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1.
BMC Vet Res ; 20(1): 181, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715073

RESUMO

BACKGROUND: The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids. CASE PRESENTATION: This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge. CONCLUSIONS: When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.


Assuntos
Doenças das Cabras , Cabras , Leiomioma , Receptores de Progesterona , Neoplasias Vaginais , Animais , Feminino , Leiomioma/veterinária , Leiomioma/patologia , Leiomioma/cirurgia , Neoplasias Vaginais/veterinária , Neoplasias Vaginais/patologia , Receptores de Progesterona/metabolismo , Doenças das Cabras/patologia
2.
Pol J Pathol ; 75(1): 8-18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741425

RESUMO

The use of chemotherapy in breast cancer management has significantly contributed to the decrease in its mortality. Currently, the prognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, the increasing use of advanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided the ability to estimate the risk of recurrence. Research has demonstrated that the ODX-RS helps to predict recurrence risk and the potential benefit of chemotherapy in breast cancer. As a result, it can assist clinicians in making decisions regarding using the chemotherapy. The goal of work is to explore the correlation between the ODX-RS and Ki-67 proliferative index (Ki-67-PI). This study included 137 patients with oestrogen positive, human epidermal growth factor receptor 2-negative early breast cancer, and had non- or early axillary disease. Patients with low Ki-67-PI were as follows: low ODX-RS in 17%, intermediate ODX-RS in 80%, and high ODX-RS in 2%. In the high Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, the results show no significant correlation between the ODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Antígeno Ki-67 , Recidiva Local de Neoplasia , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Neoplasias da Mama/patologia , Feminino , Antígeno Ki-67/análise , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Adulto , Recidiva Local de Neoplasia/patologia , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/análise , Idoso , Metástase Linfática/patologia , Proliferação de Células , Axila , Receptores de Progesterona/metabolismo , Receptores de Progesterona/análise , Idoso de 80 Anos ou mais
3.
Pol J Pathol ; 75(1): 19-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741426

RESUMO

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Inibidor p16 de Quinase Dependente de Ciclina , Imuno-Histoquímica , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Adulto , Idoso , Receptores de Progesterona/metabolismo , Idoso de 80 Anos ou mais , Metástase Linfática , Receptores de Estrogênio/metabolismo , Prognóstico
4.
Pathol Oncol Res ; 30: 1611735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689824

RESUMO

Introduction: The 21-gene analysis (OncotypeDX) is validated test for pT1-3, pN0-1 with hormone receptor (HR) positive and normal expression of human epidermal growth factor receptor-2 (HER2) breast cancer (BC) to determine the aggressiveness of the disease based on the calculation of Recurrence Score (RS). Methods: In this retrospective study the authors correlated pathological characteristics and Recurrence Score (RS) by traditional statistical methods and Observed Oriented Modeling (OOM) in a realistic cohort of BC patients. Results: OncotypeDX tests were performed in 94 tumour specimens of 90 BC patients. >83% of node-negative (pN0) and >72% of node-positive (pN1) cases could avoid chemotherapy. For pN0 cases, non-parametric correlation and tests demonstrated significant association in eight types of characteristics [progesterone receptor (PR) expression, Ki-67 value, Ki-67 group, PR group, grade, estrogen receptor (ER) expression, Nottingham Prognostic Index (NPI) and Clinical Risk]. For pN1 cases, parametric correlation and tests showed significant association in six characteristic types (number of positive nodes, ER and PR expression, PR group, Ki-67 group and NPI). Based on OOM for pN0 cases, significant associations were established in three characteristics (Ki-67 group, grade and NPI group). For pN1 cases OOM found significant associations in seven characteristics (PR group, PNI, LVI, Ki-67 group, grade, NPI group and number of positive nodes). Conclusion: First in oncology, OOM was applied, which found some other significant characteristics associated with RS than traditional statistical methods. There were few patients, where no clinical associations were found between characteristics and RS contrary to statistically significant differences. Therefore, the results of these statistical analyses can be neither applied for individual cases nor able to provide the bases for screening patients, i.e., whether they need for OncotypeDX testing or not. OncotypeDX still provides a personalised approach in BC.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Recidiva Local de Neoplasia , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/genética , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Idoso , Adulto , Prognóstico , Receptores de Progesterona/metabolismo , Hungria , Receptores de Estrogênio/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Idoso de 80 Anos ou mais
5.
World J Surg Oncol ; 22(1): 126, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725003

RESUMO

PURPOSE: This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). METHODS: Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. RESULTS: In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. CONCLUSIONS: Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Receptor ErbB-2/metabolismo , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/metabolismo , Seguimentos , Glicemia/análise , Glicemia/metabolismo , Adulto , Receptores de Estrogênio/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Receptores de Progesterona/metabolismo , Colesterol/metabolismo , Colesterol/sangue , Idoso , Resposta Patológica Completa
6.
Cancer Med ; 13(10): e7249, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38770648

RESUMO

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC. METHODS: From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group. RESULTS: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069). CONCLUSION: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.


Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzimidazóis , Neoplasias da Mama , Piperazinas , Intervalo Livre de Progressão , Piridinas , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aminopiridinas/administração & dosagem , Aminopiridinas/uso terapêutico , Receptor ErbB-2/metabolismo , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , China , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Idoso , Adulto , Estudos Retrospectivos , Progressão da Doença , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem
7.
PeerJ ; 12: e17377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766488

RESUMO

Objective: To explore the relationship between receptor heterogeneity and clinicopathological characteristics in 166 patients with invasive breast cancer during metastasis. Methods: We conducted a retrospective analysis of 166 patients diagnosed with metastatic breast cancer through biopsy, who were admitted to our hospital from January 2018 to December 2022. Statistical analysis was employed to assess the heterogeneity of receptors in both primary and metastatic lesions, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67, as well as their association with clinicopathological features such as tumor size, lymph node metastasis, treatment regimen, and disease-free survival. Results: The discordant expression rates of ER, PR, HER2, Ki-67 and Luminal classification between primary and metastatic lesions were 21.7%, 41.6%, 8.9%, 34.4% and 36.8%, respectively. There is a significant difference in disease-free survival between patients with consistent and inconsistent receptor status of primary and metastatic lesions, which is statistically significant. The median DFS for primary HER2(-) to metastatic HER2(+) was 84 months, which was relatively high. The Cox multivariate regression analysis revealed that the expression differences of ER, PR, HER2, and Ki67 were not influenced by endocrine therapy and chemotherapy. However, a statistically significant difference in HER2 expression was observed with targeted therapy. Tumor size was correlated with ER and Ki67 receptor status (P = 0.019, 0.016). Tumor size was not correlated with PR, and HER2 (P = 0.679, 0.440). Lymph node metastasis was not associated with changes in ER, PR, HER2, and Ki67. The discordant rates of ER, PR, HER2, and Ki-67 in patients with local recurrence were 22%, 23.7%, 5.1%, and 28.8% respectively, whereas those in patients with distant metastasis were 21.5%, 36.4%, 10.3%, and 31.8% respectively. Conclusions: The expression levels of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer exhibit heterogeneity, which is closely associated with the prognosis and treatment outcomes of patients.


Assuntos
Neoplasias da Mama , Antígeno Ki-67 , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Estudos Retrospectivos , Antígeno Ki-67/metabolismo , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Pessoa de Meia-Idade , Adulto , Idoso , Metástase Linfática/patologia , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Prognóstico , Metástase Neoplásica , Relevância Clínica
8.
Zhonghua Yi Xue Za Zhi ; 104(17): 1507-1513, 2024 May 07.
Artigo em Chinês | MEDLINE | ID: mdl-38706058

RESUMO

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.


Assuntos
Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Receptor ErbB-2 , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Metástase Neoplásica , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo
9.
Cancer J ; 30(3): 142-152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753748

RESUMO

ABSTRACT: Steroid receptors regulate gene expression for many important physiologic functions and pathologic processes. Receptors for estrogen, progesterone, and androgen have been extensively studied in breast cancer, and their expression provides prognostic information as well as targets for therapy. Noninvasive imaging utilizing positron emission tomography and radiolabeled ligands targeting these receptors can provide valuable insight into predicting treatment efficacy, staging whole-body disease burden, and identifying heterogeneity in receptor expression across different metastatic sites. This review provides an overview of steroid receptor imaging with a focus on breast cancer and radioligands for estrogen, progesterone, and androgen receptors.


Assuntos
Neoplasias da Mama , Imagem Molecular , Tomografia por Emissão de Pósitrons , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Feminino , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Receptores de Esteroides/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Receptores Androgênicos/metabolismo
12.
Am J Pathol ; 194(6): 1137-1153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749609

RESUMO

Preclinical models that display spontaneous metastasis are necessary to improve the therapeutic options for hormone receptor-positive breast cancers. Within this study, detailed cellular and molecular characterization was conducted on MCa-P1362, a newly established mouse model of metastatic breast cancer that is syngeneic in BALB/c mice. MCa-P1362 cancer cells express estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2. MCa-P1362 cancer cells proliferate in vitro and in vivo in response to estrogen, yet do not depend on steroid hormones for growth and tumor progression. Analysis of MCa-P1362 tumor explants revealed the tumors contained a mixture of cancer cells and mesenchymal stromal cells. Through transcriptomic and functional analyses of both cancer and stromal cells, stem cells were detected within both populations. Functional studies demonstrated that MCa-P1362 cancer stem cells drove tumor initiation, whereas stromal cells from these tumors contributed to drug resistance. MCa-P1362 may serve as a useful preclinical model to investigate the cellular and molecular basis of breast tumor progression and therapeutic resistance.


Assuntos
Adenocarcinoma , Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Receptor ErbB-2 , Receptores de Estrogênio , Animais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Feminino , Humanos , Receptor ErbB-2/metabolismo , Camundongos , Receptores de Estrogênio/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Linhagem Celular Tumoral , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/metabolismo
13.
Acta Oncol ; 63: 125-136, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587062

RESUMO

BACKGROUND AND PURPOSE: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen. PATIENTS AND METHODS: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. RESULTS: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36-0.79]; IHC-ER+ 0.55 [0.38-0.79]; GEX-ER+ 0.54 [0.37-0.77]; cytosol-PR+ 0.49 [0.34-0.72]; IHC-PR+ 0.58 [0.40-0.85]; GEX-PR+ 0.55 [0.38-0.80]). Results were similar for OS. INTERPRETATION: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.


Assuntos
Neoplasias da Mama , Tamoxifeno , Humanos , Feminino , Tamoxifeno/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , RNA Mensageiro/genética , Quimioterapia Adjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Hormônios/uso terapêutico , Receptores de Progesterona/metabolismo , Resultado do Tratamento
14.
Dis Markers ; 2024: 2540356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601434

RESUMO

Introduction: Metaplastic breast carcinoma (MBC) is a rare subgroup of breast neoplasms associated with adverse outcomes because of its aggressive nature. Typically, MBCs show triple-negative hormone receptor (HR) status. Determining the HR status of breast cancer is an integral part because it is an important prognostic factor and helps in the treatment course of the disease. This study aimed to determine the HR status of MBC, its significance, and its association with various clinicopathological parameters. Methods: This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital. A total of 140 biopsy-proven cases of MBC were enrolled in the study. Clinical and pathological data were retrieved from the institutes' archives. Immunohistochemical studies were conducted to determine the estrogen receptor (ER) and progesterone receptor (PR) status. Results: The mean age of MBC in our population was found to be 52.18 ± 12.19 years. The HR positivity rate in our population was found to be 32.9%. A significant association was found between HR status and tumor laterality, tumor size, tumor grade, tumor stage, and recurrence. ER/PR-negative MBCs were most probably associated with higher grade and higher tumor stage and were larger in size (6.62 ± 3.43 cm) than ER/PR-positive MBCs (4.20 ± 1.88 cm). Moreover, ER/PR-positive MBCs showed a higher recurrence rate than ER/PR-negative MBCs (43.5% vs. 25.5%, respectively). No statistically significant relationship was found between HR status and patient age, histological subtype, or survival rate. Conclusion: MBC is a rare breast neoplasm. MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis.


Assuntos
Neoplasias da Mama , Receptores de Progesterona , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Neoplasias da Mama/patologia , Prognóstico , Receptores de Estrogênio/metabolismo , Estrogênios , Biomarcadores Tumorais/metabolismo
15.
Breast Cancer Res ; 26(1): 67, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649964

RESUMO

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.


Assuntos
Neoplasias da Mama , Mutação , Fenótipo , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Povo Asiático/genética , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Sequenciamento do Exoma , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Perfilação da Expressão Gênica , Transcriptoma , Biomarcadores Tumorais/genética , Análise por Conglomerados , Estudos de Coortes , Adulto , Malásia/epidemiologia , Idoso , Variações do Número de Cópias de DNA
17.
Medicina (Kaunas) ; 60(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674271

RESUMO

Background and Objectives: The association between endometriosis and breast cancer still remains controversial. The aim of this study was to investigate the different subtypes of breast cancer, immunohistochemical markers, hormone receptors, and ki67 proliferation indexes in patients with and without endometriosis and/or adenomyosis. Materials and Methods: All patients with endometriosis and breast cancer were enrolled. Women with endometriosis and breast cancer (Group BC+EN+) were compared to patients with breast cancer without endometriosis (group BC+EN-) and those with endometriosis without breast cancer (group BC-EN+). General population characteristics and histological and immunohistochemical subtypes of breast cancer were compared between groups. Results: Our study included 41 cases affected by both endometriosis and/or adenomyosis and breast cancer (Group BC+EN+) that were matched (1:2) with 82 patients affected only by breast cancer (group BC+EN-) and 82 patients affected only by endometriosis and/or adenomyosis (group BC-EN+). Group BC+EN+ presented a higher percentage of ER receptor expression (83% vs. 70%, p = 0.02), as well as lower values of Ki 67% (15% vs. 24%, p < 0.0001) and HER2+ (9.8% vs. 28%, p = 0.022). These findings were more evident when comparing patients with premenopausal status, while in postmenopausal patients, this difference was no longer significant. Regarding endometriosis, no statistical differences were observed in type or specific localization of the disease among the groups with and without breast cancer. Conclusions: Patients with endometriosis presented lower aggressive breast cancer rates with higher values of ER% and lower values of Ki 67 and HER2neu+. The type and severity of endometriotic diseases seemed not to influence breast cancer occurrence.


Assuntos
Neoplasias da Mama , Endometriose , Humanos , Feminino , Endometriose/complicações , Neoplasias da Mama/complicações , Pessoa de Meia-Idade , Adulto , Antígeno Ki-67/análise , Adenomiose/complicações , Receptores de Estrogênio/análise , Receptor ErbB-2/análise , Imuno-Histoquímica , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Idoso
18.
Tidsskr Nor Laegeforen ; 144(5)2024 Apr 23.
Artigo em Norueguês | MEDLINE | ID: mdl-38651722

RESUMO

Background: Breast cancer in men accounts for around 1 % of all cases of the disease. The study aimed to identify histopathological parameters and selected biomarkers in men with breast cancer. Material and method: Retrospective study of archival material from 53 men diagnosed with breast cancer at the department of pathology, Haukeland University Hospital, in the period 1996-2020. The prevalence of the oestrogen receptor (ER), progesterone receptor (PGR) and Human Epidermal Growth Factor (HER2) biomarkers was examined. Results: Median age at time of diagnosis was 72 years. Median tumour diameter was 24 mm. Forty-nine tumours were classified histologically as invasive carcinoma of no special type (NST), 29 tumours were histologic grade 2 and 18 were grade 3. Fifty-two tumours were ER positive, 39 were PGR positive and four were HER2 positive. Twenty-five patients had lymph node metastases. Interpretation: Our findings indicate that men with breast cancer are diagnosed at an older age than women, and that men have a more advanced stage than women at the time of diagnosis. The histopathology and expression of biomarkers of breast cancer differ between men and women.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama Masculina , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/diagnóstico , Receptores de Estrogênio/metabolismo , Idoso de 80 Anos ou mais , Adulto , Feminino , Metástase Linfática , Estadiamento de Neoplasias , Gradação de Tumores , Fatores Etários
19.
EMBO J ; 43(9): 1770-1798, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565950

RESUMO

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.


Assuntos
Neoplasias da Mama , Fator de Ligação a CCCTC , Cromatina , Proteínas Serina-Treonina Quinases , Humanos , Fator de Ligação a CCCTC/metabolismo , Fator de Ligação a CCCTC/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Cromatina/metabolismo , Cromatina/genética , Feminino , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Via de Sinalização Hippo
20.
Curr Med Res Opin ; 40(5): 827-837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38597173

RESUMO

BACKGROUND: The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk factors for recurrence have been reported in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer in Japan, there has been no systematic review quantifying potential risk factors. METHODS: We performed a systematic literature review and meta-analysis using the MEDLINE, Embase, Cochrane CENTRAL, and Japan Medical Abstract Society databases to identify risk factors for recurrence in HR+/HER2- early breast cancer in Japan. The primary outcome was relapse-free or disease-free survival (RFS/DFS), and the secondary outcomes were overall survival and breast cancer-specific survival (BCSS). RESULTS: Searches identified 42 eligible publications. Meta-analyses identified lymph node metastasis (hazard ratio: 2.76 [95% confidence interval: 1.97-3.88]), large tumor size (1.67 [1.24-2.23]), high histological grade (1.50 [1.04-2.16]), and high nuclear grade (2.02 [1.61-2.54]) as risk factors for RFS/DFS. Lymph node metastasis (2.43 [1.28-4.63]), large tumor size (1.80 [1.24-2.62]), and high histological grade (2.02 [1.44-2.84]) were also risk factors for overall survival, and high progesterone status was a possible favorable prognostic factor for BCSS (0.20 [0.10-0.42]). CONCLUSIONS: Identified risk factors were consistent with the previous reports, and this study provides quantitative summary of risk factors for HR+/HER2- early breast cancer recurrence in Japan. (PROSPERO Registration ID, CRD42022338391.).


Assuntos
Neoplasias da Mama , Recidiva Local de Neoplasia , Receptor ErbB-2 , Receptores de Progesterona , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/análise , Japão/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Fatores de Risco , Receptores de Progesterona/metabolismo , Receptores de Progesterona/análise , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/análise , Metástase Linfática , Intervalo Livre de Doença
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