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      Subtype Is a Predictive Factor of Nonsentinel Lymph Node Involvement in Sentinel Node-Positive Breast Cancer Patients

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          Abstract

          Purpose

          This study aimed to identify the effect of breast cancer subtype on nonsentinel lymph node (NSLN) metastasis in patients with a positive sentinel lymph node (SLN).

          Methods

          The records of 104 early breast cancer patients with a positive SLN between April 2009 and September 2013 were retrospectively evaluated. All patients underwent axillary lymph node dissection. The effects of the tumor subtype (luminal A, luminal/HER2+, human epidermal growth factor receptor 2 [HER2] overexpression, and triple-negative) and other clinicopathological factors on NSLN metastasis were examined by univariate and multivariate statistical analyses.

          Results

          Fifty of 104 patients (48%) exhibited NSLN metastasis. Univariate and multivariate analyses revealed that tumor size and the ratio of positive SLNs were significant risk factors of NSLN metastasis in patients with a positive SLN. The rate of NSLN metastasis was higher in patients with luminal/HER2+ and HER2 overexpression subtypes than that in patients with other subtypes in the univariate analysis ( p<0.001). In the multivariate analysis, both patients with luminal/HER2+ ( p<0.006) and patients with HER2 overexpression ( p<0.031) subtypes had a higher risk of NSLN metastasis than patients with the luminal A subtype.

          Conclusion

          Subtype classification should be considered as an independent factor when evaluating the risk of NSLN metastasis in patients with a positive SLN. This result supports the development of new nomograms including breast cancer subtype to increase predictive accuracy.

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          Most cited references22

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          Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer

          Background Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. Methods Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan–Meier curves and multivariable Cox regression. Results Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor–positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal–HER2 positive. Luminal B and luminal–HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer–specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal–HER2 subtypes. Conclusion Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.
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            Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype.

            Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors. Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels. Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome. The expanded surrogate immunopanel of estrogen receptor, progesterone receptor, human HER-2, EGFR, and cytokeratin 5/6 provides a more specific definition of basal-like breast cancer that better predicts breast cancer survival.
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              A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer.

              Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up. Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Journal
                J Breast Cancer
                J Breast Cancer
                JBC
                Journal of Breast Cancer
                Korean Breast Cancer Society
                1738-6756
                2092-9900
                December 2014
                26 December 2014
                : 17
                : 4
                : 370-375
                Affiliations
                Department of Surgery, Ankara Oncology Training and Research Hospital, Ankara, Turkey.
                [1 ]Department of Surgery, Samsun Training and Research Hospital, Samsun, Turkey.
                Author notes
                Correspondence to: Kaptan Gülben. Department of Surgery, Ankara Oncology Training and Research Hospital, Kardelen mah., 2040. sok., B/27, Ankara 06370, Turkey. Tel: +90-312-3360909, Fax: +90-312-3454979, kgulben@ 123456yahoo.com
                Article
                10.4048/jbc.2014.17.4.370
                4278057
                25548586
                c0deb5cc-4273-4468-874b-5f9954e32895
                © 2014 Korean Breast Cancer Society. All rights reserved.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 July 2014
                : 25 September 2014
                Categories
                Original Article

                Oncology & Radiotherapy
                breast neoplasms,molecular subtypes,predictive value of tests,sentinel lymph node biopsy

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