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.     

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.     

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.     

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.     

Investigation of factors related to periods to ipsilateral breast tumor recurrence after breast-conserving surgery and measures for preventing recurrence in early breast cancer

BACKGROUND: The most important issue in breast-conserving surgery is avoidance of ipsilateral breast tumor recurrence (IBTR). We have investigated the factors related to the period between surgery and recurrence and the measures taken. SUBJECT AND METHODS: From April 1989 to December 2004, 888 cases (excluding cases who underwent neoadjuvant chemotherapy) of breast-conserving surgery were performed. IBTR occurred in 56 of these cases. We investigated the timing of these recurrences. Furthermore, the rate of recurrence before and after 1999 when postoperative adjuvant therapy (such as CEF and Taxanes) was started as standard treatment was investigated. RESULTS: The mean period to recurrence in the 56 patients that experienced IBTR was 41.3 months; early recurrence within two years occurred in 21 (37.5%) patients. On the other hand, recurrence from the fifth year onwards post-surgery occurred in 11 patients (19.6%). Of the factors related to the timing of recurrence, a significant difference was seen in tumor proliferative activity, ER (estrogen receptor) status, lymphatic invasion (ly), and whether the lesion was inside or outside the mammary gland tissue. Furthermore, patients experiencing an early recurrence including inflammatory type breast recurrence had a complicated course with distant metastases and their prognosis was poor. Therefore, there was delayed onset of recurrence in the ER positive and ly negative patients with decreased tumor proliferation. With regard to the timing of operation in relation to adjuvant therapy, there was an increase in the conservation rate for the patients in the later phase of the study (1999 onwards), and the number of significantly large and surgical margin positive patients that were at risk of a recurrence was high. However, early recurrence was significantly low, and standard therapy was found to inhibit recurrence. CONCLUSIONS: Although tumor proliferative activity, ER status and ly caused differences in timing of recurrence, standard adjuvant therapy, particularly chemotherapy for early recurrence, was effective in inhibiting recurrence.     

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.     

Significance of ipsilateral breast tumor recurrence after breast conserving treatment: role of surgical removal

Objective: To analyze the pattern over time (dynamics) of further recurrence and death after ipsilateral breast tumor recurrence (IBTR) in breast cancer patients undergoing breast conserving treatment (BCT). Methods: A total of 338 evaluable patients experiencing IBTR were extracted from a database of 3,293 patients undergoing BCT. The hazard rates for recurrence and mortality throughout 10 years of follow-up after IBTR were assessed and were compared to the analogous estimates associated to the primary treatment. Results: In a time frame with the time origin at the surgical treatment for IBTR, the hazard rate for further recurrence displays a bimodal pattern (peaks at the second and at the sixth year). Patients receiving mastectomy for IBTR reveal recurrence and mortality dynamics similar to that of node positive (N+) patients receiving mastectomy as primary surgery, apart from the first two-three years, when IBTR patients do worse. If the patients with time to IBTR longer than 2.5 years are considered, differences disappear. Conclusions: The recurrence and mortality dynamics following IBTR surgical removal is similar to the corresponding dynamics following primary tumor removal. In particular, patients with time to IBTR in excess of 2.5 years behave like N+ patients following primary tumor removal. Findings may be suitably explained by assuming that the surgical manoeuvre required by IBTR treatment is able to activate a sudden growing phase for tumor foci most of which, as suggested by the systemic model of breast cancer, would have reached the clinical level according to their own dynamics.     

Are ipsilateral breast tumour invasive recurrences in young (?40 years) women more aggressive than their primary tumours?

The characteristics of ipsilateral breast tumour recurrences (IBTRs) relative to those of their primary tumours (PTs) remain scarcely studied. Of 70 young (< or =40 years) premenopausal women with IBTRs, we studied a series of 63 with paired histological data. Median follow-up since IBTR was 10 years. Rates of histological types, grades or hormonal receptors were not significantly different in PTs and in IBTRs. The concordance between IBTRs and their PTs was good for histological types. IBTRs with conserved histological types tended to occur more locally, but not significantly sooner than others. These IBTRs had good concordance for hormone receptors. In discordant cases there were as many losses as appearances of the receptors. The concordance was weak for grades, with equivalent numbers of IBTRs graded lower as higher than their PTs. The 10-year overall survival rate was 70%. Neither the conservation of histological type, location, nor of the two combined were associated with deaths. Early (<2 years) IBTRs, tended to be associated with poorer survival (HR=2.24 (0.92-5.41); P=0.08). IBTRs did not display features of higher aggressiveness than PTs. Neither clinical nor histological definition of a true recurrence could be established other than the conservation of the histological type.     

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

BACKGROUND:

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

METHODS:

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

RESULTS:

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

CONCLUSIONS:

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

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: Risk factors of IBTR and validation of the MD Anderson Prognostic Index

BACKGROUND:

There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast‐conserving surgery plus radiotherapy (breast‐conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors.

METHODS:

The authors collected data from 375 patients who underwent BCT and received NAC and analyzed the risk of IBTR associated with undergoing BCT after NAC. The usefulness of the MD Anderson Prognostic Index (MDAPI) for IBTR also was validated using the current data set.

RESULTS:

The median follow‐up was 47.8 months, and the 4‐year IBTR‐free survival rate was 95.6%. Multivariate analysis demonstrated that estrogen receptor (ER) status and multifocality of the residual tumor were associated significantly with IBTR‐free survival. In addition, patients who had ER‐positive and human epidermal growth factor 2 (HER2)‐negative tumors did not develop IBTR during the observation period. Although prognostic stratification according to MDAPI was relatively good for the prediction of IBTR in the study patients, the IBTR rate in the high‐risk group was not very high and was lower than that in the intermediate‐risk group. Multivariate analyses demonstrated that IBTR was an independent predictive factor for overall survival.

CONCLUSIONS:

ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER‐positive and HER2‐negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor. Cancer 2012. © 2012 American Cancer Society.     

Pattern of local recurrence after conservative surgery and whole-breast irradiation

PURPOSE: Most recurrences in the breast after conservative surgery and whole-breast irradiation have been reported to occur within the same quadrant as the initial primary tumor. We analyzed the long-term risk of recurrence by area of the breast after whole-breast irradiation. MATERIALS AND METHODS: In all, 1,990 women with Stage 0-II breast cancer were treated with conservative surgery and whole-breast irradiation from 1970-1998. Stage was ductal carcinoma in situ in 237, T1 in 1273, and T2 in 480 patients. Of 120 local recurrences, 71 were classified as true local (confined to the original quadrant) and 49 as elsewhere (involving outside the original quadrant). Kaplan-Meier methodology was used to calculate 5-year, 10-year, and 15-year rates of recurrence (95% confidence intervals in parentheses). The median follow-up is 80 months. RESULTS: There was no apparent difference in the 15-year rate of true local vs. elsewhere recurrence, but the time to recurrence was different. The rate of true local recurrence was 2%, 5%, and 7% (5-9%) at 5, 10, and 15 years, respectively. The recurrences elsewhere in the breast were rare at 5 (1%) and 10 (2%) years, but increased to 6 (3-9%) at 15 years. This 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers of 13% (10-16%). CONCLUSIONS: Recurrence elsewhere in the breast is rare for the first 10 years, but by 15 years is nearly equal to true local recurrence even after whole-breast irradiation. The 15-year rate of elsewhere recurrence was half the rate of contralateral breast cancers. This may indicate a therapeutic effect of whole-breast radiation for other areas of the breast. Very long follow-up will be needed for partial breast irradiation with or without tamoxifen to show that the risk of elsewhere recurrence is not significantly different than after whole-breast irradiation.     

Partial breast irradiation versus whole breast radiotherapy for early-stage breast cancer: a decision analysis

PURPOSE: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. METHODS AND MATERIALS: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. RESULTS: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adjusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. CONCLUSIONS: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.     

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.     

Function-preserving surgery for breast cancer

Breast-conserving treatment is well established as a safe method of treatment for the majority of breast cancers. Issues to be addressed concerning breast-conserving treatment include the omission of radiation therapy in low-risk patients, optimal local and systemic treatment for ipsilateral breast tumor recurrence, classification of ipsilateral breast tumor recurrence into true recurrences and new primary cancers, and the selection of patients who are eligible for breast conservation after neoadjuvant chemotherapy. There is much evidence that sentinel node biopsy is an accurate method of screening for axillary nodal status in patients with early breast cancer. Clearly, the avoidance of axillary dissection improves quality of life. The feasibility, accuracy, and timing of sentinel node biopsy in patients undergoing neoadjuvant chemotherapy are not yet clear. Also, the clinical significance of micrometastasis should be evaluated to determine the optimal application of sentinel node biopsy. There is interest in replacing breast-conserving treatment by nonsurgical ablation, although additional findings are needed to show that this technique is a true advance in breast cancer treatment.     

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.     

影响乳腺癌术后局部复发因素的分析

选择主要临床与组织病理学因素和治疗因素，观察对乳腺癌术后局部复发的影响，２４２２例女性浸润性乳腺癌病人中，３年内局部复发１８２例，复发率７．５％，经过Ｌｏｇｉｓｔｉｃ回归的方法统计，年龄，绝经状态和病理类型不是影响乳腺癌术后局部复发的主要因素，而原发肿块情况，腋下淋巴结转移与否和雌激素受体状态对乳腺癌术后的局部复发的影响有意义，尤以肿块侵犯皮肤或胸壁，腋下淋巴结转移融合，雌激素受体阴性者术后复发的     

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.     

Management of local recurrence of breast cancer

This article reviews the management of isolated recurrences after primary treatment of breast cancer. These recurrences may occur within the breast after breast-conserving surgery, on the chest wall after mastectomy, or in the axilla. While often a marker of concurrent or future metastatic disease, local management with curative intent is advocated if the recurrence is isolated at presentation. Systemic therapy at this time (readjuvant) may well have benefit and should be more thoroughly investigated. Changes in breast cancer management, including sentinel lymph node biopsy, neoadjuvant chemotherapy, hormonal therapy and partial breast irradiation, may change the implications and management of isolated local breast, chest wall and axillary recurrences.     

Mode of Detection of Second Events in Routine Surveillance of Early Stage Breast Cancer Patients

IntroductionNCCN and ASCO guidelines recommend breast cancer (BC) follow-up to include clinical breast examination (CBE) every 6 months and annual mammography (AM) for 5 years. Given limited data to support CBE, we evaluated the modes of detection (MOD) of BC-events in a contemporary practice.MethodsWe conducted a retrospective review of registry patients with early stage BC (DCIS, Stage I or II) diagnosed between 2010 and 2015 with at least 5 years of follow-up. Second events were defined as malignant (contralateral primary, ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, regional node recurrence or distant relapse) or benign. MOD was categorized as patient complaint, clinical examination or breast imaging.ResultsSixty-three of 351 BC patients experienced second events. 15 had BC malignant events, including 4 distant disease, 5 contralateral primary, and 3 IBTR. 7/8 of IBTR and contralateral primary BC were AM detected. Patient complaints identified 4/4 distant relapses. Clinical exam identified 2/2 chest wall recurrences in post-mastectomy patients.ConclusionsOnly 2.8% (10/351) of early stage BC patients experienced recurrence during 5 years of follow-up. AM was the predominate MOD of both IBTR and new contralateral primary following breast conserving therapy. Patient complaints prompted evaluation for distant disease. Provider CBE was MOD in only 2/351, 0.6% 95% CI (2.1%-0.1%) of patients as chest wall recurrences postmastectomy. Given modern enhancements to imaging and lower recurrence rates, this data encourages the reassessment of guidelines for every 6-month CBE and provides basis to study telehealth in survivorship care.