Non-triple Negative Patients Research Articles

Abstract P6-14-16: Claudin-9 and its subcoat anchorage proteins ZO-1 and ZO-3 in breast cancer, the clinical and therapeutic significance

Abstract Introduction. Claudin-9 (CLDN9), a member of the claudin protein family, is thought to play a role in the control of tight junctions (TJ) in various cell types. CLDN9 protein needs intracellular subcoat proteins, primarily the Zonula Occluden (ZO)-1 and ZO-3 to anchor to the cytoskeleton in order to form TJ with other proteins, including occludin. In the body, CLDN9 is highly expressed in endocrine tissues but is relatively low in mammary tissues. The role of CLDN9 is not well understood in cancer. In the present study, we have for the first time examined the pattern of CLDN9 expression at protein and transcript levels in breast cancer and explored its clinical and therapeutic implications. Methods. CLDN9 protein and CLDN9 transcript in fresh frozen human mammary tissues were evaluated by immunohistochemistry and quantitative transcript analyses and, together with the ZO family members and occludin in our database, correlated with clinical indicators. Assessment of expression in a range of cell lines was also determined. The levels of CLDN9 transcript, was also assessed against the therapeutic responses of the patients to chemotherapies by using a dataset from TCGA database. Results. Breast tumour tissues had high levels of CLDN9 transcript in tumours versus normal tissues. However, high grade breast tumours had significantly lower levels than low grade (p=0.02 and p=0.003, grade-2 and 3 vs grade-1 respectively). Patients with metastasis also had significantly lower levels than those without (p=0.0075). Patients who died of breast cancer had higher levels of the transcript than those who survived, although this was not significant. CLDN9 expression was significantly correlated with ZO-1 (r=0.20, p< 0.001) and ZO-3 (r=0.179, p< 0.01), but not ZO-2 in our cohort. There was significant correlation with another key TJ molecule, occludin (r=0.236, p=0.11). CLDN9, together with ZO-1 and ZO-3 significantly linked to the survival of patients (1444.6 months for the low expressing group versus 1138.2 months for the high expression group, p=0.013). The expression profile of the CLDN9/ZO1/ZO3 complex also indicated potential as an independent prognostic indicator (p=0.004, HR=2.033). The prognostic value was highly applicable to non-triple negative breast cancer patients. CLDN9 transcript also appeared to have a significant impact on treatment responses; patients who were sensitive to chemotherapies had a significantly lower levels of CLDN9 transcript than those who were resistant to treatment (p< 0.000001). In human cell lines, expression levels of CLDN-9 in ER (+) breast cancer cell lines, MDAMB361, MCF7 and BT474 were high; in a ER(-) breast cancer cell line MDAMB231, the expression level of CLDN-9 was lower. Conclusion. In conclusion, CLDN9 expression was differentially expressed in human breast cancer cells lines and appeared to reflect changes in ER status. It was apparent from levels of CLDN9 in a breast cancer cohort that expression was associated with grade and metastatic disease. Of significant notice was the finding that expression of CLDN9 in an expression profile with ZO1 and ZO3 has potential as a prognostic indicator, particularly in non-triple negative patients and in those who are chemotherapy resistant. Citation Format: Xinguo Zhuang, Wen G. Jiang, Eleri Davies, Bing Xu, Tracey A. Martin. Claudin-9 and its subcoat anchorage proteins ZO-1 and ZO-3 in breast cancer, the clinical and therapeutic significance [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-16.

Methylated p16 gene is associated with negative expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer

Objective: This study was conducted to determine the relationship between p16 gene methylation and expression of relevant receptors in breast cancer (BC) for subtyping the disease. Methods: Methylation-specific PCR (MSP) was carried out to detect the methylation status of p16 gene in 240 tissue samples and 205 serum samples from BC patients treated at our hospital. Immunohistochemistry was used to determine the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Receiver operating characteristics (ROC) curve was analyzed for diagnostic value based on methylation status for triple-negative (TN) BC. Results: The overall methylation rates of the p16 gene were 36.7% (88/240) and 35.1% (72/205) in the tissue and serum samples, respectively. In patients with ER, PR and HER2-TNBC, the methylation rate of the p16 gene was significantly higher than that in non-triple negative patients (84.9%, 62/73) vs (25.9%, 35/135, P < 0.01). The methylation of p16 gene was negatively associated with the expression of ER, PR and HER2 (r = -0.661, -0.694 and -0.765, respectively, P < 0.05), but it was not correlated with the pathological characteristics of BC, such as tumor grade and lymph-node metastasis. Receiver operator characteristic (ROC) curve analysis showed that p16 gene methylation had a significant diagnostic value for TNBC with an AUC of 0.815. Therefore, p16 gene methylation is associated with the subtype of TNBC and can be used as an easy and non-invasive approach to screen patients for TNBC.

NCOG-05. MANAGEMENT OF BRAIN METASTASIS IN TRIPLE NEGATIVE BREAST CANCER

Abstract Brain metastasis is common in patients with breast cancer, and those with triple negative status have an even higher risk. Stereotactic radiosurgery (SRS) is preferred to whole brain radiation therapy (WBRT) in most patients. However, triple negative status is currently not considered when determining optimal radiation therapy. Given the aggressive nature of triple negative breast cancer, we evaluated a role for WBRT for all patients in this cohort. We conducted a single-institution retrospective cohort study to determine whether triple negative patients with brain metastases have a higher burden of intracranial disease and whether type of initial radiation therapy affects overall survival for this cohort of patients. 85 patients met the inclusion criteria for this study. 25% of patients had triple negative breast cancer, of which 91% received SRS and 53% of patients received WBRT. The average number of new brain metastases from time of initial brain imaging to radiation therapy was 0.67 (St.Dev:1.1) in the non-triple negative status patients and 2.6 (St. Dev:3.7) in the triple negative status patients (p=0.001). Using a cox proportional hazards model, it was found that whole brain radiotherapy does not significantly affect overall survival in patients with triple negative breast cancer (p = 0.96). Our findings highlight the highly aggressive intracranial nature of triple negative breast cancer. Indeed, the rate of increase in brain metastases is significantly higher for triple negative patients compared to non-triple negative patients. As a result, we evaluated whether triple negative patients would benefit from whole brain radiation regardless of findings on initial brain imaging. Despite 53% of patients receiving WBRT, our investigation found that there is no additional benefit to WBRT in triple negative breast cancer patients. These results suggest a need to re-evaluate the role of WBRT in the management of triple negative breast cancer.

Palliative care delivery according to age among metastatic breast cancer patients. ESME-MBC cohort

Abstract Background Metastatic breast cancer (MBC) may require inpatient palliative care (IPC) but literature suggests age-related disparities in palliative care delivery. This study, based on real-world data, aimed to assess the cumulative incidence function (CIF) of IPC delivery and if age is an independent factor, taking into account the competing risk of death. Methods The national multicenter ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in the 18 French Comprehensive Cancer Centers. IPC identification used ICD-10 palliative care coding. Main analysis first estimated pseudo values of 2-year and 8-year CIF of IPC. Linear regression models estimated the mean changes of pseudo-values (2 models: 2-year and 8-year CIF of IPC). Results Our analysis included 12375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% CI, 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at two and eight years, respectively. At two years, among triple-negative patients, young patients (<65 yo) had a higher CIF of IPC than older patients after adjusting for cancer characteristics, centre, and period (65+/<65: β=-0.05; 95% CI, -0.08 to -0.01). Among other tumour subtypes, older patients received short-term IPC more frequently than young patients (65+/<65: β = 0.02; 95% CI, 0.01 to 0.03). At eight years, outside large centres, IPC was delivered less frequently to older patients adjusted to cancer characteristics and period (65+/<65: β=-0.03; 95% CI, -0.06 to -0.01). Conclusions We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple negative and older non-triple negative patients needed more short-term IPC. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions. Key messages Our study highlighted particular challenge for older MBC patients diagnosed outside large French Comprehensive Cancer Centers. By identifying age at MBC diagnosis as a factor of IPC delivery, this report supports a wider implementation of IPC facilities and more age-specific interventions.

Abstract P5-07-08: Survival relevance of tamoxifen sensitivity-related microRNAs, miR-342 and miR-221/222, in breast cancer patients

Abstract BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs, which regulate the expression of target genes post-transcriptionally by RNA interference. They have emerged as one of the crucial regulators of cancer progression. Some miRNAs are reported to be related to the response of breast cancer to tamoxifen (TAM). In this study, we investigated whether the levels of TAM-resistant miRNA (miR-221/222) and TAM-sensitive miRNA (miR-342) translate to breast cancer patient survival, using multiple large databases. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA; n=1049), Gene Expression Omnibus (GEO; GSE19536 n=96, GSE22220 n=210), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=2509) datasets were used and Gene Set Enrichment Analysis (GSEA) was performed. RESULTS: MiR-342 was identified as a TAM-sensitive miRNA, and miR-221/222 were identified as TAM-resistant miRNAs by literature search. Patients with high expression of miR-342 were shown to have better survival in TCGA (OS, p=0.02; DFS, p=0.03, respectively) and in two other independent GEO cohorts (OS, p=0.02 and p=0.0007, respectively) as well as in the METABRIC cohort (OS, miR-342-3p, p=0.006; miR-342-5p, p=0.00009). By subtype analyses, high expression of miR-342 was significantly associated with better survival in ER-positive patients (p=0.04), but not in ER-negative or triple negative patients in the TCGA cohort. This association was not observed in the METABRIC cohort. Within TCGA cohort, expression of TAM-resistant miR-221/222 did not significantly impact survival. Unexpectedly, increased expression of miR-221 was shown to have increased overall survival in all patients (p=0.00904) as well as in ER-negative patients (p=0.0479) and non-triple negative patients (p=0.0106) within the METABRIC cohort. On the other hand, low expression of miR-222 was associated with increased survival of all patients (p=0.00802) as well as in non-triple negative patients (p=0.041). Lastly, GSEA demonstrated that lower miR-342 expression was significantly seen in TAM-resistant gene sets, and higher miR-342 expression was seen TAM-sensitive gene sets, but miR-221/222 did not show any significant enrichment with TAM-resistant or TAM-sensitive gene sets. Taken together with survival data, expression levels of miR-342 reflect its TAM-sensitivity related function, however, that of miR-221/222 reflect other functions in breast cancer patients. CONCLUSION: For the first time, we used “big data” from the TCGA, GEO and METABRIC cohorts to analyze multiple miRNAs with respect to TAM sensitivities and its survival impact. We demonstrated that expression of miR-342 reflected the sensitivity of the cancer cells to TAM sensitivity, however, that of miR-221/222 reflected other functions in breast cancer patients. Citation Format: Young JS, Kawaguchi T, Yan L, Qi Q, Liu S, Takabe K. Survival relevance of tamoxifen sensitivity-related microRNAs, miR-342 and miR-221/222, in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-08.

Clinical significance following breast conservation surgery with or without postoperative irradiation in Japanese women with breast cancer.

e11530 Background: Postoperative irradiation or radiotherapy following breast conservation surgery has been reported to be clinically effective in terms of prevention of local breast cancer recurrences. However, it is also true that its local recurrence rate was only 5% to 10%, suggestive of the lack of its clinical benefits in the great majority of the cases. The purpose of this study was to investigate the significance of post-operative radiotherapy in breast conservation surgery by comparing the groups with or without irradiation. Methods: We retrospectively evaluated 1197 Japanese female breast cancer patients (598 irradiation cases and 599 non-irradiation cases). Radiation was administered in a dose of 50 Gy for all conserved breast and additional 10 Gy in those with positive margins or carcinoma within 5mm from surgical margin. We examined the local recurrence rates in those with or without post-operative irradiation according to the status of surgical margin, ER and HER2 in breast cancer tissues. Results: RFS in the irradiated groups were significantly higher than non-irradiated ones in surgical margin positive (P=0.001, HR: 0.334, 95%CI: 0.14-0.79), negative (P=0.015, 0.362, 95%CI: 0.15-0.82), ER positive (P<0.001, HR: 0.249, 95%CI: 0.11-0.54), HER2 negative (P=0.002, HR: 0.316, 95%CI: 0.15-0.65) and non-triple negative patients (P=0.001, HR: 0.382, 95%CI: 0.21-0.69). However, no significant differences were detected between these two groups in ER negative (P=0.288, HR: 0.586, 95%CI: 0.22-1.57), HER2 positive (P=0.969, HR: 0.971, 95%CI: 0.22-4.24) and triple negative (P=0.336, HR: 0.282, 95%CI: 0.02-3.72) patients. Conclusions: Results of our present study could provide clinically inert information as to the selection of the breast cancer patients following conserve surgery.

P4-09-15: Clinical and Pathological Predictors of Outcome among Patients with Triple Negative Breast Cancer.

Abstract Background Triple negative (TN) breast cancer portends a poor prognosis, yet outcomes remain heterogeneous. Specific characteristics of individual TN patients that can predict outcome compared to non-triple negative (NTN) patients have yet to be well defined. Methods: A prospective oncology database at Hackensack University Medical Center was queried for all patients with invasive breast cancer between 2000 and 2005. Patients with triple negative breast cancer were identified and compared to non-triple negative patients. Numerical values were compared by Mann-Whitney test; categorical values by Chi square/Fisher exact test. Log-rank test was used to compare outcome statistics, univariate and multivariate analyses were used to identify factors affecting relapse-free survival and overall survival. Results: A total of 2,216 patients were identified (TN: n=260; NTN: n=1956). There was no difference in race (white vs non-white; TN: 82.3% vs NTN: 87.3%) or family history of breast cancer (TN: 19.2% vs NTN: 16.8%). TN patients were significantly younger (median age; TN: 55.5 vs NTN 57.7; p< .05), had larger tumors (mean cm; TN: 3.1 vs NTN: 2.4; p<.05), had higher grade tumors (% grade 3; TN:74.6 vs NTN: 26.1; p<.0001), had higher proliferation index (>20% nuclei stained for Ki-67; TN: 30.8% vs NTN: 6.7%; p<.0001), but were less likely to have lymph node metastases at presentation (TN: 35.7% vs NTN: 48.0%; p < .0001). Among node negative patients, overall survival (OS) and disease free survival (DFS) were not significantly different between TN and NTN. Among node positive patients, both OS and DFS were worse for TN patients compared to NTN patients (p < .0008). By univariate analysis, age, nodal status, tumor size and tumor grade were all independent predictors of DFS, but proliferation rate and TN status were not. In a multivariate analysis, however, age, TN status, nodal status and tumor size were all significantly associated with DFS. Conclusion: Although TN patients have poor outcomes overall, among node negative patients, TN status does not affect overall nor disease free survival. Among node positive patients, however, TN status has a significant impact on outcome. In this analysis, well established predictors of outcome, including age, tumor size, tumor stage and nodal status were all independent predictors of outcome, but TN status and Ki-67 level were not. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-15.

Neoadjuvant Chemotherapy's Role in Triple Negative Breast Cancer

Neoadjuvant chemotherapy (NC) facilitates breast conservation in women with large tumors, which are common in our inner city breast clinic. We performed this review of our NC breast cancer experience, which includes a disproportionate number of triple negative patients. Patients treated with NC were divided into two groups based on their tumor's receptor status. Patients with tumors negative for estrogen, progesterone, and HER2-neu were considered triple negative (TN) and patients with positive staining for any of these receptors were considered nontriple negative (NTN). Response to NC was considered a complete response (CR) if no residual tumor was detected at surgery, partial response (PR) if the height and width was reduced by at least 50 per cent, and no response (NR) for anything less than a PR. Differences were assessed by χ(2) analysis and Student's t test. We identified 30 patients treated with NC (11 TN and 19 NTN). Twenty-one patients (70%) were African American (11/11 TN and 10/19 NTN; P = 0.01). Age (46.8 ± 6.0 years TN vs 49.5 ± 11.7 years NTN), response rates (18% NR, 55% PR, and 27% CR TN; 37% NR, 42% PR, and 21% CR NTN), and node positivity (64% TN vs 74% NTN) were statistically similar. Two TN (20%) and seven (41%) NTN patients underwent breast conservation therapy. Our results demonstrate the association of African American race and TN breast cancer. TN cancers respond similarly to NC when compared with NTN, allowing for tumor downstaging and possible breast conservation surgery.

Cisplatin–gemcitabine therapy in metastatic breast cancer: Improved outcome in triple negative breast cancer patients compared to non-triple negative patients

Triple negative or basal-like breast cancers lack expression of estrogen, progesterone and HER2 neu receptors. There are no specific treatment guidelines for this group of patients, however, it has been postulated that their phenotypic and molecular similarity to BRCA-1 related cancers would confer sensitivity to certain cytotoxic agents like cisplatin (CDDP). The aim of the study was to retrospectively examine the clinical outcome at our institution of patients with metastatic breast cancer treated with CDDP and gemcitabine combination chemotherapy who had triple negative breast cancer compared to non-triple negative breast cancer. Thirty-six patients with metastatic breast cancer were treated with CDDP and gemcitabine combination chemotherapy, 17 of whom were triple negative (47%) and 19 were non-triple negative (53%). The median progression free survival for triple negative and non-triple negative metastatic breast cancer patients were 5.3 months and 1.7 months respectively ( p = 0.058). By multivariate Cox proportional hazard model after adjusting for age, race and menopausal status the risk of progression was reduced by 47% for triple negative compared to non-triple negative metastatic breast cancer patients (HR = 0.53, p = 0.071). Conclusions Our results suggest an improved outcome for metastatic triple negative breast cancer patients compared to non-triple negative breast cancer patients when treated with cisplatin and gemcitabine combination chemotherapy.

Circulating Tumor Cells (CTCs) and Epithelial Mesenchymal Transition (EMT) in Breast Cancer: Describing the Heterogeneity of Microscopic Disease.

Abstract Background: Circulating tumor cells (CTCs) are an independent predictor of survival in metastatic breast cancer (BC) patients. CTC are readily detected by CellSearch System based on their expression of EpCAM. Epithelial-mesenchymal transition (EMT) gives rise to cells with stem cell-like properties with increased chemotherapy resistance. Human mammary epithelial cells (HMEC) transformed by the EMT transcription factor TWIST1 and spiked into normal peripheral blood (PB) are not detected by EpCAM enrichment based conventional detection methods compared to non-transformed HMECs. We hypothesize that CTCs undergoing EMT and resultant loss of epithelial markers may escape detection by conventional detection methods. The aim of this study was to detect CTCs based on expression of EMT genes in breast cancer patient's peripheral blood.Methods: This prospective ongoing study of breast cancer patients consisted of 16 (57.1%) patients with metastatic disease, 19 (67.9%) patients with inflammatory breast cancer (IBC) and 12 (42.9%) patients with primary, non-IBC breast cancer, respectively. Isolated peripheral blood mononuclear cells (PBMC) were depleted of cells of hematopoietic origin (CD45+) using anti-CD45 coated magnetic beads. RNA extracted from CD45-depleted (CD45-) PBMC were interrogated for expression of TWIST1, SNAIL1, SLUG, ZEB1, FOXC2 and EpCAM gene transcripts by quantitative reverse transcription-PCR. Expressions of gene transcripts in CD45- PBMC from patients were compared to those of CD45- PBMC of healthy donors (HD). Expression of one or more gene transcripts was considered a positive result. Concurrently, a 7.5 mL PB sample was collected for determination of CTC by CellSearch.Results: Median age was 54 year (range: 34-72 years). Overall, the median CTC count by CellSearch was 2 (range; 0-750) per 7.5 mL of PB. TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2 were overexpressed in CD45- PBMC in 7%, 4 %, 4%, 0% and 14 % of patients, respectively. At least one of the EMT genes was overexpressed in 6 (21%) of patients. TWIST1 and SLUG were overexpressed only in IBC patients (10.5% and 5.3% of patients, respectively). Patients with triple negative breast cancer more commonly overexpressed EMT genes compared to non-triple negative patients (30.8% vs. 13.3%). There was no correlation between expression of EMT genes, EpCAM expression or CTC count measured by CellSearch, respectively.Conclusions: These data suggest that EMT genes may be involved in the dissemination of CTCs. Loss of epithelial antigen on CTC due to EMT, triggered by high expression of these genes, may be responsible for their undetection by conventional methods in a fraction of patients with early or advanced breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3011.

Comparison of serum levels of CEA and CA 15–3 in triple-negative breast cancer at the time of metastases and serum levels at the time of first diagnosis

e12017 Background: Cancer antigen 15–3 (CA 15–3) and carcinoembryonic antigen (CEA), are often used in follow up care of breast cancer and provide important clues to the clinicians for disease progression in metastatic and recurrent breast cancer. Triple-negative breast cancers are frequently defined as a single group identifiable using routine clinical tests. They are negative for estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), the so-called triple-negative breast cancers. In this study we compared the tumor markers of triple negative breast cancer and non-triple negative patients. Methods: We retrospectively analyzed serum CEA and CA 15–3 levels of both triple negative and non-triple negative breast cancer patients at the time of first diagnosis and when they developed metastatic disease. Results: 544 consecutive nonmetastatic breast cancer patients presenting at Hacettepe University Institute of Oncology, Ankara, Turkey, with a median age of 49 were evaluated. 15.1% of the patients were triple negative breast cancer. At the time of diagnosis triple negative group had lower serum CEA (2.5 ± 5.9 vs 4.0 ±16.4 p = 0.35) and CA 15–3 (23.7 ± 14.6 vs 37.1 ± 117; p = 0.021) levels compared to non-triple negative group. In patients who developed metastasis during follow up; the CEA (3.2 ± 3.8 vs 29.6 ± 106.4 p = 0.022) and CA15–3 (46.9 ± 46.3 vs 203.2 ± 534 p = 0.008) levels were also significantly lower in triple negative breast cancer group compared to non-triple negative group.In non-triple negative breast cancer patients who developed metastasis, mean serum levels of CEA and CA15–3 significantly increased compared to baseline, whereas in triple negative group who developed metastasis CEA and CA 15–3 levels did not differ significantly. Conclusions: While being a good laboratory parameter in the follow-up of patients with breast cancer metastases, tumor markers may not show the increased tumor burden in the triple-negative breast cancer patients. No significant financial relationships to disclose.

The association of metabolic syndrome with triple-negative breast cancer

1038 Background: Metabolic syndrome, a conglomerate of obesity, insulin resistance, hypertriglyceridemia, low HDL (high density lipoprotein), and hypertension is associated with an increased risk of breast cancer. However, no clear association has been shown between the highly aggressive triple-negative breast cancer and metabolic syndrome. Methods: In a retrospective review we compared triple-negative and non-triple-negative breast cancer cases for the presence of metabolic syndrome by NCEP (National Cholesterol Education Program) or AACE (American Association of Clinical Endocrinologists) definitions. Data on metabolic syndrome criteria, tumor size, grade, lymph node status, and ductal carcinoma in situ (DCIS) were reviewed. Chi-square test or Student's t-test was used for data analysis. Results: The entire cohort of 176 patients (12.5% African-American) with median age 56.5 years (range 26–91 years) comprised of 86 triple-negative cases and 90 non-triple-negative cases. A statistically significant association of triple-negative breast cancer with metabolic syndrome was observed. According to the NCEP criteria 58.1% of triple negative patients had metabolic syndrome as compared to only 36.7% of non-triple negative patients (p = 0.004). Consistently, by the AACE criteria 52.3% of triple negative patients had metabolic syndrome as compared to 34.4% of non-triple negative patients (p = 0.017). Contrary to blood glucose, triglyceride, or HDL levels, which independently showed significant association with triple-negative breast cancer, hypertension, or BMI showed no independent association. Additionally, triple-negative tumors displayed a significantly higher histologic grade and relative paucity of ductal carcinoma in situ (DCIS) when compared to the non-triple negative tumors (p < 0.001). Conclusions: The data suggests that the metabolic syndrome is significantly more prevalent in triple-negative breast cancer patients when compared to the non-triple-negative patients. Additionally, triple-negative breast cancer showed a significantly higher histologic grade and a relative absence of DCIS. Whether the presence of metabolic syndrome preferentially increases the risk of developing triple-negative-breast cancer needs to be elucidated by future prospective studies. No significant financial relationships to disclose.