A retrospective review of demographics and stage of triple-negative breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11553-e11553
Author(s):  
F. N. Rana
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Smoking Status ◽  
Linear Trend ◽  
Published Data ◽  
Breast Cancers ◽  
Demographic Risk

e11553 Background: Triple negative breast cancer (TNBC) is a recently recognized subtype of breast cancer, notable to metastasize early. It accounts for 15–20% of all breast cancers, and is more prevalent in African-American and Hispanic women, and women younger than 40 years of age. Continual decline in breast cancer deaths since 1990 has been attributed to earlier detection, better treatment including hormonal blockade in estrogen- and progesterone-receptor positive cancers, as well as the addition of Trastuzumab, a monoclonal antibody directed against the Her2/neu receptors. These hormone receptors are not found in TNBC, and therefore the traditional targets for endocrine manipulation cannot be therapeutically exploited. While lower socioeconomic status and racial predisposition to this disease have been observed, there exists a paucity of research into other demographic risk factors. We reviewed data between January 2000 to December 2005 from our tumor registry with particular attention to age, race, family history, tobacco use, and stage of presentation, comparing this subset of patients (n=39) to other records (n=303). We included only those patients in whom the status of all three receptors were recorded. Results: Comparisons were made for TNBC vs non-TNBC patients respectively as follows: mean age (59.87± yrs vs 60.09±yrs). Analysis using χ2 test (χ2=0.855) and CMH test for Linear Trend analysis (p=0.47) showed no difference in percentages in association with the 5 stages or TNBC status and no linear trend respectively. Conclusions: This data suggests that at our institution, TNBC is less prevalent (12.87%) than estimates of 15- 20% published in other studies. There was no difference in age at diagnosis (p=0.92), with black patients more likely to have TNBC (p=0.004, OR=2.75). There was no significant association between smoking status and TNBC (p=0.43). There was no significant association between a family history of cancer and TNBC (p=0.8384). When accounting for samples size, TNBC was as prevalent as non TNBC at all stages of diagnosis. These results differ from other published data and may reflect differences in statistical analysis. No significant financial relationships to disclose.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options

2014 ◽  
Vol 10 (01) ◽  
pp. 35 ◽  
Author(s):  
Bernardo L Rapoport ◽  
Simon Nayler ◽  
Georgia S Demetriou ◽  
Shun D Moodley ◽  
Carol A Benn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Treatment Options ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Breast Cancers ◽  
Metastatic Setting

Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumours, both clinically and pathologically. These cancers are characterised by the lack of expression of the hormone receptors oestrogen receptor (OR) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2 (HER2) gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomised trials. Numerous studies have now shown that TNBC has significantly higher pathological complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathological diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant and metastatic setting, including an assessment of future directions of treatment.

scholarly journals Molecular Prognostic and Predictive Markers in Triple - Negative Breast Cancer

2021 ◽  
Author(s):  
Marketa Koleckova ◽  
Katherine Vomackova ◽  
Zdenek Kolar
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Menopausal Status ◽  
Breast Cancers ◽  
Biological Behaviour ◽  
Erbb2 Protein ◽  
Apoptosis Gene

Triple-negative breast cancer (TNBC) is defined as a molecular subtype of breast cancer that lacks expression of hormone receptors (oestrogen and progesterone receptor) and HER2/neu/ErbB2 protein. It accounts for 15–20% of all invasive breast cancers. The occurrence of TNBC is often associated with younger age at the time of diagnosis and pre-menopausal status, early onset of menarche, higher body mass index (BMI) in the pre-menopausal period, race and ethnicity (African, Hispanic) and the presence of germline mutation in the BRCA1/2 genes or somatic mutation in the TP53 or PTEN genes. TNBCs are specific in its aggressive biological behaviour, shorter interval to disease progression and more frequent relapse within five years (19 to 40 months). The most of TNBCs are represented by high-grade invasive carcinomas of no special type (NST) with high proliferation index measured by Ki-67 nuclear expression, followed by metaplastic carcinomas, secretory carcinomas, and adenoid cystic carcinomas. Genetical and morphological heterogeneity inside TNBC is responsible for the higher frequency of primary and secondary resistance to systemic therapy. The scope of this chapter is to summarise the potential therapeutic agents involved in regulation of cell proliferation, migration, angiogenesis, apoptosis, gene expression and DNA damage or immune response. The insight into this issue is essential for the setting of the optimal chemotherapy regimen and targeted therapeutic strategy.

Family history and breast cancer subtype among women of Mexican descent.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 41-41
Author(s):  
Kristin Anderson ◽  
Patricia Thompson ◽  
Betsy Wertheim ◽  
Lorena Martin ◽  
Ian K. Komenaka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mexican Descent ◽  
Breast Cancers ◽  
Tumor Subtype ◽  
Degree Relative ◽  
History Of ◽  
Second Degree

41 Background: A family history of breast cancer in a first-degree relative is associated with a 2-fold increase in breast cancer risk; however, breast cancer is a heterogeneous disease and there may be differences in risk profiles driven by tumor subtype or by racial/ethnic group. Methods: We assessed prevalence of familial breast cancer and its association with tumor subtype among 914 women with breast cancer of Mexican descent enrolled in the Ella Study, a case-only, binational (U.S.-Mexico) breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancers to non triple-negative breast cancers according to family history. Results: The prevalence of family history of breast cancer in a first- or second-degree relative was 24.1%, with 13.1% having an affected first-degree relative. Among participants who were diagnosed at age < 50, prevalence of family history of breast cancer in a first- or second-degree relative was 27.4%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were significantly more likely to be diagnosed with triple-negative breast cancers compared to non triple-negative breast cancers (OR = 1.98; 95% CI, 1.26-3.11). Similar results were seen for odds of triple-negative breast cancers compared to non-triple negative breast cancers for women with affected first- or second-degree relatives (OR=2.04; 95% CI, 1.40–2.98). The odds of triple-negative breast cancer compared to non-triple negative breast cancer was 1.93 (95% CI, 1.26–2.97) for women with first-degree relatives affected with breast or ovarian cancer. Conclusions: Findings suggest that familial cancers are most likely to be associated with triple negative subtype, supporting etiologic heterogeneity by tumor subtype in this population of Hispanic women. This association may be related to the prevalence of BRCA1 founder mutations in this population, which are strongly associated with triple-negative breast cancers. Identification of such differences in risk factors can help personalize screening and prevention approaches.

scholarly journals IMMEDIATE AND LONG-TERM OUTCOMES OF DRUG TREATMENT IN PATIENTS WITH METASTATIC TRIPLE NEGATIVE BREAST CANCER

2018 ◽  
Vol 8 (3) ◽  
pp. 68-77
Author(s):  
O. V. Smirmova ◽  
V. I. Borisov ◽  
G. P. Guens
Keyword(s):  
Breast Cancer ◽  
Drug Treatment ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Clinical Feature ◽  
Breast Cancers ◽  
Long Term Outcomes ◽  
Modest Improvement

Triple-negative breast cancer (TNBC) comprises 12–20 % of all breast cancers. TNBC is defined by the absence of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC is a heterogeneous disease, with an aggressive clinical feature, a higher risk of both local and distant visceral and / or brain metastases. Recurrence usually develops between 1 and 3 years after the initial diagnosis and most deaths occur within 5 years. Epidemiologic studies illustrate a high prevalence of triple-negative breast cancers among young women. Triple-negative breast cancer is also more likely to occur in women that carry a BRCA mutation, especially if they are diagnosed at a young age. Cytotoxic chemotherapy remains the mainstay treatment for TNBC because there are currently no specific targets for treatment options (hormone receptors or HER-2 amplification). Chemotherapy combined with targeted agents including DNA repair with PARP inhibitors, EGFR inhibitors, anti-angiogenic agents and a Chk1 inhibitor produced modest improvement in response rate and overall survival. Nevertheless there’s no common standards for treatment such patients with metastatic TNBC. Progress in the development of new regimens and combination of drug treatment agents for patient with generalized TNBC remains an important challenge that could lead to improvement immediate and long-term outcomes.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

scholarly journals Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ayca Gucalp ◽  
Tiffany A. Traina
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Cytotoxic Chemotherapy ◽  
Breast Cancers ◽  
Targeted Agents ◽  
Increased Risk ◽  
Disproportionate Number

Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

scholarly journals Use of Proton Pump Inhibitors as Adjunct Treatment for Triple-Negative Breast Cancers. An Introductory Study

2014 ◽  
Vol 17 (3) ◽  
pp. 439 ◽  
Author(s):  
Wayne Goh ◽  
Inna Sleptsova-Freidrich ◽  
Nenad Petrovic
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Proton Pump ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Gastric Type ◽  
Dose Dependent

PURPOSE: Triple negative breast cancers (estrogen, progesterone and human epidermal growth factor 2 (HER2) receptor-negative) are among the most aggressive forms of cancers with limited treatment options. Doxorubicin is one of the agents found in many of the current cancer treatment protocols, although its use is limited by dose-dependent cardiotoxicity. This work investigates one of the ways to suppress cancer growth by inhibiting tumor cell ability to remove acid accumulated during its metabolism by proton pump inhibitor esomeprazole (a drug with extensive clinical use) which could serve as an addition to doxorubicin therapy. METHODS: In this work, we have investigated growth suppression of triple-negative breast cancer cells MDA-MB-468 by esomeprazole and doxorubicin by trypan blue exclusion assay. Measurement of acidification of treated cancer cells was performed using intracellular pH-sensitive probe, BCECF-AM. Finally, expression of gastric type proton pump (H+/K+ ATPase, a target for esomeprazole) on MDA-MB-468 cells was detected by immunofluorescence and Western blotting. RESULTS: We have found that esomeprazole suppresses growth of triple-negative breast cancer cell in vitro in a dose-dependent manner through increase in their intracellular acidification. In contrast, esomeprazole did not have significant effect on non-cancerous breast epithelial MCF-10A cells. Esomeprazole increases doxorubicin effects suggesting that dual treatments might be possible. In addition, response of MDA-MB-468 cells to esomeprazole could be mediated by gastric type proton pump (H+/K+ ATPase) in cancer cells contrary to previous beliefs that this proton pump expression is restricted to parietal cells of the stomach epithelia. CONCLUSION: This study provides first evidence that adjunct use of esomeprazole in breast cancer treatment might be a possible to combat adverse effects of doxorubicin and increase its effectiveness. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Patient Derived Xenograft

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

scholarly journals Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5009
Author(s):  
Swetha Vasudevan ◽  
Ibukun A. Adejumobi ◽  
Heba Alkhatib ◽  
Sangita Roy Chowdhury ◽  
Shira Stefansky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Patient Specific ◽  
Network Structures ◽  
Breast Cancers ◽  
Drug Induced ◽  
Tcga Dataset

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1–4 altered protein–protein subnetworks. Thirty-one percent of TNBC PaSSSs were found to harbor EGFR as a part of the network and were predicted to benefit from anti-EGFR therapy as long as it is combined with anti-estrogen receptor (ER) therapy. Using a series of single-cell experiments, followed by in vivo support, we show that drug combinations which are not tailored accurately to each PaSSS may generate evolutionary pressure in malignancies leading to an expansion of the previously undetected or untargeted subpopulations, such as ER+ populations. This corresponds to the PaSSS-based predictions suggesting to incorporate anti-ER drugs in certain anti-TNBC treatments. These findings highlight the need to tailor anti-TNBC targeted therapy to each PaSSS to prevent diverse evolutions of TNBC tumors and drug resistance development.

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