scholarly journals Serial evaluation of serum thymidine kinase activity is prognostic in women with newly diagnosed metastatic breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna-Maria Larsson ◽  
Pär-Ola Bendahl ◽  
Kristina Aaltonen ◽  
Sara Jansson ◽  
Carina Forsare ◽  
...  

AbstractThe rapid development of new therapies in metastatic breast cancer (MBC), entails a need for improved prognostic and monitoring tools. Thymidine kinase 1 (TK1) is involved in DNA synthesis and its activity correlates to outcome in cancer patients. The aim of this study was to evaluate serum TK1 activity (sTK1) levels in MBC patients as a tool for prognostication and treatment monitoring. 142 women with MBC scheduled for 1st line systemic treatment were included in a prospective observational study. sTK1 was measured at baseline (BL) and at 1, 3 and 6 months and correlations to progression-free and overall survival (PFS, OS) evaluated. High sTK1 levels (above median) correlated to worse PFS and OS at BL, also after adjusting for other prognostic factors. sTK1 levels were significantly associated with PFS and OS measured from follow-up time points during therapy. Changes from 3 to 6 months during therapy significantly correlated to PFS and OS, whereas early changes did not. We could demonstrate sTK1 level as an independent prognostic factor in patients with newly diagnosed MBC. Changes in sTK1 levels from 3 to 6 months correlated to PFS and OS. Future studies of sTK1 are warranted to further define its clinical utility.

2005 ◽  
Vol 23 (7) ◽  
pp. 1420-1430 ◽  
Author(s):  
Massimo Cristofanilli ◽  
Daniel F. Hayes ◽  
G. Thomas Budd ◽  
Mathew J. Ellis ◽  
Alison Stopeck ◽  
...  

Purpose Metastatic breast cancer (MBC) is incurable; its treatment is palliative. We investigated whether the presence of circulating tumor cells (CTCs) predicts treatment efficacy, progression-free survival (PFS), and overall survival (OS) in patients with newly diagnosed MBC who were about to start first-line therapy. Patients and Methods One hundred seventy-seven patients with measurable MBC were enrolled onto a prospective study. Eighty-three of the 177 patients were entering first-line treatment, and these patients are the focus of this analysis. CTCs from 7.5 mL of whole blood drawn before treatment initiation (baseline) and monthly thereafter for up to 6 months were isolated and enumerated using immunomagnetics. Results The mean (± standard deviation) follow-up time was 11.1 ± 4.4 months (median, 12.2 months). Forty-three patients (52%) had ≥ five CTCs at baseline. The median PFS was 7.2 months (95% CI, 4.9 to 9.4 months), and the median OS was more than 18 months. Patients with ≥ five CTCs at baseline and at first follow-up (4 weeks) had a worse prognosis than patients with less than five CTCs (baseline: median PFS, 4.9 v 9.5 months, respectively; log-rank, P = .0014; median OS, 14.2 v > 18 months, respectively; log-rank, P = .0048; first follow-up: median PFS, 2.1 v 8.9 months, respectively; log-rank, P = .0070; median OS, 11.1 v > 18 months, respectively; log-rank, P = .0029). CTCs before and after the initiation of therapy were strong, independent prognostic factors. Conclusion Detection of CTCs before initiation of first-line therapy in patients with MBC is highly predictive of PFS and OS. This technology can aid in appropriate patient stratification and design of tailored treatments.


2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  

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.


2021 ◽  
Vol 28 (3) ◽  
pp. 2190-2198
Author(s):  
Dalia Kamel ◽  
Veronica Youssef ◽  
Wilma M. Hopman ◽  
Mihaela Mates

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.


2017 ◽  
Vol 44 ◽  
pp. 16-21 ◽  
Author(s):  
Michael H. Antoni ◽  
Jamie M. Jacobs ◽  
Laura C. Bouchard ◽  
Suzanne C. Lechner ◽  
Devika R. Jutagir ◽  
...  

2020 ◽  
Vol 7 (1) ◽  
pp. e000413
Author(s):  
Kasper Adelborg ◽  
Dóra Körmendiné Farkas ◽  
Jens Sundbøll ◽  
Lidia Schapira ◽  
Suzanne Tamang ◽  
...  

ObjectiveWe examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population.DesignUsing population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990–2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs).ResultsAmong 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2–5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6–10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990–2006 and 2007–2017, the 1–10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible.ConclusionBreast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13021-e13021
Author(s):  
Debra A. Patt ◽  
Xianchen Liu ◽  
Benjamin Li ◽  
Lynn McRoy ◽  
Rachel M. Layman ◽  
...  

e13021 Background: Palbociclib (PA) has been approved for HR+/HER2–advanced/metastatic breast cancer (mBC) in combination with an aromatase inhibitor (AI) or fulvestrant for more than 6 years. Regardless of the labeled recommended starting dose of 125mg/day, some patients initiate palbociclib at lower doses in routine practice. This study described real-world starting dose, patient characteristics, and effectiveness outcomes of first line PA+ AI for mBC in the US clinical setting. Methods: We conducted a retrospective analysis of Flatiron Health’s nationwide longitudinal electronic health records, which came from over 280 cancer clinics representing more than 2.2 million actively treated cancer patients in the US. Between February 2015 and September 2018, 813 HR+/HER2– mBC women initiated PA+AI as first-line therapy and had ≥ 3 months of potential follow-up. Patients were followed from start of PA+AI to December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS) was defined as the time from the start of PA+AI to death or disease progression. Real-world tumor response (rwTR) was assessed based on the treating clinician’s assessment of radiologic evidence for change in burden of disease over the course of treatment. Multivariate analyses were performed to adjust for demographic and clinical characteristics. Results: Of 813 eligible patients, 68.3% were white, median age was 65.0 years, and 42.9% had visceral disease (lung and/or liver). Median duration of follow-up was 21.0 months. 805 patients had records of PA starting dose, with 125mg and 75/100mg/day being 86.5% and 13.5%, respectively. Patients who started at 75/100mg/day were more likely to be ≥75 years than those who started at 125mg/day (38.5% vs 17.1%). Other baseline and disease characteristics were generally evenly distributed. Patients who started at 125mg/day had longer median rwPFS (27.8 vs 18.6 months, adjusted HR=0.74, 95%CI=0.52-1.05) and higher rwTR (54.0% vs. 40.4%) than those patients who started 100/75mg/day (adjusted OR=1.76, 95%CI=1.13-2.74). Table presents results in detail. Conclusions: Most patients in this study initiated palbociclib at 125mg/day and dose adjustment was similar regardless of starting dose. These real-world findings may support initiation of palbociclib at a dose of 125mg/day in combination with AI for the first-line treatment of HR+/HER2- mBC. [Table: see text]


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