Can Axillary Dissection be Avoided by Improved Molecular Biological Diagnosis?

Lindahl, Thomas; Engel, Georg; Ahlgren, Johan; Klaar, Sigrid; Bjöhle, Judith; Lindman, Henrik; Andersson, Jenny; Schoultz, E. von; Bergh, Jonas

doi:10.1080/028418600750013087

Cited by 17 publications

(9 citation statements)

References 66 publications

(71 reference statements)

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“…For some surgeons and patients, these or other prognostic variables may weigh into such decisions as whether to attempt breast-conservation therapy, 21,22 use sentinel lymph node biopsy, or perform axillary lymph node dissection. 23 Prospective information afforded by CNBx clearly facilitates complex treatment planning.…”

Section: Malignant Resultsmentioning

confidence: 99%

Impact of Core-Needle Breast Biopsy on the Surgical Management of Mammographic Abnormalities

White

Halperin²,

Olson³

et al. 2001

Annals of Surgery

113

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ObjectiveTo evaluate the accuracy of percutaneous, image-guided core-needle breast biopsy (CNBx) and to compare the surgical management of patients with breast cancer diagnosed by CNBx with patients diagnosed by surgical needle-localization biopsy (SNLBx). Summary Background DataPercutaneous, image-guided CNBx is a less invasive alternative to SNLBx for the diagnosis of nonpalpable mammographic abnormalities. CNBx potentially spares patients with benign lesions from unnecessary surgery, although false-negative results can occur. For patients with malignant lesions, preoperative diagnosis by CNBx allows definitive treatment decisions to be made before surgery and may affect surgical outcomes. MethodsBetween 1992 and 1999, 939 patients with 1,042 mammographically detected lesions underwent biopsy by stereotactic CNBx or ultrasound-guided CNBx. Results were categorized pathologically as benign or malignant and, further, as invasive or noninvasive malignancies. Only biopsy results confirmed by excision or 1-year-minimum mammographic follow-up were included in the analysis. Patients with breast cancer diagnosed by CNBx were compared with a matched control group of patients with breast cancer diagnosed by SNLBx. ResultsBenign results were obtained in 802 lesions (77%), 520 of which were in patients with adequate follow-up. Ninety-five of the 520 evaluable lesions (18%) were subsequently excised because of atypical hyperplasia, mammographic-histologic discordance, or other clinical indications. There were 17 falsenegative CNBx results in this group; 15 of these lesions were correctly diagnosed by excisional biopsy within 4 months of CNBx. In two patients (0.9%), delayed diagnoses of ductal carcinoma in situ were made at 15 and 19 months after CNBx. Malignant results were obtained in 240 lesions (23%), 220 of which were surgically excised from 202 patients at our institution. Two lesions diagnosed as ductal carcinoma in situ were reclassified as atypical ductal hyperplasia and considered false-positive results (0.4%). For malignant lesions, the sensitivity and specificity of CNBx for the detection of invasion were 89% and 96%, respectively. During the first surgical procedure, 115 of 199 patients (58%) diagnosed by CNBx underwent local excision; 194 of 199 patients (97%) evaluated by SNLBx underwent local excision. For patients whose initial surgery was local excision, those diagnosed before surgery by CNBx had larger excision specimens and were more likely to have negative surgical margins than were patients initially evaluated by SNLBx. Overall, patients diagnosed by CNBx required fewer surgical procedures for definitive treatment than did patients diagnosed by SNLBx. ConclusionsDiagnosis by CNBx spares most patients with benign mammographic abnormalities from unnecessary surgery. With the selective use of SNLBx to confirm discordant results, missed diagnoses are rare. When compared with SNLBx, preoperative diagnosis of breast cancer by CNBx facilitates wider initial margins of excision, fewer positive margins, and f...

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Section: Malignant Resultsmentioning

confidence: 99%

Impact of Core-Needle Breast Biopsy on the Surgical Management of Mammographic Abnormalities

White

Halperin²,

Olson³

et al. 2001

Annals of Surgery

113

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“…Thus, 63-96% of patients would undergo ALND with no therapeutic benefit. Another argument against ALND is that currently further chemotherapy or hormonal therapy is recommended to patients with tumor size greater than 1 cm regardless of lymph node status (11). In addition, data from the National Surgical Adjuvant Breast and Bowel Project (B-04) conducted by Fisher et al (12) did not show any survival advantage of patients who had immediate ALND compared with patients who waited.…”

Section: ) -------------------------------------------------mentioning

confidence: 99%

Clinicopathological parameters and biological markers predicting non-sentinel node metastasis in sentinel node-positive breast cancer patients

Kwon

Kang

et al. 2011

Oncol Rep

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Abstract. The value of complete axillary lymph node dissection (ALND) has been questioned in invasive breast cancer (IBC) patients with positive sentinel lymph nodes (SLNs) who have no non-sentinel lymph node (NSLN) metastases. Because biological markers have not been systematically studied in this setting, we sought to identify clinicopathological characteristics and biological markers for predicting NSLN metastases in SLN-positive IBC patients. Two hundred and five IBC patients who had at least one positive SLN and received SLN biopsy and ALND were included in our study. We examined the clinicopathological characteristics of their primary tumors, SLNs and NSLNs. We also evaluated the biological markers of the primary tumors by tissue microarray and immunohistochemistry. Of the 205 patients with SLN metastases, 89 patients (43.4%) had additional metastases in NSLNs. The following factors were found to be associated with NSLN metastases: peritumoral lymphovascular invasion (p=0.01), two or more metastatic SLNs (p<0.01), SLN metastasis >2.0 mm (p<0.01) and extranodal extension (p<0.01). Primary tumors >2.0 cm showed more NSLN metastases, but the association was statistically insignificant (p=0.08). In contrast, NSLN metastases were not associated with histologic grade, histologic type, presence of extensive intraductal component, presence of high grade ductal carcinoma in situ and number of harvested SLNs. Biological markers such as E-cadherin, CD44, cyclin D1, p21, ER, PR, c-erbB2, p53, Ki-67, luminal (CK7, CK18, CK19) and basal (CK5, p63) markers were not useful predictors of NSLN metastasis in IBC patients with SLN metastases. Multivariate analysis revealed that SLN metastasis >2.0 mm (p=0.01), two or more metastatic SLNs (p=0.03) and extranodal extension (p<0.01) were independent predictors of NSLN metastasis. For the prediction of NSLN metastasis in IBC patients with SLN metastases, light microscopic evaluation of the number, size and extranodal extension of metastatic SLNs by hematoxylin and eosin staining appeared to be critical. However, the biological markers of primary tumor characterized by immunohistochemical staining, such as luminal and basal markers, hormone receptors, E-cadherin, CD44, cyclin D1, p21, c-erb-B2, p53 and Ki-67, did not appear to be helpful predictors.

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“…Breast cancer, a heterogeneous disease, presents various pathological signs such as axillary lymph node metastasis which is associated with a high risk of recurrence and considered as an important prognosis factor in the early stages of the disease [2,3]. Invasion and metastasis are two important hallmarks of malignant tumors associated with complex genetic and epigenetic alterations that allow tumors to disseminate throughout lymphatics or blood vessels, giving rise to the colonization and growth of metastatic cells in distant organs [4-6].…”

Section: Introductionmentioning

confidence: 99%

Methylation signature of lymph node metastases in breast cancer patients

et al. 2012

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BackgroundInvasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers.MethodsThe quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).ResultsThe quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis.ConclusionsThe results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.

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Can Axillary Dissection be Avoided by Improved Molecular Biological Diagnosis?

Cited by 17 publications

References 66 publications

Impact of Core-Needle Breast Biopsy on the Surgical Management of Mammographic Abnormalities

Impact of Core-Needle Breast Biopsy on the Surgical Management of Mammographic Abnormalities

Clinicopathological parameters and biological markers predicting non-sentinel node metastasis in sentinel node-positive breast cancer patients

Methylation signature of lymph node metastases in breast cancer patients

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