Publications by authors named "Edward Wight"

47 Publications

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Number 032/034-OL, April 2018) - Part 2 with Recommendations on the Therapy and Follow-up of Endometrial Cancer, Palliative Care, Psycho-oncological/Psychosocial Care/Rehabilitation/Patient Information and Healthcare Facilities.

Geburtshilfe Frauenheilkd 2018 Nov 26;78(11):1089-1109. Epub 2018 Nov 26.

Frauenselbsthilfe nach Krebs e. V., Erlangen, Erlangen/Forchheim, Germany.

The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.
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http://dx.doi.org/10.1055/a-0715-2964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261739PMC
November 2018

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Nummer 032/034-OL, April 2018) - Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer.

Geburtshilfe Frauenheilkd 2018 Oct 19;78(10):949-971. Epub 2018 Oct 19.

Frauenselbsthilfe nach Krebs e. V., Erlangen, Erlangen/Forchheim, Germany.

The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.
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http://dx.doi.org/10.1055/a-0713-1218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195426PMC
October 2018

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

Ann Surg Oncol 2014 Feb 22;21(2):401-7. Epub 2013 Oct 22.

Department of Surgery, Lindenhof Hospital, Berne, Switzerland.

Background: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients.

Methods: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19.

Results: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85).

Conclusions: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.
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http://dx.doi.org/10.1245/s10434-013-3315-9DOI Listing
February 2014

Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC.

Cancer Cytopathol 2013 Aug 13;121(8):423-31. Epub 2013 Feb 13.

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Background: Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests.

Methods: A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206).

Results: There was a significant correlation found between HPV detection by FISH and PCR (P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression (P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL.
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http://dx.doi.org/10.1002/cncy.21280DOI Listing
August 2013

[Genital cancers in the woman].

Authors:
Edward Wight

Ther Umsch 2011 Oct;68(10):535

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October 2011

Accuracy of urethral swab and urine analysis for the detection of Mycoplasma hominis and Ureaplasma urealyticum in women with lower urinary tract symptoms.

Arch Gynecol Obstet 2012 Apr 18;285(4):1049-53. Epub 2011 Oct 18.

Frauenklinik, Kantonsspital Bruderholz, 4001 Bruderholz, Switzerland.

Objectives: Our objective was to evaluate and compare the accuracy of urethral swabs and urine specimens in the detection of Mycoplasmas in women with lower urinary tract symptoms (LUTS).

Methods: During a urogynecological work-up, including cystometry, we obtained first-void urine, urethral and vaginal swabs in 207 consecutive women at our urogynecological division. Mycoplasma hominis and Ureaplasma urealyticum as well as other microorganisms were detected by standard culture methods.

Results: 131 of 207 women reported LUTS. The other 76 formed the controls. Of 207 women 50 (24.2%) had positive cultures for Mycoplasmas. The prevalence of Mycoplasmas in women with LUTS (30.3%) was statistically significant and higher in the group without LUTS (14.5%) (p = 0.011). The detection of M. hominis was most accurate using urethral swab (Specificity 99.9%, PPV 99.6%) compared to the urine specimen (96%, 75%) and vaginal swab (95.1%, 67%). Similar results could be achieved for U. urealyticum (urethral swab: specificity 98.7%, PPV 96.3%; urine specimen: 86.8%, 72%; vaginal swab: 80.5%, 65.2%).

Conclusion: In the subgroup of women less than 50 years an (detectable) infection due to Mycoplasma or Ureaplasma leads typically to LUTS with normal filling cystometry, whereas no such findings were relevant for the elderly women.
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http://dx.doi.org/10.1007/s00404-011-2109-1DOI Listing
April 2012

Prognostic impact and therapeutic implications of sentinel lymph node micro-metastases in early-stage breast cancer patients.

J Surg Oncol 2011 May;103(6):531-3

Department of Surgery, University Hospital Basel, Basel, Switzerland.

The prognostic value of sentinel lymph node (SLN) micro-metastases and the question whether patients with SLN micro-metastases should undergo axillary lymph node dissection remain a matter of great debate. Based on the current literature and on our own data, we provide suggestive evidence that SLN micro-metastases in early stage breast cancer patients appear to have prognostic value and should impact the decision-making regarding adjuvant therapy, however, do not necessarily require further surgical treatment.
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http://dx.doi.org/10.1002/jso.21693DOI Listing
May 2011

Bilateral papillary cystadenoma of the mesosalpinx: a rare manifestation of Von Hippel-Lindau disease.

Arch Gynecol Obstet 2010 Sep 16;282(3):343-6. Epub 2010 Feb 16.

Department of Obstetrics and Gynecology, University Hospital Basel, Spitalstrasse 21, Basel, Switzerland.

We report a rare case of a woman with bilateral papillary cystadenomata of the broad ligament with von Hippel-Lindau disease (VHL) (other manifestations: capillary hemangioblastomas of the spinal cord). Patient surveillance is important, because in the course of VHL-associated tumors malignant lesions may arise that are relevant for the prognosis.
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http://dx.doi.org/10.1007/s00404-010-1386-4DOI Listing
September 2010

Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study.

Indian J Surg Oncol 2010 Jan 7;1(1):59-67. Epub 2010 Aug 7.

Objectives: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted.

Background: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate.

Methods: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 ≤ 3 cm, cN0 M0) between 1998 and 2002. The SLN were examined by step sectioning and stained with hematoxylin and eosin and immunohistochemistry. None of the patients with negative SLN or SLN micrometastases (International Union Against Cancer classification, >0.2 to ≤ 2 mm) underwent a completion ALND or radiation to the axilla. Long-term overall and disease-free survivals were compared between patients with negative SLN and those with SLN micrometastases by log rank tests.

Results: The SLN was negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27 patients (27 of 224, 12%). After a median followup of 77 months (range, 24-106 months), neither locoregional recurrences nor distant metastases occurred in any of the 27 patients with SLN micrometastases. There were no statistically significant differences for overall (P = 0.656), locoregional (P = 0.174), and axillary and distant disease-free survival (P = 0.15) between patients with negative SLN and SLN micrometastases.

Conclusions: This analysis of unselected patients provides evidence that a completion level I and II ALND may be safely omitted in early-stage breast cancer patients with SLN micrometastases.
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http://dx.doi.org/10.1007/s13193-010-0013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420993PMC
January 2010

Breast cancer with non-inflammatory skin involvement: current data on an underreported entity and its problematic classification.

Breast 2010 Feb 16;19(1):59-64. Epub 2009 Dec 16.

University Hospital Basel, Department of Gynecology and Obstetrics, Spitalstrasse 21, Basel, Switzerland.

We evaluated 166 breast cancer cases with non-inflammatory skin involvement (NISI), which were classified in the TNM classification as T4b. The distribution of tumour sizes and stages was: < or =3 cm:24.1%, 3.1-5 cm:21.7%, 5.1-10 cm:33.1%, >10 cm:21.1%; stages:I/II:21.0%, III:43.4%, IV:35.6%. To assess the impact of NISI on axillary lymph node involvement (ALNI), we analyzed a sub-group of 50 patients with tumours < or =5 cm and compared them with a matched control group. NISI was found to be associated with increased ALNI (HR, 2.66; 95%CI, 1.59-4.63; p<0.0001). According to the inherent rules of tumour classification, only tumours with similar morphologic extent and prognostic significance should be combined. Since there is a high grade of heterogeneity, this basic tenet is clearly violated regarding breast cancer with NISI. Our proposal is to eliminate these tumours from the T4 category and to classify them simply by size (T1-3). Due to its prognostic significance, NISI should be indicated by an optional descriptor (e.g. S1).
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http://dx.doi.org/10.1016/j.breast.2009.11.008DOI Listing
February 2010

Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors.

Mol Cancer 2009 Nov 17;8:105. Epub 2009 Nov 17.

Laboratory for Prenatal Medicine and Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, Switzerland.

Background: With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value.

Methods: Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters.

Results: While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001).

Conclusion: Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.
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http://dx.doi.org/10.1186/1476-4598-8-105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780981PMC
November 2009

Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study.

Ann Surg Oncol 2009 Dec 4;16(12):3366-74. Epub 2009 Sep 4.

Department of Surgery, University Hospital Lausanne, Lausanne, Switzerland.

Objectives: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted.

Background: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate.

Methods: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 .2 mm to
Results: The SLN was negative in 55% of patients (123 of 224). SLN micrometastases were detected in 27 patients (27 of 224, 12%). After a median follow-up of 77 months (range, 24-106 months), neither locoregional recurrences nor distant metastases occurred in any of the 27 patients with SLN micrometastases. There were no statistically significant differences for overall (P = .656), locoregional (P = .174), and axillary and distant disease-free survival (P = .15) between patients with negative SLN and SLN micrometastases.

Conclusions: This analysis of unselected patients provides evidence that a completion level I and II ALND may be safely omitted in early-stage breast cancer patients with SLN micrometastases.
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http://dx.doi.org/10.1245/s10434-009-0660-9DOI Listing
December 2009

Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

Arch Gynecol Obstet 2010 Feb 24;281(2):339-44. Epub 2009 Jun 24.

Department of Gynecology and Obstetrics, University Hospital Basel (UHB), Spitalstrasse 21, 4031, Basel, Switzerland.

Purpose: The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS).

Methods: We analyzed the overall courses of 85 unselected ROC patients and defined the following groups: A, platinum resistant patients (n=39); subgroup A.1, those who received no or at maximum one line of palliative chemotherapy (n=15, 38.5%); subgroup A.2, those who received>or=two therapy lines (n=24, 61.5%); B, platinum sensitive patients, n=46.

Results: Group A had significantly lower OS than group B (median: 16 vs. 25 months; p=0.019). Group A.1 had significantly worse outcome compared to group A.2 (median: 5 vs. 21.5 months; p<0.001). The comparison between study group A.2 and group B showed comparable survival rates (p=0.738). Considering only the patients who had completed treatment courses, the median number of therapy lines administered was higher in group A.2 than in group B (4 vs. 3; p=0.008).

Conclusions: There is not only the known dichotomy between platinum sensitive and resistant ROC patients, but rather also within the platinum resistant subgroup itself. There is a considerably large subgroup of platinum resistant patients who will subsequently enter a phase where multiple treatment programs will be considered and administered. These patients have similar survival rates compared to those from the platinum sensitive patient group and the therapy principles of a chronic disease are applicable.
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http://dx.doi.org/10.1007/s00404-009-1159-0DOI Listing
February 2010

Systemic therapy of metastatic breast cancer: the truth beyond the clinical trials.

Oncology 2009 25;76(4):247-53. Epub 2009 Feb 25.

Department of Gynecology and Obstetrics, University Hospital Basel, Basel, Switzerland.

Objective: To depict a clear and coherent picture of the overall course of palliative treatment in an unselected study cohort over the course of time.

Methods: We compared therapy type and course of 242 women whose distant metastatic disease was diagnosed from 1990 to 2006 and who ultimately died of the disease. We divided the patients into two subgroups depending on the year of diagnosis of metastases (group A: 1998-2006 vs. group B: 1990-1997).

Results: In both subgroups, there were no significant differences in the general type of treatment and the number of administered therapy lines (no systemic therapy: 12.9 vs.13.7%, p = 0.848; endocrine therapy only: 20.4 vs. 25.2%, p = 0.430; chemotherapy only: 18.4 vs.16.9%, p = 0.735; sequential combination regimen including endocrine therapy/chemotherapy/trastuzumab: 46.9 vs. 44.2%, p = 0.694; median: 2 lines). In the cases where chemotherapy was administered, there were no differences between the number of lines among older and younger patients (median: two lines; >or=70 years vs. <70 years: p = 0.269). The median metastatic disease-specific survival increased from 16 months in the period from 1990 to 1997, to 21 months in the period from 1998 to 2000 (p = 0.062).

Conclusion: The number of patients who died from metastatic breast cancer without receiving any antineoplastic therapy was surprisingly high. The use of newer agents and regimens in the treatment of metastatic breast cancer was associated with an improved survival over time. Chemotherapy is a feasible option also among older patients.
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http://dx.doi.org/10.1159/000205387DOI Listing
April 2009

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease.

Arch Gynecol Obstet 2009 Nov 22;280(5):719-24. Epub 2009 Feb 22.

Department of Gynecology and Obstetrics, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.

Purpose: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time.

Methods: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n = 70; group B 1998-2006, n = 63).

Results: Both study groups showed similar results in survival (median recurrent disease-specific survival-A 18 months vs. B 19 months; P = 0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P = 0.0057], received more therapy lines (> or =3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P = 0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A = -10.02; 95%CI -17.99 to -2.05; P = 0.014).

Conclusions: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfilled.
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http://dx.doi.org/10.1007/s00404-009-0995-2DOI Listing
November 2009

Distant metastatic breast cancer as an incurable disease: a tenet with a need for revision.

Cancer J 2009 Jan-Feb;15(1):81-6

Department of Gynecology and Obstetrics, University Hospital Basel (UHB), Spitalstrasse 21, Basel CH-4031, Switzerland.

Purpose: Published reports provide level-III evidence in support of the hypothesis that distant metastatic breast cancer (MBC) might be curable in up to 3% of cases through a multidisciplinary approach including combination chemotherapy regimens in selected patients, usually young, and with limited metastases. Our study evaluates the rate and characteristics of long-term survivors based on a nonselective study cohort.

Patients And Methods: We analyzed the data from 149 patients in whom distant MBC was diagnosed from 1990 to 1999.

Results: Five patients (3.4%) were long-term survivors (9-14 years after initial diagnosis of MBC) without any clinical evidence of disease. They had a 2-peaked distribution of age: 3 were 41-57 years old at the diagnosis of MBC and 2 were much older (76, 79 years). Median survival time after diagnosis of MBC was 152 (range, 109-172) months. Three patients had isolated metastatic lesions, although 1 patient had multiple organ metastases and another extensive bone metastases. In 4 of 5 cases, long-term survival was achieved without the administration of chemotherapy.

Discussion: Long-term survivors in MBC comprise a relatively heterogeneous group, and the factors which lead to the quite rare situation of long-term survival can hardly be evaluated systematically. Aggressive chemotherapy regimens appear not to be a key factor for survival. Furthermore, in a nonselective study cohort, some patients clearly are not only alive but also disease-free more than 12 years after initial relapse. This fraction may be small, but the chance for survival, and even for cure, truly exists.
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http://dx.doi.org/10.1097/PPO.0b013e31818d8509DOI Listing
April 2009

Tumor size and detection in breast cancer: Self-examination and clinical breast examination are at their limit.

Cancer Detect Prev 2008 13;32(3):224-8. Epub 2008 Sep 13.

University Hospital Basel, Department of Gynecology and Obstetrics, Spitalstrasse 21, CH-4031 Basel, Switzerland.

Background: This study investigates to what extent tumor detection methods in breast cancer have changed and how this has influenced tumor size at initial diagnosis.

Methods: 1054 breast carcinomas < or =5 cm, newly diagnosed between 1990 and 2006, were evaluated for the tumor detection methods used, namely self-detection (SD, n=568), clinical breast examination (CBE, n=212), and radiological breast examination (RBE, n=237), and their corresponding tumor sizes.

Results: During the study period, the proportion of cases found by RBE increased (p<0.001), while median tumor size decreased (1990-1992: 22 mm; 2005/2006: 17 mm. Spearman rho=-0.12, p<0.001). Nevertheless, SD remained the most frequent method of tumor identification (2005/2006: 48.9%). Carcinomas found by RBE were smaller (median size: 12 mm) than those found by the other two detection forms (SD: 21 mm, CBE: 21 mm; p<0.001). Within the different methods, only in RBE was an appreciable decrease in the size of the detected tumors observed during the study period (Spearman rho=-0.14, p<0.001; SD: Spearman rho=-0.05, p=0.19; CBE: Spearman rho=-0.05, p=0.43).

Conclusion: Despite educational campaigns and high media coverage, the possibilities for improving the "classical" methods of tumor detection in breast cancer, self-detection and clinical breast examination, seem to be at their limit. The significant decrease in tumor size at time of detection observed in the last years is primarily only due to the increased use of breast imaging. Improved detection of smaller tumors may presumably be reached only by an increased use of radiological procedures.
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http://dx.doi.org/10.1016/j.cdp.2008.04.002DOI Listing
December 2008

[Pregnancy-associated breast cancer].

Ther Umsch 2008 Apr;65(4):223-9

Departement für Gynäkologie und Geburtshilfe, Universitätsspital Basel, Spitalstrasse 21, Basel.

Pregnancy-associated breast cancer is a rare disease with an incidence of 1:3000. There is no indication anymore to terminate the pregnancy since the maternal prognosis will not be influenced. Due to physiologic pregnancy-related changes in the breast, the interpretation of clinical findings, breast ultrasound and mammography is more demanding. There is often a diagnostic delay in detecting pregnancy-associated breast cancer. Mastectomy and axillary lymphonodectomy compose the surgical therapy. In the third trimester, breast conserving surgery and radiotherapy postpartum is an option. Chemotherapy can be administered relatively safe in the second and third trimester. Radiotherapy, hormonal therapy and trastuzumab are contraindicated during pregnancy. Patients with pregnancy-associated breast cancer should be seen and treated in an interdisciplinary setting, preferably in a specialized centre.
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http://dx.doi.org/10.1024/0040-5930.65.4.223DOI Listing
April 2008

Three-dimensional pathological size assessment in primary breast carcinoma.

Breast Cancer Res Treat 2009 Jul 12;116(2):257-62. Epub 2008 Jul 12.

Department of Gynecology and Obstetrics, University Hospital Basel, Basel, Switzerland.

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40 mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P = 0.0003, TV: P = 0.0009, TSA: P < 0.0001; multivariate analyses: MD: P = 0.0018, TV: P = 0.0109, TSA: P = 0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alone.
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http://dx.doi.org/10.1007/s10549-008-0115-1DOI Listing
July 2009

Sexual dysfunction after premenopausal stage I and II breast cancer: do androgens play a role?

J Sex Med 2008 Aug 28;5(8):1898-906. Epub 2008 Jun 28.

University Hospital Basel, Department Obstetrics and Gynecology, Basel, Switzerland.

Introduction: Sexual dysfunction after breast cancer has been attributed to a variety of treatment associated and psychological factors. Data on the role of a treatment-induced decrease of testosterone for the development of sexual problems in breast cancer survivors have remained inconclusive. However, androgen metabolites constitute a more reliable measure for total androgen activity.

Aim: To measure levels of total androgen activity in breast cancer patients and to investigate relevant predictors of sexual dysfunction after breast cancer.

Methods: Twenty-nine patients with a premenopausal diagnosis of Stage I or II breast cancer and terminated adjuvant treatment, completed questionnaires on sexuality, quality of relationship, body image, and depression. In addition, blood samples were taken for the analysis of sex steroids.

Main Outcome Measures: Female Sexual Function Index (FSFI), Relationship (PFB), Beck Depression Inventory, and European Organization for Research and Treatment of Cancer quality of life questionnaire. Analysis of dihydroepiandrosterone, dihydroepiandrosterone-sulfate, androstenedione, 17beta-diol, testosterone, dihydrotestosterone, androsterone, and ADT-G, 3-alpha-diol-3G, 3-alpha-diol-17G.

Results: Low levels of sex steroids reflected the medication-induced postmenopausal status independent of the type of chemotherapy treatment. Sexual dysfunction was present in 68% of the study group. Women with a history of chemotherapy were more affected in all of the FSFI-domains. The only predictor for desire was quality of relationship, while chemotherapy was predictive for problems with arousal, lubrication, orgasm, and sexual pain. Sexual satisfaction and higher FSFI sum scores were predicted by better quality of relationship and no history of chemotherapy, together explaining 54.2% and 49.7% of the variance.

Conclusions: Sexual dysfunction after breast cancer is common and women should be informed properly at an early stage of treatment. Specific interventions have to be offered considering person-related preexisting factors and couples at risk should be supported in the transition to sexual life after breast cancer.
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http://dx.doi.org/10.1111/j.1743-6109.2008.00893.xDOI Listing
August 2008

Positive correlation of cell-free DNA in plasma/serum in patients with malignant and benign breast disease.

Anticancer Res 2008 Mar-Apr;28(2A):921-5

Department of Obstetrics and Gynecology, University Hospital, Basel, Switzerland.

Background: Circulating cell-free (ccf) DNA is measurable in healthy individuals and in higher concentration in patients with benign and malignant breast disease (BD).

Patients And Methods: In paired plasma and serum samples ccf DNA was extracted and quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene.

Results: The concentration of ccf DNA in serum was higher in patients with benign and malignant BD (p = 0.023/p = 0.001) compared to healthy controls, whereas ccf DNA in plasma was higher in patients with malignant BD compared to patients with benign BD or healthy controls (p = 0.012/0.007). The ccf DNA correlated significantly between plasma and serum samples in patients with benign (p = 0.01; R: 0.677) as well as malignant BD (p = 0.01; R:0.713).

Conclusion: The positive correlation between ccf DNA in plasma and serum in patients with benign as well as malignant BD, might have a diagnostic value for discriminating between malignant and benign BD.
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June 2008

Impact of hormone replacement therapy on the histologic subtype of breast cancer.

Arch Gynecol Obstet 2008 Nov 12;278(5):443-9. Epub 2008 Mar 12.

Department of Gynecology and Obstetrics, University Hospital Basel, Spitalstrasse 21, Basel, Switzerland.

Objective: Postmenopausal hormone replacement therapy (HRT) is associated with an increase in breast cancer risk, which correlates to the duration of HRT use. We wanted to investigate a possible association between HRT use and the risk of a histologic subtype of breast cancer.

Patients And Methods: From 1995 until 2004, 497 cases of primary ductal, lobular or ductulolobular breast cancer in postmenopausal women were diagnosed at the Department of Gynecology and Obstetrics, University Hospital Basel, Switzerland. The data was derived from patient's records. HRT ever use was defined as HRT use for > or =6 months.

Results: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers, 21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ. Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5% were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women were HRT never users. HRT status could not be defined in 12 women. HRT ever use was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02-2.73). Also, menopause due to bilateral oophorectomy was associated with an increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54).

Conclusions: There is evidence that HRT as well as menopause due to bilateral oophorectomy may be associated with an increased risk for lobular cancer. This association is of major clinical relevance, since lobular breast cancer is more difficult to diagnose clinically and radiologically than ductal breast cancer.
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http://dx.doi.org/10.1007/s00404-008-0613-8DOI Listing
November 2008

Accuracy of frozen section of sentinel lymph nodes: a prospective analysis of 659 breast cancer patients of the Swiss multicenter study.

Breast Cancer Res Treat 2009 Jan 23;113(1):129-36. Epub 2008 Feb 23.

Division of General Surgery, University Hospital Basel, Basel, Switzerland.

Objective: To assess the accuracy of sentinel lymph node (SLN) frozen section in a prospective multicenter study of early-stage breast cancer patients.

Summary Background Data: The decision to perform an immediate completion axillary node dissection (ALND) is based on results of SLN frozen section. However, SLN frozen sections are not routinely performed in all centers. Moreover, the accuracy of SLN frozen section remains a matter of great debate.

Methods: Prospective multicenter trial analyzing 659 early stage breast cancer patients (pT1 and pT2
Results: SLN were identified in 98.3% (648/659) of all patients. The accuracy of frozen section was 90.1% (584/648), the sensitivity for SLN macro-metastases 98% (142/145), and the specificity 100%. A total of 47 patients with SLN micro-metastases (n=36) or isolated tumor cells (n=11) underwent a delayed completion ALND. In 96% (45/47) of these patients the ALND specimens were free of macro-metastases.

Conclusions: SLN frozen section provides highly accurate information regarding identification of SLN macro-metastases, a delayed completion ALND can be avoided in 98% of these patients. More importantly, in the present investigation the vast majority (96%) of patients with SLN micro-metastases or isolated tumor cells undergoing delayed completion ALND did not benefit from the second operation as ALND specimens were free of macro-metastases. We strongly recommend the routine use of SLN frozen section in early stage breast cancer patients.
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http://dx.doi.org/10.1007/s10549-008-9911-xDOI Listing
January 2009

Metastatic patterns at autopsy in patients with ovarian carcinoma.

Cancer 2007 Sep;110(6):1272-80

Department of Gynecology and Obstetrics, University Hospital Basel, Basel, Switzerland.

Background: Previously published studies concerning autopsy findings in ovarian cancer failed to consider the broad differences in factors that influence the course of disease. Furthermore, those studies were conducted when the currently accepted standards in diagnostics and therapy had not been fully established. The objective of the current study was to determine the frequency and sites of metastases in patients with ovarian cancer with particular attention to the clinical course and therapy.

Methods: Autopsy reports, histologic slides, and clinical files from 197 patients who died of ovarian carcinoma between 1975 and 2005 were studied. The distribution of metastatic sites (19 different organ sites) and metastatic patterns, with particular attention to clinical course (age, length of survival) and therapy (surgical treatment with curative intention, different chemotherapy regimens), were analyzed.

Results: Overall, 66.3% of patients had metastases to sites outside the abdominopelvic cavity. Patients who were aged >70 years, who had a disease duration
Conclusions: Autopsy data may yield important information concerning the metastatic potential of a malignancy and may assist physicians in making clinical management decisions. The results from the current indicated that declining autopsy rates during the last decades have limited the ability of physicians to evaluate the impact of new therapy regimens on the frequency and distribution of metastases through postmortem examination.
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http://dx.doi.org/10.1002/cncr.22919DOI Listing
September 2007

T4 breast cancer under closer inspection: a case for revision of the TNM classification.

Breast 2007 Dec 2;16(6):625-36. Epub 2007 Jul 2.

University Hospital Basel, Department of Gynecology and Obstetrics, Spitalstrasse 21, CH-4031 Basel, Switzerland.

The presence of skin involvement in breast cancer results in the classification of the tumor into the highest tumor category, and accordingly into the highest non-metastatic disease stage (current TNM classification: T4/stage III). This traditional view is no longer justifiable, as tumors that show non-inflammatory skin involvement (T4b) make up a considerably heterogeneous group with a high percentage of small-sized tumors. Classifying all lesions demonstrating this feature together results in the combination of tumors with widely differing prognostic and therapeutic implications into a single group. This violates the basic principle of the TNM concept in that only tumors exhibiting similar extension and prognosis should be grouped into one category/stage. Furthermore, the currently valid definitions of non-inflammatory skin involvement are misconceived for the substantial group of small tumors which often have ambiguous morphologic findings: the clinical classification depends on the subjective perception of the individual observer, and the pathologic staging considers histologic criteria that are not justifiable from a functional-morphological point of view. For these reasons, we strongly feel that there is a need to revise the current T4 category. We recommend that breast carcinomas currently classified as T4a-c should be eliminated from the T4 category and classified simply according to their tumor size (T1-3). The prognostically very unfavorable inflammatory carcinoma (T4d) should be maintained as the only clinicopathologic entity in the T4 category. This proposal, which will also lead to a revision of the stage III group, adheres more closely to the goals and principles of the TNM classification than do the current classification guidelines. Through the revision of the T4 category, the definitions and guidelines of inflammatory breast carcinoma should be adapted to the internationally accepted nomenclature.
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http://dx.doi.org/10.1016/j.breast.2007.05.006DOI Listing
December 2007

Selective visualization of the Fallopian tube with magnetic resonance imaging.

Reprod Biomed Online 2007 May;14(5):593-7

University Women's Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland.

At present, X-ray hysterosalpingography is used commonly as a screening method for testing Fallopian tube patency, but the results are often unreliable due to mucous plugs or muscular contractions. Selective catheterization of the tubes under X-ray control is feasible, but is rarely used due to exposure of young individuals aiming for pregnancy to a high ionizing dose. Here, a case is described of a patient whose Fallopian tubes were selectively catheterized and visualized three-dimensionally under contrast-enhanced magnetic resonance imaging (MRI) guidance using a high-viscous gadoteric acid solution (Dotarem). In this patient, bilateral peritubal adhesions caused a blockage of the fimbrial part of the tube leading to transuterine spilling of tubal fluid. Laparoscopy followed by bilateral salpingectomy was then performed, which confirmed the three-dimensional MRI images, and the excised specimens were examined histologically. The advantages of this novel technique include the avoidance of ionizing damage to the gonads and the potential for development of more elaborate interventional methods, such as ballooning and stenting. It is intended to develop contrast MRI further, both for improved non-invasive visualization and for manipulative technology of the Fallopian tubes.
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http://dx.doi.org/10.1016/s1472-6483(10)61051-6DOI Listing
May 2007

Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion axillary lymph node dissection after breast cancer surgery: a prospective Swiss multicenter study on 659 patients.

Ann Surg 2007 Mar;245(3):452-61

Department of Surgery, University Hospital Basel, Basel, Switzerland.

Objective: To assess the morbidity after sentinel lymph node (SLN) biopsy compared with SLN and completion level I and II axillary lymph node dissection (ALND) in a prospective multicenter study.

Summary Background Data: ALND after breast cancer surgery is associated with considerable morbidity. We hypothesized: 1) that the morbidity in patients undergoing SLN biopsy only is significantly lower compared with those after SLN and completion ALND level I and II; and 2) that SLN biopsy can be performed with similar intermediate term morbidity in academic and nonacademic centers.

Methods: Patients with early stage breast cancer (pT1 and pT2
Results: SLN biopsy alone was performed in 449 patients, whereas 210 patients underwent SLN and completion ALND. The median follow-ups were 31.0 and 29.5 months for the SLN and SLN and completion ALND groups, respectively. Intermediate-term follow-up information was available from 635 of 659 patients (96.4%) of enrolled patients. The following results were found in the SLN versus SLN and completion ALND group: presence of lymphedema (3.5% vs. 19.1%, P < 0.0001), impaired shoulder range of motion (3.5% vs. 11.3%, P < 0.0001), shoulder/arm pain (8.1% vs. 21.1%, P < 0.0001), and numbness (10.9% vs. 37.7%, P < 0.0001). No significant differences regarding postoperative morbidity after SLN biopsy were noticed between academic and nonacademic hospitals (P = 0.921).

Conclusions: The morbidity after SLN biopsy alone is not negligible but significantly lower compared with level I and II ALND. SLN biopsy can be performed with similar short- and intermediate-term morbidity in academic and nonacademic centers.
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http://dx.doi.org/10.1097/01.sla.0000245472.47748.ecDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1877006PMC
March 2007

Elevated level of cell-free plasma DNA is associated with breast cancer.

Arch Gynecol Obstet 2007 Oct 13;276(4):327-31. Epub 2007 Mar 13.

Laboratory for Prenatal Medicine and Gynaecological Oncology, Department of Obstetrics and Gynaecology, University of Basel, Basel, Switzerland.

Background: We analysed cell-free DNA (cfDNA) in the plasma of patients with both malignant and benign breast lesions by real-time quantitative PCR to determine whether the finding may have diagnostic and prognostic implications.

Methods: Plasma samples were obtained from 33 patients with breast cancer, 32 patients with benign breast lesions and 50 healthy women as normal controls. Circulatory cfDNA was extracted from the plasma samples and quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene.

Results: The mean concentrations of cfDNA in the plasma samples from patients with breast cancer, patients with benign breast lesions and normal controls were 2,285, 1,368 and 1,489 genome equivalents (GE) per millilitre, respectively. The level of cfDNA in the breast cancer group was significantly higher than those in the benign lesion group and control group (P = 0.007 and 0.013, respectively). These findings were associated with malignant tumour size. The levels of the cfDNA were high in patients with lymph node involvement and distant metastasis.

Conclusions: Our results suggest that levels of cfDNA in the plasma are elevated in malignant breast cancer and correlated with tumour size. These findings could have diagnostic and prognostic value for malignant breast tumours.
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http://dx.doi.org/10.1007/s00404-007-0345-1DOI Listing
October 2007

Psychological management of pregnancy-related breast cancer.

Breast 2006 Dec;15 Suppl 2:S53-9

Department of Obstetrics and Gynaecology, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.

The comprehensive care of a pregnant patient in whom breast cancer is diagnosed presents a challenge to the biomedical and psychological competence of the medical team. Illustrated by a case presentation the different phases of psychological care are delineated and discussed: the confrontation with the diagnosis of a life-threatening disease in a situation in which the beginning of a future life is celebrated. Special attention is given to breaking bad news, the establishment of a stable and trustful physician-patient relationship, communicating risk and to the extremely difficult decision-making process regarding termination or continuation of pregnancy (shared decision-making). The delicate balance between oncological care for the mother with a high-risk disease and a high-risk pregnancy and neonatal care for the foetus is outlined, including regular talks about emotions and concerns.
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http://dx.doi.org/10.1016/S0960-9776(07)70019-XDOI Listing
December 2006

Association of the presence of bone marrow micrometastases with the sentinel lymph node status in 410 early stage breast cancer patients: results of the Swiss Multicenter Study.

Ann Surg Oncol 2007 Jun 14;14(6):1896-903. Epub 2007 Mar 14.

Department of Surgery, University Hospital Basel, Basel, Switzerland.

Background: The sentinel lymph node (SLN) status has proven to accurately reflect the remaining axillary lymph nodes and represents the most important prognostic factor. It is unknown whether an association exists between the SLN status and the presence of bone marrow (BM) micrometastases. The objective of the present investigation was to evaluate whether or not such an association exists.

Methods: In the present investigation 410 patients with early stage breast cancer (pT1 and pT2
Results: BM micrometastases were detected in 28.8% (118/410) of all patients. The SLN contained metastases in 32.4% (133/410). Overall 51.2% of the patients (210/410) were SLN negative/BM negative and 12.4% (51/410) SLN positive/BM positive. Of all patients, 16.4% (67/410) were SLN negative/BM positive and 20.0% (82/410) SLN positive/BM negative. There was a statistically significant association between the SLN and BM status, both in unadjusted (Fisher's exact test: P = .004) and multiple logistic regression analysis (P = .007).

Conclusions: In the present investigation a significant association was found between a positive SLN status and the presence of BM micrometastases. Nonetheless, the percentage of non-concordance (SLN negative/BM positive and SLN positive/BM negative) was considerable. The prognostic impact of BM micrometastases in our patient sample remains to be evaluated.
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http://dx.doi.org/10.1245/s10434-006-9193-7DOI Listing
June 2007