Risk factors for local recurrence after breast-conserving surgery

Fredriksson, Irma; Liljegren, Göran; Palm-Sjövall, M; Arnesson, Lars-Gunnar; Emdin, SO; Fornander, Tommy; Lindgren, Anders; Nordgren, Hans; Idvall, Ingrid; Holmqvist, Marit; Holmberg, Lars; Frisell, Jan

doi:10.1002/bjs.4206

Cited by 60 publications

(41 citation statements)

References 39 publications

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“…The proportion of women receiving conservative surgery increased from 7% in 1980 to 51% in 1996 (Lindqvist et al, 2002). Inadequately treated in situ breast carcinoma, for example, insufficient margin control, may have contributed to the observed risk increase (Yau et al, 2002;Fredriksson et al, 2003;Kerlikowske et al, 2003;Khan and Newman, 2004).…”

Section: Discussionmentioning

confidence: 99%

Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening

2004

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Sweden was the first country to establish a nationwide breast cancer screening service. We used the Swedish Family-Cancer Database to evaluate the risk of invasive carcinoma after in situ carcinoma of the breast. Risk estimates for contralateral and ipsilateral invasive malignancies following age and histology specific in situ breast carcinomas were calculated using Poisson's regression analysis. The agreement between concordant and discordant morphologies of invasive and in situ breast cancer was measured using the kappa statistic. Women with in situ breast cancer showed a relative risk of 2.03 for contralateral and 3.94 for ipsilateral invasive breast cancer. The risk was higher for in situ carcinomas diagnosed before the age of 50 years and after lobular in situ breast cancers. A comparison of the risks during the past decades suggested that the risk of ipsilateral breast cancer has increased in Sweden but that of contralateral breast cancer has remained unchanged. In situ and the subsequent invasive breast cancers did not seem to share their morphologies.

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Section: Discussionmentioning

confidence: 99%

Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening

2004

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“…11 A linear discriminant analysis classifier was trained with 1,000 permutations and a 10-fold cross-validation. This classifier was validated on an independent data set (26), which is a consecutive series of early-stage breast cancer patients treated with BCT (n = 161).…”

Section: Translational Relevancementioning

confidence: 99%

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The addition of a radiation boost after whole-breast irradiation and adjuvant systemic therapy reduces LR rates by 40% to 60%, especially in younger patients (9,11,16,17,19,20).…”

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confidence: 99%

Local Recurrence after Breast-Conserving Therapy in Relation to Gene Expression Patterns in a Large Series of Patients

Kreike

Halfwerk

Armstrong

et al. 2009

Clinical Cancer Research

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Purpose: The majority of patients with early-stage breast cancer are treated with breastconserving therapy (BCT). Several clinical risk factors are associated with local recurrence (LR) after BCT but are unable to explain all instances of LR after BCT. Here, gene expression microarrays are used to identify novel risk factors for LR after BCT. Experimental Design: Gene expression profiles of 56 primary invasive breast carcinomas from patients who developed a LR after BCT were compared with profiles of 109 tumors from patients who did not develop a LR after BCT. Both unsupervised and supervised methods of classification were used to separate patients into groups corresponding to disease outcome. In addition, for 15 patients, the gene expression profile in the recurrence was compared with that of the primary tumor. Results: The two main clusters found by hierarchical cluster analysis of all 165 primary invasive breast carcinomas revealed no association with LR. Predefined gene sets (molecular subtypes and "chromosomal instability" signature) are associated with LR (P = 0.0002 and 0.003, respectively). Significant analysis of microarrays revealed an association between LR and cell proliferation, not captured by histologic grading. Class prediction analysis constructed a gene classifier, which was successfully validated, cross-platform, on an independent data set of 161 patients (log-rank P = 0.041). In multivariate analysis, young age was the only independent predictor of LR. Conclusions: We have constructed and cross-platform validated a gene expression profile predictive for LR after BCT, which is characterized by genes involved in cell proliferation but not a surrogate for high histologic grade.Local treatment for early-stage breast cancer can consist of mastectomy or breast-conserving therapy (BCT). Several randomized controlled trials have shown no difference in survival rates after BCT or mastectomy for stage I and II breast cancer (1-3). Unfortunately, BCT is associated with a higher rate of local recurrence (LR) compared with mastectomy (1-3). A LR rate of <1% per annum is generally considered as clinically acceptable for T1-2 N0-1 breast cancers. The choice for the primary treatment modality is therefore often based on risk factors for LR.Several of these risk factors for LR after BCT have been identified: involvement of the surgical margins by invasive carcinoma [hazard ratio (HR), 2.8-3.9] and/or extensive ductal carcinoma in situ (DCIS; HR, 2.5-4.2), vascular invasion (HR, 2.0-2.9), young age (HR, 2.4-9.2), and tumor multicentricity (HR,. The addition of a radiation boost after whole-breast irradiation and adjuvant systemic therapy reduces LR rates by 40% to 60%, especially in younger patients (9,11,16,17,19,20).The importance of preventing LR is illustrated by the updated analyses of the Early Breast Cancer Trialists' Collaborative Group showing that LR is associated with poorer survival (21) and by Voogd et al. (22) who suggest that early detection of LR could improve survival. Thus, robust r...

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“…Introduction of adjuvant radiotherapy, however, reduces the rate of local recurrence to V10%, making breast conservation a comparable alternative to modified radical mastectomy (2). The natural history of breast cancer with its localized patterns of recurrence strongly suggests that the residual ''normal'' breast is in fact at risk for harboring occult, precancerous cells.…”

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confidence: 99%

Mapping Geographic Zones of Cancer Risk with Epigenetic Biomarkers in Normal Breast Tissue

Yan

Venkataramu

Ibrahim

et al. 2006

Clinical Cancer Research

188

147

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Purpose: Genetic alterations were previously identified in normal epithelia adjacent to invasive cancers. The aim of this study was to determine DNA methylation in histologically normal tissues from multiple geographic zones adjacent to primary breast tumors. Experimental Design: First, methylation status of a 4-kb region of RASSF1A promoter was interrogated using oligonucleotide-based microarray in 144 samples (primary tumors, 47; adjacent normals, 69; reduction mammoplasty tissues, 28). Second, allelic imbalance (AI)/loss of heterozygosity (LOH) surrounding RASSF1A promoter were analyzed in 30 samples (tumors, 8; adjacent normals, 22). Third, global methylation screening of 49 samples (tumors, 12; adjacent normals, 25; reduction mammoplasty, 12) was done by differential methylation hybridization. Real-time quantitative methylation-specific PCR was used to validate the microarray findings. Results: DNA methylation in the core RASSF1A promoter was low in reduction mammoplasty tissues (P = 0.0001) when compared with primary tumors.The adjacent normals had an intermediate level of methylation. The regions surrounding the core were highly methylated in all sample types. Microsatellite markers showed AI/LOH in tumors and some of the adjacent normals. Concurrent AI/LOH and DNA methylation in RASSF1A promoter occurred in two of six tumors. Global methylation screening uncovered genes more methylated in adjacent normals than in reduction mammoplasty tissues. The methylation status of four genes was confirmed by quantitative methylation-specific PCR. Conclusions: Our findings suggest a field of methylation changes extending as far as 4 cm from primary tumors. These frequent alterations may explain why normal tissues are at risk for local recurrence and are useful in disease prognostication.

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Risk factors for local recurrence after breast-conserving surgery

Cited by 60 publications

References 39 publications

Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening

Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening

Local Recurrence after Breast-Conserving Therapy in Relation to Gene Expression Patterns in a Large Series of Patients

Mapping Geographic Zones of Cancer Risk with Epigenetic Biomarkers in Normal Breast Tissue

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