Ute S. Albert

Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer

BACKGROUND The level of adherence of various pharmacological therapies in chronic diseases varies, but is predominantly low. With tamoxifen (TAM), 23% and 50% nonadherence after 1 and 4 years have been reported. Day-to-day clinical observation suggests that adherence may even be lower with aromatase inhibitors, but limited data exist on the situation in daily clinical routine. The aim of this study was to evaluate the rate of adherent patients in a randomly selected sample of postmenopausal women with primary breast cancer, who had been assigned to an adjuvant endocrine treatment with TAM or anastrozole (ANA). MATERIALS AND METHODS We investigated a random sample of 100 postmenopausal women with breast cancer (50 TAM and 50 ANA) who had received surgery for their primary breast cancer at our hospital in 2004/2005 and thereafter had been assigned to an adjuvant endocrine treatment. We evaluated the adherence rate with a detailed questionnaire and additionally carried out a retrospective prescription check of the hospital chart as well as calling the local physicians of our patients. A patient was counted as adherent with a self-reported tablet intake of 80% or more and if a medication possession ratio of 80% or more was achieved. RESULTS Regarding the baseline characteristics, a significant difference in mean age was noticed in women on ANA versus TAM [65 (+/-3) and 72 (+/-3); P<0.001]. All women on TAM and ANA reported to be adherent (100%). After controlling for prescriptions, only 40 (80%) and 27 (69%) of the women on TAM and ANA were still classified as adherent (P<0.01 and P<0.01 versus self-report). We found no significant correlation of adherence to any baseline characteristics or side-effects in a logistic regression model. CONCLUSIONS An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in randomised clinical trials. However, a similar magnitude of adherence will be necessary in routine clinical practice to assure comparable clinical effects. Our results further support the data on suboptimal adherence of women with breast cancer on adjuvant TAM treatment. Here, we evaluated for the first time the patient reported and real-world adherence on adjuvant ANA and were able to show a similarly low adherence compared with TAM. More prospective studies are needed to increase our understanding of the underlying reasons for nonadherence in women with breast cancer.

The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer

INTRODUCTION The effects of doxorubicin/cyclophosphamide (A/C; 6 cycles) chemotherapy on bone mineral density (BMD), quantitative ultrasonography (QUS) and bone turnover markers in pre-menopausal women with oestrogen receptor-negative breast cancer (BC) were compared with age-matched controls. METHODS Among 106 women (BC=53, controls=53), BMD (spine and hip), QUS (calcaneus and phalanges) and bone marker levels were measured at baseline, 6 and 12 months. Correlations between parameters were determined by Spearmans rho. RESULTS All BC patients became amenorrhoeic after chemotherapy and remained so for the duration of treatment. BC patients had significant bone loss at all sites (P.005) and significant increases in bone turnover (P.05). There were significant correlations between BMD, QUS and bone markers (P.05). CONCLUSIONS Results confirm A/Cs deleterious influence on bone health in pre-menopausal women with BC and established QUSs utility for monitoring bone effects. Large-scale longitudinal studies are needed to further understand and prevent bone changes following chemotherapy.

Age changes of calcaneal ultrasonometry in healthy German women.

Abstract. This study assessed age changes in quantitative ultrasound sonometry (QUS) in a large sample of healthy German women. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the calcaneus were measured in 1333 women (mean age 50.5 ± 11.5 years) using the Achilles ultrasonometer (Lunar Corp., Madison, WI, USA). The short-term precision in 31 adults was 0.2% for SOS, 1.2% for BUA, and 1.3% for SI. There was an overall decline of 15% for BUA, 4% for SOS, and 31% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly (−3%), whereas postmenopausal women showed a significantly increased decline (−12%). In contrast, SOS continuously decreased from the age of 15; there was a decline of 2% from adolescence to the menopause; postmenopausal women showed a slightly larger decline (−2.5%). The SI of premenopausal women decreased by 10%, but the postmenopausal decline of almost 22% was significantly greater. SI values for premenopausal German women were comparable to those observed in the American Achilles reference population, but postmenopausal German women had significantly higher SI values of 7% due to a lower rate of aging loss.

Stufe-3-Leitlinie - Brustkrebs-Frherkennung in Deutschland

Ziel der Stufe-3-Leitlinie “Brustkrebs-Früherkennung in Deutschland” ist es, Ärzte, Frauen und Patientinnen in der Entscheidung über eine angemessene Gesundheitsversorgung im Bereich Brustkrebs-Früherkennung zu unterstützen. Das Prinzip der Brustkrebs-Früherkennung umfasst die Entdeckung und Diagnose von Brustkrebsvorstufen (Stadium 0, Carcinomata in situ), damit die Risikoreduktion einer manifesten Tumorentstehung sowie die Entdeckung und Diagnose von Brustkrebsfrühformen (Stadium I), deren gute,etwa 90%ige Heilbarkeit wissenschaftlich gesichert ist.Mit der Flächen deckenden, Sektor übergreifenden Einführung eines qualitätsgesicherten nationalen Früherkennungsprogramms auf der Basis einer Stufe-3-Leitlinie ergibt sich die Möglichkeit, zeitnah die Sterblichkeit an Brustkrebs zu senken und eine Heilung durch weniger belastende Behandlungsverfahren unter weitgehendem Erhalt der Lebensqualität zu erreichen. Hieraus ergibt sich eine wesentliche Verbesserung der frauenspezifischen Gesundheitsversorgung in Deutschland.

Impact of a single perioperative dose of dexamethasone on the incidence of surgical site infections: A case–control study

Aims:  Dexamethasone is recommended in several international guidelines to prevent postoperative nausea and vomiting, a problem especially frequent in gynecological patients. Despite the increasing use of dexamethasone for this indication there are limited data concerning potential harmful effects of corticosteroids in surgical patients, especially the potential negative impact on wound healing and surgical site infection (SSI). This case–control study was conducted to look for potentially harmful effects of a single perioperative dose of dexamethasone with respect to the occurrence of SSI in gynecological and obstetric surgery patients.

Comparison of dual-energy X-ray absorptiometry with six quantitative ultrasonometry devices in women with hip fractures

Abstract Objectives Dual-energy X-ray absorptiometry (DXA) is the gold standard for assessment of bone mineral density, an important risk factor for osteoporotic fractures. Recent reports suggest that quantitative ultrasonometry (QUS) is able to predict fractures; however, only limited data in women with hip fractures are available. Methods We examined 91 postmenopausal women who had sustained an osteoporosis-related hip fracture within the past 7 days using DXA and six different QUS devices and compared them with 91 healthy age-matched controls. Results Femoral neck (FN), total hip (TH) and lumbar spine (LS) T-scores were lower in women with hip fractures compared to matched controls: − 2.38 vs. − 1.64 (p < 0.001), − 2.36 vs. − 1.44 (p < 0.001) and − 2.05 vs. − 1.50 (p = 0.41), respectively. The T-scores of the Achilles, Sahara, InSight and Omnisence QUS devices were also lower in patients with hip fractures compared to matched controls: − 3.20 vs. − 2.36 (p < 0.001), − 2.196 vs. − 1.761 (p = 0.005), − 2.631 vs. − 1.849 (p < 0.001), − 3.707 vs. − 3.030 (p = 0.032), respectively. However, the T-scores of the DBM and QUS-2 did not differ between the two groups: − 4.543 vs. − 4.324 (p = 0.352) and − 1.7 vs. − 2.0 (p = 0.465), respectively. Compared to DXA (hip), the odds ratios of the Achilles, InSight and Sahara were comparable, while the odds ratios of the DBM, Omnisence and QUS-2 were significantly lower (p ≤ 0.05). Conclusions Compared to DXA, the Achilles, Sahara and InSight QUS devices showed similar hip fracture discrimination while the DBM, Omnisence and QUS-2 did not. Therefore, some QUS devices are able to identify a clinically meaningful risk factor in women at high risk of hip fracture.

Discontinuation rates of menopausal hormone therapy among postmenopausal women in the post-WHI study era

Abstract Objectives Many women are reluctant to take menopausal hormone therapy (MHT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of combined MHT in the last decade, reflecting changes in the post-Women’s Health Initiative era. Methods We analyzed 17 020 patients receiving combined MHT from 2004 to 2013 using the Disease Analyzer database. Results After 12 months of follow-up, 44.6% and 33.5% of patients receiving 1 mg and 2 mg, respectively, of oral combined MHT were still on treatment (p < 0.0001). The persistence rate of patients receiving < 50 μg of transdermal MHT was 39.1% after 1 year of treatment and presented no differences compared to patients receiving ≥ 50 μg of transdermal MHT with a persistence rate of 38.2%. MHT start in the years 2007–2009 was associated with higher discontinuation rates (hazard ratio 1.04, p = 0.0709) than MHT start in the years 2010–2013 (hazard ratio 0.90, p = 0.0001). Conclusions Our results indicate that patients beginning their treatments in the years 2010–2013 were more treatment-persistent than patients beginning with MHT in the early years after publication of the Women’s Health Initiative study (2004–2009). Administration of low-dose oral MHT and transdermal MHT is associated with increased persistency compared to higher doses of oral MHT.

[Stage 3 recommendations--the early recognition of breast cancer in Germany. Abridged version for medical practitioners].

ZusammenfassungZiel der Stufe-3-Leitlinie “Brustkrebs-Früherkennung in Deutschland” ist es, Ärzte, Frauen und Patientinnen in der Entscheidung über eine angemessene Gesundheitsversorgung im Bereich Brustkrebs-Früherkennung zu unterstützen. Das Prinzip der Brustkrebsfrüherkennung umfasst die Entdeckung und Diagnose von Brustkrebsvorstufen (Stadium 0, Carcinomata in situ), und damit die Risikoreduktion einer manifesten Tumorentstehung sowie die Entdeckung und Diagnose von Brustkrebsfrühformen (Stadium I), deren gute, etwa 90%ige Heilbarkeit wissenschaftlich gesichert ist.Mit der flächendeckenden, sektorübergreifenden Einführung eines qualitätsgesicherten nationalen Früherkennungsprogramms auf der Basis einer Stufe-3-Leitlinie ergibt sich die Möglichkeit, zeitnah die Sterblichkeit an Brustkrebs zu senken und eine Heilung durch weniger belastende Behandlungsverfahren unter weitgehendem Erhalt der Lebensqualität zu erreichen. Hieraus ergibt sich eine wesentliche Verbesserung der frauenspezifischen Gesundheitsversorgung in Deutschland.AbstractThe Aim of this level 3 good clinical practice guideline is to help physicians, women and patients in decision making about the appropriate health care for early detection of breast cancer. The principle of early detection of breast cancer comprise the detection and diagnosis of premalignant breast tumors (stage 0, Carcinoma in situ), risk reduction of cancer development as well as the detection and diagnosis of breast cancer at an early stage (stage I), with a 90% chance of cure as shown by a large number of clinical trials. To establish a nation wide, comprehensive quality assuring program for the early detection of breast cancer the guideline summarized in the following paper offers the basis for a timely mortality reduction of breast cancer. The cure of early stage disease will be additionally possible by less invasive treatment allowing patients to maintain quality of life. The guideline leads to a major improvement of womens health care.

Effect of anastrozole on hormone levels in postmenopausal women with early breast cancer

Abstract Objectives The aim of this study was to investigate the influence of anastrozole on serum hormone levels in postmenopausal women with hormone receptor-positive breast cancer. Methods We prospectively determined serum levels of estradiol, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone (LH) at screening, as well as after 12 and 24 months of treatment and studied the associations with markers of bone turnover and bone mineral density (BMD). Results Altogether, a full set of hormone levels was available for 70 patients. Anastrozole treatment led to decreases of 92.1% for estradiol and 11.1% for LH over the observation period (p < 0.001). Conversely, FSH, DHEAS and testosterone concentrations increased by 5.9%, 33.3% and 50%, respectively (p < 0.001). SHBG levels remained stable during the 24 months of treatment (p = 0.355). There were modest associations between FSH, SHBG, CrossLaps and N-terminal propeptide of human procollagen type I (p < 0.05). Moreover, SHBG correlated positively with the BMD of femoral neck, total hip, total hip T-score, lumbar spine and the lumbar spine T-score, whereas FSH and estradiol correlated with the lumbar spine T-score (p < 0.05). Conclusions During the 24 months of follow-up, treatment with anastrozole decreased the serum levels of estradiol and LH. Furthermore, we found notable increases of serum levels of FSH, DHEAS and testosterone in the first 12 months of treatment, stabilizing thereafter. Additionally, we were able to correlate hormone levels with markers of bone turnover and BMD for the first time in this regard.

Persistency with estrogen replacement therapy among hysterectomized women after the Women’s Health Initiative study

ABSTRACT Objectives Many women are reluctant to undergo estrogen replacement therapy (ERT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of ERT in hysterectomized women over the past decade, reflecting changes in the post-Womens Health Initiative (WHI) era. Methods We analyzed 8045 patients receiving ERT from 2004 to 2013 using the Disease Analyzer database. Results After 12 months of follow-up, only 24.6% of patients receiving 1 mg and 24.5% of patients receiving 2 mg of oral ERT were still on treatment (p < 0.0001). The persistency rate of patients receiving <50 μg of transdermal ERT was 28.6% compared to 33.5% for patients receiving >50 μg within the 12 months of follow-up. ERT that began in 2007–2009 was associated with a higher discontinuation rate (hazard ratio 1.06, p = 0.0660) than ERT that began in 2010–2013 (hazard ratio 0.88, p = 0.0001). Conclusions Our results indicate low persistency rates in women on ERT irrespective of the dose as well as the route of administration. However, a decrease in discontinuation rates was found when comparing women in the early vs. late post WHI era.