Tamoxifen and Chemotherapy for Axillary Node-Negative, Estrogen Receptor–Negative Breast Cancer: Findings From National Surgical Adjuvant Breast and Bowel Project B-23

2001 ◽  
Vol 19 (4) ◽  
pp. 931-942 ◽  
Author(s):  
Bernard Fisher ◽  
Stewart Anderson ◽  
Elizabeth Tan-Chiu ◽  
Norman Wolmark ◽  
D. Lawrence Wickerham ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Axillary Node ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Cox Proportional Hazards Models ◽  
Significant Difference ◽  
Bowel Project ◽  
Estrogen Receptor Negative

PURPOSE: Uncertainty about the relative worth of doxorubicin/cyclophosphamide (AC) and cyclophosphamide/methotrexate/fluorouracil (CMF), as well as doubt about the propriety of giving tamoxifen (TAM) with chemotherapy to patients with estrogen receptor–negative tumors and negative axillary nodes, prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study. PATIENTS AND METHODS: Patients (n = 2,008) were randomly assigned to CMF plus placebo, CMF plus TAM, AC plus placebo, or AC plus TAM. Six cycles of CMF were given for 6 months; four cycles of AC were administered for 63 days. TAM was given daily for 5 years. Relapse-free survival (RFS), event-free survival (EFS), and survival (S) were determined by using life-table estimates. Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status. RESULTS: No significant difference in RFS, EFS, or S was observed among the four groups through 5 years (P = .96, .8, and .8, respectively), for those aged ≤ 49 years (P = .97, .5, and .9, respectively), or for those aged ≥ 50 years (P = .7, .6, and .6, respectively). A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS (87% at 5 years in both groups, P = .9), EFS (83% and 82%, P = .6), or S (89% and 90%, P = .4). There were no significant differences in RFS, EFS, or S between CMF and AC in patients aged ≤ 49 or ≥ 50 years. No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM. RFS in both groups was 87% (P = .6), 87% in patients aged ≤ 49 (P = .9), and 88% and 87%, respectively (P = .4), in those aged ≥ 50 years. CONCLUSION: There was no significant difference in the outcome of patients who received AC or CMF. TAM with either regimen resulted in no significant advantage over that achieved from chemotherapy alone.

scholarly journals Malaria is associated with Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in a cohort of western Kenyan children

2020 ◽  
Author(s):  
Katherine R Sabourin ◽  
Ibrahim Daud ◽  
Sidney Ogolla ◽  
Nazzarena Labo ◽  
Wendell Miley ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Proportional Hazards ◽  
Kaposi Sarcoma ◽  
Cox Proportional Hazards ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cox Proportional Hazards Models ◽  
Malaria Exposure ◽  
Significant Difference ◽  
Transmission Region ◽  
Multiplex Bead

Abstract Background We aimed to determine whether Plasmodium falciparum (Pf) infection affects age of Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in Kenyan children. Methods Kenyan children (n=144) enrolled at age one month, from two sites with different levels of malaria transmission (stable/high malaria vs. unstable/low malaria transmission) were followed through 24 months. Plasma was tested for KSHV antibodies using enzyme-linked immunosorbent assay (ELISA) (K8.1 and LANA) and a multiplex bead-based assay (K8.1, K10.5, ORF38, ORF50, and LANA) and whole blood tested for Pf DNA using quantitative-PCR. Cox proportional hazards models were used to assess associations between Pf DNA detection, malaria annualized rate (Pf detections/person-years), and enrollment site (malaria-high vs malaria-low) with time to KSHV seroconversion. Results KSHV seroprevalence was 63% by 2 years of age when assessed by multiplex assay. Children with Pf were at increased hazards of earlier KSHV seroconversion and among children with malaria, the hazard of becoming KSHV seropositive increased significantly with increasing malaria annualized rate. Children from the malaria-high transmission region had no significant difference in hazards of KSHV seroconversion at 12 months but were more likely to become KSHV seropositive by 24 months of age. Discussion Malaria exposure increases the risk for KSHV seroconversion early in life.

Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 59-59
Author(s):  
Umang Swami ◽  
Taylor Ryan McFarland ◽  
Benjamin Haaland ◽  
Adam Kessel ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Cox Proportional Hazards Models ◽  
Risk Of Progression ◽  
The Relationship

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p < 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p < 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

1990 ◽  
Vol 8 (9) ◽  
pp. 1483-1496 ◽  
Author(s):  
B Fisher ◽  
A M Brown ◽  
N V Dimitrov ◽  
R Poisson ◽  
C Redmond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Positive Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Significant Difference ◽  
Bowel Project ◽  
Disease Free

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

scholarly journals Risk of depressive disorders after tobacco smoking cessation: a retrospective cohort study in Fukuoka, Japan

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025124 ◽  
Author(s):  
Takako Fujita ◽  
Akira Babazono ◽  
Yumi Harano ◽  
Peng Jiang
Keyword(s):  
Smoking Cessation ◽  
Cohort Study ◽  
Survival Analysis ◽  
Retrospective Cohort ◽  
Depressive Disorders ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Significant Difference

ObjectiveWe sought to examine the effect of smoking cessation on subsequent development of depressive disorders.DesignThis was a retrospective cohort study.MethodsWe used administrative claim and health check data from fiscal years 2010 to 2014, obtained from the largest health insurance association in Fukuoka, Japan. Study participants were between 30 and 69 years old. The end-point outcome was incidence of depressive disorders. Survival analysis and Cox proportional hazards models were conducted. The evaluated potential confounders were sex, age, standard monthly income and psychiatric medical history.ResultsThe final number of participants was 87 255, with 7841 in the smoking cessation group and 79 414 in the smoking group. The result of survival analysis showed no significant difference in depressive disorders between the two groups. The results of Cox proportional hazards models showed no significant difference by multivariate analysis between participants, including users of smoking cessation medication (HR 1.04, 95% Cl 0.89 to 1.22) and excluding medication use (HR 0.97, 95% Cl 0.82 to 1.15).ConclusionsThe present study showed that there were no significant differences with respect to having depressive disorders between smoking cessation and smoking groups. We also showed that smoking cessation was not related to incidence of depressive disorders among participants, including and excluding users of smoking cessation medication, after adjusting for potential confounders. Although the results have some limitations because of the nature of the study design, our findings will provide helpful information to smokers, health professionals and policy makers for improving smoking cessation.

scholarly journals Association of Mid- to Late-Life Blood Pressure Patterns With Risk of Subsequent Coronary Heart Disease and Death

2021 ◽  
Vol 8 ◽  
Author(s):  
Menghui Liu ◽  
Shaozhao Zhang ◽  
Xiaohong Chen ◽  
Xiangbin Zhong ◽  
Zhenyu Xiong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Proportional Hazards ◽  
Late Life ◽  
Cox Proportional Hazards ◽  
Atherosclerosis Risk In Communities ◽  
Cox Proportional Hazards Models ◽  
Significant Difference ◽  
All Cause Mortality

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

Efficacy of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and baseline (BL) comorbidities (CM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Proportional Hazards Models ◽  
Castration Resistant ◽  
Cox Proportional Hazards Models ◽  
The Impact ◽  
Clinical Trial Information

5023 Background: The addition of APA to ongoing ADT in pts with nmCRPC significantly prolonged metastasis-free survival (MFS), time to symptomatic progression (SymProg), and second progression-free survival (PFS2) in SPARTAN. We assessed the impact of APA on these end points in pts with or without BL CM. Methods: Using Cox proportional hazards models, treatment effect of APA was evaluated in SPARTAN pts with CM at BL, stratifying by the presence of BL diabetes/hyperglycemia (D/H), cardiovascular disease (CVD), hypertension (HTN), and renal insufficiency (RI). Results: Of 1207 SPARTAN pts, 1062 (88%) had ≥ 1 BL CM, including 703/806 (87%) APA pts and 359/401 (90%) PBO pts. A total of 226 (19%), 398 (33%), 798 (66%), and 774 (64%) pts had D/H, CVD, HTN, and RI, respectively; 323 (27%), 412 (34%), 259 (21%), and 68 (6%) pts had 1, 2, 3, and 4 CM, respectively. Incidence of CM was balanced between arms. Pts with CM were older than pts with no CM (median age, 75 vs 69 yrs, APA; 74 vs 69 yrs, PBO). MFS, SymProg, and PFS2 benefit with APA was significant in all CM subgroups, except PFS2 for pts with D/H (Table) and regardless of the number of CM. The incidence of any treatment-emergent AE was balanced between pts with and without CM. AEs with APA were not affected by any CM. Clinical trial information: NCT01946204. Conclusions: The benefit of APA + ongoing ADT in pts with nmCRPC was maintained in pts with D/H, CVD, HTN, and RI. The safety profile of APA was not affected by any CM.[Table: see text]

scholarly journals Sarcopenia is an independent predictor of hospitalization in chronic kidney disease outpatients

2019 ◽  
Author(s):  
Hye Yun Jeong ◽  
Wooyeol Ahn ◽  
Jun Chul Kim ◽  
Yu Bum Choi ◽  
Jinkwon Kim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Strength ◽  
Proportional Hazards ◽  
Handgrip Strength ◽  
Cox Proportional Hazards ◽  
Chronic Illnesses ◽  
Free Survival ◽  
Cox Proportional Hazards Models ◽  
Appendicular Skeletal Muscle

AbstractBackgroundPatients with chronic kidney disease (CKD) experience much more marked and earlier muscle wasting than subjects who do not have chronic illnesses. However, a few studies that have examined sarcopenia have been reported in CKD patients. We investigated the prevalence of sarcopenia in predialysis and dialysis outpatients with CKD and explored its relationship with the clinical outcomes.MeasurementsSarcopenia was defined as reduced muscle strength accompanied by decreased adjusted appendicular skeletal muscle (ASM), while those patients who exhibited only one of these characteristics were categorized as presarcopenic patients. ASM was measured by bioimpedence analysis, and muscle strength was evaluated by handgrips. ASM was adjusted by weight (ASM/wt). Patients were prospectively followed for up to 2 years.ResultsOne hundred seventy-nine patients were recruited (114 male and 65 female patients who were classified into 103 predialysis patients and 76 dialysis patients, with 44.7% having diabetes). Their mean age was 60.6 ± 13.5 years old. The prevalence of sarcopenia was 9.5%, while 55.9% of the patients were categorized as presarcopenic. The ASM/wt index showed significant correlations with age, handgrip strength, HOMA-IR and frailty scores. Multivariate Cox proportional hazards models demonstrated that the risk of hospitalization was significantly higher for patients with presarcopenia [hazard ratio (HR), 2.48; 95% confidence interval (CI), 1.180–5.230], and the risk of hospitalization was much higher for patients with sarcopenia than for patients in the nonsarcopenic group (HR, 9.11; 95% CI, 2.295–25.182)ConclusionsSarcopenia and presarcopenia, which were defined using the ASM/wt index and handgrip strength, predicted a poorer, hospitalization-free survival in CKD patients

scholarly journals Metastatic progression following multimodal therapy for unfavorable-risk prostate cancer

2021 ◽  
Vol 16 (4) ◽  
Author(s):  
David Guy ◽  
Rachel Glicksman ◽  
Roger Buckley ◽  
Patrick Cheung ◽  
Hans Chung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Metastatic Prostate Cancer ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Metastatic Progression ◽  
Free Survival ◽  
Cox Proportional Hazards Models

Introduction: Identifying the optimal management of unfavorable-risk (ProCaRS high intermediate-, high-, and very high-risk categories) non-metastatic prostate cancer is an important public health concern given the large burden of this disease. We compared the rate of metastatic progression-free survival among men diagnosed with unfavorable-risk non-metastatic prostate cancer who were initially treated with radiation therapy or radical prostatectomy. Methods: Information was obtained from medical records at two academic centers in Canada from 333 men diagnosed with unfavorable-risk non-metastatic prostate cancer between 2007 and 2012. Median followup was 90.4 months. Men were eligible for study if they received either primary radiation therapy (n=164) or radical prostatectomy (n=169), in addition to various adjuvant and salvage therapies when deemed clinically appropriate. Patients were matched on prognostic covariates using two matching techniques. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and confidence intervals (CI) for metastatic progression-free survival between groups. Results: After matching, treatment groups were balanced on prognostic variables except for percent core positivity. Hazard ratios from all Cox proportional hazards models (i.e., before and after matching, and with and without multivariable adjustment) showed no difference in the rate of metastatic progression-free survival between groups (adjusted unmatched HR 1.16, 95% CI 0.63, 2.13, p=0.64). Conclusions: Metastatic progression-free survival did not differ between men diagnosed with unfavorable risk non-metastatic prostate cancer who were treated with either radiation therapy or radical prostatectomy.

MicroRNA polymorphisms and esophageal cancer outcome.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 32-32 ◽  
Author(s):  
Olusola Olusesan Faluyi ◽  
Lawson Eng ◽  
Xin Qui ◽  
Dangxiao Cheng ◽  
Daniel John Renouf ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Free Survival ◽  
Cox Proportional Hazards Models ◽  
The Mean ◽  
Cancer Outcome

32 Background: Better understanding of the biology of esophageal cancer may help improve its treatment. MicroRNAs (miRs) regulate mRNA and can exert some influence on carcinogenesis. Identification of the microRNAs which regulate esophageal cancer development could potentially yield alternative therapeutic options. Objectives: We evaluated polymorphisms in miRs, miR biogenesis, binding sites of miR and their role in the survival of esophageal cancer patients. Methods: 324 esophageal cancer patients of all stages and histological subtypes were evaluated. Using Illumina Custom GoldenGate, 43 polymorphisms in miR pathways were evaluated. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 83% were male while the mean age was 65 years. 73% had adenocarcinomas while 33.6% had advanced tumors (Stage IV). The median PFS was 1.20 years, while median OS was 2.17 years. After adjustment for clinical variables, a 5’UTR polymorphism in pri-mir26a-1 (rs7372209) was significantly associated with reduced PFS [aHR=0.78, CI:0.62-0.98, p=0.04] and OS [aHR 0.71 (0.56-0.89), p=0.003]. Three other polymorphisms were significantly associated with OS but not PFS: these included two polymorphisms of miR processing genes, DDX20 (rs197412) [aHR 1.31 (1.04-1.64), p=0.02] and EIF2C1 (rs595961) [aHR 0.76 (0.60-0.97), p=0.03] as well as the CD86 3’UTR C>G (rs17281995) polymorphism, which has been predicted to affect the binding of miR337, miR582, miR200a, miR184, and miR212 [aHR 1.38 (1.03-1.85), p=0.03]. Conclusions: We report the initial association of miR related polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.

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