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.

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.

Extraesophageal symptoms of gastroesophageal reflux disease during pregnancy.

AIM: Typical symptoms of gastroesophageal reflux disease (GERD) are known to be frequent in pregnancy. The aim of this study was to gain a first estimation of the occurrence of extraesophageal symptoms in this context. METHODS: A prospective longitudinal study was performed on 166 pregnant women and in a control group of 285 women. The diagnosis of GERD was based on the Montreal classification using the reflux disease questionnaire (RDQ). Extraesophageal symptoms were recorded with a self-administered questionnaire. Typical GERD symptoms and extraesophageal GERD symptoms were recorded in each trimester of pregnancy. RESULTS: The prevalence of GERD during pregnancy was 16.9% in the first, 25.3% in the second and 51.2% in the third trimester. The prevalence of GERD in the control group was 6.3%. Asthma was reported by 3.5% of controls and by 6% of pregnant women during pregnancy. Chest pain occurred in 6% of the controls and in 1.8%, 2.4% and 2.4% during the trimesters of pregnancy, chronic cough was reported by 1.1% of controls and 1.2% of pregnant women. With the diagnosis of GERD the odds ratios and 95% confidence intervals for asthma, chronic cough and chest pain in the third trimester of pregnancy were as follows: 1.56 (0.58-4.22) for asthma, 0.91 (0.08-10.28) for chronic cough and 2.04 (0.49-8.46) for chest pain. CONCLUSION: GERD is very frequent during pregnancy with progressive incidence during the course of pregnancy. Extraesophageal symptoms of GERD have an unexpected low prevalence during pregnancy.

[Thrombophilia and HELLP syndrome in pregnancy - case report and overview of the literature]. / Thrombophilie und HELLP-Syndrom in der Schwangerschaft - Fallbericht und Literaturübersicht.

Thrombophilia is a prothrombotic state that can be caused by genetic disorders, such as the factor-V-Leiden or prothrombin mutation, as well as by acquired changes like oestrogen-induced APC resistance and the antiphospholipid syndrome. Pregnancy induces multiple procoagulant changes in the haemostatic system, increasing the risk of venous thromboembolism in women with a thrombophilia even further. Additionally, thrombophilias are suggested to be associated with a number of pregnancy complications such as recurrent miscarriage, stillbirth, preeclampsia and HELLP syndrome. Increased local activation of coagulation may directly influence trophoblast expansion and invasion, causing thereby an impaired trophoblast development and insufficient widening of spiral arteries in the first trimenon, which results in placenta-mediated pregnancy complications like preeclampsia or HELLP syndrome. Besides, macro- and microthrombosis in the vessels of placental stemm villi and spiral arteries may lead to multiple infarctions with release of necrotic trophoblast fragments and inflammatory cytokines playing an important role in the pathogenesis of recurrent pregnancy loss and stillbirth. For women with a known thrombophilia it is recommended to carry out either only postpartal or combined ante- and postpartal thrombosis prophylaxis with low-molecular weight heparins (LMWH) depending on the individual risk stratification. The effectiveness of the LMWH administration for prevention of thrombophilia-induced pregnancy complications and improvement of the pregnancy outcome is currently a matter of debate. Furthermore, an additional application of acetyIsalicylic acid (ASA) should be considered in the management of women with the antiphospholipid antibody syndrome. In the current article we present the case of a 28-year-old woman with the heterozygous prothrombin mutation, HELLP syndrome, a late miscarriage and a stillbirth in the anamnesis, who delivered 3 healthy babies under antenatal LMWH prophylaxis combined with intensive interdisciplinary prenatal care.

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.

BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC.

The aim of the current study was to investigate the role of BRCA1 gene aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC and compared with the clinical and pathologic characteristics. As a control group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation was associated with decreased intensity of BRCA1 protein expression (P = 0.002) and significant increase of median disease-free survival (DFS) of TNBC patients receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter methylation was not associated with any clinical and pathologic parameters. BRCA1 promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic breast cancer and is predictive for better response to anthracycline-based therapies.

Efficacy and patient satisfaction of breast conserving therapy for central breast cancer by the B technique.

PURPOSE: To evaluate the oncologic safety and cosmetic results after breast cancer surgery for central breast cancer by the B technique. METHODS: Seventy women with operable breast cancer located in the central portion of the breast that had received resection surgery with the B technique were recruited. The primary outcome was the oncological safety, quantified as rate of positive resection margins and the cosmetic outcome evaluated by postsurgical self-assessment of the cosmetic outcome via questionnaire. The median follow-up period was 61.4 months (range 7.9-142.6 months). RESULTS: With one exception all patients had T1-2 tumors less than 5 cm in diameter. Most patients had invasive ductal breast cancers (57.1 %), followed by ductal carcinoma-in situ (27.1 %) and invasive lobular breast cancers (8.6 %). The incidence of positive resection margins was 17.1 %. No local tumor recurrence occurred during follow-up; one patient had distant metastases. In total, 80 % of the patients reported that the cosmetic results met or exceeded their expectations. CONCLUSIONS: The B technique is a safe breast conservation surgery for the excision of tumors located in the central portion of the breast and yields a high rate of satisfactory cosmetic results.

Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial.

BACKGROUND: Safety data for combining bevacizumab, everolimus, or lapatinib with anthracycline- and taxane-based neoadjuvant chemotherapy for breast cancer are limited. PATIENTS AND METHODS: The neoadjuvant GeparQuinto trial investigates the addition of (i) bevacizumab to four cycles epirubicin/cyclophosphamide (EC) followed by four cycles docetaxel (Taxotere) in patients with human epithelial growth factor receptor (HER)2-negative tumors, (ii) everolimus to weekly paclitaxel in patients with HER2-negative tumors not responding to EC ± bevacizumab, and (iii) lapatinib instead of trastuzumab to EC-docetaxel in patients with HER2-positive tumors to improve the rate of pathological complete response. Tolerable dose, need for supportive treatments, and early signals for toxic effect were evaluated in a planned safety analysis of 270 patients. RESULTS: Treatment with chemotherapy plus bevacizumab, everolimus, or lapatinib was discontinued in 23.0%, 25.8%, and 34.5% compared with chemotherapy alone or plus trastuzumab in 19.4%, 24.1%, 3.2%, respectively. More leukopenia, infections, mucositis, and hypertension but less edema was observed by adding bevacizumab; a trend toward more thrombocytopenia, leukopenia, skin changes, and hyperlipidemia by adding everolimus; and more diarrhea, skin changes, and hot flushes but no cardiac events by substituting trastuzumab by lapatinib. CONCLUSIONS: Adding bevacizumab and everolimus to chemotherapy appeared feasible. Lapatinib at 1250 mg resulted in an increased rate of treatment discontinuations and was subsequently dose reduced to 1000 mg.

Thermodynamic study of benzocaine insertion into different lipid bilayers.

Despite the general consensus concerning the role played by sodium channels in the molecular mechanism of local anesthetics, the potency of anaesthetic drugs also seems to be related with their solubility in lipid bilayers. In this respect, this work represents a thermodynamic study of benzocaine insertion into lipid bilayers of different compositions by means of molecular dynamics simulation. Thus, the free energy profiles associated with benzocaine insertion into symmetric lipid bilayers composed of different proportions of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine were studied. From the simulation results, a maximum in the free energy (ΔG) profile was measured in the region of the lipid/solution interface. This free energy barrier appears to be very much dependent on the lipid composition of the membrane. On the other hand, the minimum free energy (ΔG) within the bilayer remained almost independent of the lipid composition of the bilayer. By repeating the study at different temperatures, it was seen how the spontaneity of benzocaine insertion into the lipid bilayer is due to an increase in the entropy associated with the process.

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.

Effect of blood loss during caesarean section on coagulation parameters.

INTRODUCTION: Venous thrombosis is the leading cause of pregnancy-related maternal morbidity and mortality. The thrombosis risk is increased by caesarean section and blood loss, though underlying mechanisms of these prothrombotic changes remain unknown. MATERIALS AND METHODS: This prospective study recruited 50 pregnant women at term undergoing elective caesarean section at University Hospital Magdeburg, Germany. Blood loss during surgery was correlated with the changes in total protein S, full length TFPI (TFPIfl), prothrombin, the endogenous thrombin potential (ETP) and resistance to activated protein C (APCsr) determined via calibrated automated thrombography. RESULTS: Mean blood loss was 506 ml (95%CI: 456 to 557 ml). Total protein S was 0.63 (95%CI: 0.60 to 0.67) U/ml preoperatively, decreased by 14.8% after caesarean section and almost normalised five days later. TFPIfl was 0.47 (95%CI: 0.41 to 0.53) U/ml before, remained unchanged immediately after and increased by 11.5% five days after surgery. Prothormbin was 1.10 (95%CI: 1.03 to 1.16) U/ml preoperatively, reduced by 10.4% immediately after and increased again five days after caesarean section, exceeding the preoperative values by 4.4% (-0.7 to 9.6). The ETP decreased by 3.9%, whereas the APCsr increased by 37.0% immediately after caesarean section. The changes in total protein S, prothrombin, thrombin generation and APC resistance showed a trend to be more pronounced in the subgroups with higher blood loss. DISCUSSION: Moderate blood loss during caesarean section hardly reduces thrombin generation but aggravates pregnancy-induced APC resistance and combined deficiency of TFPI and protein S, which can account for the increased thrombosis risk in early puerperium.

Physicochemical study of the acetonitrile insertion into polypyrrole films.

A study by molecular dynamics (MD) simulation of the acetonitrile diffusion into a polypyrrole film was carried out with atomic detail in a 0.1N lithium perchlorate solution. From the simulated trajectories, the acetonitrile behavior was estimated from bulk solution to the interior of the polypyrrole film, across the polypyrrole/solution interface, for a neutral (reduced) and charged (oxidized) state of the polymer. Among other properties, the translational diffusion coefficient and rotational relaxation time of the acetonitrile were calculated, where a diminution in the translational diffusion coefficient was measured in the interior of the polypyrrole matrix compared to bulk, independently of the oxidation state of the polymer, in contrast with the behavior of the rotational relaxation time that increases from bulk to the interior of the polymer for both oxidation states. In addition, the difference of free energy DeltaG associated to the acetonitrile penetration into the polymer was calculated. From the results, it was evidenced that the scarce affinity of acetonitrile to diffuse into the polymer in its reduced state is related with the positive uniform difference of free energy DeltaG approximately 20 kJ/mol, while in the oxidized state, an important free energy barrier of DeltaG approximately 10 kJ/mol has to pass trough for reaching stable sites inside the polymer with values of DeltaG up to -10 kJ/mol.

Study of the benzocaine transfer from aqueous solution to the interior of a biological membrane.

The precise molecular mechanism of general anesthetics remains unknown. It is therefore important to understand where molecules with anesthetic properties localize within biological membranes. We have determined the free energy profile of a benzocaine molecule (BZC) across a biological membrane using molecular dynamics simulation. We use an asymmetric phospholipid bilayer with DPPS in one leaflet of a DPPC bilayer (Lopez Cascales et al. J. Phys. Chem. B 2006, 110, 2358-2363) to model a biological bilayer. From the free energy profile, we predict the zone of actuation of a benzocaine is located in the hydrocarbon region or at the end of the lipid head, depending of the presence of charged lipids (DPPS) in the leaflet. We observe a moderate increase in the disorder of the membrane and in particular an increase in the disorder of DPPS. Static and dynamic physicochemical properties of the benzocaine, such as its dipole orientation, translational diffusion coefficient, and rotational relaxation time were measured.

Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study.

BACKGROUND: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. PATIENTS AND METHODS: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). RESULTS: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. CONCLUSION: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin.

Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.

BACKGROUND: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. PURPOSE: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. METHODS: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. RESULTS: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome. CONCLUSIONS AND IMPLICATIONS: TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.

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.

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.

Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.

PURPOSE: At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse. PATIENTS AND METHODS: Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas. RESULTS: A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection. CONCLUSIONS: This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.

Maximized reduction of primary breast tumor size using preoperative chemotherapy with doxorubicin and docetaxel.

PURPOSE: To assess the toxicity and efficacy of preoperative chemotherapy with doxorubicin and docetaxel in patients with primary operable breast cancer. PATIENTS AND METHODS: Forty-two patients with histologically confirmed primary breast cancer tumors of at least 2 cm in diameter received doxorubicin (50 mg/m(2) intravenously [IV] over 15 minutes) and docetaxel (75 mg/m(2) IV over 1 hour) every 14 (24 patients) or 21 (18 patients) days for four cycles. RESULTS: The median size of the primary tumor decreased significantly, from 4 cm (range, 2 to 10 cm) to 2 cm (range, 0 to 5 cm) on physical examination and from 3.4 cm (range, 1 to 8 cm) to 1. 8 cm (range, 0 to 4 cm) on sonography (P <.001). The overall response rate as assessed by physical examination was 93%, and complete remission of the primary tumor occurred in 33% of patients. The remission rate as assessed by sonographic measurement was 67%. Two patients (5%) had histologically confirmed complete responses. Sonography was more reliable than palpation in predicting histologically determined response. No grade 4 toxicity was noted, and grade 3 toxicity was reported with alopecia (95%), lethargy (17%), loss of appetite (10%), stomatitis (7%), leukopenia (5%), skin desquamation (5%), infection (5%), motor neuropathy (2%), and nausea (2%). The 3-week schedule was associated with less toxicity than the 2-week schedule. CONCLUSION: Preoperative combination chemotherapy with doxorubicin and docetaxel is highly effective and feasible in primary operable breast cancer.