Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial.

BACKGROUND: Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. METHODS: HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received first-line combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). RESULTS: Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1-301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥1 CTC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P = 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥1 CTC (P = 0.02). CONCLUSIONS: This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. CLINICAL TRIALS NUMBER: NCT00967031.

[Alteration of general state in a woman with polyethylene breast implants since 1967. About an exceptional clinical case]. / Altération de l'état général chez une patiente porteuse d'implants mammaires en polyéthylène depuis 1967. À propos d'un cas clinique exceptionnel.

We report the case of a patient with mammary implants for 42 years. She presented for three years a change of the general state with clinicobiological demonstrations of indefinite origin, and a progressive bilateral increase of her mammary volume until it became exceptional. The surgery of explantation allowed the retreat of two masses of almost 6kg. The analysis did not put in evidence any malignant process but confirmed that it was about prostheses in polyethylene. In one year of recession, a considerable improvement of her general state was observed.

[Paget's disease of the nipple and differential diagnosis]. / Maladie de Paget du mamelon et principaux diagnostics différentiels.

Clinical evaluation of the nipple-areolar complex is a routine component of the breast screening examination. All persistent unilateral nipple lesion should be viewed with suspicion and Paget's disease of the nipple should be considered. The diagnosis is established by nipple scrape cytology. It is a rare variant of ductal carcinoma in situ. The breast imaging work-up should include a search for an underlying malignancy, present in over 80% of cases, not infrequently multifocal. Preoperative MRI is useful if breast conservative surgery is contemplated because of the high rate of occult malignancy on mammograms and ultrasound. Erosive adenomatosis of the nipple is a benign process that may simulate Paget's disease isolated to the nipple. Less frequently, pagetoid basal cell carcinoma, Bowen's disease and melanoma may be more difficult to differentiate clinically and share the unilateral and chronic features of Paget's disease. Biopsy is needed for diagnosis. Cutaneous extension of a breast cancer is rare but should be suspected in patients with retraction and/or fixed nipple. Eczema is characterized by the bilateral nature of the process, the absence of nipple deformity, the presence of flare-ups and the favorable response to local steroid therapy.

[Diagnosis of flat epithelial atypia (FEA) after stereotactic vacuum-assisted biopsy (VAB) of the breast: What is the best management: systematic surgery for all or follow-up?]. / Lésions de métaplasie cylindriques atypiques (MCA) diagnostiquées par macrobiopsies assistées par aspiration: opportunité d'une exérèse chirurgicale?

OBJECTIVE: FEA lesions group two histological types: columnar cell hyperplasia with atypia (CCHA) and columnar cell change with atypia (CCA). The increasing use of VAB has resulted in increased detection of isolated FEA lesions. The aim of this study was to define the best management possible for these patients: which cases may not need excision? MATERIAL AND METHODS: From our database of 780 VABs carried out from 2000 to 2004, 59 patients with FEA were diagnosed. Cases in which no surgery was performed or all features were not available were excluded, thus excluding 19 cases. Forty patients with FEA were included. We reviewed clinical and mammographic characteristics, histological biopsy, and the corresponding surgically excised tissue features. RESULTS: VAB yielded 25 cases of CCHA and 15 cases of CCA. Surgery revealed seven ductal carcinoma cases (four invasive, three in situ); nine benign lesions, and 24 with atypia (19 FEA and six atypical ductal hyperplasia). We found two features related to the risk of cancer: the presence and the size of hyperplasia. All carcinomas were found within the CCHA lesions. No cancer was yielded when size was less than 10 mm within CCA lesions and lesions that were totally removed. CONCLUSION: We recommend surgical excision when CCHA greater than 10 mm is found on the VAB or it is incompletely removed. CCA lesions or CCHA less than 10 mm or totally removed may obviate systematic surgery.

[Architectural distortion and diagnostic difficulties]. / Distorsions architecturales et difficultés diagnostiques.

Identification of architectural distortion requires a good practice of mammography. Prevalence is estimated at 6% of detected abnormalities in screening programs. Under this denomination are gathered focal architectural distortion with predictive positive value (PPV) of 10% and stellate images without central densification, which are more suspicious (PPV 50%). In order to establish a diagnosis, false images must be eliminated by other views. Minimal architectural distortion have to be investigated by other techniques (sonography, MRI percutaneous biopsy) in order to define the best strategy for further management. Stellate images suggestive of radial scars must be surgically removed. The relationships between radial scars and tubular carcinoma are discussed. A particular attention is required for post traumatic or post surgical scars if it exist a high risk of local recurrence or controlateral carcinoma specially after conservative or oncoplastic surgery.