[Show abstract][Hide abstract] ABSTRACT: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts.
Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data.
We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors.
In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Background
Same-day diagnosis based on histology is increasingly being offered to patients suspected of breast cancer. We evaluated to which extent same-day diagnosis affected diagnostic accuracy and patients' anxiety levels during the diagnostic phase.
Patients and methods
All 759 women referred for same-day evaluation of suspicious breast lesions between November 2011–March 2013 were included. Diagnostic accuracy was assessed by linking all patients to the national pathology database to identify diagnostic discrepancies, in which case slides were reviewed. Patients' anxiety was measured in 127 patients by the State Trait and Anxiety Inventory on six moments during the diagnostic workup and changes over time (< = 1 week) were analyzed by mixed effect models.
Core-needle biopsy was indicated in 374/759 patients (49.3%) and in 205/759 (27%) patients, invasive or in situ cancer was found. Final diagnosis on the same day was provided for 606/759 (79.8%) patients. Overall, 3/759 (0.4%) discordant findings were identified. Anxiety levels decreased significantly over time from 45.2 to 30.0 (P = <0.001). Anxiety levels decreased from 44.4 to 25.9 (P = <0.001) for patients with benign disease, and remained unchanged for patients diagnosed with malignancies (48.6 to 46.7, P = 0.933). Time trends in anxiety were not affected by other patient or disease characteristics like age, education level or (family) history of breast cancer.
Same-day histological diagnosis is feasible in the vast majority of patients, without impairing diagnostic accuracy. Patients' anxiety rapidly decreased in patients with a benign diagnosis and remained constant in patients with malignancy.
PLoS ONE 07/2014; 9(7):e103105. DOI:10.1371/journal.pone.0103105 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gene copy number changes have an important role in carcinogenesis and could serve as potential biomarkers for prognosis and targets for therapy. Copy number changes mapping to chromosome 16 have been reported to be the most frequent alteration observed in female breast cancer and a loss on 16q has been shown to be associated with low grade and better prognosis. In the present study, we aimed to characterize copy number changes on 16q in a group of 135 male breast cancers using a novel multiplex ligation-dependent probe amplification kit. One hundred and twelve out of 135 (83%) male breast cancer showed copy number changes of at least one gene on chromosome 16, with frequent loss of 16q (71/135; 53%), either partial (66/135; 49%) or whole arm loss (5/135; 4%). Losses on 16q were thereby less often seen in male breast cancer than previously described in female breast cancer. Loss on 16q was significantly correlated with favorable clinicopathological features such as negative lymph node status, small tumor size, and low grade. Copy number gain of almost all genes on the short arm was also significantly correlated with lymph node negative status. A combination of 16q loss and 16p gain correlated even stronger with negative lymph node status (n=112; P=0.012), which was also underlined by unsupervised clustering. In conclusion, copy number loss on 16q is less frequent in male breast cancer than in female breast cancer, providing further evidence that male breast cancer and female breast cancer are genetically different. Gain on 16p and loss of 16q identify a group of male breast cancer with low propensity to develop lymph node metastases.Modern Pathology advance online publication, 7 June 2013; doi:10.1038/modpathol.2013.94.
Modern Pathology 06/2013; DOI:10.1038/modpathol.2013.94 · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic value. Previous papers on Bcl2 expression in MBC were equivocal, and the prognostic value of Bcl2 combined with mitotic index has not been studied in MBC. The aim of the present study was therefore to investigate the prognostic value of Bcl2 in combination with mitotic index in MBC. Immunohistochemical staining for Bcl2 was performed on tissue microarrays of a total of 151 male breast cancer cases. Mitotic index was scored. The prognostic value of Bcl2 expression and Bcl2/mitotic index combinations was evaluated studying their correlations with clinicopathologic features and their prediction of survival. The vast majority of MBC (94%) showed Bcl2 expression, more frequently than previously described for FBC. Bcl2 expression had no significant associations with clinicopathologic features such as tumor size, mitotic count and grade. In univariate survival analysis, Bcl2 had no prognostic value, and showed no additional prognostic value to tumor size and histological grade in Cox regression. In addition, the Bcl2/mitotic index combination as opposed to FBC did not predict survival in MBC. In conclusion, Bcl2 expression is common in MBC, but is not associated with major clinicopathologic features and, in contrast to FBC, does not seem to have prognostic value, also when combined with mitotic index.
PLoS ONE 04/2013; 8(4):e60138. DOI:10.1371/journal.pone.0060138 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pathologic nipple discharge is a symptom that frequently causes female patients to visit the outpatient breast clinic. In the vast majority of cases, the symptom is caused by a benign intraductal laesion. The options for diagnosis and treatment have long been limited; surgery was not infrequently the treatment of choice. With the advent of breast ductoscopy, a micro-endoscopic procedure, it is possible to visualise abnormalities in the ductal system. Tissue for histopathological investigation can be retrieved from the duct and the condition can be treated. The patient with nipple discharge is consequently prevented from having to undergo an invasive and fairly 'blindly' executed procedure under general anaesthesia. The miniscule dimensions of the duct in which the technique is carried out pose the greatest challenge to the further development of the ductoscope.
Nederlands tijdschrift voor geneeskunde 01/2013; 157(29):A6358.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up.
The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local pathologists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of <0,05 was considered to be significant.
A total of 929 patients who did not undergo axillary lymph node dissection were identified. After a median follow up of 77 (range 1-106) months, fifteen patients developed an isolated AR (AR rate 1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of radiotherapy (p = 0.010) significantly increased the risk of developing an AR. Distant metastasis free survival (DMFS) was significantly worse for patients with an AR compared to all other breast cancer patients (p < 0,0001).
Even after long-term follow up, the risk of developing an AR after a negative SLN in breast cancer is low. Young age and absence of radiation therapy are highly significant factors for developing an axillary recurrence. DMFS is worse for AR patients compared to patients initially diagnosed with N0 or N1 disease.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 05/2012; 38(10):925-31. DOI:10.1016/j.ejso.2012.04.016 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the prognostic meaning of lymph node micrometastases in breast cancer patients.
Between January 2000 and January 2003, 1411 patients with a cT(1-2)N(0) invasive breast carcinoma underwent surgery in 7 hospitals in the Netherlands. Sentinel lymph node biopsy was done in all patients. Based on lymph node status, patients were divided into 4 groups: (p)N(0) (n = 922), (p)N(1micro) (n = 103), (p)N(1a) (n = 285), and (p)N(≥1b) (n = 101). Median follow-up was 6.4 years.
At the end of follow-up, 1121 women were still alive (79.4%), 184 had died (13.0%), and 106 were lost to follow-up (7.5%). Breast cancer recurred in 244 patients: distant metastasis (n = 165), locoregional relapse (n = 83), and contralateral breast cancer (n = 44). Following adjustment for possible confounding characteristics and for adjuvant systemic treatment, overall survival (OS) remained comparable for (p)N(0) and (p)N(1micro) and was significantly worse for (p)N(1a) and (p)N(≥1b) (hazard ratio [HR] 1.18; 95% confidence interval [95% CI] 0.58-2.39, HR 2.47; 95% CI 1.69-3.63, HR 4.36; 95% CI 2.70-7.04, respectively). Disease-free survival (DFS) was similar too in the (p)N(0) and (p)N(1micro) group, and worse for (p)N(1a) and (p)N(≥1b) (HR 0.96; 95% CI 0.56-1.67 vs HR 1.64; 95% CI 1.19-2.27, HR 2.95; CI 1.98-4.42). The distant metastases rate also did not differ significantly between the (p)N(0) and (p)N(1micro) group and was worse for (p)N(1a) and (p)N(≥1b) (HR 1.22; 95% CI 0.60-2.49, HR 2.26; 95% CI 1.49-3.40, HR 3.49; CI 2.12-5.77).
In breast cancer patients survival is not affected by the presence of micrometastatic lymph node involvement.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to investigate the long-term outcome and technical feasibility of sternal resection.
We performed a 25-year retrospective study of 68 patients who underwent a sternectomy for sarcoma, recurrent breast cancer (BC) or radiation-induced necrosis between 1981 and 2006 in two tertiary referral centres (Erasmus Medical Center/Daniel den Hoed Cancer Center and Netherlands Cancer Center/Antoni van Leeuwenhoek Hospital, Netherlands). Patients were treated with curative intent and followed until May 2009. Medical records were reviewed for patient characteristics, indications for surgery, surgical technique, postoperative complications, and survival.
Sternal resection was performed in 43 sarcoma patients, 17 recurrent BC and 8 patients with radiation-induced necrosis with additional rib resection in the majority of patients and with clavicle resection in 13% of patients. Additional scapula, lung, breast or axilla resection, or both, was performed in 10%. Two patients died postoperatively (3%). Mild complications occurred in 24%, and severe complications (namely, pulmonary complications and reinterventions) in 16% of patients. Radical resection was achieved in 80% and 53% of sarcoma and recurrent BC patients, respectively. Five-year overall survival was 64% and 40% in sarcoma and recurrent BC patients, respectively, with 5-year disease-free survivals of 52% and 15%, respectively.
Sarcomas, recurrent BC, and radiation-induced necrosis can be successfully managed by sternal resection and reconstruction with curative intent. Low mortality and acceptable morbidity rates justify this operation in a palliative setting as well. Disease-free survival is poor among recurrent BC patients.
The Annals of thoracic surgery 10/2010; 90(4):1102-1108.e2. DOI:10.1016/j.athoracsur.2010.06.044 · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent.
BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed.
Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2 (P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses.
CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >or= 10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.
[Show abstract][Hide abstract] ABSTRACT: Extensive chest wall resections can provoke a wide variety of complications, in particular, complicated wound healing. A lower complication rate will be achieved when local factors contributing to wound healing can be identified and improved. The aim of this study is to describe these factors, irrespective of prognosis, survival, or systemic complications.
Retrospectively, the files of all patients undergoing an extended chest wall resection in a single institute during a 20-year period were retrieved. Patient demographics, use of preoperative therapy, tumor histology, the type of prosthesis (if any), and postoperative wound complications were recorded. Univariate and multivariate analysis were performed to identify factors contributing significantly to wound healing problems.
From January 1987 to December 2006, 220 patients underwent a chest wall resection, defined as resection of at least one rib, and/or part of the sternum. In 145 patients (66%) this procedure was uneventful. Multivariate analysis showed that ulceration of tumor and the use of omentum for soft tissue reconstruction comprised independent factors contributing to impaired wound healing.
Several factors leading to wound healing problems exist preoperatively. In a multidisciplinary setting, these factors should be weighed carefully against the possible benefits of an extended chest wall resection. Especially when ulceration of a tumor exists, or when omentum is considered for soft tissue reconstruction, increased risk on wound healing problems occurs. For the majority of patients chest wall resection will remain a safe and suitable procedure.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2009; 4(5):639-43. DOI:10.1097/JTO.0b013e31819d18c9 · 5.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evaluation of morbidity, mortality and oncologic outcome of patients treated with a chest wall resection for isolated breast cancer recurrences in the Internal Mammary Chain. Retrospectively we retrieved data from 29 patients. Multivariate analysis was performed to identify prognostic factors for (disease-free) survival. There were no postoperative deaths. Complications occurred in 11 patients. The median follow-up after CWR for all 16 patients still alive at the end of this study is 18.4 months. Nine patients were free of cancer. The 3-year overall and disease-free survival is 59.2% and 8.6%. The median survival is 40.7 months. After multivariate analysis for each of the four endpoints studied, only one prognostic factor remains significant for survival: systemic therapy before CRW (p=0.004). For local recurrence-free survival a first CRW recurrence (p<0.00001) and for disease-free survival radicality of the resection (p=0.008) are independent prognostic factors. Chest wall resection is a safe and effective treatment for isolated breast cancer recurrences in the IMC. Surgically treated patients have a fair survival and some of them are even cured.
Breast (Edinburgh, Scotland) 02/2009; 18(2):94-9. DOI:10.1016/j.breast.2009.01.005 · 2.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish the long-term results of a combination of radiotherapy or chemoradiotherapy and surgery for the treatment of patients with a Pancoast tumour in the Erasmus MC-Daniel den Hoed, Rotterdam, the Netherlands, with special attention for the prognostic factors.
During the period from 1 January 1991 to 31 December 2004, 36 patients underwent surgical treatment combined with radiotherapy or chemoradiotherapy for a non-small-cell bronchial carcinoma with invasion of the superior sulcus. The study was terminated on 31 January 2006. The data were analysed according to the intention-to-treat principle, with overall survival and disease-free survival as the outcome variables. Cox regression analysis revealed differences between the subgroups on the basis of which prognostic factors could be studied.
36 patients with a non-small-cell bronchial carcinoma invading the superior sulcus (Pancoast tumour) underwent multidisciplinary treatment consisting of pre-operative radiotherapy (since 2002 concomitant chemoradiotherapy), superior-sulcus resection and (partial) lung resection with intra-operative brachytherapy. 2 patients died postoperatively. In 80% of the patients there was a positive histological effect of the preoperative treatment. The median follow-up was 26 months. The 2-year overall and disease-free survival was 45 and 31%, respectively, and at 5 years this was 28 and 19%. These results were comparable with those for stage IIB lung cancer without invasion. Favourable prognostic factors were: at least 75% necrosis of the tumour after pre-treatment, lack of positive mediastinal lymph nodes, and younger age.
Nederlands tijdschrift voor geneeskunde 07/2007; 151(25):1406-11.
[Show abstract][Hide abstract] ABSTRACT: Differential path-length spectroscopy (DPS) was used to determine the local optical properties of breast tissue in vivo. DPS measurements were made on healthy and malignant breast tissue using a fibre-optic needle probe, and were correlated to the histological outcome of core-needle biopsies taken from the same location as the measurements. DPS yields information on the local tissue blood content, the local blood oxygenation, the average micro-vessel diameter, the beta-carotene concentration and the scatter slope. Our data show that malignant breast tissue is characterized by a significant decrease in tissue oxygenation and a higher blood content compared to normal breast tissue.
Physics in Medicine and Biology 07/2005; 50(11):2573-81. DOI:10.1088/0031-9155/50/11/009 · 2.92 Impact Factor