Expression of hormone receptors ERα, ERβ and PgR in HER2-positive breast cancers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10525-10525
Author(s):  
M. Litwiniuk ◽  
V. Filas ◽  
J. Moczko ◽  
R. Kaleta ◽  
J. Breborowicz
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Detection System ◽  
Statistical Significance ◽  
Her2 Status ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

10525 Background: HER-2/neu gene is amplified and overexpressed in 15–20% of invasive breast cancers. HER2-positive breast cancers have a worse prognosis than HER2-negative tumors and distinctive clinical features. They express hormone receptors for estrogen (ERα) and for progesterone (PgR) less frequently than HER2-negative tumors. The identification of the other human estrogen receptor, receptor beta (ERβ), raises a question of ERβ occurrence in HER2-positive breast cancer. Patients and methods: Formalin-fixed, paraffin embedded tissues from 90 patients with invasive HER2-positive breast cancer and from 99 patients with HER2-negative breast cancer were used in this study. The HER2 status was analyzed using HercepTest TM (IHC), and IHC 2+ results were confirmed with FISH test. Immunostaining for ERα, ERβ and PgR was performed using monoclonal antibodies against ERα, PgR (DakoCytomation) and against ERβ (CHEMICON). The EnVision detection system was applied. The data were analyzed using nonparametric Fisher-Freeman-Halton test; the statistical significance was considered when p < 0.5. Results: Only 33% of the HER2-positive breast cancers were ERα-positive compared with 63% in the HER2-negative group (p < 0.001). The expression of ERβ protein was observed in almost equal frequency in both groups (57% of HER2-positive breast cancers and 57.7% of HER2-negative tumors, p = 0.889). The expression of PgR was observed in 30% of HER2-positive breast cancers and in 68.7% of HER2-negative tumors (p < 0.001). Conclusion: The expression of ERβ (unlike that of ERα and PgR) was similar in HER2-positive and in HER2-negative breast cancers. Thus, ERβ may be a potential target in future endocrine therapy for women with HER2-positive breast cancers. No significant financial relationships to disclose.

scholarly journals CDK12 inhibition enhances sensitivity of HER2+ breast cancers to HER2-TKI via suppressing PI3K/AKT

2020 ◽  
Author(s):  
Hui Li ◽  
Jinsong Wang ◽  
Zongbi Yi ◽  
Chunxiao Li ◽  
Haijuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
High Throughput Sequencing ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Sequencing Data ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Background : While anti-HER2 tyrosine kinase inhibitors (TKIs) have radically prolonged survival and improved prognosis in HER2-positive breast cancer patients, resistance to these therapies is a constant obstacle leading to TKIs treatment failure and tumor progression.Methods : To develop new strategies to enhance TKIs efficiency by combining synergistic gene targets, we performed panel library screening using CRISPR/Cas9 knockout technique based on data mining across TCGA datasets and verified the candidate target in pre-clinical models and breast cancer high-throughput sequencing datasets.Results : We identified that CDK12, co-amplified with HER2 in a high frequency, is powerful to sensitize or re-sensitize HER2-positive breast cancer to anti-HER2 TKIs lapatinib, evidenced by patient-derived organoids (PDO) in vitro and cell-derived xenograft (CDX) or patient-derived xenograft (PDX) in vivo. Exploring mechanisms, we found that inhibition of CDK12 attenuated PI3K/AKT signal, which usually serves as an oncogenic driver and is reactivated when HER2-positive breast cancers develop resistance to lapatinib. Combining CDK12 inhibition exerted additional suppression on p-AKT activation induced by anti-HER2 TKIs lapatinib treatment. Clinically, via DNA sequencing data for tumor tissue and peripheral blood ctDNA, we found that HER2-positive breast cancer patients with CDK12 amplification responded more insensitively to anti-HER2 treatment than those without accompanying CDK12 amplification by harboring a markedly shortened progression free survival (PFS) (median PFS: 4.3 months verse 6.9 months; HR 2.26 [95% CI 1.32-3.86]; P=0.0028).Conclusions : Dual inhibition of HER2/CDK12 will prominently benefit the outcomes of HER2-positive breast cancer patients by sensitizing or re-sensitizing the tumors to anti-HER2 TKIs treatment.

Neratinib for the treatment of early-stage, hormone receptor-positive, HER2-overexpressed breast cancer

2020 ◽  
Vol 16 (17) ◽  
pp. 1165-1177
Author(s):  
Yolanda Jerez ◽  
Blanca Herrero ◽  
Marta Arregui ◽  
Blanca Morón ◽  
Miguel Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Future Directions ◽  
Her2 Positive Breast Cancer ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

HER2-positive breast cancer accounts for 18–20% of all breast cancers. Despite significant advances and the currently available adjuvant treatments for management of the disease, approximately 25% of HER2-positive early-stage breast cancer patients show relapse and die. Neratinib is an irreversible tyrosine kinase inhibitor. Multiple studies have reported its significant antitumor activity in metastatic HER2-positive breast cancer. It is administered orally and has also been tested in the adjuvant setting. In this article, we present a comprehensive review of the pharmacokinetics and pharmacodynamics of neratinib as well as its clinical efficacy, with an emphasis on early HER2-positive breast cancer and suggestions for future directions for neratinib research.

Biology and prognosis of 1,685 recently diagnosed HER2-positive breast carcinomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10501-10501
Author(s):  
S. Ménard ◽  
S. De Placido ◽  
S. Scalone ◽  
A. Molino ◽  
M. Mottolese ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Relapse Rate ◽  
Hormone Receptors ◽  
Low Frequency ◽  
Her2 Status ◽  
Breast Carcinomas ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Relapse Rates ◽  
Positive Breast Cancer

10501 Background: Understanding biology, prognosis and drug-sensitivity of HER2-positive breast cancer might help optimization of treatment of patients affected by this type of cancer. Most available studies are retrospective and suffer from the low frequency of this tumor subset. Methods: We conducted a large national retrospective/prospective study involving 1685 patients (cases) with HER2-positive (2+, 3+ score) primary breast carcinomas diagnosed in Italy in 2000/2001; for each case, in each participating center, a control was identified as the first consecutive patient with HER2-negative cancer (0, 1+ score). Results: In addition to the already known association with some pathologic parameters such as grade, hormone receptors, and ductal histotype, the four HER2 categories also displayed specific features, for example, a significantly higher frequency of p53-positivity among HER2–2+ tumors than in the other three categories, and a significantly lower frequency of lymphoid infiltration and desmoplasia, accompanied by a higher frequency of vascular invasion, in HER2–1+ as compared to HER2–0 tumors. Neither tumor size nor nodal involvement were associated with HER2 status. With a median follow-up of 4 yrs, the HER2-positive group showed a 20% relapse rate versus 14% in the HER2-negative group (p < 0.001). Analysis of relapse rates in the four HER2 categories indicated that only 3+ tumors show a significantly poorer prognosis, in both node-positive and node-negative subgroups; however, when patients who underwent invasive surgery are considered, the HER2–2+ patients also showed a significantly increased relapse rate as compared to negative cases, consistent with a stimulation of tumor cells by growth factors released at the time of surgery. Analysis of relapse rates according to type of therapy confirms the unresponsiveness to tamoxifen but sensitivity to chemotherapy, in particular taxanes, of HER2-positive tumors. Indeed, HER2-positive tumors were found to have a significantly better prognosis than HER2-negative when treated with taxanes. Conclusions: The present analysis conducted in a very large series of HER2-positive cases suggests innovative findings that can help optimization of treatment strategy for patients with HER2-positive breast cancer. No significant financial relationships to disclose.

scholarly journals Effects of Various Treatment Regimens on the Survival of HER2-positive Breast Cancer Patients with Brain Metastasis

The Physician ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. c12
Author(s):  
Shantal Edirappuli ◽  
Emma Bedowes
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Treatment Regimens ◽  
Her2 Positive Breast Cancer ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Overexpression of HER2 (human epidermal growth factor receptor 2) occurs in around 20% of breast cancers. This particular subtype is known to be very aggressive and had the worst prognosis prior to the introduction of targeted therapy. The development of anti-HER2 therapies such as trastuzumab and pertuzumab has shown to dramatically improve the prognosis of patients with HER2-positive breast cancer.

scholarly journals Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3540
Author(s):  
Hamid Maadi ◽  
Mohammad Hasan Soheilifar ◽  
Won-Shik Choi ◽  
Abdolvahab Moshtaghian ◽  
Zhixiang Wang
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Mechanism Of Action ◽  
Mechanisms Of Action ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Insight Into ◽  
Positive Breast Cancer

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

scholarly journals Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients

Breast Care ◽  
2021 ◽  
pp. 1-7
Author(s):  
Christoph Suppan ◽  
Daniel Steiner ◽  
Eva Valentina Klocker ◽  
Florian Posch ◽  
Elisabeth Henzinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Safety And Efficacy ◽  
Her2 Positive Breast Cancer ◽  
Tumor Stages ◽  
Positive Breast Cancer

<b><i>Background:</i></b> The addition of trastuzumab to standard chemotherapy has improved survival in patients with HER2-positive breast cancer in neoadjuvant, adjuvant, and metastatic settings. In higher tumor stages, the addition of pertuzumab is now a standard of care and associated with a favorable toxicity profile. We evaluated the safety and efficacy of the trastuzumab biosimilar SB3 in combination with pertuzumab in HER2-positive breast cancer patients. <b><i>Methods:</i></b> Seventy-eight patients with HER2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz were included. Summary measures are reported as medians (25th to 75th percentile) for continuous variables and as absolute frequencies (%) for count data. <b><i>Results:</i></b> Thirty-five patients received a median of 4 (3–7) cycles of trastuzumab biosimilar SB3 plus pertuzumab. All patients had a normal baseline left ventricular ejection fraction (LVEF; &#x3e;50%) prior to the initiation of SB3 plus pertuzumab treatment with a median LVEF of 60% (60–65). Twenty-one patients had a median absolute LVEF decline of 1% (–5 to 0). Two patients (5.7%) had a LVEF reduction ≤50%, but none ≥10%. There were no unexpected adverse events. Twenty-two of 35 patients (63%) were treated with trastuzumab biosimilar SB3 and pertuzumab in the neoadjuvant setting and 11 patients (50%) achieved a pathological complete response. The safety and the efficacy in this setting was comparable to the trastuzumab plus pertuzumab combination in neoadjuvantly treated matched samples. <b><i>Conclusion:</i></b> In this series of HER2-positive breast cancer patients, the combination of SB3 plus pertuzumab was consistent with the known safety and efficacy profile of trastuzumab and pertuzumab combination.

Influence of Anthropometric Characteristics in Patients With Her2-Positive Breast Cancer on Initial Plasma Concentrations of Trastuzumab

2017 ◽  
Vol 51 (11) ◽  
pp. 976-980 ◽  
Author(s):  
Jonathan González García ◽  
Fernando Gutiérrez Nicolás ◽  
Gloria Julia Nazco Casariego ◽  
José Norberto Batista López ◽  
Isaac Ceballos Lenza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Dose ◽  
Plasma Concentrations ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Initial Plasma ◽  
Anthropometric Characteristics ◽  
Secondary Objective ◽  
Positive Breast Cancer

Background: Plasma concentrations of trastuzumab <20 µg/mL in patients with gastric cancer are associated with reduced progression-free and overall survival. In breast cancer treatment, this relationship has not yet been studied, but a suboptimal pharmacodynamic exposure to trastuzumab could be a reason for therapeutic failure of treatment of HER2-positive breast cancer. Objective: The objective of the present study was to determine the proportion of nonmetastatic HER2-positive breast cancers that do not reach a minimum plasma concentration ( Cmin) of 20 µg/mL after first drug administration, established as therapeutically effective in clinical trials. The secondary objective was to identify the physiological and anthropometric characteristics that determine interindividual pharmacokinetic variability. Methods: Serum concentrations of trastuzumab were assessed by ELISA on day 1 of the second cycle before administration of the second dose ( Cmin). Results: Of 19 patients included, 9 (47.4%) had a mean Cmin of 19.0 µg/mL (±12.1) after the first administration. Body mass index (BMI) and weight was the main variable that determined the achievement of therapeutic levels after the first administration. Thus, the proportion of patients reaching the target concentration was 89% when BMI was ≤30 kg/m2 but only 11% when BMI was >30 kg/m2 ( P < 0.01). Conclusions: The standard dose of 600 mg subcutaneous trastuzumab did not ensure adequate pharmacodynamic exposure from the first administration in 52% of patients, with weight and BMI being related to the plasma levels obtained.

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