Tamoxifen, hot flashes, and breast cancer recurrence: Support for pharmacogenetics

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
J. Mortimer ◽  
S. Flatt ◽  
B. Parker ◽  
E. Gold ◽  
J. P. Pierce
Keyword(s):  
Breast Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Hot Flashes ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Adjuvant Tamoxifen ◽  
Hazards Model ◽  
Night Sweats

500 Background: Knowledge of the pharmacogenetics of the CYP2D6 enzyme has been shown to correlate with the efficacy of adjuvant tamoxifen. Women who are ‘extensive metabolizers” of CYP2D6 have an improved relapse free survival and experience more hot flashes than women who have impaired metabolism (Goetz, JCO 2005;23:9312–18). We hypothesized that the development of hot flashes on adjuvant tamoxifen was an indicator of drug metabolism and would correlate with a more favorable outcome than women who did not experience hot flashes. Methods: The WHEL trial enrolled 3,088 breast cancer survivors with stages I (T1c)-IIIA breast cancer, within 2–48 months of initial diagnosis, and age < 75 years to either a dietary intervention (n=1,537) or a control group (n=1,551). Data on the primary tumor, cancer treatment, disease status, and quality of life measures were collected at baseline and annually. Bivariate associations of vasomotor symptoms with age, race/ethnicity, menopausal status, cancer stage, ER and PR status, and time since diagnosis were tested using chi-square tests for categorical and t-tests for continuous variables. A left-truncated Cox proportional hazards model tested the association between recurrence-free survival and hot flashes, adjusting for tumor stage and grade and patient age. Women who died without a new breast cancer event were censored at their date of death; those without a new breast cancer event were censored at December 1, 2006 or the date of their most recent self-report of their breast cancer status. Results: The study sample includes 864 women treated with adjuvant tamoxifen 78% who reported hot flashes, and 69% of those reporting hot flashes also reported night sweats; 4% reported night sweats without hot flashes, and 18% reported neither hot flashes nor night sweats. A delayed entry Cox proportional hazards model adjusting for tumor stage and grade showed that those reporting hot flashes had a hazard ratio of 0.51 of recurrence during the follow-up period (95% CI 0.32–0.79) and that hot flashes were more predictive of outcome for tamoxifen treated patients than were age, grade, hormone receptor status, or stage II cancer. Conclusions: Our results contribute to the data that suggest tamoxifen side effects and efficacy may relate to an individual’s pharmacogenetics. No significant financial relationships to disclose.

scholarly journals Antibiotics modulate neoadjuvant therapy efficiency in patients with breast cancer: a pilot analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xi Zhang ◽  
Long Yu ◽  
Jiajie Shi ◽  
Sainan Li ◽  
Shiwei Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Antibiotic Administration ◽  
Hazards Model ◽  
Kaplan Meier ◽  
The Impact

AbstractMounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan–Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314–6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016–7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77–17.2, p = 0.003) and OS (HR 7.0395% CI 1.94–25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41–172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39–130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.

Prognostic Factors and Survival Outcomes among Patients with Breast Cancer and Brain Metastases at Diagnosis: A National Cancer Database Analysis

Oncology ◽  
2021 ◽  
Vol 99 (5) ◽  
pp. 280-291
Author(s):  
Brittney S. Zimmerman ◽  
Danielle Seidman ◽  
Krystal P. Cascetta ◽  
Meng Ru ◽  
Erin Moshier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Breast Cancer Diagnosis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
National Cancer Database ◽  
Hazards Model ◽  
Sites Of Metastases

Introduction: The aim of this study was to assess for clinicopathologic and socioeconomic features that predict improved survival for patients with advanced breast cancer with synchronous brain metastases at diagnosis. Methods: We utilized the National Cancer Database (NCDB) to identify all patients with brain metastases present at diagnosis, with adequate information on receptor status (ER, PR, Her2), clinical T stage of cT1-4, clinical M1, with 3,943 patients available for analysis. The association between brain metastases patterns and patient/disease variables was examined by robust Poisson regression model. Cox proportional hazards model was used to quantify the associations between overall survival (OS) and these variables. Results: In univariable analysis, OS was significantly associated with the number of sites of metastases (p < 0.0001). Patients with 2 or more additional extracranial sites of metastases had significantly worse OS (median 8.8 months, 95% confidence interval [CI] 7.8, 9.9) than patients with brain metastases only (median OS 10.6 months, 95% CI 9.4, 12.9) or brain metastases plus one other extracranial site of metastases (median OS 13.1 months, 95% CI 11.8, 14.4). Risk factors which predicted poor prognosis included triple-negative disease, high comorbidity score, poorly differentiated tumors, invasive lobular histology, multi-organ involvement of metastases, and government or lack of insurance. Factors which improve survival include younger age and Hispanic race. Discussion/Conclusion: Using a large NCDB, we identified various factors associated with prognosis for patients with brain metastases at the time of breast cancer diagnosis. Insurance status and related socioeconomic challenges provide potential areas for improvement in care for these patients. This information may help stratify patients into prognostic categories at the time of diagnosis to improve treatment plans.

scholarly journals Primary fallopian tube carcinoma: a single-institution retrospective study of 57 cases

2019 ◽  
Author(s):  
Zhihua Ma ◽  
Li Gao ◽  
Han Li ◽  
Yan Xue
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Free Survival ◽  
Residual Tumor ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Free Survival ◽  
Hazards Model ◽  
Disease Free

Abstract Background In order to identify the characteristics and factors affecting the treatment and prognosis of primary fallopian tube cancer(PFTC),we analyzed the clinical profile of PFTC in the past 10 years in our hospital, which is center in Western China. Methods A retrospective analysis was performed on 57 patients diagnosed as PFTC at the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xi’an Jiaotong University from past ten years. The clinical index and a Cox proportional hazards model was used for univariate and multivariate survival analyses. Results The mean age of PFTC at diagnosis was 57.35±9.01 years. Palpable pelvic and/or abdominal mass (68.4%) was the main clinical symptom. Preoperatively, 80.7% patients were misdiagnosed with ovarian cancer, and 43.8% of patients were at stage III. 26 patients were relapsed at the median of 18.5 (3-83) months. The 5-year overall survival (OS) rate was 15.4%, and the 5-year disease-free survival (DFS) was 11.5%. Additionally, univariate analysis showed that tumor stage and size of residual tumor were both related to 5-year OS and DFS. While level of serum carbohydrate antigen 125(CA125) pre-treatment was only related to DFS. The Cox proportional hazards model demonstrated that residual tumor size was the only independent factor related to both 5-year OS and DFS. Conclusions PFTC is a more common malignancy at post-menopause stage in women. The symptoms are not typical in most case and often diagnose at late clinical stage. Tumor stage, level of CA125, and residual lesion size affected the disease-free survival or/ and overall survival. Trial registration Not applicable.

Which benefit from subsequent chemotherapy lines beyond the second for women with metastatic breast cancer? Evidence from a single-center retrospective analysis of survivorship.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 255-255
Author(s):  
G. Bernardo ◽  
R. Palumbo ◽  
A. Bernardo ◽  
C. Teragni ◽  
F. Sottotetti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Retrospective Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Metastatic Breast ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model

255 Background: Although the true impact of chemotherapy (CT) in metastatic breast cancer (MBC) is still debated, in the routine clinical practice an increasing number of women asking for further treatment after progression receive subsequent CT lines. This study aimed to assess which benefit could be brought by the succession of CT lines in patients treated for MBC and to identify women who benefit from these treatments. Methods: This retrospective analysis included 980 women treated with CT for MBC at our Institution over a 7-year period (May 1999-July 2006). With overall survival (OS) data updated at December 1, 2008, the median follow-up was 125 months (range 48-192), OS and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: Median OS evaluated from day 1 of each CT line decreased with the line number from 34.8 months (980 patients, 1st line, range 4-208) to 22.6 months (838 patients, 2nd line), 14.6 months (684 patients, 3rd line), 12.4 months (302 patients, 4th line), 9.4 months (88 patients, 5th line), 8.2 months (45 patients, seven or more lines). Median TTF ranged from 9.2 months to 7.8 and 6.4 months for the first, second and third line, respectively, with no significant decrease observed beyond the 3rd line (median 5.2 months, range 4.8-6.2). In univariate analysis factors positively linked to a longer duration of TTF for each CT line were positive hormonal receptor status, absence of liver metastasis, adjuvant CT exposure, response to CT for the metastatic disease; in the multivariate analysis the duration of TTF for each CT line was the only one factor with significant impact on survival benefit for subsequent treatments (p<0.001). Conclusions: CT beyond the 2nd line may be beneficial in a significant subset of women treated for MBC, with improved TTF and OS. These findings could help physician in planning an appropriate strategy of subsequent schedules for women with symptomatic MBC who responded to their 1st line CT, while non responder patients should be considered for clinical trials.

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Dementia Adjudication Triggers Associated With Increased Mortality for Older Australians: Evidence From ASPREE

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 161-161
Author(s):  
Jane Banaszak-Holl ◽  
Xiaoping Lin ◽  
Jing Xie ◽  
Stephanie Ward ◽  
Henry Brodaty ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Service Planning ◽  
Cox Proportional Hazards Model ◽  
Cognitive Test ◽  
Risk Of Death ◽  
Hazards Model ◽  
Using Data

Abstract Research Aims: This study seeks to understand whether those with dementia experience higher risk of death, using data from the ASPREE (ASPirin in Reducing Events in the Elderly) clinical trial study. Methods: ASPREE was a primary intervention trial of low-dose aspirin among healthy older people. The Australian cohort included 16,703 dementia-free participants aged 70 years and over at enrolment. Participants were triggered for dementia adjudication if cognitive test results were poorer than expected, self-reporting dementia diagnosis or memory problems, or dementia medications were detected. Incidental dementia was adjudicated by an international adjudication committee using the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) criteria and results of a neuropsychological battery and functional measures with medical record substantiation. Statistical analyses used a cox proportional hazards model. Results: As previously reported, 1052 participants (5.5%) died during a median of 4.7 years of follow-up and 964 participants had a dementia trigger, of whom, 575 (60%) were adjucated as having dementia. Preliminary analyses has shown that the mortality rate was higher among participants with a dementia trigger, regardless of dementia adjudication outcome, than those without (15% vs 5%, Χ2 = 205, p &lt;.001). Conclusion: This study will provide important analyses of differences in the hazard ratio for mortality and causes of death among people with and without cognitive impairment and has important implications on service planning.

scholarly journals Evaluation of Changes on World Stock Exchanges in Connection with the SARS-CoV-2 Pandemic. Survival Analysis Methods

Risks ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 121
Author(s):  
Beata Bieszk-Stolorz ◽  
Krzysztof Dmytrów
Keyword(s):  
Survival Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stock Exchange ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stock Exchanges ◽  
Analysis Methods ◽  
Hazards Model ◽  
Kaplan Meier

The aim of our research was to compare the intensity of decline and then increase in the value of basic stock indices during the SARS-CoV-2 coronavirus pandemic in 2020. The survival analysis methods used to assess the risk of decline and chance of rise of the indices were: Kaplan–Meier estimator, logit model, and the Cox proportional hazards model. We observed the highest intensity of decline in the European stock exchanges, followed by the American and Asian plus Australian ones (after the fourth and eighth week since the peak). The highest risk of decline was in America, then in Europe, followed by Asia and Australia. The lowest risk was in Africa. The intensity of increase was the highest in the fourth and eleventh week since the minimal value had been reached. The highest odds of increase were in the American stock exchanges, followed by the European and Asian (including Australia and Oceania), and the lowest in the African ones. The odds and intensity of increase in the stock exchange indices varied from continent to continent. The increase was faster than the initial decline.

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