P. Cherel

A Six-Gene Signature Predicting Breast Cancer Lung Metastasis

The lungs are a frequent target of metastatic breast cancer cells, but the underlying molecular mechanisms are unclear. All existing data were obtained either using statistical association between gene expression measurements found in primary tumors and clinical outcome, or using experimentally derived signatures from mouse tumor models. Here, we describe a distinct approach that consists of using tissue surgically resected from lung metastatic lesions and comparing their gene expression profiles with those from nonpulmonary sites, all coming from breast cancer patients. We show that the gene expression profiles of organ-specific metastatic lesions can be used to predict lung metastasis in breast cancer. We identified a set of 21 lung metastasis-associated genes. Using a cohort of 72 lymph node-negative breast cancer patients, we developed a 6-gene prognostic classifier that discriminated breast primary cancers with a significantly higher risk of lung metastasis. We then validated the predictive ability of the 6-gene signature in 3 independent cohorts of breast cancers consisting of a total of 721 patients. Finally, we show that the signature improves risk stratification independently of known standard clinical variables and a previously established lung metastasis signature based on an experimental breast cancer metastasis model.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging in the staging and prognosis of inflammatory breast cancer

To prospectively assess fluorodeoxyglucose positron emission tomography/computed tomography (FDG‐PET/CT) staging and prognosis value in patients with suspected inflammatory breast cancer (IBC).

Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

BackgroundTo access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC).MethodsWe analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated.ResultsThe median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83).ConclusionsIn our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control.

A single-institution study of 117 pregnancy-associated breast cancers (PABC): Presentation, imaging, clinicopathological data and outcome.

BACKGROUND This retrospective single-institution study was designed to describe the main clinical, radiological and histological features, as well as the outcome of pregnancy-associated breast cancer (PABC), with a special emphasis on imaging and diagnostic difficulties. MATERIAL AND METHODS We reviewed all breast cancers diagnosed during pregnancy or during the 12 months following delivery at our institution, between 1993 and 2009. Out of a total of 16,555 new cases of breast cancer observed during this period, 117 PABC (0.7%) were diagnosed. RESULTS Mean age at diagnosis was 33.7 years. Most cancers (81.2%) were diagnosed after delivery. Intermediate or high family risk was frequent (27.5%). The most common mode of presentation was a palpable mass (89.7%). Mean time to diagnosis was 5.8 months. Sensitivity for mammography was 80.9% and for ultrasound 77%. Most prognostic factors were unfavourable: frequent lymph node involvement (51.8%), high-grade tumours, hormone receptor negativity (45.9%) and HER2 positivity (38.7%). Treatments generally included surgery (61.7% mastectomies), radiotherapy (96%) and chemotherapy (79.6%). Overall 5-year survival was 81.8%. CONCLUSION PABC is an uncommon but aggressive form of breast cancer and must be considered in the presence of any breast abnormality during pregnancy or the months following delivery. Mammography and ultrasound should both be performed at the slightest clinical suspicion. Radiologists must be aware that masses may lack typical malignant ultrasound characteristics. Biopsies should be largely performed.

Exploration des seins denses en mammographie : techniques et limites

Mammographic evaluation of dense breasts: techniques and limits Breast density is a radiological concept based on the proportion of radiopaque glandular tissue relative to radiolucent fatty tissue. Mammographic evaluation of dense breasts is more difficult, related to technical difficulties, with decreased rates for detection and characterization of breast lesions, resulting in reduced sensitivity with increased number of interval cancers at routine follow-up when compared to radiolucent breasts. We will review the definition of dense breasts and their frequency, especially their relationship with the age of patients. We will discuss the current technical problems and the impact of breast density on the efficacy of conventional mammography. We will discuss the value of digital mammography, the role of computer assisted diagnosis (CAD) systems and tomosynthesis in the evaluation of dense breasts.

Randomized phase 2 neoadjuvant trial evaluating anastrozole and fulvestrant efficacy for postmenopausal, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients: Results of the UNICANCER CARMINA 02 French trial (UCBG 0609).

Treatment strategies for locally advanced breast cancer in elderly patients too frail to receive neoadjuvant chemotherapy and the introduction of new classes of drugs in the early 2000s have led to the consideration of endocrine therapy as a neoadjuvant treatment for younger hormone receptor (HR)–positive, postmenopausal patients not eligible for primary breast‐conserving surgery (BCS).

Masses in mammography: What are the underlying anatomopathological lesions?

The semiological description of masses in mammography is based on the BI-RADS system provided by the American College of Radiology. The contour is the most discriminating morphological criterion between benign and malignant masses. Most circumscribed masses are benign. Nevertheless, due to specific histological characteristics, certain malignant lesions or lesions with a risk of malignancy may appear in the mammography in this falsely reassuring form. An indistinct contour in the mammography is suspicious and requires a tissue sample. The positive predictive value of malignancy varies according to the morphology of the contour. It is lower for microlobulated contours, increases for masked, then indistinct contours and reaches 96% for spiculated contours. However, in rare cases, certain benign lesions may appear in the form of spiculated masses. In these specific cases, a correlation between the histological results with the imaging data is essential in order to avoid failing to recognise an underlying malignant lesion that the biopsy may have underestimated.

Lésions frontières du sein

Resume Les lesions frontieres dont l’incidence croit avec l’extension du depistage organise, constituent cette frange de la pathologie situee entre les lesions strictement benignes et malignes et dont les limites apparaissent souvent floues. Elles regroupent differentes entites, neoplasie lobulaire, hyperplasie canalaire atypique a laquelle se sont ajoutees les lesions cylindriques atypiques. Leur definition est basee sur le risque relatif de developper ulterieurement un cancer du sein. Elles soulevent de multiples problemes. D’abord, leur identification diagnostique necessite de la part du pathologiste une technique histologique parfaite tant pour les biopsies guidees par imagerie que pour les resections chirurgicales. L’application stricte des criteres microscopiques doit assurer une reproductibilite satisfaisante. Ensuite, leur prise en charge doit etre fonction du type de prelevement, provenant d’une biopsie guidee par imagerie conduisant generalement a une exerese complete de la lesion et le prelevement provenant d’une resection chirurgicale. Enfin, la recherche s’applique a mieux definir les limites de chaque entite, a en preciser le plus precisement le niveau de risque pour adapter au mieux la prise en charge et a terme, trouver de nouvelles lesions selon le type de cancer et de patiente.

Comment diminuer le taux d'échecs des macrobiopsies mammaires percutanées ?

Resume Comment diminuer le taux d’echecs des macrobiopsies mammaires percutanees ? Les macrobiopsies mammaires assistees par aspiration representent une alternative efficace a la chirurgie diagnostique des anomalies mammographiques suspectes non palpables. Bien que le taux d’echec soit faible, nous aborderons chaque etape de la procedure en essayant de lister les differentes sources possibles d’echec et en proposant un certain nombre de moyens permettant de les prevenir ou de les limiter.

Hyperechoic breast images: all that glitters is not gold!

Hyperechogenicity is a sign classically reported to be in favour of a benign lesion and can be observed in many types of benign breast lesions such as hamartoma, lipoma, angiolipoma, haemangioma, haematoma, fat necrosis, fibrosis and galactocele, among others. However, some rare malignant breast lesions can also present a hyperechoic appearance. Most of these hyperechoic malignant lesions present other characteristics that are more typically suggestive of malignancy such as posterior shadowing, a more vertical axis or irregular margins that help to guide the diagnosis. Post magnetic resonance imaging, second-look ultrasound may visualise hyperechoic malignant lesions that would not have been identified at first sight and radiologists must know how to recognise these lesions.Teaching Points• Some rare malignant breast lesions can present a hyperechoic appearance.• Malignant lesions present other characteristics that are suggestive of malignancy.• An echogenic mass with fat density on mammography does not require biopsy.