Anton Haid

Morbidity of Breast Cancer Patients Following Complete Axillary Dissection or Sentinel Node Biopsy Only: A Comparative Evaluation

AbstractIntroduction The usefulness of routine axillary dissection (AD) at levels I–II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only. Method One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000. Results Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients. Conclusion SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.

BRCA1‐related breast cancer in Austrian breast and ovarian cancer families: Specific BRCA1 mutations and pathological characteristics

We identified 17 BRCA1mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high‐performance liquid chromatography (DHPLC) and the protein<0B> <0R>truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non‐Austrian origin. In addition, 6 rare missense mutations (allele frequency < 1%) with unknown biological effects were identified. Four mutations occurred more than once in the Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty‐four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty‐eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age‐related, node‐negative control group. The prevalence of grade III tumors was marginally significant . Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age‐related, node‐negative comparison group, showed no statistical difference. Int. J. Cancer 77:354–360, 1998.

Pathologic Complete Response With Six Compared With Three Cycles of Neoadjuvant Epirubicin Plus Docetaxel and Granulocyte Colony-Stimulating Factor in Operable Breast Cancer: Results of ABCSG-14

PURPOSE Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate. PATIENTS AND METHODS Patients with biopsy-proven breast cancer (T1-4a-c, N+/-, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery. RESULTS A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment. CONCLUSION Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.

Multicentric Breast Cancer: A New Indication for Sentinel Node Biopsy—A Multi-Institutional Validation Study

PURPOSE Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer. PATIENTS AND METHODS Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB. RESULTS Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates. CONCLUSION Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.

Sentinel Lymph Node Biopsy After Preoperative Chemotherapy for Breast Cancer: Findings from the Austrian Sentinel Node Study Group

BackgroundSentinel lymph node biopsy (SLNB) has become an accurate alternative to axillary lymph node dissection for early breast cancer. However, data are still insufficient as regards the combination of SLNB with preoperative chemotherapy (PC).MethodsThe Austrian Sentinel Node Study Group investigated 167 patients who underwent SLNB and axillary lymph node dissection after 3 to 6 courses of PC. SLNB was limited to patients with a clinically negative axilla after PC. Blue dye was used in 29 cases (17%), and tracers were used in 20 (12%). A combination of the two methods was applied in most patients (n = 120; 72%).ResultsAt least 1 sentinel lymph node (SLN) was identified in 144 patients (identification rate, 85%): in 86% by blue dye alone, in 65% by tracers alone, and in 88% by a combination of methods. The SLN was positive in 70 women (42%) and was the only positive node with otherwise negative axillary nodes in 39 patients (23%). In 6 cases, the SLN was diagnosed as negative although tumor infiltration was detected in an upper node of the axillary basin (false-negative rate, 8%; 6 of 76 patients; sensitivity, 92%). At least 62 patients (37%) were free of tumor cells in the SLN and in the axillary nodes.ConclusionThe results of SLNB after PC are comparable to the results of SLNB without PC. Further investigation in a prospective setting is warranted to confirm these promising results.

Adjuvant Sequencing of Tamoxifen and Anastrozole Is Superior to Tamoxifen Alone in Postmenopausal Women with Low Proliferating Breast Cancer

Purpose: To assess the predictive value of Ki67 expression in postmenopausal hormone receptor–positive early-breast cancer patients, who were either treated with adjuvant tamoxifen (TAM) alone or with TAM followed by anastrozole (ANA). Experimental Design: Expression of Ki67 was determined centrally by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospectively randomized Austrian Breast and Colorectal Cancer Study Group Trial 8, and had received TAM for 5 years, or TAM for 2 years followed by ANA for 3 years. Ki67 expression was evaluated both as a continuous variable and dichotomized to low (≤10%) and high (>10%). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic parameters. Results: Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence = 1.90, 95% CI: 1.37–2.64, P = 0.0001) and OS (adjusted HR for death = 1.78, 95% CI: 1.18–2.70, P = 0.006). In women with breast tumors expressing medium or high ER levels (n = 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P = 0.03). TAM followed by ANA was superior to TAM alone in patients with low Ki67 (adjusted HR = 0.53, 95% CI: 0.34–0.83, P = 0.005) but not in high Ki67 disease (adjusted HR = 1.18, 95% CI: 0.66–1.89, P = 0.68). Conclusions: Adjuvant sequencing of TAM and ANA is superior to TAM alone, particularly in postmenopausal women with medium or high ER expressing, low proliferating breast cancer. Clin Cancer Res; 17(24); 7828–34. ©2011 AACR.

Sentinel Node Biopsy in Patients with Multicentric Breast Cancer using a Subareolar Injection Technique

SummaryBackground: Multicentric breast cancer is regarded by most authors as a contraindication for sentinel node (SN) biopsy. However, if the SN concept were valid for multicentric carcinoma as it is for unifocal cancer, patients with a negative SN may have the advantage not only of a more accurate lymph node staging but also decreased morbidity resulting from the procedure. The purpose of this study was to evaluate the feasibility and accuracy of SN biopsy in patients with multicentric breast cancer using a subareolar injection technique for SN mapping. Methods: Forty-eight patients (mean age 56.6 years) with multicentric invasive carcinoma of the breast underwent sentinel lymph node mapping using vital blue dye alone (n=22) or in combination with99mTC nanocolloid (n=26) injected under the areola. Removal of SN(s) was followed by axillary dissection of levels I and II in all patients to evaluate the false negative rate. Results: A mean number of 1.8 SNs were identified in 46 of 48 patients (identification rate: 95.8%). Twenty-five patients had a positive SN, 21 a negative SN. Axillary dissection confirmed the SN to be negative in 20 of 21 patients, whereas one patient revealed positive non-sentinel lymph nodes (false negative rate: 3.8%). Overall SN biopsy accurately predicted axillary lymph node status in 45 of 46 patients (97.8%). Conclusions: SN biopsy using a subareolar injection technique accurately staged the axilla in multicentric breast cancer and may become an alternative to complete axillary lymph node dissection in node negative patients with multicentric breast cancer.ZusammenfassungGrundlagen: Das multizentrische Mammakarzinom gilt als Kontraindikation für die Sentinel Lymphknotenbiopsie. Ist das Konzept des leitenden Lymphknotens auch bei diesen Patientinnen anwendbar, hätte dies den Vorteil einer verminderten Morbidität bei zumindest gleich genauem Lymphknotenstagings. Ziel dieser Studie war Möglichkeit und Aussagekraft der SLB beim multizentrischen Mammakarzinom zu untersuchen. Methodik: Bei 48 Patienten (mittleres Alter: 56,6 Jahre) mit multizentrischem Mammakarzinom wurde ein Sentinel Lymphknotenmapping durch subareoläre Injektion von Vitalblau alleine (n=22) oder in Kombination mit einem Radiokolloid (n=26) durchgeführt. Intraoperativ wurde der leitende Lymphknoten aufgesucht und entfernt, anschließend zur Evaluierung der falsch negativen Rate eine Axilladissektion durchgeführt. Ergebnisse: Bei 46 von 48 Patientinnen (Auffindungsrate 95,8%) konnten im Mittel 1,8 Sentinel Lymphknoten gefunden werden. Davon waren 25 tumorbefallen, 21 waren tumorfrei. Die Aufarbeitung des Axilladissektates bestätigte die Tumorfreiheit des leitenden Lymphknotens in 20 Patientinnen, bei einer Patientin fanden sich Metastasen in Nicht-Sentinel Lymphknoten (falsch negative Rate: 3,8%; Gesamtgenauigkeit: 97,8%). Schlußfolgerungen: Die Sentinel Lymphknotenbiopsie ist beim multizentrischen Mammakarzinom mit gleicher Auffindungsrate und Anzahl falsch negativ beurteilter leitender Lymphknoten möglich wie beim unifokalen Karzinom. Patientinnen mit negativen Sentinel Lymphknoten kann auch beim multizentrischen Mammakarzinom eine Axilladissektion erspart werden.

Heart luxation through a right-sided traumatic pericardial defect.

Abstract A traumatic defect of the pericardium is a rarely diagnosed entity. We present a patient with a right-sided luxation of the heart which was incidentally diagnosed during a thoracic CT performed for other reasons. Despite of the threatening strangulation of the great vessels, the patient had a stable circulation until surgical repair of the pericardial defect.

Sentinel node biopsy after preoperative chemotherapy in breast carcinoma - Is it safe?

SummaryBackground: Preoperative chemotherapy (PC) and sentinel node biopsy (SNB) are two modern approaches in the treatment for breast cancer, both aiming at a reduction in surgery. While PC is mainly applied to large primary tumours, SNB is indicated for early breast cancer. By gradually expanding the indication for both methods, a group of patients is going to emerge that may benefit from both methods. The Austrian Sentinel Node Biopsy Study Group of the Austrian Breast and Colorectal Cancer Study Group is trying to find out whether adequate safety can be assured when PC and SNB are combined. Methods: Seventy patients with SNB after PC are compared with 1567 patients without PC (identification rate, IR). In order to compare the false negative rate (FNR), those 315 successful SNBs were studied where an obligatory axillary lymph node dissection (ALND) was carried out in the early stage. Results: With PC as preoperative treatment for tumours, complete remission (CR) was achieved in 27.7 % of the cases (complete pathological remission, pCR, in 17.4 %), partial remission (PR) in 33.3 %, a stable disease (SD) for 26.1 % and a progressive disease (PD) in 2.9 %. At the time of surgery there was no evidence of palpable lymph nodes in the axilla. In 59 cases (84.3 %) a sentinel node (SN) could be identified after PC. In the non-PC group, an SN was identified in 1368 of 1567 procedures (87.3 %).After pretreatment with PC, the FNR amounted to 6.2 %. In the non-PC group, the FNR makes up 5.2 %. Conclusions: With regard to IR and safety (FNR), the SNB after PC is comparable to the SNB of patients without preoperative treatment.ZusammenfassungGrundlagen: Präoperative Chemotherapie (PC) und sentinel node biopsy (SNB) sind zwei moderne Ansätze in der Therapie des Mammakarzinoms, die beide auf die Verringerung des operativen Eingriffs abzielen.Während PC in erster Linie bei großen Primärtumoren angewandt wird, kommt SNB vorwiegend bei frühen Tumorstadien zum Einsatz. Durch die schrittweise Erweiterung der Indikation für beide Methoden, entsteht eine Patientengruppe, die von beiden Verfahren profitieren könnte. Die „Österreichische Arbeitsgruppe Sentinel Node Biopsy“ beschäftigt sich deshalb mit der Frage, ob die Kombination von PC und SNB mit ausreichender Sicherheit durchführbar ist. Methodik: 70 Patientinnen mit SNB nach PC werden mit 1567 Patientinnen ohne PC verglichen (Identifikationsrate, Falsch-Negativ-Rate). Ergebnisse: Bei Vorbehandlung von Tumoren mit PC wurde in 27,7 % eine komplette Remission erreicht (in 17,4 % eine pathologisch komplette Remission), in 33,3 % eine partielle Remission, in 26,1 % eine stable disease und in 2,9 % eine progressive disease. Bei der Operation lag jeweils ein klinisch negativer axillärer Lymphknotenstatus vor.In 59 Fällen (84,3 %) konnte ein sentinel lymph node (SN) nach PC identifiziert werden. Bei unbehandelten Tumoren wurde in 1368 von 1567 Prozeduren ein SN identifiziert (87,3 %).Die Falsch-Negativ-Rate lag nach Vorbehandlung mit PC bei 6,2 %. Zum Vergleich der Falsch-Negativ-Rate wurden jene erfolgreichen 315 Sentinel-node-Biopsien herangezogen, bei denen in der Anfangsphase obligat eine Axilladissektion angeschlossen wurde; diese beträgt 5,2 %. Schlußfolgerungen: SNB nach PC ist bezüglich der Identifikationsrate und der Sicherheit (Falsch-Negativ-Rate) mit der SNB von unbehandelten Patienten vergleichbar.

Abgeschlossene und derzeit laufende adjuvante Therapieprotokolle bei Patientinnen mit operablem Mammakarzinom (II)

Background: Between 1984 and 1996 4336 patients with operated breast cancer were included in trials of the Austrian breast cancer study group.ZusammenfassungGrundlagen: Seit 1984 wurden 4336 Patientinnen mit Mammakarzinom österreichweit in adjuvante Therapiestudien eingebracht. Methodik: Basierend auf Prognosefaktoren, wurden Patientinnen nach 2 Therapiearten randomisiert. Ergebnisse: Die größte, jemals in Österreich durchgeführte Studie bei postmenopausalen Patientinnen wurde bereits abgeschlossen. 5 weitere Studien sind offen für die Randomisierung. Schlußfolgerungen: Der Ansatz, Studien österreichweit anzubieten und einheitliche Studienkonzepte zu bewerben, ist außerordentlich erfolgversprechend und muß weiter verfolgt werden.SummaryBackground: Between 1984 and 1996 4336 patients with operated breast cancer were included in trials of the Austrian breast cancer study group. Methods: Based on prognostic factors patients were randomised with 2 different treatment groups. Results: The largest ever performed oncological trial (study VI) in postmenopausal breast cancer patients is already finished. 5 other trials are open for randomisation. Conclusions: It is the intention of the Austrian breast cancer study group to accrue patients for ongoing trials in whole Austria and to increase the number of randomised patients.