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.     

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.     

Omitting radiotherapy in women ≥ 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe

Purpose

The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET).

Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation

PURPOSE: To determine whether excision of an in-breast tumor recurrence (IBTR) plus 5000 cGy in 25 fractions to the new operative area is both tolerated and effective as treatment for an IBTR after previous lumpectomy and whole breast irradiation.METHODS AND MATERIALS: Thirty-nine women with an IBTR after lumpectomy and breast irradiation for invasive carcinoma (n = 31) or ductal carcinoma in situ (n = 8) were treated with excision of the IBTR and radiotherapy (RT), 5000 cGy in 25 fractions, to the operative area using electrons of appropriate energy. The interval from completion of the first course of RT to diagnosis of the IBTR ranged from 16 to 291 months (median 63).RESULTS: The repeat course of RT to the new operative area was well tolerated in all patients, and no late sequelae occurred other than skin pigmentation changes. Eight patients, including 2 with suspicious bone scans at the time of IBTR, developed distant metastases, and 7 died 21-71 months (median 48) after retreatment. One patient was alive with distant metastases at 27 months after retreatment. Four of the 8 patients who developed distant metastases also had a second IBTR, and 3 died with persistent disease in the breast. An additional 4 patients, for a total of 8, had a second IBTR. Three were alive and free of disease after mastectomy, and 1 was alive and free of disease after mastectomy and additional RT for chest wall recurrence. An additional patient developed recurrence in the axilla 9 months after reirradiation and was treated with surgery; she died free of disease at 63 months. One patient underwent mastectomy for suspected persistent disease 2 months after completion of repeat RT; no evidence of recurrent tumor was found in the removed breast. Thus, 30 women (76.9%) had an intact breast free of tumor at death or at last follow-up 1-180 months (median 51.5) after reirradiation. Using the Kaplan-Meier life table analysis, the estimated overall and disease-free 5-year survival rate for the 39 patients was 77.9% and 68.5%, respectively.CONCLUSION: For select patients with an IBTR after lumpectomy and breast irradiation, excision of the IBTR followed by repeat external beam RT to the operative area may be an acceptable alternative to mastectomy.     

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer

PurposeAccelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation.Methods and MaterialsThis was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period.ResultsFrom 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience.ConclusionsAPBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.     

Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: risk factors and impact on distant metastases

BACKGROUND: The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group. METHODS: Patients (N = 1901)with unilateral breast cancer < or = 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR. RESULTS: At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676-5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis. CONCLUSIONS: Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases.     

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.     

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.     

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.     

Correlation between first disease-free interval from mastectomy to second disease-free interval from chest wall resection.

Between 24 November 1977 and 16 September 1988, 18 consecutive chest wall resections for recurrent breast cancer after failure of radiotherapy, were evaluated as of 1 January 1990. Chest wall involvement was the only site of recurrence in 14 patients (Group I), and the most painful of the multiple recurrences in the remaining four (Group II). Of Group I, chest wall recurrence was local in eight patients (four with necrosis after radiotherapy), regional in four, and distant in two. Chest wall reconstruction was effected by contralateral breast flap in six, by random cutaneous flap in seven and by myocutaneous flap in the remaining five. Cosmetic results were better if both marlex mesh and myocutaneous flap were used. Of Group I, at surgical/pathological staging, one recurrence with sarcomatous findings, two multiple recurrences and residual cancer in all necrosed local recurrences were found: in three of these cases radionecrosis was prominent. Mortality was 0% and surgical morbidity 5%. For Group I, median disease-free interval from mastectomy was extended from 1611 days to 3220 by recurrence resection, and disease-free interval from chest wall resection was 28% cancer-free at 1657 days, without any difference between the local vs regional-distant recurrence. Correlation factor between first and second disease interval was 0.99 and R2 was 0.98. For Group II, survival was 0% at 635 days. Chest wall resection must be considered as an important part of palliative treatment in breast cancer, but the results reflects the biology of the disease more than the chest wall surgery.     

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.     

Breast tumor recurrence following lumpectomy with and without breast irradiation: an overview of recent NSABP findings.

The latest findings from the NSABP B-06 trial on ipsilateral breast tumor recurrence (IBTR) continue to demonstrate that through 9 years of follow-up more patients treated with radiation remained IBTR free as compared to those receiving no radiation (P less than 0.001), regardless of age, nodal status, or tumor size. There is no significant difference in distant disease-free survival (DDFS) or survival between the two lumpectomy groups despite the highly significant difference in their probability of remaining IBTR free. A recent analysis shows that when a patient is diagnosed with an IBTR, the risk of distant metastatic disease increases, indicating that an IBTR is a marker for, not a cause of, distant metastatic disease. An IBTR indicates a greater risk for distant disease when the primary tumor was removed. Mastectomy or breast irradiation following lumpectomy eliminates or reduces the opportunity for identifying a marker of risk for distant disease, thus emphasizing the importance of an IBTR beyond the need for its removal. Since an IBTR is associated with a relative risk of 3.41 for the development of distant metastatic disease, systemic therapy subsequent to an IBTR should be considered. Evidence presented from recent NSABP studies indicates the value of systemic therapy for lowering the incidence of IBTR following lumpectomy and breast irradiation.     

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.     

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.     

Molecular markers for prognosis after isolated postmastectomy chest wall recurrence

BACKGROUND: Local chest wall recurrence after mastectomy occurs in 10-20% of patients with operable breast carcinoma. The objective of the current study was to assess the prognostic value of molecular markers at the time of local recurrence and to compare these markers with clinical variables. METHODS: Between 1975 and 1999, the authors treated 113 patients at their institution for postmastectomy chest wall recurrences with full-course external beam radiotherapy. Patients who presented primarily with lymph node recurrences or with simultaneous distant metastasis were excluded. Follow-up from the time of chest wall recurrence was 10.13 years. All clinical and pathologic data from the original diagnosis and from the time of chest wall recurrence were entered into a computerized database. Paraffin-embedded tumor specimens from the chest wall recurrences were available for 43 patients and were constructed into tissue microarrays for immunohistochemical staining of estrogen receptor, progesterone receptor (PR), p53, HER-2/neu, and cyclin D. RESULTS: Overall survival after chest wall recurrence for the entire cohort was 46% at 5 years and 28% at 10 years. The distant metastasis-free survival rate was 49% at 5 years and 40% at 10 years. Local-regional control of disease was achieved in 79% of patients at 10 years. In multivariate analysis, significant factors for distant metastasis after local recurrence were time to recurrence (< 2 years from the original diagnosis to chest wall recurrence) and PR status (distant metastasis-free survival rate: 84% [PR-positive] vs. 38% [PR-negative]; P = 0.007). The only significant factor for local-regional disease progression was HER-2/neu status. Patients with positive HER-2/neu status had a local-regional progression-free rate of 59%, compared with 92% for patients with negative HER-2/neu status. CONCLUSIONS: The prognosis for patients after local-regional recurrence of breast carcinoma is relatively poor. Longer time to local recurrence and positive PR status were associated with favorable distant metastasis-free rates and long-term survival. Positive HER-2/neu status was associated with poorer local-regional control of disease. Implications for systemic therapy and further studies are discussed.     

Recurrence dynamics of breast cancer according to baseline body mass index

BackgroundIn cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy.MethodsWe retrieved BMI from 734 of 777 patients with node-positive breast cancer from a phase III randomised clinical trial, which compared different chemotherapy regimens and had a median follow-up of 15.4 years. Cumulative incidence estimation as well as piecewise exponential models were carried out to estimate the distant recurrence dynamics, in all patients, as well as in subgroups based on the ER status, with the ER-positive group being further split according to the menopausal status.ResultsIn patients with ER-negative breast cancer, time-dependent analyses revealed that the hazard of late relapses could mainly be attributed to the overweight and obese patients. Within the subgroup of premenopausal patients with ER-positive tumours, obesity was associated with an early high narrow peak of distant recurrences followed by another main peak after 5 years of follow-up. The risk for overweight patients was intermediate between obese and normal-weight patients. In the postmenopausal subgroup of patients with ER-positive tumours, the distant recurrence rate was significantly more elevated in the overweight patients compared to the other BMI categories, and a second late peak of recurrences was also observed for the obese patients.ConclusionThese results demonstrate that the patient's BMI at diagnosis is associated with cancer recurrence dynamics. Patient adiposity should therefore be central to the exploration of late adjuvant treatment modalities.     

Early detection of recurrences in the follow-up of primary breast cancer in an asymptomatic or symptomatic phase

AIMS AND BACKGROUND: Periodic follow-up after primary treatment for breast cancer is a common procedure for the early detection of recurrent disease in the asymptomatic state. Anyway, there is no clinical evidence that treatment of metastases may improve the prognosis if applied in the asymptomatic state. The aim of the present study was to investigate the modality of detection of the first relapse in the asymptomatic vs the symptomatic state. METHODS: We retrospectively analyzed 717 breast cancer patients who had been consecutively referred to the Parma Oncology Division during the period 1986 to December 1988. Recurrences were detected in the course of periodic follow-up. RESULTS: A total of 211 of the 408 patients evaluated had a first relapse with a median follow-up of 94.7 months. Local and distant recurrences were 49% and 47%, respectively. Bone recurrences represented 24% of the total first recurrences, then chest wall recurrences in 23%, local regional nodes in 13%, lung in 7%, liver in 4%, and brain in 2%. The distribution of the studied patients according to recurrence site and asymptomatic or symptomatic state was different: 69% of asymptomatic patients (110) had a local recurrence vs 31% of symptomatic patients (101). A difference in survival was recorded in favor of cases detected in the asymptomatic state (P <0.001). CONCLUSIONS: The present study suggests that an early detection of local recurrence might have a favorable impact on the prognosis of patients followed after primary treatment for breast cancer. It should be considered that any difference in survival could also be explained by several "biases" and that breast cancer follow-up is still an area of investigation open to discussion in which many questions remain to be clarified.     

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.