M. van Beurden

Effectiveness of behavioral techniques and physical exercise on psychosocial functioning and health-related quality of life in breast cancer patients and survivors--a meta-analysis.

Objective: To evaluate the effect of behavioral techniques and physical exercise on psychosocial functioning and health‐related quality of life (HRQoL) outcomes in breast cancer patients and survivors.

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study

BRCA1/2 mutation carriers are offered gynaecological screening with the intention to reduce mortality by detecting ovarian cancer at an early stage. We examined compliance and efficacy of gynaecological screening in BRCA1/2 mutation carriers. In this multicentre, observational, follow-up study we examined medical record data of a consecutive series of 888 BRCA1/2 mutation carriers who started annual screening with transvaginal ultrasonography and serum CA125 between 1993 and 2005. The women were annually screened for 75% of their total period of follow-up. Compliance decreased with longer follow-up. Five of the 10 incident cancers were interval tumours, diagnosed in women with a normal screening result within 3–10 months before diagnosis. No difference in stage distribution between incident screen-detected and interval tumours was found. Eight of the 10 incident cancers were stage III/IV (80%). Cancers diagnosed in unscreened family members had a similar stage distribution (77% in stage III/IV). The observed number of cases detected during screening was not significantly higher than expected (Standardized Incidence Ratio (SIR): 1.5, 95% confidence interval: 0.7–2.8). For the subgroup that was fully compliant to annual screening, a similar SIR was found (1.6, 95% confidence interval: 0.5–3.6). Despite annual gynaecological screening, a high proportion of ovarian cancers in BRCA1/2 carriers are interval cancers and the large majority of all cancers are diagnosed in advanced stages. Therefore, it is unlikely that annual screening will reduce mortality from ovarian cancer in BRCA1/2 mutation carriers.

Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up

A retrospective study was performed to assess the histopathologic findings in high-risk women undergoing bilateral prophylactic (salpingo)-oophorectomy. The medical files of BRCA1 or BRCA2 mutation carriers and members of a hereditary breast/ovarian cancer (HBOC) family, who had undergone prophylactic surgery, were reviewed. In all, 38 women underwent a bilateral oophorectomy (26 BRCA1, three BRCA2 and nine HBOC, respectively). A total of 90 women underwent bilateral salpingo-oophorectomy (58 BRCA1, six BRCA2, one BRCA1 and 2, 25 HBOC, respectively). At the time of salpingo-oophorectomy, five of 58 BRCA1 carriers (8.6%) were diagnosed with an occult carcinoma: two fallopian tube carcinomas, two ovarian carcinomas and one case was defined as a fallopian tube/ovarian carcinoma. No occult carcinomas were found in the other groups. Of the 38 patients, who underwent a bilateral oophorectomy (mean follow-up 45 months), three of 26 BRCA1 mutation carriers (3.4 in 100 women-years) developed peritoneal papillary serous carcinoma (PPSC) during follow-up. So far, no PPSC have occurred in the 90 women, who underwent a salpingo-oophorectomy (mean follow-up 12 months), including 58 BRCA1 carriers (0 in 60 in women-years). These results contribute to the thesis that BRCA1 germline mutation carriers are not only at risk for ovarian cancer, but also for fallopian tube carcinoma and peritoneal papillary serous carcinoma. Our data suggest that PPSC risk among BRCA2 carriers is lower than among BRCA1 carriers.

Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands

BACKGROUND Recent studies suggested an improved overall survival (OS) for BRCA2- versus BRCA1-associated epithelial ovarian cancer (EOC), whereas the impact of chemotherapy is not yet clear. In a nationwide cohort, we examined the results of primary treatment, progression-free survival (PFS), treatment-free interval (TFI), and OS of BRCA1 versus BRCA2 EOC patients. METHODS Two hundred and forty-five BRCA1- and 99 BRCA2-associated EOC patients were identified through all Dutch university hospitals. Analyses were carried out with the Pearsons Chi-square test, Kaplan-Meier, and Cox regression methods. RESULTS BRCA1 patients were younger at EOC diagnosis than BRCA2 patients (51 versus 55 years; P < 0.001), without differences regarding histology, tumor grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Complete response rates after primary treatment, including chemotherapy, did not differ between BRCA1 (86%) and BRCA2 patients (90%). BRCA1 versus BRCA2 patients had a shorter PFS (median 2.2 versus 3.9 years, respectively; P = 0.006), TFI (median 1.7 versus 2.8 years; P = 0.009), and OS (median 6.0 versus 9.7 years; P = 0.04). Differences could not be explained by age at diagnosis, FIGO stage or type of treatment. CONCLUSIONS PFS and OS were substantially longer in BRCA2- than in BRCA1-associated EOC patients. While response rates after primary treatment were similarly high in both groups, TFI, as surrogate for chemosensitivity, was significantly longer in BRCA2 patients.

Characteristics of breast cancer patients who experience menopausal transition due to treatment

Objective To identify patient-related and treatment-related factors associated significantly with climacteric symptoms in young patients who experience menopausal transition due to adjuvant treatment for breast cancer. Methods This cross-sectional study used questionnaire data collected to screen breast cancer patients for participation in a multicenter trial on the efficacy of supportive interventions for treatment-induced menopausal symptoms. The screening instrument included questions on sociodemographics, menopausal history and current menopausal status and symptoms, treatment history and lifestyle factors. Univariate and multivariate analyses were used to identify factors associated significantly with two major menopausal symptoms, hot flushes/night sweats and vaginal dryness. Results In total, 435 patients were included in this study. Hot flushes/night sweats exhibited a significant, negative association with education and a significant positive association with alcohol consumption, and having been treated with the combination of chemotherapy and hormonal therapy. Vaginal dryness was positively associated with combined treatment with chemotherapy and hormonal therapy. Conclusions Menopausal symptoms among young breast cancer patients who experience menopausal transition due to adjuvant treatment are associated with a number of sociodemographic, lifestyle and treatment-related factors. Carefully designed interventions to prevent or alleviate these symptoms should take these factors into account.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: an individual patient data meta-analysis of 22 RCTs

This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics.

Characteristics of Lynch syndrome associated ovarian cancer

OBJECTIVE To describe clinical characteristics of Lynch syndrome associated ovarian cancer and the efficacy of surveillance in the early detection of these ovarian cancers. METHODS All Lynch syndrome associated ovarian cancer cases identified in either the Dutch Lynch syndrome registry (DLSR) between 1987 and 2016, and/or the cohort at the University Medical Center Groningen (UMCG) between 1993 and 2016 were included. Clinical data on age at diagnosis, mutation type, histological type, FIGO stage, treatment, follow-up and gynecological surveillance were collected. RESULTS A total of 46/798 (6%) women in the DLSR and 7/80 (9%) in the UMCG cohort were identified as LS associated ovarian cancer patients. The median age at ovarian cancer diagnosis was 46.0 years (range 20-75 years). The most frequently reported histological type was endometrioid adenocarcinoma (40%; n = 21) and serous carcinoma (36%; n = 19). Most tumors (87%; n = 46) were detected at an early stage (FIGO I/II). Forty-one of 53 (77%) patients were diagnosed with ovarian cancer before LS was diagnosed. In the other 12/53 (23%) women, ovarian cancer developed after starting annual gynecological surveillance for LS; three ovarian cancers were screen-detected in asymptomatic women. Overall survival was 83%. CONCLUSION Ovarian cancer in women with LS has a wide age-range of onset, is usually diagnosed at an early stage with predominantly endometrioid type histology and a good overall survival. The early stage at diagnosis could not be attributed to annual gynecological surveillance.

Impact of risk-reducing salpingo-oophorectomy in premenopausal women

Abstract Objectives: To describe implications of premenopausal risk-reducing salpingo-oophorectomy (RRSO) on quality of life, endocrine symptoms, sexual function, osteoporosis, cardiovascular health, metabolic syndrome, cognitive impairment and safety of hormone replacement therapy. Methods: We searched the following electronic databases: The Cochrane Library, EMBASE, PsycInfo, and MEDLINE. We selected controlled and uncontrolled trials of premenopausal women undergoing RRSO. Two authors independently assessed studies for inclusion. Reference lists of included reports were searched manually for additional studies. Results: Surgical menopause leads to more menopausal complaints and sexual dysfunction than natural menopause. Overall quality of life is not affected by surgery. In the limited literature, there is no evidence that RRSO leads to more osteopenia in comparison with natural menopause at a young age. Cohort studies show a slight impaired cardiovascular health. Cognitive function decreases later in life in premenopausal oophorectomized women. Short-term hormone replacement therapy seems to decline postmenopausal complaints and does not seem to increase the risk for breast carcinoma in mutation carriers without a personal history of breast carcinoma. Conclusions: The conclusions of this systematic review are limited by the absence of randomized, controlled trials. There is growing evidence from observational studies that RRSO may impact negatively on all-cause non-survival endpoints.

Does anti-Müllerian hormone predict change in menopausal symptoms following risk-reducing salpingo-oophorectomy? A prospective observational study

Abstract Objectives: The aim of this study was to investigate whether serum anti-Müllerian hormone (AMH) predicts symptom burden after risk-reducing salpingo-oophorectomy (RRSO) in order to individualize counseling. Methods: Patient-reported menopausal symptoms, sexual functioning, and psychological distress (depression and anxiety) were assessed 1 day before (T0) and 6 weeks (T1) and 7 months (T2) after RRSO. AMH was assessed before RRSO. Multivariable regression analysis was used to investigate the association between AMH and short-term and long-term change in symptom burden following RRSO. Results: Ninety-one premenopausal women at high risk of ovarian cancer were included. Presurgical AMH was not related significantly to change in symptoms post RRSO. As a secondary outcome we found that regular menses before RRSO was associated specifically with long-term increase in hot flushes (sr = 0.40, p = 0.001; total R2 = 0.171) and depression (sr = 0.29, p = 0.012; total R2 = 0.132). Earlier receipt of chemotherapy was associated with long-term improvement in sexual functioning (sr = 0.24, p = 0.041; total R2 = 0.348). Conclusion: In this cohort, AMH was not a significant predictor of change in symptoms following RRSO. Regular menses prior to RRSO and earlier receipt of chemotherapy were significantly, but relatively weakly, associated with changes in outcomes 6 weeks and/or 7 months after RRSO.

Abstract P6-12-06: Effect and moderators of exercise on fatigue in patients with breast cancer: Meta-analysis of individual patient data

Background - Fatigue is one of the most common and disabling complaints in patients with breast cancer and can effectively be reduced by physical exercise, with small to moderate effect sizes. To identify heterogeneity in responses to exercise and to further personalize exercise prescriptions, moderators of exercise effects on fatigue should be investigated. However, most randomized controlled trials (RCTs) are not adequately powered for such analyses. Therefore we conducted meta-analyses using the individual patient data of several exercise RCTs. The aim is to investigate the effect and moderators of physical exercise on cancer-related fatigue in patients with breast cancer. Methods - Within the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium, principal investigators of 34 exercise RCTs worldwide have shared their individual patient data. Twenty-two of these RCTs included patients with breast cancer with a total sample size of 3,061. Different questionnaires to assess level of fatigue were used, which was acknowledged by using z-scores in the analysis. A one-step individual patient data meta-analysis, using a linear mixed-effect model adjusted for baseline fatigue, with a random intercept on study (to account for study clustering) was undertaken to investigate effect of exercise on fatigue. The result, a between-group difference in z-scores, corresponds to a Cohen9s d effect size. An interaction term was included in the model to assess potential moderators including demographic (age, marital status, education), clinical (body mass index, presence of distant metastasis), intervention-related (intervention timing, delivery mode and duration), and exercise-related (exercise type, frequency, intensity, duration) characteristics. Results – Exercise significantly reduced fatigue reported by women with breast cancer (β= -0.15, 95% CI -0.21;-0.09). This effect did not differ significantly between patients with different demographic and clinical characteristics ( p -values interaction >0.05). Also, neither timing (during or post-treatment) and duration of the intervention, nor exercise-related factors moderated intervention effects on fatigue. Supervised exercise had significantly larger effects on fatigue than unsupervised exercise (β difference = -0.17, 95%CI -0.28;-0.05). Compared to the control group, supervised exercise significantly improved fatigue (β = -0.21, 95%CI = -0.28;-0.14), while unsupervised exercise did not (β = -0.04, 95%CI = -0.14;0.06). Conclusion – Exercise significantly reduces fatigue in patients with breast cancer across subgroups formed on the basis of age, marital status, education level, body mass index, and presence of distant metastasis. The effect of exercise is significantly larger when performed under supervision. Hence, exercise, and preferably supervised exercise, represents a viable intervention for the prevention and treatment of fatigue among patients with breast cancer. Citation Format: van Vulpen JK, Sweegers MG, Kalter J, Peeters PH, Courneya KS, Newton RU, Aaronson NK, Jacobsen PB, Steindorf K, Stuiver MM, Hayes S, Mesters I, Knoop H, Goedendorp M, Mutrie N, Thorsen L, Schmidt M, Sonke GS, Bohus M, James EL, Oldenburg HS, Velthuis MJ, Nollet F, Wenzel J, Wiskemann J, Galvao DA, Chinapaw MJ, Irwin ML, Griffith KA, van Weert E, Daley AJ, McConnachie A, Schulz K-H, Short CE, Plotnikoff RC, Potthoff K, van Beurden M, van Harten WH, Schmitz KH, Winters-Stone KM, Taaffe DR, van Mechelen W, Kersten M-J, Verdonck-de Leeuw IM, Brug J, Buffart LM, May AM. Effect and moderators of exercise on fatigue in patients with breast cancer: Meta-analysis of individual patient data [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-06.