Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes

AimsGATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases.MethodsImmunohistochemical staining of GATA3, GCDFP15 and mammaglobin was performed in a cohort of 1637 cases of primary invasive breast carcinoma. The association of GATA3 expression with different histological and surrogate intrinsic subtypes was assessed and compared with the expression of GCDFP15 and mammaglobin.ResultsThe overall positivity of GATA3 across the various immunohistochemistry-based surrogate intrinsic subtypes was 99.51% for luminal A-like, 97.70% for luminal B-like, 68.50% for HER2 overexpression and 20.16% for triple negative breast cancers. GATA3 expression was positively correlated with estrogen receptor (ER)-positive (luminal subtypes) breast carcinomas. For luminal-like and HER2 overexpression subtypes, GATA3 was much more sensitive than GCDFP15 and mammaglobin. For triple negative tumours, GATA3 was less sensitive than GCDFP15.ConclusionsGATA3 exhibits a relatively high sensitivity for breast carcinomas. It is more sensitive than GCDFP15 and mammaglobin in luminal-like and HER2 overexpression subtypes. GATA3 expression is associated with breast carcinomas of luminal subtype and low histological grade.

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Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-203786 ◽

2016 ◽

Vol 70 (1) ◽

pp. 25-32 ◽

Cited By ~ 1

Author(s):

Carla Thomas ◽

Cleo Robinson ◽

Ben Dessauvagie ◽

Benjamin Wood ◽

Greg Sterrett ◽

...

Keyword(s):

Gene Expression ◽

Breast Carcinoma ◽

Expression Profiling ◽

Proliferative Activity ◽

Breast Cancers ◽

Breast Carcinomas ◽

Ki 67 ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Formalin Fixed

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.

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Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

International Journal of Cancer Research and Molecular Mechanisms ◽

10.16966/2381-3318.148 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Duman BB ◽

Cil T

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Maintenance Therapy ◽

Hormone Receptor ◽

Tumor Heterogeneity ◽

Hormone Receptors ◽

Triple Negative ◽

Neoadjuvant Treatment ◽

Metastatic Breast ◽

Her2 Overexpression

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.

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Epigenetic Regulation of Immunotherapy Response in Triple-Negative Breast Cancer

Cancers ◽

10.3390/cancers13164139 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4139

Author(s):

Pere Llinàs-Arias ◽

Sandra Íñiguez-Muñoz ◽

Kelly McCann ◽

Leonie Voorwerk ◽

Javier I. J. Orozco ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Immune Escape ◽

Checkpoint Inhibitors ◽

Early Stage ◽

Regulatory Elements ◽

Her2 Overexpression ◽

Breast Cancers ◽

Cancer Subtypes

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor and progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression. This malignancy, representing 15–20% of breast cancers, is a clinical challenge due to the lack of targeted treatments, higher intrinsic aggressiveness, and worse outcomes than other breast cancer subtypes. Immune checkpoint inhibitors have shown promising efficacy for early-stage and advanced TNBC, but this seems limited to a subgroup of patients. Understanding the underlying mechanisms that determine immunotherapy efficiency is essential to identifying which TNBC patients will respond to immunotherapy-based treatments and help to develop new therapeutic strategies. Emerging evidence supports that epigenetic alterations, including aberrant chromatin architecture conformation and the modulation of gene regulatory elements, are critical mechanisms for immune escape. These alterations are particularly interesting since they can be reverted through the inhibition of epigenetic regulators. For that reason, several recent studies suggest that the combination of epigenetic drugs and immunotherapeutic agents can boost anticancer immune responses. In this review, we focused on the contribution of epigenetics to the crosstalk between immune and cancer cells, its relevance on immunotherapy response in TNBC, and the potential benefits of combined treatments.

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Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance

Clinical Medicine Insights Pathology ◽

10.4137/cpath.s31563 ◽

2015 ◽

Vol 8 ◽

pp. CPath.S31563 ◽

Cited By ~ 72

Author(s):

Jaafar Makki

Keyword(s):

Gene Expression ◽

Breast Carcinoma ◽

Clinical Course ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Molecular Classification ◽

Developed Countries ◽

Breast Cancers ◽

Wide Scope ◽

Histological Subtypes

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality, with an incidence of ≥1,000,000 cases occurring worldwide annually. It is one of the most common human neoplasms, accounting for approximately one-quarter of all cancers in females worldwide and 27% of cancers in developed countries with a Western lifestyle. They exhibit a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. Breast cancers can be classified into distinct subgroups based on similarities in the gene expression profiles and molecular classification.

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HER-2/neu expression in ovarian clear cell carcinomas

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200301000-00005 ◽

2003 ◽

Vol 13 (1) ◽

pp. 28-31 ◽

Cited By ~ 1

Author(s):

H. Iwamoto ◽

H. Fukasawa ◽

T. Honda ◽

S. Hirata ◽

K. Hoshi

Keyword(s):

Breast Carcinoma ◽

Cell Carcinoma ◽

San Francisco ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Metastatic Breast ◽

Breast Carcinomas ◽

Ovarian Clear Cell Carcinoma ◽

Clinical Prognosis ◽

Her 2

HER-2 /neu is a 185-kDa glycoprotein and a transmembrane receptor with tyrosine kinase activity. Its overexpression is observed in 25–30% of primary breast carcinomas and is associated with a poor clinical prognosis. Recently, the U.S. Food and Drug Administration and the Japanese Ministry of Health, Welfare, and Labor approved the use of trastuzumab (Herceptin, Genentech, South San Francisco, CA) for the treatment of patients with metastatic breast carcinomas overexpressing HER-2 /neu. Results of clinical trials with Herceptin suggest that it may prolong the survival of patients with advanced metastatic breast carcinoma. Relatively little is known concerning the relationship between HER-2 /neu status and ovarian clear cell carcinoma. If HER-2 /neu overexpression status were demonstrable in ovarian clear cell carcinoma and a clinical correlation between overexpression and prognosis could be established, a rationale for clinical use of Herceptin for this tumor could be established. Our aim was to evaluate HER-2 /neu status in ovarian clear cell carcinomas. Fifteen ovarian clear cell carcinoma cases were immunostained for HER-2 /neu using HercepTest (DAKO, Glostrup, Denmark). Overexpression of HER-2 /neu was detected in only one case. Unlike in breast carcinoma, HER-2 /neu overexpression appeared to be uncommon in ovarian clear cell carcinomas. Herceptin may thus target only a small proportion of ovarian clear cell carcinomas and be of limited clinical value for treatment of this carcinoma.

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The financial impact of trastuzumab in metastatic breast cancer: The experience of the Institut Curie

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.663 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 663-663

Author(s):

M. A. Doz ◽

C. D. Le Tourneau ◽

M. S. Guilhaume ◽

V. Dieras ◽

A. Vincent-Salomon ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Single Agent ◽

Metastatic Breast ◽

Financial Impact ◽

Her2 Overexpression ◽

Breast Cancers ◽

Financing System ◽

High Level ◽

The Cost

663 Purpose: To estimate, in term of public health on the scale of a region, the cost of trastuzumab and to point out the financial impact of this new targeted therapy in the adjuvant setting. Methods: To understand the consequences of the spending on of trastuzumab at a macroeconomic level in the French hospital financing system, we decided to focus on an establishment in particular, and to analyze the increasing spending of trastuzumab at a micro-economic level, to provide a cost analysis of patients treated with trastuzumab for HER2-overexpressing metastatic breast cancer. We retrospectively reviewed 137 medical reports of patients who received trastuzumab either in combination with chemotherapy or as a single agent and in maintenance therapy. Median age of the patients was 52 years (range 32- to 79+). Eighty five percent had 3+ HER2 overexpression and fifteen percent had 2+ HER2 (FISH amplified). Results: Median survival from first treatment with trastuzumab was 38.5 months (range 0,04–53,06+). The cost of the first year treatment is in average €43,435.58 per patient, for the second year €36,419.01 and for the third year €37,198.94. Drugs cost represents 78% of the hospital stays cost for a patient and 2.9% of the budget of Institut Curie. Conclusions: This retrospective analysis showed the very high level of expenses of trastuzumab to treat metastatic breast cancers. With the adjuvant use of trastuzumab, it is expected that these expenses are going to increase exponentially. No significant financial relationships to disclose.

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Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers?

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.580 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 580-580 ◽

Cited By ~ 8

Author(s):

T. Petit ◽

M. Wilt ◽

J. Rodier ◽

D. Muller ◽

J. Ghnassia ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative ◽

Pathological Complete Response ◽

Complete Response ◽

Her2 Overexpression ◽

Breast Cancers ◽

Platinum Compounds ◽

Response To Chemotherapy ◽

Chemotherapy Efficacy

580 Background: BRCA1 being involved in DNA repair and apoptosis, its mutations may influence response to chemotherapy. In vitro studies demonstrated that loss of BRCA1 function increased sensitivity to platinum compounds and induced resistance to anthracyclines. BRCA1-related breast cancers tend to be ductal carcinomas with high tumor grade, absence of hormonal receptors and no HER2 overexpression, so called triple-negative. We retrospectively analyzed anthracycline-based neoadjuvant chemotherapy efficacy in triple- negative tumors according to BRCA1 status. Methods: 393 breast cancer pts were treated with FEC100 neoadjuvant chemotherapy (FU 500 mg/m2, epirubicine 100 mg/m2, cyclophosphamide 500 mg/m2) between 1/2000 and 12/2006. Out of them, 14% had a triple-negative phenotype (55 pts). Patients with young age at diagnosis or family history of breast cancer were offered genetic testing for BRCA1 and BRCA2 mutations. Twelve of these patients had a BRCA1 deleterious mutation with a triple-negative tumor. Characteristics of these 12 pts at diagnosis were: median age = 38, tumor stage = 7 T2N0, 2 T2N1, 2 T3N0, 1 T3N1. Results: Pathological complete response was defined as absence of invasive tumor in breast and axillary nodes. After 6 cycles of FEC100, 42% of patients with triple-negative tumors (23/55) had a pathological complete response, compared to 17% (2/12) with a BRCA1 mutation. Only one of the 12 BRCA1 patients had an axillary node involvement. Conclusions: In our series, BRCA1 deleterious mutations decreased anthracycline-based chemotherapy efficacy in triple- negative breast cancers. Platinum compounds should be evaluated in these BRCA1-related tumors. No significant financial relationships to disclose.

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