Clinical-Epidemiological profile of patients with triple-negative breast cancer at instituto Mario Penna, Belo Horizonte, Minas Gerais

Introduction: Triple-negative breast cancer (TNBC) does not express estrogen and progesterone receptors, and does not overexpress the human epidermal growth factor 2. It represents 15%‒20% of breast cancers and have worse prognosis, with scarce available therapies and overall survival (OS) of 18 months. For these particularities, research on TNBC is important for its greater understanding. Objectives: To describe the clinical-epidemiological profile of patients with TNBC at Instituto Mário Penna (IMP). To compare findings with data from the literature. Methods: Consultation of breast immunohistochemistry (IHC) performed at IMP between July/2012 and June/2017. TNBC were selected. Data were collected from patients in electronic medical records. Maximum follow-up until December/2018. Database and statistical analysis using the SPSS program. Bibliographic review used the key phrase: “triple-negative breast cancer”. Results: 1,343 breast IHC performed at IMP in the studied period, 168 were TNBC (12.5%). Mean age of 53.4 years. Mean follow-up of 41.7 months. Neoadjuvant chemotherapy (CT) performed in 46.4%, with 12.8% of complete pathological response. Mean SG of 23.6 months, 20.2% progressed before the end of the treatment. Tumor mean size of 4.04 cm. Mortality of 22%, with 31.5% without information on death in the medical record, and about 17% on average with missing information. Table 1 shows the frequency distribution of the variables evaluated. Discussion: TNBC is a heterogeneous group of diseases, more commonly found in people aged under 40 years, of African descent, diagnosed at an advanced stage and with a high histological grade. Earlier metastasis, preferably visceral. More sensitive to CT, but with worse OS compared to other subtypes. Use of platinum, capecitabine and recent studies with immunotherapy are promising, in the search for better outcomes. Conclusion: The profile of patients with TNBC in IMP is compatible with that described in the literature. This study is a hypothesis generator and the basis for more complex research. High rates of missing information are a limiting factor.

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Prognostic Value of HER2-Low Expression in Non-Metastatic Triple-Negative Breast Cancer and Correlation with Other Biomarkers

Cancers ◽

10.3390/cancers13236059 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6059

Author(s):

William Jacot ◽

Aurélie Maran-Gonzalez ◽

Océane Massol ◽

Charlotte Sorbs ◽

Caroline Mollevi ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Prognostic Value ◽

Triple Negative ◽

Histological Grade ◽

Univariate Analysis ◽

Relapse Free Survival ◽

Free Survival ◽

Few Data

HER2-low breast cancer (i.e., HER 1+ or 2+, without gene amplification) is an emerging subtype for which very few data are available, especially within the triple-negative breast cancer (TNBC) group. Our aim was to evaluate HER2 expression and its prognostic value in a large retrospective series of patients with non-metastatic TNBC (median age: 57.7 years; range: 28.5–98.6). Among the 296 TNBC samples, 83.8% were HER2 0, 13.5% were HER2 1+, and 2.7% were HER2 2+ (HercepTestTM and 2018 ASCO/CAP guidelines for HER2 scoring). CK5/6 and/or EGFR-expressing androgen receptors and FOXA1-expressing tumors were classified as basal-like (63.8%) and molecular apocrine-like (MA, 40.2%), respectively. Compared with HER2 0 tumors, HER2 1+/2+ tumors exhibited a lower histological grade (1/2) (35.4% vs. 18.2%, p = 0.007) and MA profile (57.5% vs. 36.7%, p = 0.008). Moreover, patients with HER2 1+/2+ tumors were older (p = 0.047). After a median follow-up of 9.7 years, HER2 2+ tumors (compared with HER2 0/1+ tumors) were associated with worse relapse-free survival (RFS) (HR = 3.16, 95% CI [1.27; 7.85], p = 0.034) in a univariate analysis. Overall survival (OS) and RFS were not different in the HER2 0 and 1+/2+ groups. HER2 levels were not significantly associated with OS or RFS in a multivariate analysis.

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Current and emerging treatment options in triple-negative breast cancer

Oncology Reviews ◽

10.4081/oncol.2010.5 ◽

2011 ◽

Vol 4 (1) ◽

pp. 5

Author(s):

Omer Dizdar ◽

Kadri Altundag

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Histological Grade ◽

Treatment Options ◽

Growth Factor Receptor ◽

Immunohistochemical Analysis ◽

Endocrine Treatment ◽

Breast Cancers ◽

Chemotherapy Drugs

Triple-negative breast cancer is defined by the lack of estrogen receptor, progesterone receptor and HER2 expression with immunohistochemical analysis. Triplenegative breast cancers are poorly differentiated, characterized by high histological grade and occur at a younger age. Treatment options are limited as these tumors are naturally resistant to existing targeted therapies, i.e., endocrine treatment and trastuzumab. An improved understanding of the biology of TNBC has led to evaluation of DNA-damaging chemotherapy drugs and targeted agents, including poly (ADP-ribose) polymerase inhibitors, epidermal growth factor receptor inhibitors, angiogenesis inhibitors, etc., in the treatment of TNBC. This review focuses on outlining the current and emerging treatment options in patients with triple-negative breast cancer.

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Outcomes of patients with triple-negative breast cancer treated with radiation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.26_suppl.88 ◽

2014 ◽

Vol 32 (26_suppl) ◽

pp. 88-88

Author(s):

Siddhartha Yadav ◽

Maha Saada Jawad ◽

Jessica Wobb ◽

J. Ben Wilkinson ◽

Dhiraj Yadav ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Tumor Stage ◽

Treatment Modalities ◽

Breast Cancers ◽

Breast Irradiation ◽

Radiation Group

88 Background: This study compares outcomes between different types of loco-regional treatment modalities used in patients with triple negative breast cancers. Methods: 299 patients with triple negative breast cancer diagnosed between April 2004 and August 2011 at a single institution and who were treated with radiation therapy were included in an IRB-approved retrospective review. Electronic charts were reviewed for demographic and pathologic data as well as outcome data including locoregional and distant recurrence. The median follow up period was 3 years. 200 (70%) patients underwent lumpectomy with whole breast irradiation (WBI). 68 (22.7%) patients received mastectomy and radiation while 31(10.4%) patients were treated with lumpectomy with accelerated partial breast irradiation (APBI). Results: Forty-nine patients (16.4%) experienced recurrence (10 local; 6 contralateral; 3 regional; 36 distant). There was a significant (p<0.0001) difference in the proportion of patients that experienced a recurrence in each treatment group: 34% (n=23) in mastectomy with radiation group; 12% (n=23) in lumpectomy with WBI group; 10% (n=3) in lumpectomy with APBI group. On univariate analysis, tumor size, tumor stage, nodal stage, overall stage, total number of positive nodes, total number of nodes removed, and whether or not the patients had an axillary lymph node dissection were significantly associated with recurrence (p<0.05). When these predictor variables, including treatment type, were examined using a stepwise cox proportional hazards regression model for recurrence, the only variables that remained significant were tumor stage (p= 0.0003) and the number of positive nodes (p= 0.0008). Survival curves were significantly different (p = 0.016) between the lumpectomy with WBI group and the mastectomy with radiation group. Over all follow-up times, the probability of survival was smallest for the mastectomy with radiation group. Conclusions: The recurrence pattern for triple negative breast cancers treated with radiation therapy was primarily distant for all treatment modalities. In our patient population, tumor stage and number of positive lymph nodes predicted for recurrence while radiotherapy technique did not.

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Treatment patterns and associated adverse events among patients with metastatic triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12576 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12576-e12576 ◽

Cited By ~ 2

Author(s):

Virginia G. Kaklamani ◽

Neil M. Schultz ◽

Debra E. Irwin ◽

Nicole Fulcher ◽

Virginia Noxon ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Average Length ◽

Treatment Patterns ◽

Administrative Claims ◽

Breast Cancers ◽

Treatment Type

e12576 Background: Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancers and about 4% are metastatic (mTNBC) at diagnosis. This research aims to describe treatment patterns and associated adverse events (AEs) among mTNBC patients. Methods: MarketScan Commercial Claims and Encounters and Medicare Supplemental Database, linked to an oncology EMR database, was used to identify patients with mTNBC. Demographic factors, clinical characteristics, mTNBC treatment patterns (treatment type and initial regimen), and the incidence of associated AEs (rates per 100 person-years) were tabulated. Patients seen in oncology practices between January 1, 2011 and June 30, 2015 were included in the study and were required to have continuous enrollment overlap in the administrative claims data for 6 months before the first diagnosis and throughout the variable-length follow-up period. Follow-up ended due to death, end of continuous enrollment, or end of study (whichever occurred earlier). Results: The study identified 163 mTNBC patients with a mean age of 55 years. The average length of follow-up was 569 days and 34% died during the study period. Diabetes mellitus (22%) and anemia (16%) were the most common comorbid conditions at baseline. During the follow-up period, the majority of mTNBC patients received treatment (76%); the most common first-line treatments included cyclophosphamide (60%), paclitaxel (56%), doxorubicin (52%), carboplatin (25%), and docetaxel (23%), averaging 96 days in duration. In 47% of patients, treatment ended due to a switch. Over 96% of the patients experienced at least one AE during treatment, the most common being hematological (neutropenia, leukopenia, and anemia), gastrointestinal (nausea and vomiting), and other (pyrexia, fatigue, and dyspnea) [see table]. Conclusions: Several different chemotherapy agents were used to treat mTNBC. Adverse events were common among mTNBC patients initially treated with chemotherapy; the highest incident AEs were hematological. [Table: see text]

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Androgen receptor and FOXA1 coexpression define a “luminal-AR” subtype of feline mammary carcinomas, spontaneous models of breast cancer

BMC Cancer ◽

10.1186/s12885-019-6483-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Elie Dagher ◽

Violette Royer ◽

Paul Buchet ◽

Jérôme Abadie ◽

Delphine Loussouarn ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancers ◽

Cancer Specific Survival ◽

Ki 67 ◽

Mammary Carcinomas ◽

Definition Of

Abstract Background Invasive mammary carcinomas that spontaneously develop in female cats are associated with high mortality, and resemble the most aggressive human breast cancers, especially triple-negative breast cancer (TNBC). Transcriptome studies showed that TNBCs are a heterogeneous group that includes a potentially hormone-dependent subtype named luminal-AR. Some authors proposed an immunohistochemical definition of the luminal-AR subtype, which is not only positive for Androgen Receptor (AR), but also either positive for the transcription factor Forkhead box A1 (FOXA1), or negative for basal markers. The objectives of this study were to describe AR and FOXA1 expressions in feline mammary carcinomas (FMCs), their prognostic value, and if their coexpression could define a “luminal-AR” subtype of triple-negative mammary carcinomas in cats. Methods In a previously described retrospective cohort of 180 female cats with FMCs, with a 2-year follow-up post-mastectomy, we assessed AR, FOXA1, ER, PR, Ki-67, HER2, and CK14 expressions by automated immunohistochemistry. Results Of the 180 FMCs, 57 (32%) were luminal; i.e., ER and/or PR positive, and 123 (68%) were triple-negative (ER–, PR– and HER2–) FMCs. AR overexpression (found in 33 cases/180, 18%) and FOXA1 index ≥1% (64/180, 36%) were associated with a longer disease-free interval, overall survival, and cancer-specific survival in cats with FMC. Analysis of AR, FOXA1 and CK14 coexpression in triple-negative FMCs showed that AR+ triple-negative FMCs were heterogeneous: there existed an AR+ FOXA1+ CK14– subgroup (n = 7) associated with a better cancer-specific survival by multivariate survival analysis (HR = 0.26, 95% CI: 0.07–0.89, p = 0.03) compared to AR+ FOXA1–CK14+ triple-negative FMCs (n = 46) (HR = 1.00), independently of the pathologic tumor size and pathologic nodal stage. The non-basal-like subtype of triple-negative FMCs that coexpresses AR and FOXA1 (the AR+ FOXA1+ CK14– subgroup) could represent the equivalent of the luminal-AR subgroup of human triple-negative breast cancer. Conclusions We identified an AR+ FOXA1+ CK14– subgroup of triple-negative FMCs that might correspond to the luminal-AR subgroup of human triple-negative breast cancers. Cats with FMC may be interesting spontaneous animal models to investigate new strategies targeting the androgen receptor, especially in the aggressive subtype of AR+ basal-like triple-negative mammary carcinomas with loss of FOXA1 expression (the AR+ FOXA1–CK14+ subgroup).

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Current and emerging treatment options in triple-negative breast cancer

Oncology Reviews ◽

10.4081/oncol.2010.43 ◽

2011 ◽

pp. 5-13

Author(s):

Omer Dizdar ◽

Kadri Altundag

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Histological Grade ◽

Treatment Options ◽

Growth Factor Receptor ◽

Immunohistochemical Analysis ◽

Endocrine Treatment ◽

Breast Cancers ◽

Chemotherapy Drugs

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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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e12017 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e12017-e12017

Author(s):

D. Sener Dede ◽

S. Aksoy ◽

N. Bulut ◽

O. Dizdar ◽

Z. Arik ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Serum Levels ◽

Breast Cancers ◽

Negative Group ◽

Breast Cancer Patients ◽

Serum Cea

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.

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Triple-negative breast cancer in Hong Kong Chinese patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22127 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22127-e22127

Author(s):

J. Tsang ◽

T. L. Lai ◽

D. H. Lau ◽

G. K. Au ◽

D. T. Chua

Keyword(s):

Breast Cancer ◽

Hong Kong ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Hong Kong Chinese ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her 2

e22127 Background: There is increasing data showing that breast cancer is a heterogeneous disease which should be assessed separately in different populations, as it differs substantially between Chinese and Caucasian women. Triple-negative breast tumours which are negative for ER, PR and HER-2 neu receptors are associated with younger age at presentation, tumour of higher grade with larger size and a poorer prognosis. There is recent suggestion that the prognostic outlook of Chinese triple-negative breast cancers might be somewhat different from those in the Western population, but few studies have attempted to understand the role of ethnic factor in the triple-negative entity. Methods: We conducted a preliminary retrospective comparison of 170 Hong Kong Chinese primary breast cancer patients seen as new cases during January 2004 and December 2004 in a teaching hospital. Clinico-pathological features of triple-negative tumours were compared to their non-triple-negative counterpart. Results: Triple negative breast cancer accounted for 12.4% of all breast cancer patients seen in the year of 2004 (n = 21). It is associated with more cancers with grade 3 tumour (68.4% vs 36.8%; p = 0.02) but there was no statistically difference between the age of presentation, tumour size, extensive intraductal component, lymph node status and rate of local relapse or metastasis after adjuvant therapy. Subset analysis further revealed that when triple negative breast cancer patients (n = 21) were compared to the HER-2 positive patients (n = 40) in the studied population, HER-2 positive patients were still associated with higher proportion of node positive disease (57.5% vs 30.0%; p = 0.04). Disease free survival and overall survival were not studied due to limited follow-up time. Conclusions: Our preliminary findings suggested that Hong Kong Chinese triple-negative breast cancers are associated with a more favourable outlook and might behave differently when compared to their Western counterpart. Further large-scale study of the ethnic factor with long-term follow-up is warranted. No significant financial relationships to disclose.

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Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

Chemotherapy Research and Practice ◽

10.1155/2011/696208 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 17

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.

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

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j34608 ◽

2014 ◽

Vol 17 (3) ◽

pp. 439 ◽

Cited By ~ 29

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.

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