scholarly journals PCN218 The IMPACT of Guideline-Concordant Treatment on Outcomes Among Elderly Women with HER2 Positive Metastatic Breast Cancer

2020 ◽  
Vol 23 ◽  
pp. S461
Author(s):  
A. Vyas ◽  
M. Gabriel ◽  
S. Kurian
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Elderly Women ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
The Impact

Impact of PIK3CA mutations and p95HER2 expression on the outcome of HER2-positive metastatic breast cancer patients treated with a trastuzumab-based therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 629-629
Author(s):  
Andrea Fontana ◽  
Giacomo Allegrini ◽  
Mazhar al Zoubi ◽  
Paola Collecchi ◽  
Chiara Mazzanti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
Rank Test ◽  
Her2 Positive ◽  
Pik3ca Mutations ◽  
Mutational Status ◽  
Clinical Resistance ◽  
The Impact

629 Background: Currently, no biomarkers of trastuzumab (T) clinical resistance have been validated. The aim of this pilot study was to evaluate the impact of PIK3CA mutations and p95HER2 (pHER2 truncated form) expression on the efficacy of a T based-therapy in a HER2-positive metastatic breast cancer (MBC) patients (pts). Methods: 107 HER2-positive MBC pts, treated in the last 10 years, were evaluated. Median age was 54 years (25-79); ECOG performance status was 0 in 56% of pts; all pts received several lines of treatment including T; biomarkers molecular analysis was performed in 70 tumor specimens. The IHC expression of p95HER2 was evaluated by a monoclonal antibody that specifically recognizes only the HER2 external domain; the HER2 integrity was defined by the presence of a homogeneous membrane staining (moderate or intense) in at least 30% of the cells, otherwise the HER2 was defined as p95HER2 positive. PIK3CA mutations in exons 9 and 20 were detected by automated sequencing. The molecular data were correlated to Time to progression (TTP) of the first line treatment including T and the Overall Survival (OS) by using the Kaplan-Meir method and the log-rank-test. Results: p95HER2 positive pts and PIK3CA mutations in exon 9 or 20 were detected in 42% and 22% of tumor specimens, respectively. p95HER2 positive tumors showed a shorter TTP and OS that did not reach statistical significance; PIK3CA mutations correlated with a worse TTP (median 7,6 vs 11,3 months) and OS (median 20,1 vs 41,0 months, p= 0,046). Conclusions: These preliminary results suggest a possible role of PIK3CA mutational status in predicting the outcome of MBC pts treated with T.

scholarly journals Population pharmacokinetic modeling of pyrotinib in patients with HER2-positive advanced or metastatic breast cancer

2020 ◽  
Author(s):  
Haini Wen ◽  
Yixi Liu ◽  
Da Xu ◽  
Kaijing Zhao ◽  
Zheng Jiao
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Total Protein ◽  
Metastatic Breast ◽  
Patient Characteristics ◽  
Population Pharmacokinetic ◽  
Phase I Clinical Trials ◽  
Her2 Positive ◽  
Protein Levels ◽  
The Impact

Objective: Pyrotinib, a novel oral irreversible dual pan-ErbB tyrosine kinase inhibitor (TKI), has been approved in China for the treatment of HER2-positive advanced or metastatic breast cancer. This study aimed to perform a population pharmacokinetics (PK) analysis of pyrotinib and to evaluate the impact of certain HER2-positive breast cancer patient characteristics on pyrotinib's PK. Method: A total of 1152 samples, provided by 59 adult female patients from two phase I clinical trials, were analyzed by nonlinear mixed-effects modeling. Monte Carlo simulation was conducted to assess the impact of covariates following exposure to pyrotinib. Results: The PK of pyrotinib was adequately described by a one-compartment model with first-order absorption and elimination. Patient's age and total protein levels can affect pyrotinib's apparent volume of distribution, and concomitant use of montmorillonite powder had significant effects on the bioavailability of pyrotinib. No PK interactions were observed between capecitabine and pyrotinib. Conclusion: In this study, a population PK model of pyrotinib was developed to determine the influence of patient characteristics on the PK of pyrotinib. While patient age and total protein levels can significantly affect the apparent distribution volume of pyrotinib, the magnitude of the impact was limited, thus no dosage adjustment was recommended. Furthermore, concomitant use of montmorillonite powder for diarrhea can decrease the bioavailability of pyrotinib by 50.3%.

The first two lines of chemotherapy for anthracycline-naïve metastatic breast cancer: A comparative study of efficacy between anthracyclines and nonanthracyclines.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1061-1061
Author(s):  
Wei-Wu Chen ◽  
Twan Ying Chang ◽  
Shu-Min Huang ◽  
Ching-Hung Lin ◽  
Chiun Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Palliative Chemotherapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
University Hospital ◽  
Rank Test ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
The Impact

1061 Background: For anthracycline-naïve metastatic breast cancer (AN-MBC) patients, past evidence indicated that anthracyclines are beneficial in the first-two lines of palliative chemotherapy but with considerable toxicities. However, with the provision of newer chemotherapies, comparative studies addressing the efficacy between anthracyclines and non-anthracyclines in the first-two lines of palliative chemotherapy for AN-MBC were lacking. Methods: We collectedclinicopathological characteristics of AN-MBC patients who had received palliative chemotherapy in National Taiwan University Hospital between 2001 and 2006. Patients were classified as anthracycline or non-anthracycline group according to the first-two lines of chemotherapy. Kaplan-Meier method and log-rank test were used for the estimation and comparison of both overall survival (OS) and time to treatment failure of the first-two lines (TTF2).Cox proportional hazard model was used for OS and TTF2. Best composite response rate (BCRR) were compared with logistic regression test. Results: A total of 109 (43.1%) patients in the anthracycline group and 144 (56.9%) patients in non-anthracycline group were analyzed. Between these two groups, the distributions of clinicopathological variables were generally similar and their median OS (33.3 vs 34.2 months, p = 0.179), TTF2 (13.3 vs 12.7 months, p = 0.104), and BCRR (59.5 vs 61.1%, p = 0.81) were not significantly different. Subgroup analysis showed that patients in the anthracycline group had a trend toward better OS in the estrogen receptor (ER) negative/ human epidermal growth factor receptor type II (HER2) positive subtype (median OS 58.0 vs 31.2 months, p = 0.081). In multivariate analysis, patients in the anthracycline group had a trend toward better OS (HR 0.72, 95% CI 0.52 - 1.00, p = 0.052). However, the exclusion of ER-/Her2+ subtype attenuated the impact of early anthracycline treatment on OS (HR 0.82, 95% CI 0.56 - 1.18, p = 0.28). Conclusions: Our study demonstrated that anthracyclines may not be mandatory in the first-two lines of palliative chemotherapy for AN-MBC but may be more beneficial to ER-/Her2+ subtype patients.

scholarly journals Guideline-Concordant Treatment Among Elderly Women With HER2-Positive Metastatic Breast Cancer in the United States

2020 ◽  
Vol 18 (4) ◽  
pp. 405-413
Author(s):  
Ami M. Vyas ◽  
Hilary Aroke ◽  
Stephen Kogut
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Diagnosis ◽  
Elderly Women ◽  
Decomposition Analysis ◽  
Metastatic Breast ◽  
The United States ◽  
Patient Treatment ◽  
Study Cohort ◽  
Her2 Positive

Background: It is crucial to identify whether women with HER2-positive (HER2+) metastatic breast cancer (MBC) are treated according to treatment guidelines and whether treatment disparities exist. This study examined guideline-concordant treatment among women with HER2+ MBC and determined the magnitude of differences in treatment between those with positive and negative hormone receptor (HR) status using a nonlinear decomposition technique. Methods: A retrospective observational cohort study was conducted using the SEER-Medicare linked database. The study cohort consisted of women aged ≥66 years diagnosed with HER2+ MBC in 2010 through 2013 (n=241). Guideline-concordant initial treatment after cancer diagnosis was defined based on the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. A multivariable logistic regression was performed to identify significant predictors of guideline-concordant treatment. A postregression decomposition was conducted to identify the magnitude of disparities in treatment by HR status. Results: Of 241 women included in the study, a total of 76.8% received guideline-concordant treatment. These women were significantly more likely to have positive HR status (P=.0298), have good performance status (P=.0009), and more oncology visits (P<.0001). With 1-year increments in age at cancer diagnosis, the likelihood of receiving guideline-concordant treatment reduced by 5% (P=.0356). The decomposition analysis revealed that 19.0% of the disparity in guideline-concordant treatment between women with positive and negative HR status was explained by differences in their characteristics. Enabling characteristics (marital status, income, and education) explained the highest (22.8%) proportion of the disparity. Conclusions: Nearly one-quarter of the study cohort did not receive guideline-concordant treatment. Our findings suggest opportunities to improve cancer care for elderly women with negative HR status who are unpartnered or have lower socioeconomic status. The high unexplained portion of the disparity by HR status can be due to patient treatment preferences, propensity to seek care, and organizational and physician-level characteristics that were not included in the study.

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a study in 107 patients

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
M Wallwiener ◽  
AD Hartkopf ◽  
S Riethdorf ◽  
J Nees ◽  
FA Taran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
The Impact

scholarly journals Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

Breast Cancer ◽  
2021 ◽  
Author(s):  
Takamichi Yokoe ◽  
Sasagu Kurozumi ◽  
Kazuki Nozawa ◽  
Yukinori Ozaki ◽  
Tetsuyo Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

scholarly journals Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Disease ◽  
Positive Impact ◽  
Metastatic Breast ◽  
Normal Liver ◽  
Liver Parenchyma ◽  
Breast Cancer Patients ◽  
Radiation Induced ◽  
The Impact

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

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