Concomitant Ductal Carcinoma In Situ Research Articles

Does concomitant ductal carcinoma in situ affect the clinical outcome in breast cancer patients with invasive ductal carcinoma: An Asian perspective.

BackgroundDuctal carcinoma in situ (DCIS) is an established precursor to invasive ductal carcinoma (IDC) and its coexistence with IDC appear to favor reduced biological aggressiveness. Its prognostic implication and ability to affect clinical outcome has been understudied in Asia. This study aims to explore if concomitant DCIS affects the clinical behavior and outcomes among Asians.AimStages I to III breast cancer patients with histological proven IDC, diagnosed and treated in a single institution from June 1, 2004 to June 30, 2014 were included in this study. Statistical analyses were conducted using Χ 2 test, independent t test, multivariate logistic regression and Kaplan–Meier test.Methods and ResultsA total of 818 patients were identified, including 224 and 594 patients with isolated IDC (No‐DCIS) and IDC with coexisting DCIS (IDC‐DCIS) respectively. Patients with IDC‐DCIS were found to have smaller tumors (median: 22 mm, p ≤ .01), estrogen receptor positivity (p = .001), progesterone receptor positivity (p < .001) and associated with better pathological stage (p = .001). Patients with No‐DCIS were 1.6 times more likely to develop disease progression (95% CI: 1.1–2.3, p = .027) and subsequently associated with distant recurrences (20.5% vs. 13.6%, p = .02). The breast cancer specific 5 year overall survival rate for patients with No‐DCIS and those with IDC‐DCIS was 90.9% (95% CI: 86.2%–94.5%) and 93.7% (95% CI: 91.4%–95.5%), respectively (p = .202).ConclusionThe presence of DCIS component in IDC among Asians is associated with favorable tumor biological profile, thereby indicating reduced disease aggressiveness. Our study is the first to report the clinical significance in terms of disease progression and distant recurrences among Asians.

Presence of Non-classic LCIS Is Not a Contraindication to Breast Conservation in Patients with Concomitant Invasive Breast Cancer or DCIS.

Non-classic lobular carcinoma in situ (NC-LCIS) represents a spectrum of lesions, histologically distinct from classic LCIS (C-LCIS) and ductal carcinoma in situ (DCIS). Several studies have reported on the safety of breast conservation (BCS) in patients with DCIS or invasive breast cancer and concomitant C-LCIS, yet there are no data addressing this question for patients with concomitant NC-LCIS. We evaluated local recurrence (LR) after BCS in patients with DCIS or invasive cancer and concomitant NC-LCIS. We searched institutional databases using natural language processing to identify patients with DCIS or invasive breast cancer and concomitant NC-LCIS treated with BCS between 2000 and 2015. Charts were reviewed to collect demographics, disease and treatment details, and recurrence events. All results represent descriptive analyses. We identified 71 patients with DCIS (n = 13) or invasive cancer (n = 58) and concomitant NC-LCIS treated with BCS. Median patient age was 59 years (33-77 years), and median invasive tumor size was 1.2 cm (0.1-6.9 cm); 62% of DCIS and 79% of invasive cancer patients had hormone receptor (HR)-positive disease. Among DCIS patients, seven (54%) received radiation and none hormonal therapy. Among those with invasive cancer, 52 (90%) received radiation, 17 (29%) received chemotherapy and 44 of 55 with HR-positive disease (78%) received hormonal therapy. At median follow-up of 79 months (1-265 months), the LR rate was 8% and 2% among patients with DCIS and invasive cancer, respectively. NC-LCIS is rarely present in association with DCIS or invasive cancer, and it does not appear to impact LR outcomes following BCS.

Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component

BackgroundInvasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.MethodsConsecutive ER-positive, HER2-negative, N0–1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.ResultsA total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.ConclusionsIDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.

Prognostic Marker Expression In Microinvasive Breast Cancer

Abstract Introduction/Objective Microinvasive breast carcinoma (Mi) is defined as invasive carcinoma (IC) less than 1 mm in greatest dimension. Depletion of the focus during further immunohistochemical investigation is commonly observed. Studies on prognostic marker expression report high concordance between the Mi and concomitant ductal carcinoma in-situ (DCIS). Compared to IC, Mi has a higher rate of Her2 positivity, indicating aggressive phenotype and potential variation in marker expression over time. We aimed to verify the concordance between Mi and DCIS in patients with pure Mi, as well as between foci of Mi and IC in patients with both. Methods A total of 21 cases of Mi and 9 cases with both IC and Mi disease were identified and evaluated for pathologic characteristics and ER, PR, and Her2 expression by immunohistochemistry. The rate of Her2 in Mi was compared to national benchmarks for IC. Results Mi was associated with high grade DCIS. 100% concordance of Her2 expression between Mi and DCIS was present in 14/21 cases where Mi was not depleted. Discrepancy between ER/PR was seen in two cases (Mi negative/DCIS focally positive). 50% of these Mi cases were Her2 positive, compared to the 13–25% generally reported for IC. Overall, by extrapolating Mi status from the concomitant DCIS when the Mi became depleted, 38% of Mi was positive for Her2. 100% concordance between foci of Mi and IC in patients presenting with both was observed. Conclusion Mi had a more aggressive prognostic marker phenotype compared to IC based on Her2 positivity. Concordance of prognostic marker expression between Mi and concomitant DCIS supports reporting of the DCIS status when the Mi becomes depleted, with only rare ER/PR discrepancies observed. Concordance between foci of Mi and IC in patients with both does not support time-based variation in marker expression. However, further investigation is warranted to uncover potential changes.

374 Poster - Does concomitant DCIS affect the clinical outcome in breast cancer patients with invasive ductal carcinoma: An Asian perspective

Background: Ductal carcinoma in situ (DCIS) is an established precursor to invasive ductal carcinoma (IDC) and its coexistence with IDC appear to favour reduced biological aggressiveness. Its prognostic implication and ability to affect clinical outcome has been controversial with no prior Asian studies. This study aims to be the first to explore if concomitant DCIS affects the clinical behavior in terms of disease progression and overall survival among Asian patients with IDC.

Prognostic value of ductal carcinoma in situ component in invasive ductal carcinoma of the breast: a Surveillance, Epidemiology, and End Results database analysis.

BackgroundThe prognostic implication of concomitant ductal carcinoma in situ (DCIS) in invasive ductal carcinoma (IDC) remains controversial. Our objective was to investigate whether concomitant DCIS affects survival outcomes in patients with IDC.Materials and methodsPatients with nonmetastatic breast cancer who underwent surgery in 2010–2014 were included from the Surveillance, Epidemiology, and End Results program. Statistical analyses were conducted using χ2 test, linear-by-linear association, one-way analysis of variance, Kaplan–Meier method, Cox proportional hazards regression model, and propensity score matching (PSM).ResultsA total of 61,745 patients were identified, including 44,630 (72.3%), 13,559 (22.0%), and 3,556 (5.7%) patients with no DCIS component reported (No-DCIS), DCIS <25% (L-DCIS), and ≥25% (H-DCIS), respectively. Patients with H-DCIS were more likely to be younger (p<0.001), have smaller tumors (p<0.001), good/moderate differentiation (p<0.001), human epidermal growth factor receptor 2–positive disease (p<0.001), receive mastectomy (p<0.001), and not receive radiotherapy (p<0.001) and chemotherapy (p<0.001). The median follow-up was 27 months, and the 2-year breast cancer-specific survival (BCSS) in patients with No-DCIS, L-DCIS, and H-DCIS was 97.3%, 98.0%, and 98.5%, respectively (p<0.001). Before PSM, H-DCIS was an independent favorable prognostic factor for BCSS; patients with H-DCIS had better BCSS compared to patients with No-DCIS (hazard ratio [HR] 0.674, 95% CI: 0.528–0.861, p=0.002), while the BCSS between No-DCIS and L-DCIS was similar (HR 0.944, 95% CI: 0.840–1.061, p=0.334). However, this survival advantage disappeared after PSM; there was significantly different BCSS between patients with No-DCIS and H-DCIS (HR 0.923, 95% CI: 0.653–1.304, p=0.650). H-DCIS was not associated with BCSS as compared to No-DCIS in the breast-conserving surgery (p=0.295) and mastectomy (p=0.793) groups.ConclusionIn breast cancer, patients with H-DCIS have unique clinicopathologic features compared to patients with No-DCIS. Before PSM, H-DCIS was associated with favorable BCSS as compared to No-DCIS. However, the survival advantage disappeared after PSM.

Impact of Detection Method and Accompanying Ductal Carcinoma in Situ on Prognosis of T1a,bN0 Breast Cancer.

Background: T1a,bN0 breast cancer is not easily detected. Before mammography became widespread, most cases were discovered only after the development of symptoms. The presence of ductal carcinoma in situ (DCIS) affects the detectability of associated invasive cancer; however, the prognostic value of concomitant DCIS is controversial. This study compared the characteristics of screening-detected and symptom-detected T1a,bN0 breast cancer, and investigated the impact of accompanying DCIS on detection and prognosis.Patients and Methods: Data were collected from a single hospital between 2000 and 2009. Of 5,690 primary breast cancers patients, 438 met the criteria for T1a,bN0M0. Logistic regression models were used to identify prognostic indicators and their association with the detection method. Survival analyses were performed to estimate distant relapse-free survival (DRFS) and breast cancer-specific survival (BCSS).Results: Tumors in 79 and 359 patients were detected by screening and development of symptoms, respectively. Symptomatic cancer patients were younger, more likely to receive a mastectomy, and had larger accompanying DCIS lesions; their 10-year DRFS rates were worse than those of patients with screening-detected tumors (91.1% vs. 100% respectively, p=0.049). Patients with large accompanying DCIS (≥2 cm) had markedly worse 10-year DRFS (77.1% vs. 97.4%, p<0.001) and BCSS (94.3% vs. 98.9%, p<0.001).Conclusion: T1a,bN0 breast cancers detected owing to symptoms are more likely to have larger accompanying DCIS. T1a,bN0 patients with large accompanying DCIS have worse DRFS and BCSS. It is important to consider associated DCIS size when evaluating prognosis in T1a,bN0 breast cancer patients.

Expression of vacuole membrane protein 1 and its prognostic value in invasive ductal carcinoma of the breast

To investigate the expression of vacuole membrane protein 1 (Vmp1) and its prognostic value in invasive ductal carcinoma (IDC) and concomitant ductal carcinoma in situ (DCIS) of the breast. The expression and location of Vmp1 in the breast tissues from 102 patients with IDC and 32 concomitant DCIS were detected by immunohistochemical SP method, and the relationship with clinicopathologic parameters was analyzed. Vmp1 expression was observed in the cytoplasm of the cancer cells in 57.8% (59/102) cases, and correlated with grade (χ(2) = 12.644, P = 0.002), pTNM stage (χ(2) = 11.987, P = 0.001), node status (χ(2) = 9.341, P = 0.002), tumor diameter (χ(2) = 7.630, P = 0.022) as well as Nottingham Prognostic Index (NPI;χ(2) = 15.561, P = 0.000). The expression of Vmp1 in concomitant DCIS was higher than that in IDC (81.3% vs 56.3%; χ(2) = 4.655, P = 0.031). In this cohort, the mean disease-free survival was 81.2 months; the 5-year overall survival rate was 90.2% (92/102) and the disease-free survival rate was 81.4% (83/102). Vmp1 expression had significant influence on disease-free survival time, with Vmp1-negative patients showing poor prognosis (χ(2) = 11.192, P = 0.001). COX's proportional hazards regression model revealed that Vmp1 was a protective factor, with relative risk < 1. The detection of Vmp1 in IDC may be helpful for prognosis prediction; the patients with Vmp1 expression may have a better prognosis.

Abstract P2-10-35: The grade of accompanying DCIS in IDC as important prognostic factor

Abstract Backgrounds: The issue of whether concomitant ductal carcinoma in situ (DCIS) affects the prognosis of with invasive breast cancer is important but studies of this have reported inconsistent results. So we aimed to assess the character and prognostic difference in infiltrating ductal carcinoma (IDC) according to accompanying DCIS status. Methods: We reviewed the medical records of the patients who underwent surgery for IDC. Male patients, patients who had received neoadjuvant chemotherapy, patients with synchronous bilateral breast cancer, follow-up periods &amp;lt;6months or those with other malignancies were excluded from the study. In cases in which a DCIS component was present in IDC, the degree of differentiation and the presence of necrosis were assessed to subdivide DCIS into two groups; low and high grade. Results: A total of 1751 patients were included, and 1384 patients (79.0%) had concomitant DCIS; 337 had low-grade DCIS, and 1047 patients had high-grade DCIS. The low-grade DCIS group had a significantly lower TNM stage than the high-grade DCIS group. The majority of cases with low-grade DCIS, were ER-positive (85.2%), PR-positive (81.3%) and had low Her-2 (98.7%). When we analyzed the survival rates according to the presence of DCIS, no statistical significance was founded. However, a subgroup analysis showed that the patients with low-grade DCIS survived significantly longer than other patients, whereas those with high-grade DCIS had poorer survival (5 year event-free survival rate; low-grade DCIS vs. without DCIS vs. high-grade DCIS, 97% vs. 93% vs. 86%, p = 0.001). Specially, in patients with lymph node involvement, accompanying high-grade DCIS was independent predictor distant metastasis (HR 5.0, p = 0.026, 95% CI 1.21–20.92). Conclusion: The important factor that affect prognosis of IDC with DCIS is not the presence itself of DCIS component but the grade of DCIS. The patients with low-grade DCIS had a good prognosis and those with high-grade DCIS had a poor prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-35.

Abnormal expression of Nek2 and β-catenin in breast carcinoma: clinicopathological correlations

NIMA-related kinase 2 (Nek2) and β-catenin are important centrosome regulatory factors. The aim of this study was to detect the possible disparity in their expression among normal breast tissue, invasive ductal carcinoma (IDC), concomitant ductal carcinoma in situ (DCIS), and pure DCIS, and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of Nek2 and β-catenin in breast cancer tissues from 60 cases of pure DCIS, 348 cases of IDC and 137 cases of concomitant DCIS with that in normal breast tissues from the same 137 concomitant DCIS patients as controls. As compared with normal tissue, expression of Nek2 and β-catenin in the cytoplasm was significantly increased in IDC and DCIS (P < 0.05), and variation in expression was also observed in different grades of IDC (P < 0.01). Also, cytoplasmic expression of Nek2 and and of β-catenin were correlated with each other in IDC and DCIS (P < 0.01). In addition, they were both related to Ki67 immunoreactivity (P < 0.05). Furthermore, our study also revealed a correlation between their expression and some clinicopathological factors. We found that Nek2 cytoplasmic expression was associated with grade and tumour size (P < 0.01) in IDC, whereas β-catenin cytomembrane expression showed significant variation with grades, TNM stages, lymphoid node status, oestrogen receptor status, and molecular subtype (P < 0.05); a difference in expression was also observed between IDC and DCIS (P < 0.05). Also, β-catenin cytoplasmic expression was associated with TNM stage (P < 0.05). Expression of Nek2 at the mRNA level was detected in 50 pairs of breast cancer specimens and matched normal tissues by reverse transcriptase polymerase chain reaction, and the result showed increased expression in IDC. This study suggests that abnormal expression of Nek2 and β-catenin might be one of the mechanisms of tumorigenesis, especially of abnormal tumour proliferation. They may represent new potential targets for therapeutic intervention.

Abstract B12: Associations between invasive breast cancer with and without a DCIS component and breast cancer risk factors in African American and European American women

Abstract Introduction: Breast cancer presents as several clinically distinct forms, including invasive ductal carcinoma (IDC) with an associated ductal carcinoma in situ (DCIS) component, and pure IDC. The absence of concomitant DCIS was previously associated with a significantly worse prognosis for IDC, even after adjustment for stage and tumor size. Evidence from gene expression studies suggests that the absence of a DCIS component is associated with an altered tumor microenvironment, which may involve a distinct pathway of cancer development, with unique risk factors and prognoses. The absence of a DCIS component in IDC has not previously been examined in relation to the breast cancer disparities between African-American (AA) and European-American (EA) women. Methods: IDC breast cancer patients with or without a DCIS component were identified by examining pathological reports from the Women's Circle of Health Study, an on-going case-control study examining racial disparities in women diagnosed with breast cancer in NYC and NJ. Through in-person interviews information was collected on known and suspected breast cancer risk factors. In this case-case analysis, we examined these factors in relation to IDC with and without a DCIS component, adjusting for self-reported race and also stratified by race. Interactions were assessed with the Wald Chi-square. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived to estimate the odds of having pure IDC compared to patients with a DCIS component. Results: Of 729 women with IDC, 19.5% were confirmed to have pure IDC and 80.5% IDC with a DCIS component. EA women were less likely than AA women to present with pure IDC without a DCIS component (OR=0.66; 95% CI 0.43–0.99). Women who breastfed were less likely to have pure IDC than IDC with a DCIS component (OR=0.65; 95% CI 0.40–1.04). Stratified analyses by race did not reveal major differences from unstratified analyses for breastfeeding (OR=0.64; 95% CI 0.35–1.16, OR=0.68; 95% CI 0.28–1.64 in AA and EA women, respectively). AA women with a body mass index (BMI) ≥30 compared to a BMI &amp;lt;25 were less likely to have pure IDC than IDC with DCIS (OR=0.52; 95% CI 0.25–0.97), whereas EA women with a high BMI were more likely to have pure IDC (OR=1.36; 95% CI 0.67–2.76, p for interaction=0.01). Pure IDC was directly and inversely associated with family history of breast cancer in EA and AA women, respectively (OR=1.89; 95% CI 1.01–3.55, OR=0.84; 95% CI 0.42–1.67, respectively, p for interaction=0.09). Conclusion: Compared to EA women, AA women are more likely to present with pure IDC without a DCIS component. Stratified analyses suggest that risk factors associated with pure IDC may be significantly different between AA and EA women. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B12.

Expressions and significances of Nek2 and β-catenin in breast invasive ductal carcinoma

Objective To investigate the expression and significance of NIMA related kinases 2 ( Nek2) and β-catenin (β-cat) in breast invasive ductal carcinoma (IDC) and concomitant ductal carcinoma in situ (DCIS). The roles of Nek2 and β-acat in the development and progression of breast cancer were explored. Methods The protein expression of Nek2 and β-cat in the tissues from 186 patients with IDC, 75 concomitant DCIS, 80 normal tissue adjacent to carcinoma and 40 fibroadenoma of breast was detected by using immunohistochemistry. Their relationship between clinicopathologic parameters was analyzed. Results There were correlations between the Nek2 expression in cytoplasm and grade(x2=8. 756;P 0. 05), the Nek2 expression in cytoplasm had a correlation with the β-cat expression in cytoplasm (r=0. 226,P<0.05) in concomitant DCIS, and the same relationship could also be seen in IDC (r=0. 368,P<0.01). There was significant difference in the β-cat expression on the cytomembrane between IDC and concomitant DCIS (Z=-3. 804,P<0. 01). In the normal tissue adjacent to carcinoma and fibroadenoma, the Nek2 expression in cytoplasm and nuclei Was low or negative;the β-cat expression on the cytomembrane was high but that Was low in cytoplasm.Conclusion Centrosome regulatory factor Nek2 and β-cat can support a new way to explore the mechanisms of breast tumorigrenesis.And they may become a new antitumor drug target in the future. Key words: Breast invasive ductal carcinoma; Nek2; β-catenin

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer

Background:The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).Methods:We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.Results:Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).Conclusion:IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.

Does ductal carcinoma in situ accompanying invasive carcinoma affect prognosis?

Ductal carcinoma in situ (DCIS) often accompanies invasive breast cancer. The prognostic implication of this is unclear. We sought to determine whether concomitant DCIS affects outcomes in patients with invasive disease. A nested cohort study was performed of 1,709 invasive breast cancer patients. Clinicopathologic data, along with survival and recurrence data, were collected prospectively. Concomitant DCIS was noted in 434 (25.4%) patients. Median follow-up was 59 months. On univariate analysis, the presence of DCIS was associated with a trend toward improved 5-year disease-free survival (93.6% vs 90.5%; P = .089) and overall survival (95.3% vs 92.6%; P = .058). Further, DCIS was associated with younger patient age (median 65 vs 68 years; P < .0001), smaller tumor size (median 1.37 vs 1.44 cm; P = .069), fewer palpable tumors (27.4% vs 33.3%; P = .051), more high-grade tumors (19.1% vs 15.8%; P = .045), and invasive ductal histology (90.6% vs 79.0%; P < .0001). On multivariate analysis, DCIS was not, however, an independent predictor of improved disease-free (odds ratio [OR], 0.715; P = .217) or overall survival (OR, 0.770; P = .251). Although the presence of DCIS is often associated with favorable features, it is not an independent predictor of improved outcome in patients with concomitant invasive breast cancer.

The status of cyclooxygenase-2 expression in ductal carcinoma in situ lesions and invasive breast cancer correlates to cyclooxygenase-2 expression in normal breast tissue

There is a paucity of data on cyclooxygenase (COX)-2 expression in normal breast tissue and on the changes in COX-2 expression from normal tissue via ductal carcinoma in situ (DCIS) lesions to invasive cancer. The aim of this study, therefore, was to investigate COX-2 protein expression in normal breast tissue, DCIS, and invasive breast cancer in samples from the same patients. In 39 patients, we investigated and compared COX-2 expression in paired samples of invasive cancer and normal adjacent breast epithelium by immunohistochemistry with a monoclonal COX-2 antibody. Furthermore, in 29 of these cases, we also analyzed a concomitant DCIS lesion. Patients without COX-2 expression in normal breast tissue also do not express COX-2 in invasive breast cancer and in DCIS lesions, respectively. Conversely, COX-2 expression in normal breast tissue was an indicator for COX-2 expression in the paired breast tumors. There was no significant correlation between COX-2 expression and pathologic tumor stage, nodal status, hormone receptor status, tumor size, grading, and lymphovascular space involvement. This is the largest study to date investigating COX-2 in paired samples of breast tumors and normal adjacent breast tissue. Our data are consistent with the hypothesis that COX-2 overexpression is an early event in breast carcinogenesis.