in a breast treated previously with radiation therapy. Attempts have been made to characterize ipsilateral breast tumor recurrences (IBTRs) as either true recurrences of the treated malignancy or new primary carcinomas, because cancers that represent new primary tumors may be associated with a more favorable prognosis compared with cancers that represent true recurrences. METHODS: The authors studied the clonality of IBTRs relative to the initial invasive carcinomas by using a polymerase chain reaction loss-of-heterozygosity molecular comparison assay in 29 patients who received breast-conserving therapy (BCT). RESULTS: Twenty-two IBTRs (76%) were related clonally to the initial carcinoma, and 7 IBTRs (24%) were clonally different. Clonally related IBTRs were more frequently higher grade (72.2% vs 14.3%; P = .009) and developed sooner after initial treatment (mean time to IBTR, 4.04 years in clonally related IBTRs vs 9.25 years in clonally different IBTRs; P = .002). Six patients subsequently developed distant metastases, and 5 of those patients (83.3%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 30% of all patients. The proportion of IBTRs that were related clonally at 5 years, 10 years, and 15 years after BCT were 93%, 67%, and 33%, respectively. CONCLUSIONS: Clinical classifications of IBTRs were unreliable methods for determining clonality in many patients. Molecular clonality assays provided a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and also provided a more accurate assessment of the efficacy of various forms of local therapy.     

Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation

BACKGROUND:

The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast‐conserving therapy (BCT) using accelerated partial breast irradiation (APBI).

METHODS:

In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4‐Gy fractions). One thousand two hundred fifty‐five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow‐up was 60 months.

RESULTS:

Fifty patients (3.5%) developed an IBTR for a 5‐year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3‐year rates of disease‐free survival, cause‐specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively.

CONCLUSIONS:

With 5 years of follow‐up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3‐year survival outcomes after salvage treatments. Cancer 2012. © 2012 American Cancer Society.     

Late local recurrences in a randomised trial comparing conservative treatment with total mastectomy in early breast cancer patients.

BACKGROUND: A randomised trial was conducted comparing wide lumpectomy and breast irradiation with modified radical mastectomy. As the follow-up was long (mean duration 22 years), we analysed the variation in the effect of treatment over time. PATIENTS AND METHODS: The trial included 179 patients with a breast cancer measuring 相似文献   

Late breast recurrence after lumpectomy and irradiation

For 276 patients with early breast cancer followed from 10-21 years after lumpectomy and radiotherapy, the recurrence rate in the treated breast was 15.6%, and 7.2% developed contralateral breast cancer. Only 63% of breast recurrences occurred within 5 years, and the remainder were "late failures," with 5 of the 43 recurrences observed after 10 years. The proportion of failures occurring late was greater for T1 than for T2 tumors (53% vs 25%). Twenty-six percent of early recurrences were inoperable, and an adverse impact of early recurrence on 10-year survival was clearly demonstrable. Late recurrences were all operable and did not appear to be associated with decreased survival. Only 16 of the 36 patients (44%) with operable breast recurrence ever developed metastatic disease, and 5 year survival following salvage therapy was 62%. Although the treated breast remains at continuous cancer risk even beyond 5 year, the prognosis of late recurrence appears quite similar to that of contralateral breast cancer. We do not consider the phenomenon of late recurrence to lend support to a policy of primary mastectomy, just as the existence of contralateral breast cancer does not justify routine "prophylactic" contralateral mastectomy.     

Impact of Trastuzumab on Ipsilateral Breast Tumor Recurrence for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer after Breast-Conserving Surgery

PurposeTrastuzumab is effective in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, few studies have reported the effect of trastuzumab on ipsilateral breast tumor recurrence (IBTR), whose incidence is higher in the HER2-positive subtype than in other subtypes.MethodsWe retrospectively investigated 959 patients who underwent breast-conserving surgery (BCS), chemotherapy, and radiotherapy for HER2-positive breast cancer between 2000 and 2017. IBTR was compared between the patients who received neoadjuvant or adjuvant trastuzumab (Tmab group) for a total duration of 1 year and those who received no trastuzumab (N-Tmab group).ResultsPropensity score matching designated 426 and 142 patients in the Tmab and N-Tmab groups, respectively. The median follow-up period for all patients after matching was 73.79 months. The IBTR-free survival rate was significantly higher in the Tmab group than in the N-Tmab group (10-year IBTR-free survival rate, 92.9% vs. 87.3%; p = 0.002). The multivariate analysis showed a significant association between the N-Tmab and Tmab group (hazard ratio, 3.03; 95% confidence interval, 1.07–8.59) and IBTR in addition to close or positive resection margin and hormone receptor (HR) positivity. The subgroup analysis showed that adjuvant treatment with trastuzumab significantly reduced IBTR among the patients with HR-negative or lymph node-negative breast cancer.ConclusionSignificantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvant/neoadjuvant trastuzumab treatment for HER2-positive breast cancer.     

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.     

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   

Impact of locoregional treatment on the early-stage breast cancer patients: a retrospective analysis

Although adequate locoregional treatment improves local and regional control in early-stage breast cancer, uncertainty still exists about the role of locoregional therapy with respect to survival. To study the impact of surgery and radiotherapy on locoregional control and survival, we combined the data of three European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer Group trials including early-stage breast cancer patients with long-term follow-up. Risk ratios (RR) were estimated for locoregional recurrence and overall survival using Cox regression models. All analyses were adjusted for tumour size, nodal status, age, adjuvant radiotherapy, adjuvant chemotherapy and trial. The combined data-set consisted of 3648 patients. The median follow-up period was 11 years. 5.9% of the patients who underwent mastectomy and 10.8% of the patients who underwent breast-conserving therapy had a locoregional recurrence (P<0.0001). The risk of death after breast-conserving therapy was similar compared with mastectomy (RR 1.07, P=0.37). Adjuvant radiotherapy after mastectomy was associated with a lower risk for locoregional recurrence (RR 0.43, P<0.001) and death (RR 0.73, P=0.001). Patients with 1-3 positive nodes benefited the most from radiotherapy after mastectomy. Breast-conserving therapy was associated with an impaired locoregional control. However, breast-conserving therapy was not associated with a worse overall survival. Adjuvant radiotherapy in mastectomised patients was associated with both a significantly superior locoregional control and overall survival. The effect of adjuvant radiotherapy was most profound in patients who had 1-3 positive nodes.     

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.