http://repub.eur.nl/res/aut/34669/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/40022/ 2013-03-01T00:00:00Z BACKGROUND: The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC). METHODS: From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n = 351) or mutation carriers who had a previous unilateral BC (n = 294), respectively. The risks of PBC and CBC were calculated using the Kaplan-Meier survival method with death considered as a competing risk event. RESULTS: Women with BRCA-associated OC had lower 2-year, 5-year, and 10-year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P =.03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P <.001). In BRCA mutation carriers with a previous unilateral BC, the 2-year, 5-year, and 10-year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P =.06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P <.001). CONCLUSIONS: Patients with BRCA-associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted. Cancer 2013. © 2012 American Cancer Society. In patients with breast cancer susceptibility gene (BRCA)-associated ovarian cancer, the risk of breast cancer is lower than in mutation carriers without ovarian cancer and is lower than the risk of dying from ovarian cancer. The current data may contribute to tailored counseling for these patients. Copyright http://repub.eur.nl/res/pub/37206/ 2012-01-01T00:00:00Z OBJECTIVE: The impact of axillary treatment in daily practice on 5-year regional recurrence rate in breast cancer patients with isolated tumor cells or micrometastases in the sentinel node (SLN). BACKGROUND: Axillary dissection is recommended in patients with tumor-positive SLNs. But, in recent studies, regional recurrence rates seemed low if dissection was omitted. METHODS: We identified all patients in The Netherlands with invasive breast cancer who had an SLN biopsy before 2006, favorable primary tumor characteristics, and node-negative disease, isolated tumor cells or micrometastases as final nodal status. The primary endpoint was regional recurrence rate. To investigate differences in recurrence rates between patients with and without axillary treatment, a proportional hazard regression was carried out correcting for potential confounders. RESULTS: In total, 857 patients with node-negative disease, 795 patients with isolated tumor cells, and 1028 patients with micrometastases in the SLN were included. Without axillary treatment, the 5-year regional recurrence rates were 2.3%, 2.0%, and 5.6%, respectively. Compared with patients who underwent axillary treatment, the adjusted hazard ratio for regional recurrence in patients who underwent an SLN procedure only was 1.08 (95% CI, 0.23-4.98) for node-negative disease, 2.39 (95% CI, 0.67-8.48) for isolated tumor cells, and 4.39 (95% CI, 1.46-13.24) for micrometastases. Doubling of tumor size, grade 3 and negative hormone receptor status were also significantly associated with recurrence. CONCLUSIONS: Not performing axillary treatment in patients with SLN micrometastases is associated with an increased 5-year regional recurrence rate. Axillary treatment is recommended in patients with SLN micrometastases and unfavorable tumor characteristics. Copyright http://repub.eur.nl/res/pub/34112/ 2011-12-01T00:00:00Z Background: Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. Objective: To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. Methods: The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. Results: Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. Discussion: These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright http://repub.eur.nl/res/pub/34136/ 2011-11-01T00:00:00Z Objective: Clarification of the role of several aspects of self-concept regarding psychological distress in women at risk of hereditary breast cancer will help to target counselling and psychosocial interventions more appropriately. In this study, we aimed (1) to examine the role of general self-esteem and specific aspects of self-concept (i.e. stigma, vulnerability, and mastery) in psychological distress in women at risk of hereditary breast cancer and (2) to compare the relative importance of these self-concept aspects in psychological distress in women with low versus high self-esteem. Methods: General and breast-cancer-specific distress, self-esteem, self-concept, and demographics were assessed in 246 women being at risk of hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. Results: In the total study group, self-esteem was negatively associated with general distress. Furthermore, feeling stigmatized was strongly associated with more breast-cancer-specific distress, and to a lesser degree with general distress. In women with low-self esteem, feelings of stigmatization were strongly associated with higher levels of both breast-cancer-specific and general distress, while a sense of mastery was associated with less general distress. For women with high self-esteem, feelings of both stigmatization and vulnerability were associated with more breast-cancer-specific distress, whereas there were no significant associations with general distress. Discussion: Psychosocial interventions or support groups for women at risk of hereditary breast cancer should focus on self-esteem and feelings of stigmatization and isolation, and consequently tailor the interventions on specific items for respective women. http://repub.eur.nl/res/pub/26448/ 2011-04-21T00:00:00Z Objective: Understanding women's motives concerning breast reconstructive surgery will contribute to a better counselling and care for the increasing number of women choosing post-mastectomy breast reconstruction (BR). Methods: We interviewed 31 women who opted for implant or deep inferior epigastric perforator (DIEP)-flap BR after therapeutic or prophylactic mastectomy. Motives for BR in general and for the selected type of BR were investigated following a phenomenological qualitative research approach. Results: Women opting for implant BR were concerned with surgery-related issues, such as recovery time, number of scars and impact of surgery. They wanted to return to their daily life and restore their body image as soon as possible. Patients choosing DIEP-flap BR were more focussed on regaining a natural breast and wanted to benefit from the advantages of autologous tissue. Women scheduled for prophylactic mastectomy saw BR as an integral part of their treatment. Patients opting for BR after therapeutic mastectomy wanted to regain a complete body image with BR. Conclusions: Patients' motives for implant BR were primarily related to surgical issues, whereas women who chose DIEP-flap BR especially focussed on regaining a breast that resembles their own lost breast as well as possible. Clinical variables (such as therapeutic or prophylactic mastectomy, breast irradiation, and waiting lists) need to be taken into account when considering a certain type of BR, as these can be of great importance in the decision-making process. http://repub.eur.nl/res/pub/32580/ 2009-08-13T00:00:00Z BACKGROUND: The association of isolated tumor cells and micrometastases in regional lymph nodes with the clinical outcome of breast cancer is unclear. METHODS: We identified all patients in the Netherlands who underwent a sentinel-node biopsy for breast cancer before 2006 and had breast cancer with favorable primary-tumor characteristics and isolated tumor cells or micrometastases in the regional lymph nodes. Patients with node-negative disease were randomly selected from the years 2000 and 2001. The primary end point was disease-free survival. RESULTS: We identified 856 patients with node-negative disease who had not received systemic adjuvant therapy (the node-negative, no-adjuvant-therapy cohort), 856 patients with isolated tumor cells or micrometastases who had not received systemic adjuvant therapy (the node-positive, no-adjuvant-therapy cohort), and 995 patients with isolated tumor cells or micrometastases who had received such treatment (the nodepositive, adjuvant-therapy cohort). The median follow-up was 5.1 years. The adjusted hazard ratio for disease events among patients with isolated tumor cells who did not receive systemic therapy, as compared with women with node-negative disease, was 1.50 (95% confidence interval [CI], 1.15 to 1.94); among patients with micrometastases, the adjusted hazard ratio was 1.56 (95% CI, 1.15 to 2.13). Among patients with isolated tumor cells or micrometastases, the adjusted hazard ratio was 0.57 (95% CI, 0.45 to 0.73) in the node-positive, adjuvant-therapy cohort, as compared with the node-positive, no-adjuvant-therapy cohort. CONCLUSIONS: Isolated tumor cells or micrometastases in regional lymph nodes were associated with a reduced 5-year rate of disease-free survival among women with favorable early-stage breast cancer who did not receive adjuvant therapy. In patients with isolated tumor cells or micrometastases who received adjuvant therapy, disease-free survival was improved. Copyright http://repub.eur.nl/res/pub/25348/ 2009-03-31T00:00:00Z Background: Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1) the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2) reasons for PM and reasons for postponing it, 3) the need for additional psychological interventions, and factors associated, and 4) the frequency of psychiatric/psychological treatment history.Methods: During a 30 months period, women at high risk considering PM were offered a psychological consultation. The content of these, and follow-up, consultations were analyzed.Results: Most women (70 out of 73) accepted the psychological consultation, and 81% proceeded with PM. Main reasons for undergoing PM were to reduce anxiety about cancer, and to reduce the cancer risk. Uncertainty about surgery and the need for further information were the reasons given most frequently for postponing PM. Additional psychological support was given to 31% before and 14% after PM. The uptake of additional support was significantly higher in women with a BRCA1/2 mutation. A history of psychiatric/psychological treatment was present in 36%, mainly consisting of depression and grief after death of a mother.Conclusion: The uptake-rate of the standard psychological consultation indicates a high level of acceptability of this service for women deciding about PM. Since anxiety is one of the main reasons for considering PM, and depression and grief were present in a third, a standard consultation with a psychologist for high-risk women considering PM may be indicated. This may help them arrive at an informed decision, to detect and manage psychological distress, and to plan psychological support services. http://repub.eur.nl/res/pub/29454/ 2008-09-01T00:00:00Z Background: Data on distant disease-free interval (DDFI) and the localization of the first distant metastasis (DM) in BRCA1- and BRCA2-associated breast cancer (BC) patients are as yet scarcely available. Patients and methods: We identified 57 BRCA1-associated and 31 BRCA2-associated BC patients, diagnosed between 1980 and 2001, and developing DM disease before 2004, July 1. DDFI, the site(s) of first DM and post-relapse survival of these patients were compared with those of 192 sporadic BC patients. Results: As compared to sporadic patients, BRCA1 patients developed less often bone DM (30% vs. 51%; P = 0.005), but tended to develop more often lung DM (26% vs. 16%; P = 0.07), and DM at multiple sites (44% vs. 32%; P = 0.11). In BRCA2-associated compared to sporadic patients, first DM more commonly occurred in lymph nodes (23% vs. 7%; P = 0.007) and at multiple sites (48% vs. 32%; P = 0.08). Adjuvant systemic therapy appeared to be most effective in BRCA2 mutation carriers. Post-relapse survival was worse for BRCA1- and better for BRCA2-associated patients as compared to sporadic patients, but differences disappeared after adjustment for ER-status, site of first DM and DDFI. Conclusion: The site of first DM is different between BRCA1- and BRCA2-associated and sporadic BC patients. Differences in post-relapse survival could be explained by differences in site of first DM, in ER-status and in DDFI. Treatment efficacy may differ dependent on genetic status. http://repub.eur.nl/res/pub/36550/ 2007-12-01T00:00:00Z Background: BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce. Methods: From 358 high-risk women (including 236 BRCA1/2 carriers) undergoing PM between 1994 and 2004, relevant data on the occurrence of BC in relation to PM, complications in relation to breast reconstruction (BR), mutation status, age at PM and preoperative imaging examination results were extracted from the medical records, and analyzed separately for women without (unaffected, n = 177) and with a BC history (affected, n = 181). Results: No primary BCs occurred after PM (median follow-up 4.5 years). In one previously unaffected woman, metastatic BC was detected almost 4 years after PM (primary BC not found). Median age at PM was younger in unaffected women (P < .001), affected women more frequently were 50% risk carriers (P < .001). Unexpected (pre)malignant changes at PM were found in 3% of the patients (in 5 affected, and 5 unaffected women, respectively). In 49.6% of the women opting for BR one or more complications were registered, totaling 215 complications, leading to 153 surgical interventions (71%). Complications were mainly related to cosmetic outcome (36%) and capsular formation (24%). Conclusions: The risk of developing a primary BC after PM remains low after longer follow-up. Preoperative imaging and careful histological examination is warranted because of potential unexpected (pre)malignant findings. The high complication rate after breast reconstruction mainly concerns cosmetic issues. http://repub.eur.nl/res/pub/36503/ 2007-03-01T00:00:00Z Aim of the study: Results on tumour characteristics and survival of hereditary breast cancer (BC), especially on BRCA2-associated BC, are inconclusive. The prognostic impact of the classical tumour and treatment factors in hereditary BC is insufficiently known. Methods: We selected 103 BRCA2-, 223 BRCA1- and 311 non-BRCA1/2 BC patients (diagnosis 1980-2004) from the Rotterdam Family Cancer Clinic. To correct for longevity bias, analyses were also performed while excluding index patients undergoing DNA testing ≥2 years after BC diagnosis. As a comparison group, 759 sporadic BC patients of comparable age at and year of diagnosis were selected. We compared tumour characteristics, the occurrence of ipsilateral recurrence (LRR) and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS) between these groups. By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in hereditary BC. Results: We confirmed the presence of the particular BRCA1-phenotype. In contrast, tumour characteristics of BRCA2-associated BC were similar to those of non-BRCA1/2 and sporadic BC, with the exception of a high risk of CBC (3.1% per year) and oestrogen-receptor (ER)-positivity (83%). No significant differences between BRCA2-associated BC and other BC subgroups were found with respect to LRR, DDFS, BCSS and OS. Independent prognostic factors for BC-specific survival in hereditary BC (combining the three subgroups) were tumour stage, adjuvant chemotherapy, histologic grade, ER status and a prophylactic (salpingo-)oophorectomy. Conclusions: Apart from the frequent occurrence of contralateral BC and a positive ER-status, BRCA2-associated BC did not markedly differ from other hereditary or sporadic BC. Our observation that tumour size and nodal status are prognostic factors also in hereditary BC implies that the strategy to use these factors as a proxy for ultimate mortality appears to be valid also in this specific group of patients.