Node-negative Breast Carcinoma Research Articles

The Impact of the Oncotype DX Breast Cancer Assay on Treatment Decisions for Women With Estrogen Receptor-Positive, Node-Negative Breast Carcinoma in Hong Kong

BackgroundThe Oncotype DX Breast Cancer Assay is validated to assess risk of distant recurrence and likelihood of chemotherapy (CT) benefit in estrogen receptor-positive ESBC in various populations. In Hong Kong, > 80% of breast cancers are early stage breast cancer (ESBC) and > 60% of these women receive CT. This prospective study measured changes in CT type and recommendations, as well as physician impression of assay impact in a homogenous Chinese population. MethodsConsecutive patients with estrogen receptor-positive, T1-3 N0-1mi M0 ESBC were offered enrollment. After surgery, physicians discussed treatment options with patients, then ordered the assay, then reassessed treatment recommendation considering assay results. Changes in treatment recommendation, CT utilization, physician confidence, and physician rating of influence on their treatment recommendations were measured. ResultsA total of 146 evaluable patients received pre- and post-testing treatment recommendations. CT recommendations (including changes in intensity of CT) were changed for 34 of 146 patients (23.3%; 95% confidence interval, 16.7%-31.0%); change in intensity occurred in 7 of 146 (4.8%). There were 27 changes in treatment recommendations of adding or removing CT altogether (18.5% change; 95% confidence interval, 12.6%-25.8%). CT recommendations decreased from 52.1% to 37.7%, a net absolute reduction of 14.4% (P < .001; 27.6% net relative reduction). Pre-assay, 96% of physicians agreed/strongly agreed that they were confident in their treatment recommendation; post-assay, 90% of physicians agreed/strongly agreed with the same statement. Thirty percent of physicians agreed/strongly agreed that the test had influenced their recommendation, similar to the proportion of changed recommendations. ConclusionsThe Oncotype DX Assay appears to influence physician ESBC adjuvant treatment recommendations in Hong Kong.

Abstract P2-06-05: LINC00478: A novel tumor suppressor in breast cancer

Abstract Background: LncRNAs may play a role in cancer and serve as new potential targets for improving cancer diagnosis, prognosis or treatment. Long intergenic non-protein coding RNA 478 (LINC00478), the miR99a-let-7c cluster host gene, has been shown to be downregulated in estrogen-independent ER-positive (ER+) breast cancer cells. However, its expression in breast tumors and its significance in recurrence has not been well characterized. Methods: The clinical relevance of LINC00478 in ER+ breast tumors was first determined by analysis of the expression levels in MiTranscriptome database (RNAseq-based), which contains ∼8000 most differentially expressed lncRNAs for each cancer and/or tissue type. Additionally, the expression of LINC00478 mRNA was determined in a) a cohort of matched pairs of primary and (nodal) metastatic tumors (n=18) (RNA-seq) and b) a cohort of 60 paraffin-embedded ER-positive, node-negative breast carcinomas with Oncotype DX recurrence scores (QRT-PCR). Results: LINC00478 was significantly downregulated in patients with ER-positive tumors compared to uninvolved normal breast tissue. In RNA-seq analysis, metastatic tumors had significant low expression as compared to matched primary tumors (FC: -2.2 fold-down; P=0.0027). Quantitative RT-PCR analysis showed that LINC00478 expression was significantly lower in ER+ node-negative patients with Oncotype DX high recurrence score when compared with low recurrence score patients (FC: -4.14-fold down; P=0.02). Conclusion: We document for the first time that LINC00478 functions as a tumor suppressor in ER-positive breast cancer. Its loss is associated with tumor progression and recurrence/metastasis. Novel strategies that focus on re-expression of LINC00478 might be useful for targeting breast cancer and preventing the metastases. Citation Format: Gökmen-Polar Y, Zavodszky M, Chen X, Gu X, Kodira C, Badve S. LINC00478: A novel tumor suppressor in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-05.

Validation of Intratumoral T-bet+ Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer.

We previously observed T-bet(+) lymphocytes to be associated with a good prognosis in a cohort of women with familial breast cancer. To validate this finding, we evaluated lymphocyte T-bet expression in an independent unselected prospectively accrued series of women with lymph node-negative breast carcinoma. T-bet and clinicopathologic data were available for 614 women. Hormone receptors, HER2, Ki-67, CK5, EGFR, p53, and T-bet status were determined using IHC and/or biochemical methods. Tumors were assigned to luminal A, luminal B, HER2, and basal subtypes based on the expression of IHC markers. Multiple cutpoints were examined in a univariate penalized Cox model to stratify tumors into T-bet(+/high) and T-bet(-/low). Fisher exact test was used to analyze T-bet associations with clinicopathologic variables, IHC markers, and molecular subtype. Survival analyses were by the Cox proportional hazards model. All tests were two sided. A test with a P value < 0.05 was considered statistically significant. T-bet(+/high) tumor status was significantly associated with large tumor size, high grade, hormone receptor negativity, CK5, EGFR and p53 positivity, high Ki-67, and basal subtype. With a median follow-up of 96.5 months, T-bet(-/low) tumor status was associated with a reduced disease-free survival compared with T-bet(+/high) tumor status in multivariate analysis (P = 0.0027; relative risk = 5.62; 95% confidence intervals, 1.48-50.19). Despite being associated with adverse clinicopathologic characteristics, T-bet(+) tumor-infiltrating lymphoid cells are associated with a favorable outcome. This supports their role in Th1-mediated antitumor activity and may provide insight for the development of new therapeutic strategies.

Lack of CD151/integrin α3β1 complex is predictive of poor outcome in node-negative lobular breast carcinoma: opposing roles of CD151 in invasive lobular and ductal breast cancers.

Background:The proposed involvement of CD151 in breast cancer (BCa) progression is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and invasive lobular carcinoma (ILC) represent distinct disease entities. Here we evaluated clinical significance of CD151 alone and in association with integrin α3β1 in patients with ILC in context of the data of our recent IDC study.Methods:Expression of CD151 and/or integrin α3β1 was evaluated in ILC samples (N=117) using immunohistochemistry. The findings were analysed in relation to our results from an IDC cohort (N=182) demonstrating a prognostic value of an expression of CD151/integrin α3β1 complex in patients with HER2-negative tumours.Results:Unlike in the IDCs, neither CD151 nor CD151/α3β1 complex showed any correlation with any of the ILC characteristics. Lack of both CD151 and α3β1 was significantly correlated with poor survival (P=0.034) in lymph node-negative ILC N(−) cases. The CD151−/α3β1− patients had 3.12-fold higher risk of death from BCa in comparison with the rest of the ILC N(−) patients.Conclusions:Biological role of CD151/α3β1 varies between ILC and IDC. Assessment of CD151/α3β1 might help to identify ILC N(−) patients with increased risk of distant metastases.

Expression levels of SF3B3 correlate with prognosis and endocrine resistance in estrogen receptor-positive breast cancer

De novo or acquired resistance to endocrine therapy limits its utility in a significant number of estrogen receptor-positive (ER-positive) breast cancers. It is crucial to identify novel targets for therapeutic intervention and improve the success of endocrine therapies. Splicing factor 3b, subunit 1 (SF3B1) mutations are described in luminal breast cancer albeit in low frequency. In this study, we evaluated the role of SF3B1 and SF3B3, critical parts of the SF3b splicing complex, in ER-positive endocrine resistance. To ascertain the role of SF3B1/SF3B3 in endocrine resistance, their expression levels were evaluated in ER-positive/endocrine-resistant cell lines (MCF-7/LCC2 and MCF-7/LCC9) using a real-time quantitative reverse transcription PCR (qRT-PCR). To further determine their clinical relevance, expression analysis was performed in a cohort of 60 paraffin-embedded ER-positive, node-negative breast carcinomas with low, intermediate, and high Oncotype DX recurrence scores. Expression levels of SF3B1 and SF3B3 and their prognostic value were validated in large cohorts using publicly available gene expression data sets including The Cancer Genome Atlas. SF3B1 and SF3B3 levels were significantly increased in ERα-positive cells with acquired tamoxifen (MCF-7/LCC2; both P<0.0002) and fulvestrant/tamoxifen resistance (MCF-7/LCC9; P=0.008 for SF3B1 and P=0.0006 for SF3B3). Expression levels of both MCF-7/LCC2 and MCF-7/LCC9 were not affected by additional treatments with E2 and/or tamoxifen. Furthermore, qRT-PCR analysis confirmed that SF3B3 expression is significantly upregulated in Oncotype DX high-risk groups when compared with low risk (P=0.019). Similarly, in publicly available breast cancer gene expression data sets, overexpression of SF3B3, but not SF3B1, was significantly correlated with overall survival. Furthermore, the correlation was significant in ER-positive, but not in ER-negative tumors.This is the first study to document the role of SF3B3 in endocrine resistance and prognosis in ER-positive breast cancer. Potential strategies for therapeutic targeting of the splicing mechanism(s) need to be evaluated.

Abstract 4372: MiR-449a promotes breast cancer progression by activating the NF-κB pathway

Abstract INTRODUCTION MicroRNAs (miRs) have been implicated in various human malignancies and are being developed as diagnostic, predictive, and prognostic biomarkers. Our previous global profiling studies found miR-449a to be over-expressed in archival lymph node-negative invasive ductal breast carcinoma samples (n=74) when compared to normal tissues. Furthermore, miR-449a expression level was significantly associated with relapse. The mechanism(s) by which miR-449a functions remains unknown, and the aim of the current study was therefore to elucidate the roles and mRNA targets of miR-449a in breast cancer. MATERIAL AND METHODS MiR-449a expression was evaluated in six human breast cancer cell lines (T47D, MDA-MB-468, MDA-MB-231, MCF-7, MDA-MB-453, and ZR75-1). Three of these cell lines, T47D, MMDA-MB-468, and MDA-MB-231, were selected and used to assess the biological effects of miR-449a on cell viability, clonogenicity, cell migration, and invasion. Downstream target genes were identified by combining in silico miRWalk prediction and cell line/patient sample microarray data. Targets were validated using qRT-PCR and luciferase reporter assays. RESULTS Consistent with our global profiling work, several (4/6) of the tested breast cancer cell lines over-expressed miR-449a. CDC20B, the miR-449a host gene and an essential regulator of cell division, was also over-expressed. Knockdown of miR-449a resulted in significantly decreased cell viability, clonogenic survival, migration, and invasion. MiR-449a candidate targets were then identified by integrating in silico prediction algorithms, cell line mRNA expression profiling (Affymetrix Human Genome U133 Plus 2.0), and clinical specimen mRNA expression data. Two genes, CRIP2 (Cysteine rich protein 2, a transcription factor) and PRKAG1 (Protein Kinase, AMP-Activated, Gamma 1 Non-Catalytic), were verified as miR-449a targets using qRT-PCR. Moreover, direct interactions between miR-449a and the 3′-UTRs of both CRIP2 and PRKAG1 were confirmed using luciferase reporter assays. Inhibition of CRIP2 by miR-449a allowed for NF-κB-induced transcription of survival, proliferation, and growth-related genes, providing further evidence for the role of miR-449a in breast cancer progression. CONCLUSIONS MiR-449a is over-expressed in breast cancer cells, promoting cellular proliferation, migration, and invasion. One mechanism by which miR-449a functions is to down-regulate CRIP2, leading to NF-kB activation and possible cancer progression. Further investigations into gene regulation by miR-449a may reveal other promising targets for the management of breast cancer. Citation Format: Wei Shi, Matthew Lee, Ryunosuke Kogo, Jeff Bruce, Christine How, Kenneth W. Yip, Fei-Fei Liu. MiR-449a promotes breast cancer progression by activating the NF-κB pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4372. doi:10.1158/1538-7445.AM2014-4372

Characteristics of Breast Carcinoma Cases With False-Negative Sentinel Lymph Nodes

BackgroundIn the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses. Patients and MethodsWe analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling. ResultsThere was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (≥ 1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both. ConclusionFalse-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both.

Assessment of the efficacy and safety of methylene blue dye for sentinel lymph node mapping in early breast cancer with clinically negative axilla

Background : The benefits of sentinel lymph node (SLN) biopsy in breast cancer patients with clinically negative axillary nodes are now well established. SLN biopsy has been performed using different techniques including injection of isosulfan blue dye (IBD), radioactive colloid, and methylene blue. The aim of this study was to assess the safety and efficacy of methylene blue dye (MBD) as a mapping agent for SLN biopsy in axillary node negative breast carcinoma. Materials and Methods: Between February 2010-2012, a total of 27 female patients of 18 years and above, with established diagnosis of breast carcinoma with clinically negative ipsilateral axillary lymph nodes were studied. After induction of anesthesia, 5 ml of 1% methylene blue was infiltrated into the subareolar tissue on the affected side. The lymph nodes receiving the blue dye were excised as the SLN. Modified radical mastectomy (MRM) was completed and the excised breast with the axillary tissue was sent for histopathological examination to correlate with the findings of the SLN biopsy. Results: The incidence of breast cancer was highest at 41-50 years. Of 27 cases, SLN was identified in 24 cases using MBD. The identification rate was 88.9%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.8, 100, 100, and 86.7%, respectively. Conclusion: This study confirms the safety and efficacy of methylene blue as a mapping agent for SLN biopsy in axillary node negative breast cancer.

Abstract P5-09-09: ESRP1 and ESRP2 expression in tamoxifen resistance

Abstract Background: Current standard of care therapies with antiestrogens targeting estrogen receptor α (ER) signaling improve disease-free survival (DFS) in early-stage of breast cancer. However a significant number of cases exhibit de novo or acquired endocrine resistance and recur. It is thus important to identify novel targets of resistance and select these patients for additional therapeutic options which might include continued/extended hormonal therapy. The Oncotype Dx recurrence score (RS) in current practice predicts the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, ER+ breast cancer. However, Oncotype Dx does not provide the mechanistic basis for endocrine resistance. In this study, we aimed to investigate the impact of two epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) expression on recurrence and endocrine resistance such as tamoxifen of ER+ breast cancer. Methods: Publicly available gene expression datasets were analyzed for the overexpression of ESRP1 and ESRP2 in breast cancer. To validate the in silico findings for the ESRP1 and ESRP2 expression, we further performed quantitative real-time RT-PCR (qRT-PCR) in a cohort of 60 paraffin-embedded ER-positive node-negative breast carcinomas with low, intermediate, and high (19, 21, and 20 cases, respectively) Oncotype DX scores. To further determine the correlation between endocrine resistance and ESRP1/ESRP2 expression, we evaluated their expression levels in an established in vitro model of ER+/tamoxifen-resistance (MCF7/LCC2: an acquired tamoxifen resistant model of human breast cancer). Results: Using publicly available breast cancer gene expression datasets, we have identified that overexpression of the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) correlates with worse prognosis in ER+ significantly, but not in ER- breast cancers. qRT-PCR analysis further revealed that ESRP1 and ESRP2 expressions are positively correlated with high Oncotype Dx scores (P &amp;lt;0.05). In vitro, ESRP1 and ESRP2 levels were increased 7.48-fold (P = 0.008) and 2.98-fold (P = 0.0007) in ERα-positive cells with acquired tamoxifen resistance (MCF-7 LCC2), respectively. Thus, ESRP1 expression was slightly elevated more than ESRP2. Furthermore, both ESRP1 and ESRP2 levels did not change in response to E2 alone or E2 and tamoxifen treatment in combination. Conclusion: These findings suggest a role for the elevated expression of ESRP1 and ESRP2 in tamoxifen resistance and recurrence of ER+ breast cancer. Further studies are ongoing to determine their mechanistic role in ER+ cancer and methods of targeting ESRP1 &amp; 2. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-09-09.

Quantitative assessment of lymph vascular space invasion (LVSI) provides important prognostic information in node-negative breast cancer

BackgroundSome studies investigating the prognostic value of lymph vascular space invasion (LVSI) have shown an association between LVSI and disease-free survival. Definitive criteria and optimal determination of this parameter remain unclear, however, especially regarding the clinical relevance of LVSI quantification. Patients and methodsA subset of node-negative breast carcinomas from premenopausal patients from the European Organization for the Research and Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy patients with T1–T3, N0–2, and M0 breast cancer (BC) was selected and scored for LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells was determined in the largest tumor embolus within the lymph vessels. These two parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The optimal cutoff for this parameter was calculated in a test set (N = 120), tested in a validation set (N = 238), and compared with simple quantitation of the number of LVSI foci. ResultsTumors with a single LVSI focus are not associated with increased risk for relapse [hazard ratio (HR) 1.423, 95% confidence interval (CI) 0.762–2.656]. The LVSI TB had higher sensitivity and specificity compared with simple determination of the number of LVSI foci. LVSI TB was independently associated with disease-free survival in the validation set (HR 2.366, 95% CI 1.369–4.090, P = 0.002) in multivariate analysis and provided prognostic information in both the low- and high-risk node-negative BC groups (P < 0.001 and P = 0.007, respectively). ConclusionThe determination of the number of LVSI foci multiplied by the number of tumor cells gives the most reliable quantitative assessment of this parameter, which can provide prognostic information in node-negative BC.

Association of Tumour Stiffness on Sonoelastography with Axillary Nodal Status in T1 Breast Carcinoma Patients

To evaluate whether tumour stiffness on sonoelastography is associated with axillary nodal metastasis in T1 breast carcinoma patients. Between May 2006 and December 2010, 200 consecutive women (mean age, 51.6; range, 27 - 81 years) who underwent B-mode ultrasound (US), sonoelastography, and curative surgery with axillary nodal evaluation for clinically node negative T1 breast carcinomas (mean invasive tumour size, 12.4; range, 3 - 20 mm at pathology) were identified. The association between the elasticity score of the tumour and histopathological axillary nodal status was evaluated using a logistic regression model after controlling for imaging and clinicopathological variables of the tumour. The overall incidence of axillary nodal metastasis was 15.5 % (31 of 200). Axillary nodal metastasis was significantly more frequent in tumours with elasticity scores ≥4 than in tumours with elasticity scores <4 (21.7 % vs. 4.2 %; P < 0.001). At multivariate analysis, an elasticity score ≥4 [odds ratio (OR), 6.95; P = 0.004], US size >10 mm (OR, 5.98; P = 0.022), and lymphovascular invasion (OR, 10.68; P < 0.001) of tumours were independently associated with axillary nodal metastasis. Tumour stiffness on sonoelastography is independently associated with axillary nodal metastasis in T1 breast carcinoma patients. • Prediction of axillary nodal status using imaging techniques is valuable. • High ultrasound elasticity scores of T1 tumours were associated with axillary metastasis • Node-positive T1 tumours frequently had elasticity scores 4 or 5. • Sonoelastography might render axillary surgery unnecessary in T1 breast carcinoma patients.

The Significance of Time Interval From Clinical Presentation to Definitive Breast Surgery in Node Negative Breast Carcinoma With Long-term Follow-up: Clinical Implications

[1.40-2.64]; PR Z 2.04 [1.57-2.66]. Black race was associated with metastasis (1.90 [1.26-2.85]). Laterality, gender, income, and education were not significantly associated with case-control status. In a multivariate regression model, all relationships retained significance except for estrogen receptor negativity. Conclusions: Poorly differentiated, hormone receptor negative tumors and lobular carcinomas were associated with the presentation of metastatic disease in small, node negative breast cancers. Black race was also independently associated with metastatic disease. Author Disclosure: T. Churilla: None. C.A. Peters: None.

Interferon-inducible guanylate binding protein (GBP2) is associated with better prognosis in breast cancer and indicates an efficient T cell response

Recently, interferon-inducible guanylate binding protein (GBP2) has been discussed as a possible control factor in tumor development, which is controlled by p53, and inhibits NF-Kappa B and Rac protein as well as expression of matrix metalloproteinase 9. However, the potential role that GBP2 plays in tumor development and prognosis has not yet been studied. We analyzed whether GBP2 mRNA levels are associated with metastasis-free interval in 766 patients with node negative breast carcinomas who did not receive systemic chemotherapy. Furthermore, response to anthracycline-based chemotherapy was studied in 768 breast cancer patients. High expression of GBP2 in breast carcinomas was associated with better prognosis in the univariate (P < 0.001, hazard ratio 0.763, 95 % CI 0.650-0.896) as well as in the multivariate Cox analysis (P = 0.008, hazard ratio 0.731, 95 % CI 0.580-0.920) adjusted to the established clinical factors age, pT stage, grading, hormone and ERBB2 receptor status. The association was particularly strong in subgroups with high proliferation and positive estrogen receptor status but did not reach significance in carcinomas with low expression of proliferation associated genes. Besides its prognostic capacity, GBP2 also predicted pathologically complete response to anthracycline-based chemotherapy (P = 0.0037, odds ratio 1.39, 95 % CI 1.11-1.74). Interestingly, GBP2 correlated with a recently established T cell signature, indicating tumor infiltration with T cells (R = 0.607, P < 0.001). GBP2 is associated with better prognosis in fast proliferating tumors and probably represents a marker of an efficient T cell response.

A randomised trial of primary tamoxifen versus mastectomy plus adjuvant tamoxifen in fit elderly women with invasive breast carcinoma of high oestrogen receptor content: long-term results at 20 years of follow-up

Long-term analysis of a randomised trial in Nottingham comparing tamoxifen versus surgery as initial treatment demonstrated that in oestrogen receptor (ER)-unselected cases, surgery achieved better local control, with no difference in overall survival. It was suggested that for patients with ER-rich tumours, local control and survival may be comparable. We now present long-term follow-up of a randomised trial designed to address this clinical scenario. One hundred and fifty three fit elderly (≥70 years) women with clinically node-negative primary invasive breast carcinoma <5 cm of high ER content [histochemical (H) score ≥100] were randomised 2:1 to primary tamoxifen (Tam) (N = 100) or mastectomy with adjuvant tamoxifen (Mx + Tam) (N = 53). With median follow-up of 78 months, there was no statistically significant difference in 10-year rates of regional recurrence (9.0% versus 7.5%), metastasis (8.0% versus 13.2%), breast cancer-specific survival (89.0% versus 86.8%) or overall survival (64.0% versus 66.0%) between Tam and Mx + Tam; however, local control was inferior with Tam (local failure rates 43.0% versus 1.9%; P < 0.001). Irrespective of the degree of ER positivity, surgery achieved better local control. However, there was excellent and similar survival in both groups. Tam could be considered in those who are 'frail', refuse or prefer not to initially undergo surgery.

A nomogram to predict individual prognosis in node-negative breast carcinoma

BackgroundCurrently, the benefit of chemotherapy (CT) in node-negative breast carcinoma (NNBC) is discussed. The evaluation of classical clinical and histological factors is limited to assess individual outcome. A statistical model was developed to improve the prognostic accuracy of NNBC. MethodsA total of 305 node-negative breast carcinomas who underwent surgery (+/– radiotherapy) but no adjuvant treatment were selected. Putative prognosis factors including age, tumour size, oestrogen receptor (ER), progesterone receptor (PgR), Scarff–Bloom–Richardon (SBR) grading, urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and thymidine kinase (TK) were evaluated. The developed model was internally validated using Harrell’s concordance index. A prognosis index (PI) was proposed and compared with Adjuvant! Online program. ResultsAge (p<0.001), pathological tumour size (pT) (p<0.001), PgR (p=0.02), and PAI-1 (p⩽0.001) were included in the Cox regression model predicting Breast cancer specific survival (BCSS) at 5-years. Internal validation revealed a concordance index of 0.71. A PI score was derived from our nomogram. The PI score was significantly associated with BCSS (hazard ratio (HR): 4.1 for intermediate, p=0.02, HR: 8.8, p<0.001 for high group) as compared to Adjuvant! Online score (HR: 1.4, p=0.14). ConclusionA nomogram can be used to predict probability survival curves for individual breast cancer patients.

An unusual case of invasive papillary carcinoma of the breast

Invasive papillary carcinoma is a rare variant of breast cancer. We report an unusual case of invasive papillary carcinoma of the breast with high nuclear grade, brisk mitosis, necrosis, extensive apocrine differentiation, and intense lymphoplasmacytic infiltrate; additionally triple-negativity for estrogen and progesterone receptors and Her2 neu. The patient underwent modified radical mastectomy and adjuvant chemotherapy. But, it was a node negative breast carcinoma. Increasing the awareness of this clinicopathologic entity would be helpful in avoiding overtreatment of patients with this cancer even if the tumor has negative morphological and immunohistochemical prognosticators.

The value of step-sectioning in the diagnosis of lymph node micrometastasis in breast cancer

Objectives: Routine practice is to examine one histological section for evaluating secondary tumor deposits in the axillary lymph nodes in patients with breast cancer. The aim of the present study is to evaluate whether multiple levels of histological section detect significantly more metastatic deposits in axillary lymph nodes from breast cancer resection specimen than the standard practice of examining one section. Methods: A retrospective study of 30 patients with node negative breast cancer was performed whose specimens were received at AL-Jamhuri Teaching Hospital and private laboratories in Mosul city between the years 2008 and 2010. The original slides and the paraffin wax blocks containing the lymph nodes were retrieved from the archive, and 4 extra levels (separated by 30 µm) were cut from each block and were stained with H & E stain. Results: Of the 30 cases with node negative breast carcinoma, 4 (13.3%) were found to contain extra tumor deposits at deeper levels that were not detected at the original sections. Conclusion: Multiple levels of histological sections separated by relatively small intervals detect more tumor deposits in the axillary lymph nodes than the current practice of examining a single section.

P4-09-29: A Nomogram To Predict Prognosis in Node-Negative Breast Carcinoma.

Abstract Background: Currently, the usefulness of conventional markers for breast carcinoma is limited to assess individual outcome. A statistical model was developed to improve the prognostic accuracy using multiple conventional and emerging prognostic biomarkers. Methods: A total of 305 node-negative breast carcinomas who underwent surgery (+/− radiotherapy) but no adjuvant treatment was selected. Putative prognosis factors including age, tumor size, ER, PR, SBR grading, urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and thymidine kinase (TK) were evaluated. The developed model was internally validated using Harrell's concordance index and calibrated. An external validation of the new model is warranted. Results: Age (p&amp;lt;0.001), PR (p= 0.02), and PAI-1(p=&amp;lt;0.001) were included in the Cox regression model predicting overall survival at 5-years. Internal validation revealed a concordance index of 0.711 to 0.694 before and after calibration. Conclusion: A nomogram can be used to predict probability survival curves for individual breast cancer patients and the effect of treatment options can be evaluated using these models. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-29.

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node‐negative breast cancer

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node-negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status. The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation-Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis. In total, 75 patients had HER2-positive BC (10.7%). At a mean follow-up of 4.9 years (standard deviation, 2.6 years; range, 0.5-10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2-positive BC had worse distant recurrence-free survival (DRFS) than patients with HER2-negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94-14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07-0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20-1.82; P = .029). The current results indicated that patients with T1a/T1b, lymph node-negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2-positive and HR-negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti-HER2 adjuvant therapy.

Unnecessary Axillary Surgery for Patients With Node-Negative Breast Cancer Undergoing Total Mastectomy

To identify factors associated with the use of axillary lymph node dissection (ALND) as the initial axillary staging in node-negative breast cancer patients undergoing total mastectomy. California Cancer Registry study. Academic research. Women treated with total mastectomy for Tis, T1, or T2 node-negative breast carcinoma treated between January 1, 2004, and December 31, 2008. Proportions of patients who underwent ALND without prior sentinel lymph node dissection were compared by demographic characteristics. Of 18,238 women treated with total mastectomy for Tis, T1, or T2 node-negative breast carcinoma, 35.1% underwent initial axillary staging by ALND without prior sentinel lymph node dissection. On multivariable analyses, patients were significantly more likely to undergo ALND if they had T2 disease or were 65 years or older, were hormone receptor negative, of Hispanic or Asian/Pacific Islander race/ethnicity, of lower socioeconomic quintile, operated on during earlier years of the study period, and not treated by a hospital cancer program approved by the American College of Surgeons. More than one-third of patients in California who underwent total mastectomy for treatment of early-stage node-negative breast carcinoma received ALND without prior sentinel lymph node dissection; furthermore, certain subsets of patients have higher odds of undergoing ALND alone. To avoid the unnecessary morbidity of ALND in early-stage breast carcinoma, further research is required to elucidate how tumor, patient, and system factors can be modified to improve delivery of optimal breast cancer care.