Oumar Camara

Pathologic Complete Response After Neoadjuvant Chemotherapy Plus Trastuzumab Predicts Favorable Survival in Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: Results From the TECHNO Trial of the AGO and GBG Study Groups

PURPOSE To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. PATIENTS AND METHODS Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m(2)) followed by four 3-week cycles paclitaxel (175 mg/m(2)) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue. RESULTS Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure. CONCLUSION Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.

Monitoring the Response of Circulating Epithelial Tumor Cells to Adjuvant Chemotherapy in Breast Cancer Allows Detection of Patients at Risk of Early Relapse

PURPOSE To demonstrate that it is possible to monitor the response to adjuvant therapy by repeated analysis of circulating epithelial tumor cells (CETCs) and to detect patients early who are at risk of relapse. PATIENTS AND METHODS In 91 nonmetastatic primary breast cancer patients, CETCs were quantified using laser scanning cytometry of anti-epithelial cell adhesion molecule-stained epithelial cells from whole unseparated blood before and during adjuvant chemotherapy. RESULTS Numbers of CETCs were analyzed before therapy, before each new cycle, and at the end of chemotherapy. The following three typical patterns of response were observed: (1) decrease in cell numbers (> 10-fold); (2) marginal changes in cell numbers (< 10-fold); and (3) an (sometimes saw-toothed) increase or an initial decrease with subsequent reincrease (> 10-fold) in numbers of CETCs. Twenty relapses (22%) were observed within the accrual time of 40 months, including one of 28 patients from response group 1, five of 30 patients from response group 2, and 14 of 33 patients from response group 3. The difference in relapse-free survival was highly significant for CETC (hazard ratio = 4.407; 95% CI, 1.739 to 9.418; P < .001) between patients with decreasing cell numbers and those with marginal changes and between patients with marginal changes and those with an increase of more than 10-fold (linear Cox regression model). CONCLUSION These results show that peripherally circulating tumor cells are influenced by systemic chemotherapy and that an increase (even after initial response to therapy) of 10-fold or more at the end of therapy is a strong predictor of relapse and a surrogate marker for the aggressiveness of the tumor cells.

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

PURPOSE The management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine. PATIENTS AND METHODS Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m(2)/d, topotecan 1.0 mg/m(2) plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m(2)/d plus gemcitabine 800 mg/m(2) on day 1 and 600 mg/m(2) on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire). RESULTS The trial enrolled 502 patients with a mean age of 60.5 years (+/- 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia. CONCLUSION Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

Sensitivity and specificity of unenhanced MR mammography (DWI combined with T2-weighted TSE imaging, ueMRM) for the differentiation of mass lesions

ObjectiveThis study was performed to assess the sensitivity and specificity for malignant and benign mass lesions of a diagnostic approach combining DWI with T2-weighted images (unenhanced MR mammography, ueMRM) and compare the results with contrast-enhanced MR mammography (ceMRM).Materials and methodsConsecutive patients undergoing histopathological verification of mass lesions after MR mammography without prior breast interventions (contrast-enhanced T1-weighted, T2-weighted and DWI sequences) were eligible for this retrospective investigation. Two blinded observers first rated ueMRM and then ceMRM according to the BIRADS scale. Lesion size, ADC values and T2-weighted TSE descriptors were assessed.ResultsThis study examined 81 lesions (27 benign, 54 malignant). Sensitivity of ueMRM was 93% (observer 1) and 86% (observer 2), respectively. Sensitivity of ceMRM was 96.5% (observer 1) and 98.3% (observer 2). Specificity was 85.2% (ueMRM) and 92.6% (ceMRM) for both observers. The differences between both methods and observers were not significant (P ≥ 0.09). Lesion size measurements did not differ significantly among all sequences analyzed. Tumor visibility was worse using ueMRM for both benign (P < 0.001) and malignant lesions (P = 0.004).ConclusionSensitivity and specificity of ueMRM in mass lesions equal that of ceMRM. However, a reduced lesion visibility in ueMRM may lead to more false-negative findings.

Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring

IntroductionIn adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting.MethodWe used MAINTRAC® analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients.ResultsMAINTRAC® analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy.ConclusionThe response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring.

Magnetic resonance imaging of inflammatory breast carcinoma and acute mastitis. A comparative study

The aim of this study was to evaluate the potential of magnetic resonance mammography (MRM) to distinguish inflammatory breast carcinomas (IBC) from acute mastitis (AM). This study compared MRM examinations of two selected groups of patients: 48 subjects with IBC and 42 patients with AM. No statistical differences were revealed between the two groups for morphology of masses and of non-mass-like enhancement, breast enlargement, diffuse skin thickening, abnormal nipple configuration, prominent vessels, and also for cutaneous/subcutaneous, perimamillar and diffuse oedema. However, initial and postinitial dynamic characteristics significantly differed between the two groups (p < 0.001). In IBC, more masses with a greater average size were detected (p < 0.05). The following morphological criteria were also observed more often in IBC (p < 0.05): T2-hypointensity of masses (77.5%/18.2%), blooming sign (62.5%/31.8%), infiltration of pectoralis major muscle (interruption of fat plane: 54.2%/16.7%; pathological enhancement: 33.3%/7.1%), perifocal (66.7%/33.3%), prepectoral (72.9%/31.0%) and intramuscular pectoral oedema (41.7%/7.1%). The main localisation of AM was subareolar, of IBC central or dorsal (p < 0.001). The discrimination between AM and IBC remains a diagnostic challenge because of overlapping imaging features. However, the combination of multiple dynamic and morphological MRM criteria seems to have the potential for a differential diagnosis.

Ultrasound-guided, percutaneous cryotherapy of small (< or = 15 mm) breast cancers.

Rationale and Objective:The purpose of this study was to investigate the feasibility, efficacy, and safety of ultrasound-guided percutaneous cryotherapy of stage T1 breast cancers. Materials and Methods:Thirty patients with biopsy-confirmed breast cancers with tumor diameters of 15 mm or smaller (range, 5–15 mm; median, 12 mm) underwent cryotherapy. After local anesthesia, a 3-mm cryo probe was placed into the tumor under ultrasound guidance. All tumors were subjected to 2 freeze cycles with an interposing thawing cycle. The size of the iceballs, their distance to the skin, and the temperature at the tip of the probe were closely monitored during the procedure. The patients underwent surgery within 6 weeks and the specimens were evaluated histologically. Results:The median minimum temperature reached –146°C (range, −117°C to −167°C). In 5 of 29 patients, remnant ductal carcinoma in situ was detectable histologically after cryotherapy beyond the margin of the cryosite in the specimens after open surgery. In 24 patients, no viable tumor cells were found. No severe side effects occurred. In one patient, the cryo procedure was not performed completely because of technical problems. Discussion:Percutaneous cryotherapy is a feasible and safe procedure in minimally invasive therapy for small breast cancers. Residual ductal carcinoma in situ may be attributable to the beginning of a learning curve or by false-negative detection in preinterventional imaging. Magnetic resonance mammography might aid in treatment planning and for therapy monitoring to better define target tissue and to correlate the tumor margin with the iceball.

Inflammatory Breast Carcinoma in Magnetic Resonance Imaging: A Comparison with Locally Advanced Breast Cancer

RATIONALE AND OBJECTIVES Although inflammatory breast carcinoma (IBC) accounts for 1%-4% of all breast cancer cases, the appearance of this highly malignant tumor in magnetic resonance imaging (MRI) is still not well characterized. The aim of this study was to identify typical imaging features of IBC in comparison with noninflammatory locally advanced breast carcinoma (LABC). MATERIALS AND METHODS MRIs of 48 patients with IBC were compared with an equivalent cohort of 52 subjects with LABC. Age and histopathologic subtype were equivalent between the two groups. To delineate characteristic features, a multitude of dynamic and morphologic parameters were evaluated using T1- and T2-weighted sequences. RESULTS No significant differences of prevalences could be found for the following criteria: dynamic tumor signal characteristics, prominent vessels, perifocal edema, axillary lymph node involvement, morphology of focal masses, and morphologic pattern of non-mass like enhancement. Otherwise, the quantity of focal masses and the spatial distribution of the tumoral infiltration significantly differed between the two cancer groups. The following parameters occurred more frequently in the IBC cases: edema (cutaneous/subcutaneous 81.3%, perimamillar 70.8%, diffuse 89.6%, prepectoral 72.9%, intramuscular pectoral 41.7%), thickening (75.0%) and pathologic enhancement (60.4%) of Coopers ligaments, skin thickening (83.3%), punched-out sign (initially strong, focal increase of some dermal or subcutaneous parts followed by slow-continuous enhancement of the surrounding skin; 56.3%). CONCLUSIONS Inflammatory breast carcinoma seems to represent a specific biological entity resulting in typical MRI characteristics. Some of the parameters are supposed to visualize the characteristic extensive lymphovascular infiltration and therefore may improve the diagnosis of IBC.

Clinical MR-mammography: are computer-assisted methods superior to visual or manual measurements for curve type analysis? A systematic approach.

RATIONALE AND OBJECTIVES Enhancement characteristics after administration of a contrast agent are regarded as a major criterion for differential diagnosis in magnetic resonance mammography (MRM). However, no consensus exists about the best measurement method to assess contrast enhancement kinetics. This systematic investigation was performed to compare visual estimation with manual region of interest (ROI) and computer-aided diagnosis (CAD) analysis for time curve measurements in MRM. MATERIALS AND METHODS A total of 329 patients undergoing surgery after MRM (1.5 T) were analyzed prospectively. Dynamic data were measured using visual estimation, including ROI as well as CAD methods, and classified depending on initial signal increase and delayed enhancement. RESULTS Pathology revealed 469 lesions (279 malignant, 190 benign). Kappa agreement between the methods ranged from 0.78 to 0.81. Diagnostic accuracies of 74.4% (visual), 75.7% (ROI), and 76.6% (CAD) were found without statistical significant differences. CONCLUSIONS According to our results, curve type measurements are useful as a diagnostic criterion in breast lesions irrespective of the method used.

Prognostic role of platinum sensitivity in patients with brain metastases from ovarian cancer: results of a German multicenter study

BACKGROUND Ovarian cancer is the leading cause of death in women with gynecological malignancies. Brain metastases are considered an uncommon metastatic site. Only few data exist on prognostic factors for this patient collective. PATIENTS AND METHODS A multicenter retrospective chart review was carried out including all patients with histologically confirmed ovarian cancer from six different German hospitals from 1981 to 2008. Overall, 4277 cases of patients with ovarian cancer were screened and patients with brain metastasis were identified and analyzed regarding various clinical variables and survival. RESULTS A total of 74 women with brain metastases were identified, resulting in an incidence of 1.73%. In multivariate analysis, the following clinical parameters had a significant impact on overall survival: multiple lesions [hazard ratio (HR) 4.4, 95% confidence interval (CI) 2.0-9.7] and low grading (HR 3.1, 95% CI 1.7-5.8) were associated with a negative impact. Platinum sensitivity (HR 0.23, 95% CI 0.12-0.48) was significantly associated with a favorable outcome. Good performance status (60%-80% HR 0.48, 95% CI 0.23-0.99 and 90%-100% HR 0.21, 95% CI 0.08-0.53) also had a positive impact on overall survival. CONCLUSIONS Platinum sensitivity is the most important prognostic factor in patients with ovarian cancer metastatic to the brain. This novel finding should be considered in the strategy of multimodal therapy for brain metastases in ovarian cancer.