Breast cancer therapy in women under 35 years and between 50 and 69 years: influence of the observation period.

PURPOSE: In recent years, therapeutic strategies based on tumour biology have increased significantly. We aimed to provide an overview of the recent changes in patient characteristics, treatment procedures and survival factors for two groups of patients: women younger than 35 years and women between 50 and 69 years. METHODS: We used data from the population-based Cancer Registry Magdeburg. Subjects included women with non-metastatic breast cancer treated between 2000 and 2015. We compared between two observation periods: 2000-2007 and 2008-2015. RESULTS: There was an increase in patient survival from the first to the second observation period. Tumour characteristics and treatment modalities changed, especially in the group of older patients. The proportion of prognostically more favourable tumour subtypes, such as Luminal A, increased significantly. Between 2008 and 2015, there were more hormone receptor-positive, lymph-node-negative, human epidermal growth factor receptor-2 (HER2)-negative and well-differentiated tumours. Surgical methods were associated with significantly reduced radicality, while the rate of neoadjuvant therapy increased in both groups. There was a decrease in cyclophosphamide, methotrexate and 5-fluoruracil (CMF) and anthracycline therapies, but taxane-containing chemotherapy increased. While tamoxifen was used more frequently in younger patients in the later observation period, its use was reduced in older patients, superseded by aromatase inhibitors. Furthermore, the use of immune therapy increased. CONCLUSION: In both age groups, but primarily in older patients, there were significant changes in tumour biology and treatment options between the two observation periods. These changes have led to a continuous improvement in patient outcomes.

Puerperal mastitis in the past decade: results of a single institution analysis.

PURPOSE: Although puerperal mastitis is a common disease, published data are poor. Increasing rates of community-acquired MRSA (CA-MRSA) cases are reported in the USA. However, information about common pathogens and CA-MRSA in Germany is still insufficient. The aim of this study was to investigate the most common pathogens of puerperal mastitis in the last decade, its therapy, resistance rate and the effectiveness of the current treatment strategies. METHODS: The pathogens, the respective antibiograms and the treatment strategies of patients treated for puerperal mastits at the University Clinic Magdeburg (Germany) between 2006 and 2016 were retrospectively reviewed. Statistical analysis was performed using SPSS Version 21. RESULTS: In our series, 59 cases with puerperal mastitis were reviewed, 26 (44.1%) of these developed a breast abscess. In 37 of 59 (67.3%) cases the symptoms occurred in the first 8 weeks postpartum. The most common pathogens were Staphylococcus aureus (64.9%) and Coagulase-negative Staphylococcus (13.5%). Methicillin-resistant Staphylococcus aureus (MRSA) was found in one case. Of the 19 cases with Staphylococcus aureus, 17 were resistant to Penicillin. Conservative management was mainly performed with Flucloxacillin (60%), which was successful in most cases. Sixteen of 26 (61.5%) women with abscesses underwent ultrasound (US)-guided needle aspiration. CONCLUSION: In this cohort, MRSA was not a main pathogen responsible for breast abscesses. Conservative treatment strategies remained constant during the observed period and Flucloxacillin was the most frequent antibiotic used. The analysis of the courses of diseases leads to the conclusion that surgical incision is progressively replaced by US-guided needle aspiration.

Laparoscopic-assisted vaginal hysterectomy versus vaginal hysterectomy for benign uterine diseases: a prospective, randomized, multicenter, double-blind trial (LAVA).

OBJECTIVE: To compare the impact of peritoneal closure on postoperative pain after vaginal (VH) and laparoscopic-assisted vaginal hysterectomy (LAVH). STUDY DESIGN: A prospective, randomized, double-blind study was designed to investigate as primary outcome the postoperative pain after VH and LAVH with and without peritoneal closure. The postoperative pain was measured using visual analogue scale (VAS). RESULTS: The patients were recruited between August, 2007 and July, 2014. A total of 192 patients with benign uterine diseases were eligible for analysis and were divided in four groups: LAVH and VH with and without peritoneal closure (PC), respectively. The patients' characteristics including parity, BMI, previous abdominal operations, and uterus weight were well balanced between the groups. The patients who received LAVH were significantly younger (p = 0.0443). LAVH was associated with increased postoperative pain and reduced patients' mobility in the first 72 and 24 h, respectively, after surgery. The use of analgesics remained similar in all four groups. The operating time was significantly shorter after VH (VH + PC 59 ± 17; VH - PC 56 ± 19) than after LAVH (LAVH + PC 106 ± 29 min; LAVH - PC 99 ± 30) (p < 0.0001). The PC did not affect the patients' outcome. The blood loss, the hemoglobin drop, the hospital stay, and the rate of intra- and postoperative complications rate were similar in all four groups. No conversation to laparotomy occurred in whole study population. CONCLUSION: VH is associated with shorter operating time and reduced postoperative pain compared to LAVH.

Tumor characteristics and therapy of elderly patients with breast cancer.

INTRODUCTION: Elderly breast cancer patients aged ≥75 years are underrepresented in most studies. Therefore, data on cancer characteristics, adjuvant treatment and survival in elderly patients are missing. PATIENTS AND METHODS: In this retrospective study, we compared tumor characteristics and adjuvant therapy in 973 women with invasive, non-metastasized breast cancer aged ≥75 years with 3377 younger postmenopausal patients (50-74 years old). Time dynamics of tumor characteristics were investigated, comparing two observation periods between the years 2000-2004 versus 2005-2008. RESULTS: Compared to younger women, older patients were more often treated with mastectomy and less likely to receive adjuvant treatment. Although the overall survival rate increased over the observation period in both age groups, the older study group was characterized by shorter disease-free survival. Additionally, we observed an increase in about 1.65 years in the age at diagnosis as well as an increasing rate of breast-conserving surgery and sentinel lymph node biopsy for the whole study population between 2000 and 2008. Furthermore, we found a reduction in the proportion of estrogen receptor-positive tumors in the younger women and a decrease in G3-tumors in both age groups over the study time. CONCLUSION: The older group's reduced disease-free survival could be explained by the tumor characteristics and differences in the adjuvant treatment. Remarkably, elderly women are more likely to be overtreated surgically while being undertreated in terms of adjuvant therapy.

Platelet Count After Chemotherapy is a Predictor for Outcome for Ovarian Cancer Patients.

Elevated platelet count occasionally is associated with gynecologic malignancies. We investigated the level of platelet count in 450 patients with gynecologic tumors. Ovarian cancer patients have increased platelet count associated with the course of treatment and disease progression. In multivariate analysis, the decrease of platelet count less than 25% after chemotherapy was an unfavorable prognostic factor for PFS (HR, 1.948; 95% CI, 1.083-3.505; p = 0.026) and overall survival (HR, 2.093; 95% CI, 1.022-4.287; p = 0.043). An insufficient decrease of the platelet count increased the risk of recurrence. Thus platelet count could be used for monitoring the disease progression and to predict treatment response.

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.

BRCA1 promoter methylation is a marker of better response to platinum-taxane-based therapy in sporadic epithelial ovarian cancer.

BACKGROUND: The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum-taxane-based therapy in sporadic ovarian cancer. PATIENTS AND METHODS: BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients. RESULTS: BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum-taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32-0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation. CONCLUSIONS: BRCA1 promoter methylation is predictive for better response to platinum-taxane-based therapy in EOC.

Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44).

BACKGROUND: We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m(2); q3w) followed by four cycles docetaxel (100 mg/m(2); q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy. RESULTS: TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment [OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002], lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis. CONCLUSIONS: The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.

The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use.

BACKGROUND: We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC). PATIENTS AND METHODS: A total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0-3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded. RESULTS: Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice. CONCLUSION: RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.

Intraoperative Ultrasound in the Treatment of Breast Cancer.

Purpose: The aim of this study was to investigate the value of intraoperative ultrasound in breast-conserving operations and to compare it with standard procedures. Methods: For this purpose 307 women with palpable breast cancers and 116 patients with non-palpable breast cancers were compared retrospectively. In the group with palpable breast cancers 177 patients were treated by US-guided operations and 130 patients underwent palpation-guided breast-conserving operations. As primary outcomes, the resection margins and the rate of re-operations were evaluated. Results: With regard to disease-free resection margins, intraoperative ultrasound was significantly superior to palpation alone. In the group of patients in whom the tumours were extirpated with the help of palpation, R1 resections were observed almost twice as often (16.9 %) as in the US-guided group (8.5 %). In the group with non-palpable breast cancers, intraoperative ultrasound was employed in 61 patients. As a control, 43 cases were evaluated in whom the breast-conserving operation was performed after wire marking. In this group US-guided tumour removal proved to be superior to that after wire marking for tumours that did not exhibit any intraductal components. Otherwise the redo resection rate was reduced by use of ultrasound. Furthermore, the surgeon was able by means of intraoperative ultrasound to identify "problematic" margins and to excise them in the same sitting. Conclusions: The US-guided, breast-conserving operations led to a lower rate of R1 resections and redo operations in comparison to operations with palpation alone or those after wire marking.

Comparative study of surgical margins and cosmetic outcome in lumpectomy versus segmental resection in breast cancer.

OBJECTIVE: The aim of the present retrospective study was to compare two breast-conserving techniques, segmental resection and standard lumpectomy, for the treatment of breast cancer regarding their oncological safety. Quality of life aspects were evaluated by assessing the respective postsurgical cosmetic results. PATIENTS AND METHODS: 190 women with breast cancer located in the superior and lateral quadrant were included in the study. Sixty patients were treated with segmental resection (group 1), whereas 130 underwent standard lumpectomy (group 2). Tumor sizes were determined and excised tissue specimens were analyzed for positive or negative resection margins. Patients were given a 16-item questionnaire for the postsurgical self-assessment of the cosmetic outcome. RESULTS: No statistically significant difference was found concerning the number of positive resection margins between the groups (25 vs. 30%, p = 0.46). Exceptions were ventral margins, which predominated in group 2 (p = 0.016). Group 1 revealed a significantly larger maximum tumor size with negative margins as compared to group 2 (26.6 vs. 17.0 mm). General satisfaction with the cosmetic results was comparable between groups. CONCLUSIONS: Segmental resection surgery, as a method of breast conservation therapy, can be used to treat larger breast lesions as compared to standard lumpectomy.

Significant changes in circulating plasma levels of IGF1 and IGFBP3 after conventional or dose-intensified adjuvant treatment of breast cancer patients with one to three positive lymph nodes.

The insulin-like growth factor 1 (IGF1) and its binding protein IGFBP3 (insulin-like growth factor binding protein 3) play a pivotal role during the growth and development of tissues. The purpose of this study was to evaluate the influence of anthracycline- and taxane-containing adjuvant chemotherapy in breast cancer patients on the circulating plasma levels of IGF1 and its main binding protein, IGFBP3. This investigation was part of a prospective randomized phase III study in which breast cancer patients were treated with either conventional or dose-intensified adjuvant chemotherapy. The factors were quantified in the plasma of 151 patients with a commercially available sandwich enzyme immunoassay. Before therapy, both parameters were within the normal range in most patients (n=145 and n=144). After therapy, both factors had increased significantly by 29% (IGF1) and 19% (IGFBP3), with the highest increase being observed in the dose-intensified group. Correlations with patient and tumor characteristics revealed a relatively higher increase in both parameters in premenopausal patients, patients with lower-grade tumors, more positive lymph nodes, larger tumor volume, and positive hormone receptor status. No correlation was found with the HER2 expression of the tumors.

Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial.

BACKGROUND: Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites. PATIENTS AND METHODS: Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) on day 1 and gemcitabine as 4-h infusion (350 mg/m(2)) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil. RESULTS: The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size

Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

PURPOSE: The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. METHOD: Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. RESULTS: Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). CONCLUSIONS: The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.