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... Show moreBackground 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. Show less
Purpose: Scalp cooling can prevent chemotherapy-induced alopecia (CIA). Previously, the post-infusion cooling time (PICT) could be successfully reduced in docetaxel-treated patients from 90 to 45... Show morePurpose: Scalp cooling can prevent chemotherapy-induced alopecia (CIA). Previously, the post-infusion cooling time (PICT) could be successfully reduced in docetaxel-treated patients from 90 to 45 and 20 min. Therefore, it seems plausible that the PICT can be shortened for paclitaxel-treated patients as well. Methods: Patients treated with weekly paclitaxel were included in this multi-centre trial and randomly assigned to a PICT of 45 or 20 min. The results were compared to a standard PICT of 90 min, derived from prospective collected data from the Dutch Scalp Cooling Registry. The primary endpoint was the percentage of patients who decide to not wear a wig or head covering. Secondary endpoints were the degree of CIA assessed with the Dean scale for assessment of hair loss; alopecia graded according to NCI CTC toxicity version 4.03 (CTCAE4.03); tolerance of scalp cooling and perceived distress of CIA. Results: Ninety-one patients were enrolled in this study; 74 patients were evaluable for hair loss. Hair preservation was successful in 27 patients (75%) with a PICT of 45 min and in 31 patients (82%) with a PICT of 20 min. There was no difference in success rate with the standard PICT of 90 min (85%, p = 0.29). Similar success rates were seen when using the Dean scale and CTCAE assessment, with no differences between groups (p = 0.12 and p = 0.38). Conclusions: A 20 min PICT is as effective as 45 and 90 min to prevent weekly paclitaxel-induced alopecia and should be the new standard of care. Show less
Hellemond, I.E.G. van; Smorenburg, C.H.; Peer, P.G.M.; Swinkels, A.C.P.; Seynaeve, C.M.; Sangen, M.J.C. van der; ... ; Dutch Breast Canc Res Grp BOOG 2020
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... Show morePurpose 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. Show less
Hellemond, I.E.G. van; Smorenburg, C.H.; Peer, P.G.M.; Swinkels, A.C.P.; Seynaeve, C.M.; Sangen, M.J.C. van der; ... ; Dutch Breast Canc Res Grp BOOG 2019
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... Show moreThe 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. Show less
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... Show moreThe 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. Show less
Hellemond, I. van; Smorenburg, C.H.; Peer, P.; Swinkels, A.; Seynaeve, C.M.; Sangen, M. van der; ... ; Tjan-Heijnen, V.C. 2018
