Anti-MUC1 Antibody in Nipple Aspirate Fluids Correlates with Tumor Aggressiveness in Breast Cancer: A Feasibility Study

Antibodies against MUC1 are found in circulation of breast cancer (BC) patients. We hypothesized that anti-MUC1 antibodies might be present in even a higher concentration in nipple aspirate fluid (NAF) and could be used to predict aggressiveness of BC. Serum and NAF samples were collected from high risk lesions, BC, and healthy contralateral breasts. ELISA was used to measure the amount of IgG, IgM, and IgA against a tumor-specific MUC1 peptide derived from the extracellular tandem repeat domain of MUC1. Tumor characteristics were recorded prospectively; 120 NAF samples were obtained from a total of 77 women in the study. There was no significant difference of anti-MUC1 antibody levels compared to BC with other lesions. Anti-MUC1 IgG level in NAF was higher in triple negative tumors (P=0.02); serum anti-MUC1 IgG levels were significantly higher in patients with ER (−) tumor and recurrent disease (P=0.01); NAF anti-MUC1 IgA levels were significantly higher in patients with LVI and Her2-neu (+) tumors (P<0.05). These results show that NAF could be a reliable biomarker to predict tumor aggressiveness in BC. A larger study will be needed to confirm these data and to investigate the potential of anti-MUC1 antibodies in NAF and serum to predict disease outcome.

Download Full-text

Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

Tumori Journal ◽

10.1177/03008916211012341 ◽

2021 ◽

Vol 107 (1_suppl) ◽

pp. 12-12

Author(s):

D Aissaoui ◽

M Bohli ◽

R Ben Amor ◽

J Yahyaoui ◽

A Hamdoun ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Response ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Molecular Subtypes ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

Download Full-text

TBC1D9: An Important Modulator of Tumorigenesis in Breast Cancer

Cancers ◽

10.3390/cancers13143557 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3557

Author(s):

Charu Kothari ◽

Alisson Clemenceau ◽

Geneviève Ouellette ◽

Kaoutar Ennour-Idrissi ◽

Annick Michaud ◽

...

Keyword(s):

Breast Cancer ◽

Effective Treatment ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Study Analysis ◽

Tumor Aggressiveness ◽

Domain Family ◽

Proliferative Index ◽

Tumorigenic Potential ◽

The Difference

Triple-negative breast cancer (TNBC) is a major concern among the different subtypes of breast cancer (BC) due to the lack of effective treatment. In a previous study by our group aimed at understanding the difference between TNBC and non-TNBC tumors, we identified the gene TBC1 domain family member 9 (TBC1D9), the expression of which was lower in TNBC as compared to non-TNBC tumors. In the present study, analysis of TBC1D9 expression in TNBC (n = 58) and non-TNBC (n = 25) patient tumor samples validated that TBC1D9 expression can differentiate TNBC (low) from non-TNBC (high) samples and that expression of TBC1D9 was inversely correlated with grade and proliferative index. Moreover, we found that downregulation of the TBC1D9 gene decreases the proliferation marginally in non-TNBC and was associated with increased migratory and tumorigenic potential in both TNBC and luminal BC cell lines. This increase was mediated by the upregulation of ARL8A, ARL8B, PLK1, HIF1α, STAT3, and SPP1 expression in TBC1D9 knockdown cells. Our results suggest that TBC1D9 expression might limit tumor aggressiveness and that it has a differential expression in TNBC vs. non-TNBC tumors.

Download Full-text

Triple negative breast cancer and age: Tumor characteristics and outcomes

Journal of Geriatric Oncology ◽

10.1016/j.jgo.2013.09.013 ◽

2013 ◽

Vol 4 ◽

pp. S28

Author(s):

L. Loftus ◽

G. Sokol ◽

R. Ismail-Khan

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Tumor Characteristics

Download Full-text

PD-L1 expression and TOP3A mutation as prognostic factors for adjuvant chemotherapy in triple negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.541 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 541-541

Author(s):

Xue Wang ◽

Peng Yuan ◽

Feng Du ◽

Lina Cui ◽

Fangchao Zheng ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Disease Free Survival ◽

Genetic Alterations ◽

Functional Enrichment ◽

Pathway Enrichment Analysis ◽

Genetic Characteristics ◽

Significant Difference

541 Background: Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is markedly heterogeneous and lacks specific targets. The aim of this study is to explore potential predictors and therapeutic targets based on clinical and genetic characteristics. Methods: 138 patients with triple-negative breast cancer after surgical treatment were 1:1 randomly assigned to the paclitaxel combined with carboplatin (TCb) group or the epirubicin combined with cyclophosphamide sequential paclitaxel (EC-T) adjuvant chemotherapy group. PD-L1 was retrospectively analyzed by surgically resected specimens, and 733 cancer-related genes were detected by NGS. Pathway enrichment analysis was performed using DAVID for functional enrichment genetic alterations. Cox regression models and Kaplan-Meier were used to evaluate disease-free survival (DFS). Results: In this study, there was no significant difference in DFS between the TCb and EC-T groups. 31 (22.5%) of 138 TNBC patients were positive for PD-L1 expression, including 15 (10.9%) patients positive for PD-L1 in tumor cells (TCs) and 29 (21.0%) patients positive for PD-L1 in tumor-infiltrating immune cells (TICs). Patients with positive PD-L1 expression, either in TCs or TICs, achieved better DFS [HR=0.13 (95% CI: 0.02-0.93), p=0.016], the difference was also shown in the EC-T group [HR=0 (95% CI: 0- inf), p=0.037], but not in the TCb group [HR=0 (95% CI: 0.04-2.1), p=0.189]. In addition, we identified 7 patients with mutations in DNA topoisomerase IIIα(TOP3A), a homologous recombination (HR)-related gene, and patients with mutations in this gene had worse DFS than those without mutations [HR=4]. However, there was no statistically significant association between BRCA mutation and response to either therapeutic regimens. Conclusions: In this TNBC patient population, immunohistochemistry (IHC) and NGS analyses identified potential prognostic markers. PD-L1 positive and TOP3A mutation were significantly associated with early triple-negative breast cancer prognosis.

Download Full-text

Prevalence of germline testing criteria in breast cancer patients in the Brazilian public health system: A retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10597 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10597-10597

Author(s):

Robson dos Santos dos Santos Borges ◽

Laisa Gabrielle Silva ◽

Mariana do Nascimento Vilaca ◽

Alexandre Ribas De Carvalho ◽

João Paulo Solar Vasconcelos ◽

...

Keyword(s):

Public Health ◽

Breast Cancer ◽

Overall Survival ◽

Health System ◽

Triple Negative ◽

Public Health System ◽

Significant Difference ◽

Epidemiological Characteristics ◽

Germline Testing ◽

Testing Criteria

10597 Background: Identification of a germline mutation in a breast cancer predisposition gene has implications for the patients and their families. The National Comprehensive Cancer Network (NCCN) has published guidelines for genetic testing. In Brazil, this assessment is covered by health insurance in accordance with criteria defined by the National Supplementary Health Agency (ANS). For the majority of the population, served by the public health system (SUS), the assessment is not routinely available. Methods: In order to determine the prevalence rates of NCCN and ANS criteria for germline testing in breast cancer (primary outcome) we retrospectively analyzed data from patients treated at two SUS oncology centers in Belo Horizonte, Minas Gerais, Brazil, between 01/01/18 and 12/31/19. The secondary outcomes were comparisons between the groups with and without germline testing criteria (NCCN and ANS) regarding overall survival, clinical and epidemiological characteristics. The association between qualitative variables was calculated using the Chi-square and Fisher tests. The Kaplan-Meier method was used to analyse the survival data and the differences between the groups were tested using the log-rank test. The level of significance was 5%. Results: A total of 357 patients were included in the final analysis. The presence of germline testing criteria were found in 126 patients (35%) according to NCCN guidelines and in 82 patients (23%) according to ANS guidelines. None of them were tested for germline mutations. The most common criteria were women up to 60 years old with triple negative tumors (n = 43, 12% of all patients) and diagnosis of cancer up to 45 years old (n = 75, 21% of all patients) according to ANS and NCCN criteria, respectively. When the group of patients who met at least one criterion for germline testing were compared with the group who did not met any criteria, we found in the first group: more ductal carcinomas and less lobular tumors (p = 0.009), more grade 3 tumors (p = 0.002), more triple negative tumors (p < 0.001), more neoadjuvant treatments (p = 0.008) and less hormonal therapies (p = 0.011). After a median follow up of 13.5 months there were 22 deaths in the cohort, 7 in the group with testing criteria (5.7%) and 15 in the group without testing criteria (6.4%). There was no statistical significant difference between the groups in terms of overall survival (p = 0.77). Conclusions: To our knowledge this is the first study to evaluate the prevalence of NCCN and ANS criteria for germline testing in patients with breast cancer treated in the Brazilian public health system. Our results show that more than a third of those patients are candidates for germline testing. Moreover, the data highlight a serious shortcoming in the management of breast cancer and must be considered in the development of public health policies for routine germline testing in that population.

Download Full-text

Expression of Transgelin in Triple Negative and Non Triple Negative Breast Cancer: A Differential Study

Tumori Journal ◽

10.1177/0300891620914150 ◽

2020 ◽

Vol 106 (1_suppl) ◽

pp. 20-20

Author(s):

NS Tolba ◽

AS Alsedfy ◽

SW Skandar ◽

YM El-Kerm

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

High Rate ◽

Targeted Treatment ◽

Her2 Status ◽

Altered Expression ◽

Wide Range ◽

Significant Difference

Introduction: Triple negative breast cancer (TNBC) is defined by the absence of ER expression, PR expression and HER2 amplification. No targeted treatment is available for TNBC and chemotherapy remains the best therapeutic option. However, in the case of recurrence or chemo-resistance, therapeutic options are very limited. TNBC presents a high rate of proliferation and is highly aggressive having low survival rate. As the complexity of this disease is being simplified over time, new targets are also being discovered for the treatment of this disease. Therefore, there is still need for new biomarkers, which would serve for targeted treatment. Transgelin was proposed as a new potential cancer biomarker. Altered expression of Transgelin has been described in a wide range of cancers, often with contradictory results. The aim of the study was to compare Transgelin expression across molecular subtypes of breast cancer, to identify if it can be used as a future molecular targeted protein for TNBC. Material and Methods: Transgelin immunohistochemistry was applied on 60 retrospectively collected paraffin blocks of patients presenting with invasive breast carcinoma (NST) having different molecular subtypes. Blocks were collected between 2015 and 2016 from Pathology department, Medical Research Institute, Egypt. Her2 equivocal cases were excluded from the study. Results: Transgelin expression was positive in 23 cases and negative in 37 cases. There was a statistically significant difference between (Transgelin +) and (Transgelin -) cases being highly expressed in TNBC in comparison to other molecular subtypes. It was also highly expressed in tumors with large size, high grade, positive lymph-vascular invasion status & lymph node metastasis. There was no statistically significant difference between (Transgelin+) and (Transgelin-) as regards age and Her2 status. Conclusions: Transgelin is an aggressive biomarker differentially expressed among the molecular breast cancer subtypes with high expression in TNBC. Transgelin may provide a potential target for future treatment of TNBC.

Download Full-text

Clinicopathological, Treatment and Event-Free Survival Characteristics in a Moroccan Population of Triple-Negative Breast Cancer

Breast Cancer Basic and Clinical Research ◽

10.1177/1178223420906428 ◽

2020 ◽

Vol 14 ◽

pp. 117822342090642

Author(s):

Fatima Zahra Mouh ◽

Meriem Slaoui ◽

Rachid Razine ◽

Mohammed EL Mzibri ◽

Mariam Amrani

Keyword(s):

Breast Cancer ◽

Retrospective Study ◽

Survival Rate ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Menopausal Status ◽

Age At Menarche ◽

Event Free Survival ◽

Free Survival ◽

Significant Difference

Introduction: Triple-negative breast cancer (TNBC) is a group of breast carcinoma characterized by the lack of expression of estrogen and progesterone hormone receptors (ER, PgR) and HER2. This form is also characterized by its aggressiveness, a low survival rate, and the absence of targeted therapies. This study was planned to evaluate the clinical features, treatment, and prognosis characteristics of TNBC in a population of Moroccan patients. Methods: In this retrospective study, a total of 905 patients diagnosed with breast cancer at the National Institute of Oncology in Rabat, Morocco, have been included. Based on molecular subtype, patients were divided into 2 categories: TNBC and non-TNBC patients. Data were recorded from patients’ medical files and analyzed using SPSS 13.0 software (IBM). Results: Overall, 17% of the patients had TNBC. At diagnosis, the median age of TNBC cases was 47 years, with extreme ages of 40 and 55 years. The median follow-up time was 30 months (10-53 months) and the 3-year survival rate was 76%. No significant difference was observed among the patients in terms of age at diagnosis, age at menarche, age at the time of first birth, nulliparity, oral contraception, and family history of breast cancer. Menopausal status and the number of pregnancy were significantly higher in the non-TNBC group. The percentage of grade 3 (G3) tumors was higher in the TNBC group ( P < .001). Using neoadjuvant, adjuvant chemotherapy and radiotherapy, a net benefit in the event-free survival was registered for the 2 groups. Conclusions: This retrospective study was very informative and showed that women with TNBC had a less favorable prognosis than non-TNBC cases. Clinical data demonstrated that risk factors including age, premenopausal status, parity, hormonal contraceptive use, advanced disease, and a high histologic grade were independently associated with TNBC. However, large tumors and high Scarff-Bloom and Richardson grade prevail in TNBC cases with a higher incidence of lymph node metastases.

Download Full-text

Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.5664 ◽

2006 ◽

Vol 24 (36) ◽

pp. 5652-5657 ◽

Cited By ~ 671

Author(s):

Bruce G. Haffty ◽

Qifeng Yang ◽

Michael Reiss ◽

Thomas Kearney ◽

Susan A. Higgins ◽

...

Keyword(s):

Breast Cancer ◽

Distant Metastasis ◽

Triple Negative ◽

Early Stage ◽

Prognostic Significance ◽

Conservative Surgery ◽

Hazard Ratio ◽

Breast Cancer Patients ◽

Locoregional Relapse ◽

Significant Difference

Purpose To determine the prognostic significance of triple negative breast cancers with respect to locoregional relapse and distant metastasis in conservatively managed breast cancer patients. Patients and Methods A database of conservative managed (conservative surgery followed by radiation) patients, in whom all three markers (estrogen receptor, progesterone receptor, and HER2/neu) were available, was reviewed. Patients were classified as triple negative if they tested negative for all three markers. Of 482 patients with all three markers available, 117 were classified as triple negative. Results As of September 2005, with a median follow-up time of 7.9 years, of the 482 patients in the study, there have been 53 in-breast relapses, 10 nodal relapses, 77 distant relapses, and 69 deaths. At 5 years, the triple negative cohort had a poorer distant metastasis-free rate compared with the other subtypes (67% v 82%, respectively; P = .002). Triple negative subtype was an independent predictor of distant metastasis (hazard ratio = 2.14; 95% CI, 1.31 to 3.53; P = .002) and cause-specific survival (hazard ratio = 1.79; 95% CI, 1.03 to 3.22; P = .047). There was no significant difference in local control between the triple negative and other subtypes (83% v 83%, respectively). Of 99 BRCA-tested patients in this cohort, 10 had deleterious mutations in BRCA1, and seven had mutations in BRCA2. Of 10 BRCA1 patients, eight were triple negative, whereas only one of seven BRCA2 patients was triple negative (P < .001). Conclusion Patients classified as triple negative have a poor prognosis. However, there was no evidence that these patients are at higher risk for local relapse after conservative surgery and radiation. Patients with BRCA1 mutations develop predominantly triple negative tumors.

Download Full-text

Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.808 ◽

2019 ◽

Vol 7 (21) ◽

pp. 3534-3539

Author(s):

Nada A. S. Alwan ◽

Furat N. Tawfeeq

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtype ◽

Clinical Stage ◽

Lymph Node Involvement ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Cancer Subtypes ◽

Significant Difference

BACKGROUND: Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour. AIM: To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions. PATIENTS AND METHODS: The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes. RESULTS: The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement. CONCLUSION: The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

Download Full-text