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Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review.

ABSTRACT: Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

SUBMITTER: Fernandes L

PROVIDER: S-EPMC7737195 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review.

Fernandes Leonor L de Matos Leonor Vasconcelos LV Cardoso Débora D Saraiva Marlene M Medeiros-Mirra Renata R Coelho Andreia A Miranda Helena H Martins Ana A

CNS oncology 20201020 4

Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to i ...[more]

PMID: 33078616

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PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer.

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| S-EPMC7227113 | biostudies-literature

Gene expression analysis of HER2+ breast leptomeningeal carcinomatosis

Project description:Patient-derived primary HER2+ Leptomeningeal carcinomatosis (Lepto) cell lines were established. RNA-seq in various breast cancer cell lines were conducted to characterize the established cell lines. Gene expression analysis clearly indicated thatt Lepto cell lines are transcriptionally different from HER2 positive and negative metastatic breast cancer cell lines such as BT474 and MDA-MB-231 cells.

2021-07-05 | GSE179280 | GEO

Response to Olaparib in a Patient with Germline BRCA2 Mutation and Breast Cancer Leptomeningeal Carcinomatosis.

Project description:Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic cancer that disproportionately affects patients with advanced breast cancer. Moreover, those with BRCA1/2-mutated disease more often experience leptomeningeal metastasis. Treatment options for LC are limited and often include significant toxicities. PARP inhibitors offer an important potential treatment for patients with BRCA1/2-mutated breast and ovarian cancers, but clinical studies excluded patients with central nervous system (CNS) metastases, including LC. Efficacy data in this area are therefore limited, although a phase I study of olaparib in glioblastoma did show CNS penetration. Here we report a case of a patient with BRCA2-mutated breast cancer and solitary recurrence in the leptomeninges with ongoing complete response to treatment with the PARP inhibitor olaparib. PARP inhibitors may be an important treatment option for patients with BRCA-mutated disease and LC, and warrant further study.

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Prognostic significance of tumor-infiltrating lymphocytes in premenopausal, luminal breast cancer treated with adjuvant endocrine therapy.

Project description:PurposeTumor-infiltrating lymphocytes (TILs) have strong prognostic value in triple-negative and HER2-enriched breast cancer, but their prognostic role in luminal breast cancer (LBC) is less clear. Here, we assessed the overall TIL levels and CD8+ T-cells in relation to the prognosis of LBC patients from China.Methods and resultsA total of 596 patients with LBC who were premenopausal and treated with adjuvant endocrine therapy were included. Among them, 160 cases were evaluated for CD8 by immunohistochemical (IHC) staining. Whole-section hematoxylin and eosin and IHC staining were visually assessed for stromal TILs (sTILs), stromal CD8+ T-cells (sCD8), and intratumoral CD8+ T-cells (iCD8). Multivariable analyses were used to test the associations between TILs and disease-free survival (DFS) and overall survival (OS) with the adjustment for clinicopathologic characteristics and treatment. High sTILs (≥10%) were associated with high histologic grade (P<0.001), luminal B/HER2- (P<0.001), luminal B/HER2+ subtype (P=0.002), and high Ki67 expression (≥25%; P=0.014). Similar associations were observed for sCD8 but not for iCD8. While sTILs and sCD8 were not associated with either DFS or OS, the presence of iCD8 (≥1%) was associated with better DFS in both univariate (HR=0.51, 95% CI 0.26-0.96, P=0.042) and multivariate (HR=0.48, 95% CI 0.25-0.92, P=0.027) analyses. Similar but less significant associations were found for iCD8 and OS (adjusted HR=0.35, 95% CI 0.11-1.10, P=0.073).ConclusionsAmong Chinese premenopausal patients with LBC, iCD8 demonstrated suggestive associations with favorable outcome. In contrast, although sTILs and sCD8 were associated with more aggressive tumor features, they did not appear to be associated with clinical outcome.

| S-EPMC8661243 | biostudies-literature

A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis.

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| S-EPMC4403836 | biostudies-literature

Symptom Map of Endocrine Therapy for Breast Cancer: A Scoping Review.

Project description:BACKGROUND:Multiple symptoms associated with endocrine therapy have a detrimental impact on medication adherence and quality of life. OBJECTIVE:The purpose of this scoping review is to map the symptoms during endocrine therapy for breast cancer to provide implications for current practice and suggestions for future research. METHODS:The PubMed, CINAHL, and China Science Periodical Databases were searched to identify related studies published in English and Chinese languages. References of included articles were reviewed for additional eligible studies. Of the 2551 articles identified, 57 articles met inclusion criteria and were included in this scoping review. RESULTS:Evidence for the 16 most studied symptoms and 15 most prevalent symptoms were synthesized. Five key symptoms associated with endocrine therapy were identified, including joint/muscle pain, hot flashes, low sexual interest/desire, joint/muscle stiffness, and fatigue/lack of energy. Rarely studied but highly prevalent symptoms and other gaps in the symptom science during endocrine therapy for breast cancer were identified. CONCLUSION:Nurses caring for women receiving endocrine therapy for breast cancer should assess the 5 key symptoms identified. There remain substantial gaps in the science related to the symptom experience during endocrine therapy for breast cancer. Future studies should focus on the domains of symptom intensity and distress, specific understudied symptoms, symptom clusters, and development of symptom assessment instruments specific to symptoms associated with endocrine therapy. IMPLICATIONS FOR PRACTICE:This scoping review identified 5 well-studied and highly prevalent symptoms that should be assessed in women with breast cancer receiving endocrine therapy.

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Health care resource utilization and treatment of leptomeningeal carcinomatosis in the United States.

Project description:BackgroundThe economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges.MethodsThe IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis.ResultsWe identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%).ConclusionsLC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs.

| S-EPMC7716175 | biostudies-literature

Prolactin and endocrine therapy resistance in breast cancer: The next potential hope for breast cancer treatment.

Project description:Breast cancer, a hormone-dependent tumour, generally includes four molecular subtypes (luminal A, luminal B, HER2 enriched and triple-negative) based on oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Multiple hormones in the body regulate the development of breast cancer. Endocrine therapy is one of the primary treatments for hormone-receptor-positive breast cancer, but endocrine resistance is the primary clinical cause of treatment failure. Prolactin (PRL) is a protein hormone secreted by the pituitary gland, mainly promoting mammary gland growth, stimulating and maintaining lactation. Previous studies suggest that high PRL levels can increase the risk of invasive breast cancer in women. The expression levels of PRL and PRLR in breast cancer cells and breast cancer tissues are elevated in most ER+ and ER- tumours. PRL activates downstream signalling pathways and affects endocrine therapy resistance by combining with prolactin receptor (PRLR). In this review, we illustrated and summarized the correlations between endocrine therapy resistance in breast cancer and PRL, as well as the pathophysiological mechanisms and clinical practices. The study on PRL and its receptor would help explore reversing endocrine therapy-resistance for breast cancer.

| S-EPMC8581311 | biostudies-literature

The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment.

Project description:Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

| S-EPMC8196711 | biostudies-literature

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