Search

Background Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients. Methods Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P -values were 2-sided. Results This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P -interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P -interaction = .24). Conclusion In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole. [ABSTRACT FROM AUTHOR]

In August 2017, cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2−) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2− ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2‐year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing‐risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43‐57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27‐36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first‐line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first‐line: 29%‐13%; second‐line: 26%‐19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first‐line therapy. What's new? In the Netherlands, inhibitors of cyclin‐dependent kinase 4/6 (CDK 4/6) are eligible for reimbursement by health insurers. The present report describes implementation patterns of CDK4/6 inhibitors for the treatment of advanced breast cancer since 2017, based on data and observations collected from seven hospitals across the Southeast Netherlands. Analyses show that about half of patients with HR+/HER2‐ metastatic breast cancer are treated with CDK4/6 inhibitors. Following the implementation of these therapies, use of first‐line chemotherapy decreased significantly. Reduced chemotherapy use may have beneficial effects on quality of life for patients, adding value to overall gains in survival. [ABSTRACT FROM AUTHOR]

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule. Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous). Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82–1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98–1.66) for intermittent versus continuous second-line chemotherapy. Second-line PFS was positively influenced by prior hormonal therapy for metastatic disease and longer first-line PFS duration, while triple-negative tumor status had a negative influence. Patients with a shorter time to progression (TTP) in first-line (≤10 months) had a higher probability of starting second-line treatment if they received intermittent compared to continuous chemotherapy (OR 1.97; 95% CI: 1.02–3.80). Conclusion: We recommend continuous scheduling of both the first- and second-line chemotherapy for advanced breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2–3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. Methods: We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan–Meier methods and Cox proportional hazards models were used for analyses. Results: Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45–1.49), osteoporosis HR 1.10 (95% CI 0.26–4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40–1.42), osteoporosis HR 1.86 (95% CI 0.43–8.01)]. Moreover, bisphosphonate use did not impact DRFS. Conclusion: No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS. [ABSTRACT FROM AUTHOR]

Background: The Stop&Go study randomized patients with advanced breast cancer to intermittent (two times four) or continuous (eight subsequent cycles) first- and second-line chemotherapy. Methods: QoL was measured with RAND-36 questionnaires every 12 weeks. The primary objective was to estimate differences in changes from baseline between intermittent and continuous treatment. An effect size of 0.5 SD (5 points) was considered clinically meaningful. Results: A total of 398 patients were included with a median follow-up of 11.4 months (IQR 5.6–22.2). Mean physical QoL baseline scores were 38.0 resp. 38.2, and mental scores 45.0 resp. 42.4 for intermittent and continuous treatment. Physical QoL declined linearly in the intermittent arm causing a clinically meaningful difference of 5.40 points at 24 months (p < 0.001), while scores in the continuous arm stabilized after a small decline of ± 3.4 points at 12 months. Conversely, mental QoL was fairly stable and even improved with 1.58 (p = 0.005) and 2.48 points (p < 0.001) at 12 months for intermittent and continuous treatment, respectively. When comparing arms for both components in changes from baseline, the maximum differences were 2.46 (p = 0.101) and 1.95 points (p = 0.182) for physical and mental scores, both measured at 30 months and in favor of continuous treatment. Conclusion: Intermittent first- and second-line chemotherapy in patients with HER2-negative advanced breast cancer showed a trend for worse impact on QoL compared to continuous chemotherapy, with neither significant nor meaningful differences in course. We recommend prescribing chemotherapy continuously until progressive disease or unacceptable toxicity. Trial registration EudraCT 2010-021519-18; BOOG 2010-02 [ABSTRACT FROM AUTHOR]

Background: Low skeletal muscle index (SMI) in metastatic colorectal cancer (mCRC) patients is associated with poor outcomes. The prognostic impact of SMI changes during consecutive palliative systemic treatments is unknown. Methods: This is a retrospective analysis of the phase 3 CAIRO3 study. The CAIRO3 study randomized 557 patients between maintenance capecitabine + bevacizumab (CAP‐B) or observation, after six cycles capecitabine + oxaliplatin + bevacizumab (CAPOX‐B). Upon first disease progression (PD1), CAPOX‐B was reintroduced until second progression (PD2). SMI was assessed by computed tomography (CT) (total 1355 scans). SMI and body mass index (BMI) changes were analyzed for three time‐periods; p1: during initial CAPOX‐B, p2: randomization to PD1, and p3: PD1 to PD2. The association between absolute and change in SMI and BMI (both per 1 standard deviation) during p1‐p3, with PD1, PD2, and survival was studied by Cox regression models. Results: This analysis included 450 of the 557 patients randomized in the CAIRO3 study. Mean SMI decreased during p1: mean −0.6 SMI units [95% CI −1.07;‐0.26] and p3: −2.2 units [−2.7;‐1.8], whereas during p2, SMI increased + 1.2 units [0.8‐1.6]. BMI changes did not reflect changes in SMI. SMI loss during p2 and p3 was significantly associated with shorter survival (HR 1.19 [1.09‐1.35]; 1.54 [1.31‐1.79], respectively). Sarcopenia at PD1 was significantly associated with early PD2 (HR 1.40 [1.10‐1.70]). BMI loss independent of SMI loss was only associated with shorter overall survival during p3 (HR 1.35 [1.14‐1.63]). Conclusions: In mCRC patients, SMI loss during palliative systemic treatment was related with early disease progression and reduced survival. BMI did not reflect changes in SMI and could not identify patients at risk of poor outcome during early treatment lines. [ABSTRACT FROM AUTHOR]

Purpose and Methods: Nowadays more people are becoming older. The median age of a patient with non-Hodgkin's lymphoma (NHL) at diagnosis is over 60 years. The incidence of NHL in elderly has increased in the last decades. Therefore, in the future, NHL will be diagnosed more often in the elderly. Data of all patients in the south-east of the Netherlands with newly diagnosed NHL between January 1991 and January 1995 were analysed in a retrospective multicentre population-based study to investigate if and how elderly patients (> 60 years) with advanced NHL (Ann Arbor Staging > or = IIB) of intermediate- and high-grade malignancy were treated. Treatment modalities applied, outcome, and causes of death were evaluated. Treatment was considered inadequate if it deviated from the standard anthracycline-containing chemotherapy (CNOP/CHOP) for a minimum of six cycles.Results: The entry criteria were met by 68 patients. Of these patients, 57 (83.8%) were treated and 11 (16.2%) were not treated. The treatment consisted of CHOP (36 patients), CNOP (6 patients), chlorambucil (13 patients), or COP (2 patients). Forty-two of 68 patients had adequate treatment, but 14 of 42 (33.3%) patients had a suboptimal numbers of cycles (< 6). Of 28 patients with adequate chemotherapy, only 16 had the optimal number of cycles and dose; the result is that the treatment of 76.5% (52/68) of patients differed from that of their younger counterparts. The most important reason for treatment not being optimal was high age (23%) or poor performance (35%). In the appropriately treated patients, 62.5% (10/16) had a complete response. Survival in the CHOP/CNOP-treated group was better than in other groups. The main cause of death in the total study group was NHL. The results cannot be explained by the different international prognostic index.Conclusion: A significant subset (76.5%) of elderly people with intermediate/high-grade NHL received suboptimal therapy, mainly because of a suboptimal performance status. However, a significant part of the patients (23%) were not treated optimally because of high age, despite a good performance. For improving the overall survival in the elderly, it is not only the schedule that is important, but also the intention to treat the elderly patient. [ABSTRACT FROM AUTHOR]

This article reports on a clinical trial to study if combination treatment is better than sequential treatment in patients with advanced colorectal cancer. The purpose of the study was to determine the optimal use of cytotoxic drugs in advanced cases. The study divided patients into two groups. The first group got first-line treatment of capecitabine, second-line treatment of irinotecan and third-line treatment with capecitabine plus oxaliplatin. The other group was given capecitabine plus irinotecan for first-line treatment and capecitabine plus oxaliplatin for second-line treatment. The study concludes that combination treatment did not significantly improve overall survival compared to sequential therapy.

Purpose: The treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid mismatch repair deficiency/microsatellite-instable (dMMR/MSI) tumors, and in-depth biomarker analyses were performed to inform precision immunotherapy approaches., Patients and Methods: Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol, a pan-cancer clinical trial that treats patients with cancer based on their tumor molecular profile with off-label anticancer drugs (NCT02925234). Patients received nivolumab (four cycles of 240 mg every 2 weeks, thereafter 480 mg every 4 weeks). The primary endpoint was clinical benefit (CB: objective response or stable disease ≥16 weeks). Whole-genome sequencing and RNA sequencing were performed on pretreatment tumor biopsies., Results: A total of 130 evaluable patients were enrolled with 16 different cancer types. CB was observed in 62% [95% confidence interval (CI), 53-70], with an objective response in 45% (95% CI, 36-54). After a median follow-up of 14.5 months (95% CI, 13-19), the median progression-free survival was 18 months (95% CI, 9-not reached), and the median overall survival was not reached. Whereas CB was not, or only weakly, associated with markers of adaptive immune cell infiltration, CB was strongly associated with expression of a broad set of innate immune receptors/ligands. This clearly contrasted findings in melanoma, in which markers of adaptive immunity dominated the biomarker landscape., Conclusions: Nivolumab proved highly effective in advanced dMMR/MSI tumors. Expression of key innate immune receptors/ligands was the main predictor of a good treatment outcome, contrasting findings in melanoma and strengthening the rationale for tumor type-specific biomarkers for guiding immunotherapy., (©2024 American Association for Cancer Research.)

Background: The DATA study evaluated the use of two different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2-3 years of tamoxifen. We hereby present the follow-up analysis, which was performed after all patients reached a minimum follow-up of 10 years beyond treatment divergence., Methods: The open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301457). Postmenopausal women with hormone receptor-positive breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen treatment were assigned to either 3 or 6 years of anastrozole (1 mg orally once a day). Randomisation (1:1) was stratified by hormone receptor status, nodal status, HER2 status, and prior tamoxifen duration. The primary outcome was adapted disease-free survival, defined as disease-free survival from 3 years after randomisation onwards. Adapted overall survival was assessed as a secondary outcome. Analyses were performed according to the intention-to-treat design., Findings: Between June 28, 2006, and August 10, 2009, 1912 patients were randomly assigned to 3 years (n = 955) or 6 years (n = 957) of anastrozole. Of these, 1660 patients were eligible and disease-free at 3 years after randomisation. The 10-year adapted disease-free survival was 69.2% (95% CI 55.8-72.3) in the 6-year group (n = 827) and 66.0% (95% CI 62.5-69.2) in the 3-year group (n = 833) (hazard ratio (HR) 0.86; 95% CI 0.72-1.01; p = 0.073). The 10-year adapted overall survival was 80.9% (95% CI 77.9-83.5) in the 6-year group and 79.2% (95% CI 76.2-81.9) in the 3-year group (HR 0.93; 95% CI 0.75-1.16; p = 0.53)., Interpretation: Extended aromatase inhibition beyond 5 years of sequential endocrine therapy did not improve the adapted disease-free survival and adapted overall survival of postmenopausal women with hormone receptor-positive breast cancer., Funding: AstraZeneca., Competing Interests: VCGT-H reports grants and personal fees from AstraZeneca during the conduct of the study and outside the submitted work; grants and personal fees from Novartis and Lilly; grants from Roche, Pfizer, Daiichi Sankyo, and Gilead outside the submitted work. VCGT-H has a consulting role for AstraZeneca, Lilly, and Novartis. SWML reports grants from AstraZeneca during the conduct of the study; grants from Lilly outside the submitted work. SMEG reports grants from AstraZeneca during the conduct of the study; grants from Roche, Pfizer, Novartis, Lilly, Daiichi Sankyo, and Gilead; personal fees from AstraZeneca outside the submitted work. IJHV reports grants from AstraZeneca during the conduct of the study; grants from Pfizer and Lilly outside the submitted work. ACPS and ALTI report grants from AstraZeneca during the conduct of the study. CHS is chair of the Board of Dutch national breast cancer guidelines. JRK reports grants from AstraZeneca, MSD, Eisai, Lilly, and GSK outside the submitted work. JRK has been a Data Safety Monitoring Board or Advisory Board member for the Alison trial (UMCG) and the TEIPP trial (EMC). AHH reports grants from the Dutch Breast Cancer Research Group during the conduct of the study and outside the submitted work. AHH has been an Advisory Board member for Lilly. AHH received support from Pfizer to attend the ESMO 2022 congress. SCL reports grants from AstraZeneca during the conduct of the study and outside the submitted work; grants from Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMW, A Sister's Hope [Z]aan de Wandel, and Agendia outside the submitted work; consulting fees from AstraZeneca, ERC (EU), and NWO (Dutch Research Council); payment or honoraria from Daiichi Sankyo; other financial support for attending meetings from Daiichi Sankyo, ESMO, ERC (EU), and NWO (Dutch Research Council); non-financial support from Genentech (drug), Roche (drug), Gilead Sciences (drug), Novartis (drug), Agendia (gene expression tests), and AstraZeneca (drug). SCL has a patent (UN23A01/P-EP) pending on a method for assessing homologous recombination deficiency in ovarian cancer cells. SCL is chair of the Trial Steering Committee of the PIONEER trial (Cambridge University) and Member of the Health Council of the Netherlands – Independent scientific advisory body for government and parliament. The other authors have declared no conflicts of interests., (© 2023 The Authors.)

Background: This study aims to evaluate whether changes in therapeutic strategies have improved survival of patients diagnosed with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer (ABC) in real-world., Methods: All 1950 patients systemically treated for HR+/HER2- ABC and diagnosed between 2008 and 2019 in eight hospitals were retrieved from the SONABRE Registry (NCT-03577197). Patients were categorized per three-year cohorts based on year of ABC diagnosis. Tests for trend were used to examine differences in baseline characteristics, Kaplan-Meier methods and Cox proportional hazards for survival analyses, and competing-risk methods for 3-year use of systemic therapy., Findings: Over time, patients were older (≥70 years, 37%, n = 169/456 in 2008-2010, 47%, n = 233/493 in 2017-2019, p = 0.004) and more often had multiple metastatic sites at ABC diagnosis (48%, n = 220/456 in 2008-2010, 56%, n = 275/493 in 2017-2019, p = 0.002). Among patients with metachronous metastases the prior exposure to (neo-) adjuvant therapies increased over time (chemotherapy, 38%, n = 138/362 in 2008-2010, 48%, n = 181/376 in 2017-2019, p = <0.001; endocrine therapy, 64%, n = 231/362 in 2008-2010, 72%, n = 271/376 in 2017-2019, p = <0.001). Overall survival significantly improved from median 31.1 months (95% CI:28.2-34.3) for patients diagnosed in 2008-2010 to 38.4 months (95% CI:34.0-41.1) in 2017-2019 (adjusted hazard ratio = 0.76, 95% CI:0.64-0.90; p = 0.001). Three-year use of CDK4/6 inhibitors increased from 0% for patients diagnosed in 2008-2010 to 54% for diagnosis in 2017-2019. Conversely, three-year use of chemotherapy was 50% versus 36%, respectively., Interpretation: Over time, patients diagnosed with HR+/HER2- ABC presented with less favourable patient characteristics. Nevertheless, we observed that overall survival of ABC increased between 2008 and 2019, with increased use of endocrine/targeted therapies., Funding: The SONABRE Registry is supported by the Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); Novartis BV; Roche; Pfizer; and Eli Lilly & Co. Funding sources had no role in the writing of the manuscript., Competing Interests: MM report grants institutional grants from Gilead. SG reports institutional grants from Novartis BV, Roche, Pfizer, Eli Lilly, Daiichi Sankyo and Gilead, and personal fees from Astra-Zeneca. VTH reports institutional grants and personal fees from Roche, Novartis, Pfizer, and Eli Lilly, personal fees from Accord Healthcare, institutional grants from AstraZeneca, Eisai, Daiichi Sankyo and Gilead. All remaining authors have declared no conflicts of interest., (© 2022 The Authors.)

This review aims to evaluate the role of chemotherapy-containing regimens in the treatment of advanced breast cancer (ABC), with the purpose to optimize selection, sequencing and duration of treatment with the currently available agents for clinical practice. Data from observational as well as randomized phase II and III studies were included. Chemotherapy yielded a median overall survival (OS) of 2 years in registration studies, with comparable efficacy of different agents. Combining chemotherapy agents did not yield OS improvement and caused greater toxicity compared with single-agent chemotherapy. Continuing chemotherapy till progression or unacceptable toxicity generated greater efficacy without detrimental impact on quality of life compared with a limited amount of cycles. In real-world studies, benefits after third-line chemotherapy were modest compared with first- and second-line. Furthermore, effects of previous chemotherapy predicted effects of next-line therapy in real-world. Physicians increasingly prescribed capecitabine or taxanes as first- or second-line chemotherapy over time., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2-3 years of tamoxifen. This planned side-study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate-use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T-scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6- and 3-year group respectively (p = 0.18), during follow-up. Only two patients (3-year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6- and 3-year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD-change during anastrozole in the lumbar spine showed a T-score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole-use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The DATA study (NCT00301457) compared 6 and 3 years of anastrozole in postmenopausal women with hormone receptor-positive early breast cancer after 2-3 years of tamoxifen. Patients with chemotherapy-induced ovarian function failure (CIOFF) were also eligible, but could be at risk of ovarian function recovery (OFR). The current analysis compared the survival of women with CIOFF with definitely postmenopausal women and examined the influence of OFR on survival. Therefore, we selected patients from the DATA study aged 45-57 years at randomization who had received (neo)adjuvant chemotherapy. They were classified by reversibility of postmenopausal status: possibly reversible in case of CIOFF (n = 395) versus definitely postmenopausal (n = 261). The former were monitored by E2 measurements for OFR. The occurrence of OFR was incorporated as a time-dependent covariate in a Cox-regression model for calculating the hazard ratio (HR). We used the landmark method to calculate residual 5-year survival rates. When comparing CIOFF women with definitely postmenopausal women, the survival was not different. Among CIOFF women with available E2 follow-up values (n = 329), experiencing OFR (n = 39) had an unfavorable impact on distant recurrence-free survival (HR 2.27 [95% confidence interval [CI] 0.98-5.25; p = 0.05] and overall survival (HR 2.61 [95% CI 1.11-6.13; p = 0.03]). After adjusting for tumor features, the HRs became 2.11 (95% CI 0.89-5.02; p = 0.09) and 2.24 (95% CI 0.92-5.45; p = 0.07), respectively. The residual 5-year rate for distant recurrence-free survival was 76.9% for women with OFR and 92.1% for women without OFR, and for 5-year overall survival 80.8% and 94.4%, respectively. Women with CIOFF receiving anastrozole may be at increased risk of disease recurrence if experiencing OFR., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen., Methods: We identified all patients with chemotherapy-induced ovarian function failure. Women who underwent a bilateral ovariectomy or used luteinizing hormone-releasing hormone agonists before random assignment were excluded. Plasma estradiol and follicle-stimulating hormone levels were monitored until 30 months after random assignment at local laboratories. We aimed to determine the ovarian function recovery (OFR) rate during AI use by the cumulative incidence competing risk method and analyzed the trend of estradiol levels during AI use by a nested case-control approach in which a subset of control subjects were compared with the OFR patients excluding the value at OFR diagnosis., Results: The 329 eligible patients had a median age of 50.0 years (range = 45-57 years) at random assignment. Thirty-nine patients developed OFR, corresponding with a 30-month recovery rate of 12.4%. Of these, 11 (28.2%) were age 50 years or older at AI initiation. The estradiol level decreased statistically significantly by 37.8% (95% CI = 27.4% to 46.7%) over the initial 30 months of AI treatment in both groups. However, the estradiol levels in the women who experienced OFR remained statistically significantly higher (difference = 20.6%, 95% CI = 2.0% to 42.7%) prior to OFR diagnosis compared with those who did not experience OFR., Conclusions: The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.

An electronic health record (EHR) should provide 4 key functionalities: (a) documenting patient data; (b) facilitating computerised provider order entry; (c) displaying the results of diagnostic research; and (d) providing support for healthcare providers in the clinical decision-making process.- Computerised provider order entry into the EHR enables the electronic receipt and transfer of orders to ancillary departments, which can take the place of handwritten orders.- By classifying the computer provider order entries according to disorders, digital care pathways can be created. Such care pathways could result in faster and improved diagnostics.- Communicating by means of an electronic instruction document that is linked to a computerised provider order entry facilitates the provision of healthcare in a safer, more efficient and auditable manner.- The implementation of a full-scale EHR has been delayed as a result of economic, technical and legal barriers, as well as some resistance by physicians.

Background: Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach., Methods: In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy., Results: For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively)., Conclusion: First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer., Methods: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome., Results: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group., Conclusions: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.), (2009 Massachusetts Medical Society)