Lysine-urethane-based tissue adhesion for mastectomy-an approach to reducing the seroma rate?

PURPOSE: Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu® without drainage is equal/ non-inferior to standard mastecomy with drainage. METHODS: The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups. RESULTS: Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu® compared to standard drainage couldn't be reached. DISCUSSION: The present evaluation shows no advantage of the tissue adhesive TissuGlu® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.

Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto.

Background: In the neoadjuvant GeparSixto study, adding carboplatin to taxane- and anthracycline-based chemotherapy improved pathological complete response (pCR) rates in patients with triple-negative breast cancer (TNBC). Here, we present survival data and the potential prognostic and predictive role of homologous recombination deficiency (HRD). Patients and methods: Patients were randomized to paclitaxel plus nonpegylated liposomal doxorubicin (Myocet®) (PM) or PM plus carboplatin (PMCb). The secondary study end points disease-free survival (DFS) and overall survival (OS) were analyzed. Median follow-up was 47.3 months. HRD was among the exploratory analyses in GeparSixto and was successfully measured in formalin-fixed, paraffin-embedded tumor samples of 193/315 (61.3%) participants with TNBC. Homologous recombination (HR) deficiency was defined as HRD score ≥42 and/or presence of tumor BRCA mutations (tmBRCA). Results: A significantly better DFS (hazard ratio 0.56, 95% CI 0.34-0.93; P = 0.022) was observed in patients with TNBC when treated with PMCb. The improvement of OS with PMCb was not statistically significant. Additional carboplatin did not improve DFS or OS in patients with HER2-positive tumors. HR deficiency was detected in 136 (70.5%) of 193 triple-negative tumors, of which 82 (60.3%) showed high HRD score without tmBRCA. HR deficiency independently predicted pCR (ypT0 ypN0) [odds ratio (OR) 2.60, 95% CI 1.26-5.37, P = 0.008]. Adding carboplatin to PM significantly increased the pCR rate from 33.9% to 63.5% in HR deficient tumors (P = 0.001), but only marginally in HR nondeficient tumors (from 20.0% to 29.6%, P = 0.540; test for interaction P = 0.327). pCR rates with carboplatin were also higher (63.2%) than without carboplatin (31.7%; OR 3.69, 1.46-9.37, P = 0.005) in patients with high HRD score but no tmBRCA. DFS rates were improved with addition of carboplatin, both in HR nondeficient (hazard ratio 0.44, 0.17-1.17, P = 0.086) and HR deficient tumors (hazard ratio 0.49, 0.23-1.04, P = 0.059). Conclusions: The addition of carboplatin to neoadjuvant PM improved DFS significantly in TNBC. Long-term survival analyses support the neoadjuvant use of carboplatin in TNBC. HR deficiency in TNBC and HRD score in non-tmBRCA TNBC are predictors of response. HRD does not predict for carboplatin benefit.

Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial.

Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort. Patients and methods: Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%, P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.

Zoledronate for patients with invasive residual disease after anthracyclines-taxane-based chemotherapy for early breast cancer - The Phase III NeoAdjuvant Trial Add-oN (NaTaN) study (GBG 36/ABCSG 29).

BACKGROUND: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. PATIENTS AND METHODS: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. RESULTS: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. CONCLUSION: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.

Breast reconstruction and revision surgery for implant-associated breast deformities using porcine acellular dermal matrix: a multicenter study of 156 cases.

BACKGROUND: Acellular dermal matrix is increasingly used as caudolateral coverage for breast implants in immediate breast reconstruction after skin-sparing mastectomy or in the correction of implant-associated breast deformities. Matrices of human, bovine, and porcine origin are available. The purpose of this retrospective multicenter study was to report experiences with porcine acellular dermal matrices, as only limited data can be found in the literature. METHODS: In the hospital databases of five institutions, 127 patients were identified who underwent breast reconstructions in 156 breasts using an acellular porcine dermal matrix. Medical records were reviewed. Patients were divided into three groups: immediate expander-implant or direct to implant reconstructions (n = 98), delayed expander-implant reconstructions (n = 14), and revision surgery for implant-associated breast deformities (n = 44). RESULTS: With a mean follow-up of 19.6 months, total major complication rate was 7.1 %: implant loss (3.2 %), skin flap necrosis (2.6 %), delayed skin healing (2.6 %), hematoma (1.9 %), seroma (1.3 %), infection (0.6 %), and capsular contracture (0.6 %). Total minor complication rate was 22.9 %, with seroma being the most frequent complication (19.2 %). In the group of immediate breast reconstructions, 20.4 % of the breasts had received radiotherapy in the past. These patients exhibited a significantly higher rate of seroma than patients without prior radiotherapy (35.0 vs. 14.9 %, p = 0.031). CONCLUSIONS: Complication rates using porcine acellular dermal matrix in breast reconstruction are comparable to complication rates reported in studies using human acellular dermal matrices. Thus, porcine acellular dermal matrices can safely be applied in breast reconstructive surgery.

Survival after adding capecitabine and trastuzumab to neoadjuvant anthracycline-taxane-based chemotherapy for primary breast cancer (GBG 40--GeparQuattro).

BACKGROUND: The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracycline-taxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years. RESULTS: Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low. CONCLUSIONS: Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates.

Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial.

The eLEcTRA trial compared efficacy and safety of letrozole combined with trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR) positive metastatic breast cancer (MBC). Patients were randomized to either letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as first-line treatment. Additional 35 patients with HER2 negative and HR positive tumors received letrozole alone (arm C). Median time to progression in arm A was 3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39% for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01-8.84) and 77% in arm C (odds ratio 5.34, 95% CI 1.83-15.58). The eLEcTRA trial showed that the combination of letrozole and trastuzumab is a safe and effective treatment option for patients with HER2 positive and HR positive MBC.

[Preoperative CT angiography for planning free perforator flaps in breast reconstruction]. / Präoperative CT Angiografie zur Planung freier Perforans-Lappenplastiken (DIEP-Flaps) zur Brustrekonstruktion.

Preoperative Doppler ultrasonography for planning free perforator flaps is widely established to identify preoperatively perforators. The method allows one to localise the penetrating point of the perforator through the abdominal fascia. By this means it is not possible to see the intramuscular course or the position of the perforator in relation to the inferior epigastric artery. Lately the technique of computed tomographic angiography provides an opportunity for visualising the course of perforator vessels in these tissues. This paper summarises our experience with the preoperative CT angiography in our breast centre. Since spring 2009 we have reconstructed the breasts of 44 female patients by using free flaps from the lower abdominal wall. 6 of these were bilateral. In a total number of 50 breast reconstructions we used 23 deep inferior epigastric perforator (DIEP) flaps and 27 muscle-sparing transverse rectus abdominis muscle (TRAM) flaps. In addition to the preoperative ultrasonography, a CT angiography of the lower abdomen was conducted in 29 patients. On average they showed at least 2 perforators on the left as well as right abdominal sides, which could be used as flap vessels based on their signal intensity. Based on their estimated microsurgical dissection complexity, the perforator vessels could be classified into 3 groups: 1) direct perforators of category A with short intramuscular course (39%), 2) perforators with long intramuscular course of category B (50%) and 3) "turn around" perforators of category C, which pass medially around the rectus abdominis (11%). The technique of CT angiography permits a reliable preoperative visualisation of perforators in their entire course and facilitates the selection of the supplying perforator as well as the intraoperative procedure for the surgeon. The suggested classification of perforators into 3 groups simplifies the preoperative assessment of the microsurgical dissection effort. Compared to the commonly used Doppler ultrasonography there are disadvantages like the additional cost factor and the radiation exposure. However, in our experience the more detailed planning increases the safety of flap raising and reduces surgery time, so that we consider CT angiography a positive tool to facilitate free perforator flaps.

uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial.

The plasminogen activator system is a complex system with multiple interactions and members participating in fibrinolysis, cell migration, angiogenesis, wound healing, embryogenesis, tumor cell dissemination, and metastasis in a variety of solid tumors. Increased levels of uPA and/or PAI-1 in primary tumor tissues of breast cancer patients correlate with tumor aggressiveness and poor clinical outcome. Patients with high tumor tissue antigen content of uPA and/or PAI-1 have a worse probability of disease-free and overall survival than patients with low levels of both of the biomarkers, serving as prognostic markers. The clinical utility of uPA and PAI-1 has been proven on the highest level of evidence (LOE-I). Next to being clinically useful prognostic factors allowing estimates of the course of disease in early breast cancer, uPA and PAI-1 may also serve as predictive factors predicting response to systemic therapy. Node-negative primary breast cancer patients with high uPA/PAI-1 levels benefit significantly from adjuvant chemotherapy. The aim of the ongoing NNBC-3 trial is to determine the benefits of a sequential anthracycline-docetaxel regimen in high-risk node-negative breast cancer patients compared to the current standard of anthracycline-based chemotherapy. At present, uPA and PAI-1 provide the unique opportunity to allow validated and clinically relevant risk assessment of breast cancer patients, over and above that provided by established risk factors. Therefore, in the evidence-based, annually updated AGO guidelines for breast cancer management, the German Working Group for Gynecological Oncology (AGO) has recommended both biomarkers as risk-group-classification markers for routine clinical decision making in node-negative breast cancer, next to established clinical and histomorphological factors.

Ultrasound and mammography guided wire marking of non-palpable breast lesions: analysis of 741 cases.

PURPOSE: Aim of the study were to evaluate the success of ultrasound and mammography guided wire marking of non-palpable breast lesions and the results of specimen mammography/ultrasonography, completeness of resection, and number of secondary resections (during the initial surgical session and as a separate intervention) were analysed. MATERIALS AND METHODS: Between May 1994 and December 2004, 668 women with 741 non-palpable breast lesions underwent surgery at the Greifswald University Department of Gynaecology and Obstetrics. Ultrasound directed wire marking was used in 418, mammography directed marking in 284 cases. In 39 lesions, both techniques were combined. RESULTS: Out of all lesions approached with ultrasound directed wire marking, 88 (21.1 %) were malignant. Among lesions marked during mammography, 52 (19.3 %) were malignant. Specimen ultrasonography indicated that 90.9 % of lesions were resected completely. Specimen mammography demonstrated complete resection in 89.1 %. On histological examination, 19.5 % of the malignant lesions marked with sonographic guiding and 36.5 % of the malignant lesions marked with mammographic guiding did not have clear margins. Secondary resections (during the first procedure) for incomplete specimens were needed in 10 patients in whom sonographic localisation had been used, and in 25 patients in whom mammographic localisation had been employed. A second surgical session for secondary resection was required in 5.5 % of lesions marked with ultrasound and in 12.3 % of lesions marked with mammography guidance. CONCLUSION: Sonography directed wire localisation appears to be superior to the respective mammographic method. Ultrasound guided wire marking should be considered the preferred method for all mammographic lesions with an ultrasonographic equivalent and no micro-calcifications.

Complete extirpation of benign breast lesions with an ultrasound-guided vacuum biopsy system.

OBJECTIVES: To investigate whether ultrasound-guided vacuum biopsy (VB) with curative intent is suitable for the complete extirpation of selected sonographically detectable benign lesions of the breast, and to establish the limitations of the method with regard to lesion size and complications, the extent of scar formation and the prognostic value. METHODS: One hundred and nine patients underwent hand-held, ultrasound-guided VB (8G or 11G needle) between June 2000 and September 2003. Of these, 45 (41%) women underwent ultrasound-guided extirpation of 46 lesions, and 42 women with 43 lesions were followed up clinically and sonographically for an average of 5.9 months. The complete extirpation rate, residual lesions, and patient satisfaction with the intervention were evaluated. RESULTS: Removal of all sonographic evidence of lesions (median diameter, 13 mm) was achieved in 86% of cases (8G needle, 80%; 11G needle, 89%). 19% of the patients had suspected scar formation at the biopsy site. A palpable lesion in the breast could be removed by VB in 90% of cases. None of the patients developed infections and there were no hemorrhages requiring intervention, or damage to the skin or chest wall. A total of 95% of the patients stated that they would prefer this approach to open excision for possible future intervention. CONCLUSIONS: VB is an ambulatory procedure associated with a low degree of pain. It has a high degree of patient acceptance and, as a minimally invasive biopsy technique for benign lesions, is a good alternative to open excision. The rate of complications is low and is similar to that observed with conventional microbiopsy.

Non-palpable breast lesions in asymptomatic women: diagnostic value of initial ultrasonography and comparison with mammography.

AIM: This prospective double-blind study was designed to assess (i) if primary breast screening by ultrasonography is capable of detecting breast cancer independent of tissue density and (ii) if the rate of unnecessary biopsies remains acceptable when diagnostics are based on ultrasonography. PATIENTS AND METHODS: Bilateral breast ultrasonography was performed in 448 asymptomatic women as the initial diagnostic method. Sonograms were interpreted using a set of standardized diagnostic criteria. Subsequently, mammograms were obtained. The radiologists reading the mammograms were blinded to the sonographic results. RESULTS: Overall, 3 non-palpable breast cancers were detected by ultrasound and mammography. All 3 ultrasonographically detected breast cancers were smaller than 1 cm (0.7, 0.7, 0.6 cm). All 3 carcinomas were correctly detected by both methods. For ultrasonography, the false positive rate was 1.1% (n=5) and for mammography 0.6% (n=3). When both methods were combined, the rate of unnecessary open biopsies was 1.6% (n=7). The ratio of benign to malignant lesions was 3.7/1. CONCLUSION: Without prior mammography, primary high-resolution breast ultrasonography is capable of detecting non-palpable breast carcinomas in asymptomatic women at an early stage. The rate of unnecessary open biopsies is low and the ratio of benign to malignant biopsies acceptable.

[Prevention of preeclampsia]. / Prävention der Präeklampsie.

Preeclampsia is accompanied by high fetal and maternal morbidity and mortality and to a high degree responsible for preterm delivery. The pathophysiologic mechanisms underlying this disease remain poorly understood. Accordingly, only few causative or preventive therapeutical strategies are known. One such example for a preventive strategy is the use of aspirin (ASA) which directly affects the imbalance of vasodilative prostacycline and vasoconstrictive thromboxane. Recently, some studies are indicating a preventive effect of vitamin C and E substitution. In contrast, early antihypertensive therapy did not prevent later progression of the disease. Furthermore, sodium restriction, calcium and magnesium substitution, fish oil substitution, or steroid therapy are without any effect regarding the later development of preeclampsia. It is of utmost importance to further elucidate underlying pathophysiological mechanisms to improve therapeutical and preventive strategies.

[Chemoprevention of breast cancer: a literature review and report on the current status in Germany]. / Medikamentöse Prävention des Mammakarzinoms: eine Ubersicht über die Literatur und den Stand in Deutschland.

The prevention of breast cancer is increasingly of focus in health-politics policies and has gained a valid position in the area of medical intervention. Data from a current meta-analysis of all four randomised Tamoxifen prevention studies illustrate a reduction of 38 % (Odds ratio 0.62; 95 % CI 0.42-0.89) in the incidence of breast cancer. This observation lead to registration of this drug in the USA for the prevention of breast cancer in women with a calculated 5-year risk of > 1.66 %. In addition to Tamoxifen, further substances are currently being tested with the aim of improving the therapeutic index whilst reducing incidence and mortality rates. These are primarily substances which have proven efficacy in the treatment of breast cancer (other antioestrogens, aromatase inhibitors and GnRH-analogues) or those whose mechanism of action predict a preventative effect (retinoids, phytooestrogens, substitution preparations e. g. Tibolone). In Germany, chemoprevention is currently only to be recommended within study protocols, as to date no substance is approved in the indication 'prevention of breast cancer'. A essential contribution to the accrual of valid data is the conduct of breast cancer prevention trials. The participation of women with high risk of breast cancer in Germany is, in contrast to comparable international studies, problematic. Data on the current knowledge and attitude of the female population towards such trials (gathered via a questionnaire of the DACH in 7 000 women) show that only 19.5 % of the women questioned during a consultation with a gynaecologist were aware of the possibility of active chemoprevention. However, 55.3 % stated that they would be prepared to take such a substance, were chemoprevention possible. Studies for both pre- and post-menopausal women with increased risk of breast cancer are currently active in Germany (GISS and IBIS-II of the study group GABG - German Adjuvant Breast cancer Group). An intensive information campaign to raise public awareness of breast cancer risk amongst women and their physicians is planned in conjunction with the IBIS-II study (www.brustkrebsvorbeugen.de). Latest literature recommendations for prevention of breast cancer (Chlebowski et al.) have been assessed.

[Palliative therapy of breast cancer]. / Palliative Therapie des Mammakarzinoms.

Metastatic breast cancer is considered an incurable disease. The choice of drug or drug combination in palliative therapy is determined by the subjective symptoms of the patient and by the more objective parameters age and general health status, localization of metastases and aggressiveness of the disease, which is described by the necessity to achieve remission. The relation between the effectiveness aimed for and the subjective quality of life is described by the term 'therapeutic index'. With receptor-positive tumours and under low remission pressure, endocrine therapy is the method of choice when considering sustaining the quality of life--here aromatase inhibitors have replaced the former gold standard anti-estrogen tamoxifen. With receptor-negative tumors or under high remission pressure the therapy decision is far more difficult. The cytostatic therapy can be performed as mono- or polychemotherapy. In both cases taxanes show a higher effectiveness when compared to standard therapies, with Docetaxel giving the highest response rate and (as shown in a recent Cochrane analysis) increasing overall survival with a HR of 0.88. We describe taxane-containing therapy regimes in the context of modern therapy options. Current data presented by 4 chosen studies are described, as well as AGO recommendations on palliative therapy.

Risk perception and psychological strain in women with a family history of breast cancer.

BACKGROUND: The thinking in health psychology is that patients' willingness to adopt preventive health behavior is contingent on their perceiving an increased risk of disease and is influenced by accompanying psychological stress. In counseling women with a family history of breast cancer, physicians focus on encouraging the patient to undergo early detection examinations as recommended. Therefore, it is essential to examine how women in this risk group perceive their own chances of developing breast cancer and to assess the psychological effects of their situation. MATERIAL AND METHODS: 129 women with at least one first or second degree relative who had developed breast cancer were enrolled in a questionnaire study. The object was to ascertain the extent to which these women may be expected to realistically estimate their own probability of contracting the disease and what influence risk perception and psychological strain have on their willingness to make use of diagnostic opportunities for early detection. Additionally, the effects on their physical and mental well-being were analyzed. RESULTS: Among the women of the study group, a family history of breast cancer did not always correlate with the subject's perception of an increased risk of contracting the disease compared. On the whole, the majority of the women overestimated their personal risk despite prior genetic counseling. Only slightly less than one quarter of the study group correctly estimated their risk; another quarter underestimated it. The majority of those women who exhibited an increased risk perception were also those who overestimated their probability of personally contracting the disease. They underwent recommended screening examinations significantly less often than women with a low risk perception. However, women subjected to intense psychological strain showed above-average participation in screening programs. CONCLUSIONS: Women with a family history of breast cancer often find it difficult to realistically estimate their own risk of contracting the disease. Increased risk perception had a negative effect on participation in recommended breast cancer screening. Therefore, an effort should be made to correct the patient's overestimation of her personal risk. Integrating psychological counseling in screening programs is essential considering that women from high-risk groups are subjected to increased psychological strain. Further studies are required to more precisely evaluate other psychosocial factors in the behavior of women in risk group toward screening.

[Adjuvant chemotherapy of cervix carcinoma--results of a phase II study]. / Die adjuvante Chemotherapie des Zervixkarzinoms-Ergebnisse einer Phase II-Studie.

OBJECTIVE: Therapies involving a radical operation and radiation treatment for cervical carcinoma in stages I and II are not sufficiently effective in patient subgroups with high risk for recurrence. In recent publications, patients with high risk cervical cancer had with adjuvant simultaneous radio-chemotherapy a better disease free and overall survival but a higher toxicity compared with patients received an adjuvant radiotherapy alone. MATERIAL AND METHODS: 34 patients with at least 2 risk factors for recurrence of cervical cancer were treated with adjuvant chemotherapy after radical hysterectomy. The protocol consisted of 3 cycles of ifosfamide 1.6 g/m2 (d 1-3) and carboplatin (AUC 4, d1) every three weeks. For cell protection 21 patients received amifostine 740 mg/m2 d1-3; this was followed by standard radiation therapy (50.4 Gy percutaneous and high-dose-rate-after-loading for 21 patients, 2 x 5 Gy). The dose determination of the substances and their toxicity were investigated. RESULTS: Patient (p) data: Median age 43 years (range: 25-70); pT1b-2a: n = 22; pT2b: n = 12; pN1: n = 28; pN0: n = 6; G3: n = 10; adeno- and adenosquamous carcinoma: n = 9, G3: n = 10, R1-resection: n = 5. 70.6% of these high-risk patients were disease-free after a median observation time of 40 (18-62) months. Median number of cycles of chemotherapy: 2.8. There was no more dose escalation than carboplatin according to AUC 4 possible. Hematologic toxicity (CTC grading, % of 96 documented cycles): anemia-grade 3-4: 30; -grade 1-2: 10.4; leukopenia-grade 3-4: 13, -grade 1-2: 21.7; alopecia-grade 3: all p.; cerebral neurotoxicity-grade 3-4: 8.3, -grade 1-2; 17.7; diarrhea under radiotherapy-grade 3-4: 2 p., -grade 1-2: 6 p. CONCLUSION: This combined sequential adjuvant therapy was effective and had an acceptable level of toxicity. A phase III study comparing adjuvant sequential chemo-radiotherapy with and without Erythropoeitin to counteract the negative effects of anemia started in Germany in 1999 and had randomized now about 270 patients.

[Improved diagnosis through digital mammography with the assistance of computer algorithms]. / Verbesserte Diagnosefindung durch den Einsatz von Computeralgorithmen in der digitalen Mammographie.

OBJECTIVE: The aim of this survey was to determine improved diagnostics through digital mammography with assistance of computer algorithms and new investigation techniques. MATERIAL AND METHODS: In general, the presented procedures are practicable with all digital mammography procedures. In our clinic the largest clinical experience exists with the only FDA certified full field mammography device Senograph 2000D (GE Medical Systems). RESULTS: First results from initial studies are shown, which are to evaluate the new procedures. The so-called post processing with visualization of microcalcifications, computer-assisted diagnosis, tomosynthesis, energy subtraction, contrast media in mammography and teleradiology are considered in particular. CONCLUSION: Digital mammography represents a promising procedure, opening new possibilities for improved diagnostic in mammography.

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study.

BACKGROUND: A randomized, double-blind, multicenter study was conducted to compare the anti-tumor activity of letrozole vs. tamoxifen in postmenopausal women with ER and/or PgR positive primary untreated breast cancer. PATIENTS AND METHODS: Three hundred thirty-seven postmenopausal women with ER and/or PgR positive primary untreated breast cancer were randomly assigned once daily treatment with either letrozole 2.5 mg or tamoxifen 20 mg for four months. At baseline none of the patients were considered to be candidates for breast-conserving surgery (BCS) and 14% of the patients were considered inoperable. The primary endpoint was to compare overall objective response (CR + PR) determined by clinical palpation. Secondary endpoints included overall objective response on ultrasound and mammography and the number of patients who qualified for BCS. RESULTS: Overall objective response rate (clinical palpation) was statistically significantly superior in the letrozole group, 55% compared to tamoxifen, 36% (P < 0.001). Secondary endpoints of ultrasound response, 35% vs. 25% (P = 0.042), mammographic response, 34% vs. 16% (P < 0.001), and BCS, 45% vs. 35% (P = 0.022) between the letrozole and tamoxifen groups, respectively, showed letrozole to be significantly superior. Both treatments were well tolerated. CONCLUSIONS: This study shows that letrozole is more effective than tamoxifen as preoperative therapy in postmenopausal patients with ER and/or PgR positive primary untreated breast cancer and is at least as well tolerated.

[Initial clinical experiences with digital full-field mammography]. / Erste klinische Erfahrungen mit der digitalen Vollfeldmammographie.

OBJECTIVE: Digital full-field mammography has been used at the Department of Radiology of Charité Medical Center in Berlin since June 1999. This study compares the new digital technique with conventional mammography including a survey of its value in breast imaging and an outline of future prospects. MATERIAL AND METHODS: More than 1,000 of a total of over 5,000 mammographies performed between June 1999 and April 2000 have been obtained using the digital full-field mammography system Senographe 2000D (GE Medical Systems). The digital mammograms were compared with previous conventional films and conventional mammographies performed during the same period (Philips UC Diagnost, Senographe DMRplus). RESULTS: Digital mammographies were equal to conventional ones in all cases and seemed to be superior in detecting microcalcifications in dense glandular tissue. Adequate assessment was possible despite the lower spatial resolution compared to conventional mammography. Additional magnified images were obtained with both techniques for differentiating microcalcifications. CONCLUSIONS: Digital full-field mammography appears to be at least equal to the conventional technique and even superior in some respects. In our experience, the lower spatial resolution of digital mammography has no major disadvantages. The digital system provides new options for electronic storage of mammograms, telemammography, and computer-aided diagnosis.