Disease progression of metastatic breast cancer by first relapse site after definitive radiotherapy.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 36-36
Author(s):  
Kenshiro Shiraishi ◽  
Keiichiro Tada ◽  
Jiro Kawamori ◽  
Atsushi Fukuuchi ◽  
Tsunehiro Nishi
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Definitive Radiotherapy ◽  
Distant Relapse ◽  
Metastatic Setting ◽  
Metastatic Relapse ◽  
First Relapse

36 Background: Bone metastasis as initial distant relapse is commonly considered to have better prognosis than other sites in metastatic breast cancer. To elucidate true clinical course of metastatic disease, it is essential that we prospectively manage patients since primary setting. Methods: Overall, 3,417 patients with breast cancer treated with mastectomy (n = 379, 11.1%) or breast-conserving surgery (n = 3,029, 88.6%) followed by definitive radiotherapy at two institutions in Center of Tokyo between 1980 and 2014 were included in the study. Information on all patients was prospectively collected and rigorously-controlled. Initial metastatic relapse sites included bone, brain, and other (mainly visceral). Intrinsic subtypes of tumor were classified as luminal A, luminal-human epidermal growth factor receptor 2 (HER2), luminal B, triple negative, and HER2 identified by routine immunohistochemistry and histological grade. Cumulative incidence rates of overall survival (OS) for each affected site after metastatic relapse were estimated according to Kaplan-Meier method. Results: Median follow-up time for living patients was 113 months. A total of 370 patients experienced metastatic progression as first relapse event. Median duration of OS after initial metastatic relapse was 69 month in all subtypes. No difference was seen in OS among five subtypes after initial bone or brain relapse. Meanwhile, OS of luminal subtypes after initial other-site relapse was better than that of triple negative and HER2 subtypes (P = .003). Notably, OS rates of bone and non-bone/brain metastasis groups as initial relapse site were almost identical (P= .626). Conclusions: We find no difference in mortality after metastatic relapse between bone and other site except for brain metastasis as initial relapse in breast cancer patients following definitive radiotherapy in our cohort without primary metastatic setting. Careful consideration is needed for initial distant relapse regardless of which site is involved. However, prognosis of metastatic breast cancer after definitive radiotherapy is favorable based on real world data, attributable mainly to improved systemic therapy and modern multidisciplinary approach.

scholarly journals Advancements in the Treatment of Metastatic Breast Cancer (MBC): The Role of Ixabepilone

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Massimo Cristofanilli
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Safety Data ◽  
Metastatic Breast ◽  
Response To Treatment ◽  
Epothilone B ◽  
Metastatic Setting

Successful management of breast cancer in the metastatic setting is often confounded by resistance to chemotherapeutics, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially concerning. As such, a therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease. Notably, treating in the neoadjuvant setting might allow clinicians to explore the predictive value of biomarkers and response to treatment, as pharmacogenomic approaches to therapy continue to evolve. In this article, we review the efficacy and safety data of ixabepilone as a monotherapy and as a component of combination therapy for metastatic and primary breast cancer.

scholarly journals The Incidence of Brain Metastases Among Patients with Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative ◽  
Screening Program ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

scholarly journals O28: M6A DEMETHYLASE FTO A POTENTIAL TARGET IN BRAIN METASTATIC BREAST CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
S Keelan ◽  
S Charmsaz ◽  
S Purcell ◽  
D Varešlija ◽  
S Cocchiglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Disease Progression ◽  
Therapeutic Target ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Potential Therapeutic Target ◽  
Rna Methylation ◽  
Pharmacological Inhibition

Abstract Introduction Brain metastasis (BrM) occurs in 10-30% of patients with advanced breast cancer (BC). BrM is increasing in incidence and confers a poor prognosis. We aimed to investigate the contribution of global epi-transcriptomic alterations in N6-methyladenosine (m6A) RNA-methylation as a therapeutic target in brain metastatic breast cancer. Method In preliminary studies we have demonstrated m6A demethylase – FTO as the main contributor to the progression of ER+ breast cancer. Furthermore an association between FTO and reduced disease-free-survival (n=870, p=0.018) was observed. Here we conducted an epigenetic inhibitor screen using two therapeutic agents, ethyl-ester-meclofenamic acid (MA2) and FB23-2 on matched 2D cell line, 3D organoid cultures and patient-derived xenografts (PDX) explant models of brain metastasis. Result Upon integration of mapped global RNA methylation landscape with matched proteomic analysis, we observed genome-wide RNA hypo-methylation of key pluripotency genes, including SOX2 and KLF4, as key players underlying tumour progression to the brain.  Genetic and pharmacological inhibition of FTO in novel ex vivo models of BrM significantly reduced protein expression levels of KLF4 and SOX2. Moreover, pharmacological inhibition of FTO with MA2 and FB23-2, inhibited cell proliferation in endocrine-resistant BC and patient BrM cells. We translate our findings to the clinic by demonstrating the efficacy of anti-FTO therapies in several unique PDX and 3D organoid BrM models. Conclusion Our results reveal epi-transcriptional remodelling events as a key mechanism in BrM. This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in BrM. Take-home message This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in brain metastatic breast cancer.

scholarly journals Staging Investigations in Asymptomatic Early Breast Cancer Patients at the Cancer Centre of Southeastern Ontario

2021 ◽  
Vol 28 (3) ◽  
pp. 2190-2198
Author(s):  
Dalia Kamel ◽  
Veronica Youssef ◽  
Wilma M. Hopman ◽  
Mihaela Mates
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Receptor Status ◽  
Cancer Centre ◽  
Radiological Staging

Background: In 2012, the American Society for Clinical Oncology (ASCO) identified five key opportunities in oncology to improve patient care, recommending against imaging tests for the staging of patients with early breast cancer (EBC) at low risk for metastases. Similarly, the European Society of Medical Oncology (ESMO) guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcomes of staging investigations (SIs) in aEBC at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 with any receptor status were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SIs were recorded. Data were analyzed to determine associations between the use of SIs and clinical characteristics (chi-square tests, independent samples t-tests and Mann–Whitney U tests). Results: From 2012 to 2014, 295 asymptomatic EBC patients were identified. The mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Stage distribution was as follows: stage I 42%, stage IIA 37% and stage IIB 21%. Receptor status was as follows: ER+ 84%, HER2+ 13% and triple negative 12%. Adjuvant chemotherapy was received by 36%, Trastuzumab by 10% and endocrine therapy by 76% of patients. Baseline SIs were performed in 168 patients (57%) for a total of 332 tests. Overt metastatic disease was found in five patients (one bone scan and four CT scans). Seventy-one out of the 168 patients (42%) who received initial staging imaging underwent 138 follow-up imaging tests, none of which were diagnostic for metastases. Nine patients with suspicious CT findings underwent biopsies, of which four were malignant (one metastatic breast cancer and three new primaries). Factors significantly associated with SI were as follows: younger age (p = 0.001), premenopausal status (p = 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001), triple negative status (p = 0.007) and use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3-year period at our institution, more than 50% of aEBC patients underwent a total of 470 initial and follow-up staging tests, yielding a cancer diagnosis (metastatic breast cancer or second primary cancer) in four patients. We, therefore, conclude that routine-staging investigations in aEBC patients have low diagnostic value, supporting current guidelines that recommend against the routine use of SI in this population.

Carboplatin-Paclitaxel in triple-negative metastatic breast cancer during pregnancy with neoplastic thrombosis

2021 ◽  
Author(s):  
Francesca Monari ◽  
Giovanni Grandi ◽  
Isotta Guidotti ◽  
Francesco Torcetta ◽  
Rachele Battista ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast

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

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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