Correlation between MRI and biopsies under second look ultrasound.

The term "second look" lesions in MRI refers to lesions detected by MRI that were not initially seen on mammography or ultrasound. The objectives of our study were to analyse the displacement of targets between MRI and ultrasound; to define discriminating BIRADS morphological criteria to predict benign or malignant character and better establish the indications of second look ultrasound and biopsy; and to analyse the agreement between ultrasound and MRI in terms of morphological criteria. A retrospective and monocentric review was performed of the records of consecutive patients with breast abnormalities (mass or non-mass) initially detected by MRI that were not initially seen on mammography or ultrasound. All patients with abnormalities found during the performance of second look ultrasound and biopsied were included in the study. All lesions were documented using the BIRADS lexicon for MRI and ultrasound. Of 100 included patients, 108 lesions were detected by MRI, found via second look ultrasound and biopsied between January 2008 and 2010. All of the included patients were followed-up for a variable period, from 2 to 5 years. Eighty-two upon 108 biopsied lesions (76%) were benign and 26/108 lesions (24%) were malignant. This study confirmed the switch from procubitus to decubitus essentially displaces the tumour in the antero-posterior direction. It showed that the risk factors were not reliable criteria for establishing an indication for second look ultrasound. This study also showed that circumscribed contours and a progressive enhancement curve (type I) for masses on MRI had the strongest negative predictive value of greater than 0.85. In ultrasound, the round or oval shape, circumscribed contours and the parallel orientation to the skin favoured benignity with a NPV of greater than 0.85. For masses, the study showed that the agreement in interpretation of the benign versus suspicious morphological criteria between the MRI and the ultrasound was very weak for the shape (Kappa=0.09) and weak for the contours (Kappa=0.23). Finally, the MRI overestimated the size of the targets compared to ultrasound (Student t-test, p=0.0001). The performance of second look ultrasound has to be performed after the detection of an abdnormality on MRI even for lesion classified BIRADS 3. The biopsy indications must be wide with insertion of a clip and a control MRI. Only this control allows to stop the investigation if the biopsied lesion is benign.

p53 mutations and overexpression in locally advanced breast cancers.

Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53 mutations could be a late event in this non-familial form of breast cancer.

[Promising results of bimonthly chemotherapy with high dose cyclophosphamide and epirubicin in induction treatment of inflammatory cancer of the breast]. / Résultats prometteurs d'une chimiothérapie bimensuelle avec cyclophosphamide et épirubicine à forte dose dans le traitement d'induction du cancer du sein inflammatoire.

Forty-eight patients with inflammatory breast cancer were treated by an induction regimen with cyclophosphamide (1200 mg/m2), and epirubicin (75 mg/m2). Four to six courses were given every two weeks, whatever the absolute leukocyte counts, before mastectomy, loco-regional radiation, and conventional, or reinforced, for selected patients, chemotherapy. Main toxicity was leukopenia, with grade IV in 25% of cases. However, febrile neutropenia was rare, and relative dose intensity was 102% after four courses, and 97% after six courses. Complete disappearance of inflammatory signs was observed in 90% of patients. Three patients had a pathological complete response, and ten patients had negative axillary lymph nodes. Furthermore, 13 patients had a major pathological response. With a median follow-up of 42 months, progression-free survival and overall survival are 48% and 66%, respectively.