Background. Adjuvant systemic treatment for early stage breast cancer significantly reduces the risk of mortality but is associated with side effects, reducing patients' quality of life. Decisions... Show moreBackground. Adjuvant systemic treatment for early stage breast cancer significantly reduces the risk of mortality but is associated with side effects, reducing patients' quality of life. Decisions about adjuvant treatment are preference sensitive and are thus ideally suited to a shared decision making (SDM) approach. Whether and how SDM affects patients' trust in their oncologist is currently unknown. We investigated the association between patients' trust in their oncologist and 1) observed level of SDM in the consultation, 2) congruence between patients' preferred and perceived level of participation, and 3) patient and oncologist characteristics. Methods. Decision consultations (n = 101) between breast cancer patients and their medical oncologist were audio-recorded and transcribed verbatim. Patients' trust in their oncologist was measured using the Trust in Oncologist Scale (TiOS). The observed level of SDM was scored using the 12-item Observing Patient Involvement In Decision Making scale (OPTION-12), preferred level of participation with the Control Preferences Scale, and perceived level of participation with an open question in telephonic interviews. Results. The average TiOS score was high overall (mean [SD] = 4.1 [.56]; range, 2.6-5.0). Low levels of SDM were observed (mean [SD] = 16 [11.6]; range, 2-56). Neither observed nor perceived level of participation in SDM was associated with trust. Patients' preferred and perceived role in decision making was incongruent in almost 50% of treatment decisions. Congruence was not related to trust. A larger tumor size (beta = 4.5, P = 0.03) and the use of a risk prediction model during the consultation (beta = 4.1, P = 0.04) were associated with stronger trust. Conclusion. Patients reported strong trust in their oncologist. While low levels of SDM were observed, SDM was not associated with trust. These findings suggest it may not be necessary to worry about negative consequences for trust of using SDM or risk prediction models in oncological consultations. Considering the increased emphasis on implementing SDM, it is important to further explore how SDM affects trust in clinical practice. Show less
Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within... Show moreDelayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22-2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84-1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted. Show less
Background. Breast cancer screening has been presented to women as mostly positive for decades, despite voices raising issues related to harms since its introduction. Public communications about... Show moreBackground. Breast cancer screening has been presented to women as mostly positive for decades, despite voices raising issues related to harms since its introduction. Public communications about breast cancer screening tended to use persuasive techniques aimed at maximizing uptake. Concern about the harm of overdetection is more recent, and awareness of overdetection among the public is limited. We aimed to assess the impact of extensive information on treatment following overdetection in breast screening on women's acceptance of screening, and to assess correlates of acceptance. Methods. We performed an online survey among women aged 45-75 from the general public in the Netherlands and Australia, asking women their maximum acceptable ratio of overdetection, per breast cancer death avoided, for four treatment scenarios (randomized order): mastectomy; lumpectomy; lumpectomy plus radiotherapy; lumpectomy plus radiotherapy and hormone therapy. The effect of treatment was assessed using General Linear Models, controlling for socio-demographics, experience, and psychological characteristics. Results. Four-hundred Australian and 403 Dutch women responded. Around half of the women would always screen, even at a 6:1 overdetection-to-death-avoided ratio. Acceptance was highest for the lumpectomy scenario, decreasing with more invasive treatment. In multivariate analyses the effect of treatment remained (p<0.001). Higher acceptance was seen for women with children (p=0.04), screening experience (p<0.001), and less understanding of overdetection (p<0.001). A learning effect was seen: acceptance was highest for the first scenario shown. Conclusions. Acceptance of overdetection was high, but decreased after the first scenario and with invasiveness of treatment. This provides a first indication that with more knowledge and understanding, women may move from uncritical acceptance of screening towards a more informed decision that involves a trade-off of the benefits and harms. Show less
Matsuda, A.; Inoue, K.; Momiyama, M.; Kobayashi, K.; Kubota, K.; Ohkubo, T.; ... ; Yamaoka, K. 2019
The 10-item Perceived Efficacy in Patient-Physician Interactions (PEPPI-10) questionnaire was used as an indirect measure of the patients' perception of the strength of their therapeutic connection... Show moreThe 10-item Perceived Efficacy in Patient-Physician Interactions (PEPPI-10) questionnaire was used as an indirect measure of the patients' perception of the strength of their therapeutic connection with their physician. The English version of the PEPPI-10 could serve as a valuable research tool for analyzing the relationship between patient and physician. The incidence of breast cancer is amongst the highest in Japan, and Patient Reported Outcome is often used as an outcome measure for breast cancer. It is particularly important to establish a strong patient-physician interaction for patients with breast cancer, since these patients require long-term treatment. We designed the present study to assess the reliability and validity of the Japanese version of the PEPPI-10 in female Japanese breast cancer outpatients. A cross-sectional study was performed at the Saitama Cancer Center, Japan. From August 2014 to August 2015, the Japanese versions of the PEPPI-10 that measure patient-perceived self-efficacy and the Brief Illness Perception Questionnaire (BIPQ) that measure illness perception were used for 92 breast cancer patients who received outpatient chemotherapy (mean age: 52.9 years, Cancer Stage I or Stage II : 82.6%, receiving adjuvant chemotherapy: 69.6%). We found that the Japanese version of the PEPPI-10 scale had a high coefficient of internal consistency (Cronbach's a coefficient, 0.83) for reliability, and concurrent validity analysis indicated that the utility of PEPPI-10 was moderately correlated with that of the BIPQ. In conclusion, the Japanese version of the PEPPI-10 is a useful tool that can empower breast cancer outpatients during the course of their treatment. Show less
Bredart, A.; Anota, A.; Dick, J.; Cano, A.; Pauw, A. de; Kop, J.L.; ... ; Dolbeault, S. 2019
Background We performed a comprehensive assessment of the psychometrics of the "Psychosocial Aspects in Hereditary Cancer" (PAHC) questionnaire in French, German and Spanish. Methods Women... Show moreBackground We performed a comprehensive assessment of the psychometrics of the "Psychosocial Aspects in Hereditary Cancer" (PAHC) questionnaire in French, German and Spanish. Methods Women consecutively approached in Cancer Genetic Clinics completed the PAHC, distress and satisfaction questionnaires at pre-testing (T1) and after test result disclosure (T2). In addition to standard psychometric attributes, we assessed the PAHC ability to respond to change (i.e. improvement or deterioration from T1 to T2) in perceived difficulties and computed minimal important differences (MID) in PAHC scores as compared with self-reported needs for additional counselling. Results Of 738 eligible counselees, 214 (90%) in France (Paris), 301 (92%) in Germany (Cologne) and 133 (77%) in Spain (Barcelona) completed the PAHC. A six-factor revised PAHC model yielded acceptable CFA goodness-of-fit indexes and good all scales internal consistencies. PAHC scales demonstrated expected conceptual differences with distress and satisfaction with counselling. Different levels of psychosocial difficulties were evidenced between counselees' subgroups and over time (p-values < .05). MID estimates ranged from 8 to 15 for improvement and 9 to 21 for deterioration. Conclusion The PAHC French, German and Spanish versions are reliable and valid for evaluating the psychosocial difficulties of women at high BC risk attending genetic clinics. 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
Objective: To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers.Summary of Background Data:... Show moreObjective: To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers.Summary of Background Data: Although breast-conserving therapy (breast-conserving surgery followed by radiotherapy) has been associated with more local recurrences than mastectomy, no differences in overall survival have been found in randomized trials performed in the general breast cancer population. Whether breast-conservation can be safely offered to BRCA1/2 mutation carriers is debatable.Methods: The study comprised a cohort of women with invasive breast cancer diagnosed <50 years and treated between 1970 and 2003 in 10 Dutch centers. Germline DNA for BRCA1/2 testing of most-prevalent mutations covering similar to 61%) was mainly derived from paraffin-blocks. Survival analyses were performed taking into account competing risks.Results: In noncarriers (N = 5820), as well as in BRCA1 (N = 191) and BRCA2 (N = 70) mutation carriers, approximately half of the patients received breast-conserving therapy. Patients receiving mastectomy followed by radiotherapy had prognostically worse tumor characteristics and more often received systemic therapy. After adjustment for these potential confounders, patients who received breast-conserving therapy had a similar overall survival compared with patients who received mastectomy, both in noncarriers (hazard ratio [HR] = 0.95, confidence interval [CI] = 0.85-1.07, P = 0.41) and BRCA1 mutation carriers (HR = 0.80, CI = 0.42-1.51, P = 0.50). Numbers for BRCA2 were insufficient to draw conclusions. The rate of local recurrences after breast-conserving therapy did not differ between BRCA1 carriers (10-year risk = 7.3%) and noncarriers (10-year risk = 7.9%).Conclusion: Our results, together with the available literature, provide reassurance that breast-conserving therapy is a safe local treatment option to offer to BRCA1 mutation carriers with invasive breast cancer. 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
Suriyamurthy, S.; Baker, D.; Dijke, P. ten; Iyengar, P.V. 2019
To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these... Show moreTo improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies. However, one of the main challenges of this approach is identifying which mutations are true drivers, as tumors typically contain many additional passenger mutations that do not actually contribute to tumor development. Besides this, many patients often relapse after prolonged treatment due to the emergence of acquired resistance, limiting the clinical effectiveness of targeted treatments. In this thesis, we focussed on using genetically engineered mouse models to identify candidate cancer genes and therapy resistance mechanisms in two different breast cancers: invasive lobular carcinoma (ILC) and triple-negative breast cancer (TNBC). For ILC, we used transposon-based insertional mutagenesis (TIM) to uncover several novel cancer genes driving ILC development. Besides this, we also developed a novel computational approach (IM-Fusion) for improving the discovery of cancer genes from TIM screens and explored mechanisms of resistance in Fgfr2-driven ILC. For TNBC, we used CRISPR-based iterative mouse modeling combined with comparative oncogenomics to identify novel drivers of BRCA1-deficient TNBC. Finally, using combined in-vivo/in-vitro screens, we identified Parg as a driver of treatment resistance in BRCA2-deficient TNBC. Show less
Bakker, A.; Zee, J. van der; Tienhoven, G. van; Kok, H.P.; Rasch, C.R.N.; Crezee, H. 2019
Objective: Hyperthermia therapy (HT), heating tumors to 40?45??C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been... Show moreObjective: Hyperthermia therapy (HT), heating tumors to 40?45??C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been proven in multiple randomized trials. However, published outcome after RT?+?HT varies widely. We performed a systematic review to investigate whether there is a relationship between achieved HT dose and clinical outcome and thermal toxicity for patients with recurrent breast cancer treated with RT?+?HT. Method: Four databases, EMBASE, PubMed, Cochrane library and clinicaltrials.gov, were searched with the terms breast, radiotherapy, hyperthermia therapy and their synonyms. Final search was performed on 3 April 2019. Twenty-two articles were included in the systematic review, reporting on 2330 patients with breast cancer treated with RT?+?HT. Results: Thirty-two HT parameters were tested for a relationship with clinical outcome. In studies reporting a relationship, the relationship was significant for complete response in 10/15 studies, in 10/13 studies for duration of local control, in 2/2 studies for overall survival and in 7/11 studies for thermal toxicity. Patients who received high thermal dose had on average 34% (range 27%?53%) more complete responses than patients who received low thermal dose. Patients who achieved higher HT parameters had increased odds/probability on improved clinical outcome and on thermal toxicity. Conclusion: Temperature and thermal dose during HT had significant influence on complete response, duration of local control, overall survival and thermal toxicity of patients with recurrent breast cancer treated with RT?+?HT. Higher temperature and thermal dose improved outcome, while higher maximum temperature increased incidence of thermal toxicity. Show less
