Metastatic Breast Cancer Survival according to HER2 and Topo2a Gene Status

The aim of this study was to determine the relationship between amplification of HER2 (Human epidermal growth factor receptor 2) and Topo2a (topoisomerase 2a) and their influence on prognosis in metastatic breast cancer (MBC) patients. Amplification of both HER2 and Topo2a genes was determined by chromogenic in situ hybridization (CISH) in primary tumor tissue of 71 MBC patients. Starting point for follow-up was the time of diagnosis of metastatic disease. Although there was significant correlation between HER2 amplification and Topo2a alterations, Topo2a amplification was not strictly related to HER2 amplification. Follow-up of patients showed that there was no difference in MBC survival between HER2-nonamplified and HER2-amplified patients for subgroup as whole, but there was significant difference in MBC survival between patients with and without Topo2a amplification. HER2 amplification showed prognostic value in subgroups of patients, as well as Topo2a. Combination of these two genes with different status (nonamplified, amplified, coamplified) indicated that they might have additive effect. Also, it has been shown that Topo2a-amplified cases have poorer survival than Topo2a-nonamplified, when treated with CMF therapy.Topo2a amplification seems to be more promising biomarker of MBC survival, than HER2, and potential marker of resistance to CMF therapy.

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Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0646-4630 ◽

2018 ◽

Vol 78 (11) ◽

pp. 1056-1088 ◽

Cited By ~ 19

Author(s):

Achim Wöckel ◽

Jasmin Festl ◽

Tanja Stüber ◽

Katharina Brust ◽

Mathias Krockenberger ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Tumor Biology ◽

Metastatic Breast ◽

Current Guideline ◽

Gynecology And Obstetrics ◽

Safety Margins ◽

Starting Point ◽

Diagnosis Therapy

Abstract Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.

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Association of the neutrophil to lymphocyte ratio with survival patients with in metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11544 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11544-e11544

Author(s):

Ozan Unlu ◽

Sevda Aygun ◽

Hilbrahim Petekkaya ◽

Gizem Gecmez ◽

Emir C. Roach ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Neutrophil To Lymphocyte Ratio ◽

Breast Cancer Patients ◽

Lymphocyte Ratio ◽

Significant Difference

e11544 Background: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. Although various markers are considered while making a decision to treatment modality, clinicians investigate for new prognostic factors for reason of highly variable responses of individuals. Therefore, this study estimates the survival probability of the neutrophil to lymphocyte ratio (NLR) for patients with metastatic breast cancer. Methods: We included the patients with metastatic breast carcinoma who were treated for metastasis. NLR were calculated and patients were divided into four quartiles (25th, 50th and 75th NLR; the lowest being the 1st quartile, the highest being 4th quartile ). Survival status was retrieved from our cancer registry. Survival analysis, stratified by NLR quartiles, was used to evaluate the predictive value of NLR. Results: Eighty-one patients with metastatic breast cancer were included in this study. Median age of diagnosis of the patients was 47 (26-83), the majority of them had grade II (%37) and grade III (%29.6) tumors and were metastatic at the time of their initial diagnosis. ER (+), PR (+) and HER2 (+) percentages were confirmed as 82%, 73% and 24% ,respectively. Ten percent of the patients were triple negative. Median follow-up time was 26 months and 29 patients died during the follow up period. We analyzed the overall survival among NLR quartiles. When we compared the quartiles with the highest and lowest NLR values, the quartile with the lowest NLR values had longer median overall survival than the quartile with the highest NLR values (212 vs. 27 months; p=0.01). The second and third quartiles, however, showed no statistically significant difference of overall survival between four quartiles. Conclusions: NLR can be a prognostic factor for overall survival in metastatic breast cancer patients.

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Impact of metastases directed radiation therapy on CDK4/6 inhibitors dose reduction and treatment discontinuation for metastatic HR+/HER2- breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.562 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 562-562

Author(s):

Icro Meattini ◽

Erika Scoccimarro ◽

Calogero Saieva ◽

Isacco Desideri ◽

Luca Visani ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Dose Reduction ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Adverse Event Rate ◽

Her2 Breast Cancer ◽

Significant Difference ◽

Epidermal Growth

562 Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) represent the standard I-II line for hormonal receptors positive/human epidermal growth factor receptor 2 negative metastatic breast cancer (MBC) patients. Metastases directed radiotherapy (RT) for these patients is commonly used with palliative or radical schedules during systemic treatment. Although encouraging preliminary results were published, there is still a lack of robust data on the safety concerning RT during CDK4/6i treatment. Methods: we analyzed at Our Institution 85 consecutive patients treated in I (n=47) and II line (n=38) for MBC with CDK4/6i between April 2017 and September 2019 (22 ribociclib, 63 palbociclib). Overall, 25 (29.4%) patients received metastases directed RT during CDK4/6i treatment, including 14 concomitant (16.5%) and 11 sequential (12.9%). Estimated CDK4/6i half-life is 26 and 30 hours for palbociclib and ribociclib, respectively. Five half-lives are required to reduce drug concentration by 95-97%; thus, we also analyzed CDK4/6i treatment as non-concomitant or sequential to RT. Main endpoints of our analysis were impact of RT on CDK4/6i dose reduction and discontinuation, overall adverse events rate (any grade and grade ≥2), and neutropenia grade ≥2 as per CTCAE scale version 5.0. Results: at a median follow up of 12 months (range 3-29), we observed a CDK4/6i dose reduction in 35 patients (41.2%) and 5 patients (5.9%) discontinued treatment due to adverse events; 82 patients (96.5%) experienced any grade of toxicity, 72 (84.7%) a grade ≥2 and 70 patients (82.4%) neutropenia grade ≥2. We did not observe significant difference in terms of CDK4/6i dose reduction or discontinuation, any grade or grade ≥2 toxicity, neutropenia grade ≥2 in the comparison between patients receiving RT versus no RT and between patients receiving concomitant RT versus sequential RT versus no-RT (Table). Conclusions: our results showed that the prescription of a metastases directed RT during treatment with a CDK4/6i as I-II line for MBC did not significantly impact on dose reduction or discontinuation caused by an exceeding in adverse event rate. Although these promising results, caution should be used and cooperative initiatives strongly encouraged. [Table: see text]

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A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2− metastatic breast cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211022890 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110228

Author(s):

Yi Li ◽

Wei Li ◽

Chengcheng Gong ◽

Yabin Zheng ◽

Quchang Ouyang ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Treatment Options ◽

Objective Response ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Progression Free Survival ◽

Subsequent Treatment ◽

Significant Difference

Introduction: Endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) are standard treatment options for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) metastatic breast cancer (MBC). However, the efficacy of standard subsequent therapies after CDK4/6i-based treatment is unclear. This study aimed to examine physician practice patterns and treatment outcomes of subsequent therapies administered after progression on palbociclib therapy in clinical practice. Methods: The study included 200 patients with HR+/HER2– MBC who underwent subsequent treatments after progressing on palbociclib-based regimens in five Chinese institutions between August 2017 and April 2020. The treatment pattern, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were reported. Results: A total of 200 patients were included, of whom 147 (73.5%) and 53 (26.5%) received subsequent chemotherapy and endocrine therapy, respectively. The frequently used monochemotherapy regimens were taxane ( n = 29), capecitabine ( n = 21), and vinorelbine ( n = 17), while the endocrine therapy regimens were chidamide plus exemestane ( n = 16) and everolimus plus exemestane ( n = 9). The overall median PFS (mPFS) was 5.5 months, with no significant difference in mPFS between the chemotherapy and endocrine therapy groups ( p = 0.669). However, among patients not sensitive to prior palbociclib treatment, those administered chemotherapy had significantly longer PFS than those administered endocrine therapy ( p = 0.006). The mPFS with endocrine therapy after first-, second-, and subsequent-line palbociclib was 13.4, 3.1, and 4.1 months, respectively ( p = 0.233); in contrast, the mPFS with chemotherapy was 7.2, 6.5, and 4.9 months after first-, second-, and subsequent-line palbociclib, respectively ( p = 0.364). The median OS was not achieved. The ORR was 10.6% among the 198 patients included in the analysis. Conclusions: Physicians prefer chemotherapy over endocrine therapy for the treatment of patients with HR+/HER2– MBC who develop progression on palbociclib. Sensitivity to previous palbociclib treatment might be one of the indicators for predicting response to subsequent treatment. ClinicalTrials.gov identifier: NCT04517318

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

Neuro-Oncology ◽

10.1093/neuonc/noaa285 ◽

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.

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Preservation of quality of life in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial)

European Journal of Cancer ◽

10.1016/j.ejca.2021.05.025 ◽

2021 ◽

Vol 153 ◽

pp. 223-233

Author(s):

Volkmar Mueller ◽

Andrew Wardley ◽

Elisavet Paplomata ◽

Erika Hamilton ◽

Amelia Zelnak ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Epidermal Growth Factor Receptor ◽

Metastatic Breast Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Epidermal Growth

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

Current Oncology ◽

10.3390/curroncol28030203 ◽

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.

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