Jean-Yves Pierga

High rates of breast conservation for large ductal and lobular invasive carcinomas combining multimodality strategies

The literature reports low rates of breast conservation after neoadjuvant chemotherapy for operable breast cancers not amenable to initial breast-conserving surgery. This study aims to compare the outcome of lobular vs ductal carcinomas after neoadjuvant chemotherapy. Between 1989 and 1999, 750 patients with clinical stage II/IIIA ductal (672) or lobular (78) invasive breast carcinomas were treated at the Institut Curie with primary anthracycline-based polychemotherapy followed by either breast conservation (surgery and/or radiotherapy) or mastectomy. Median follow-up was 10 years. Clinical response to primary chemotherapy was significantly worse for lobular than for ductal carcinomas (47 vs 60%; P=0.04), but only histological grade remained predictive in multivariate analysis. Breast conservation was high for both ductal and lobular carcinomas (65 and 54%; P=0.07), due, in part, to the use of radiotherapy, either exclusive or preoperative, for respectively 26 and 40% of patients. The lobular type had no adverse effect, neither on locoregional control nor on overall survival, even in the group of patients treated with breast conservation.

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

BackgroundnWe conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker.nnnMethodsnWe collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided.nnnResultsnData from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008).nnnConclusionsnCTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab

BackgroundnWe present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab.nnnPatients and methodsnNonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4u2009ml of blood, respectively, with the CellSearch System.nnnResultsnFrom October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (Pu2009<u20090.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5u2009ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, Pu2009<u20090.01, HR 2.80) and shorter 3-year overall survival (OS) (Pu2009<u20090.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value.nnnConclusionnIn this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.

Are we able to predict survival in ER-positive HER2-negative breast cancer? A comparison of web-based models.

Background:Several prognostic models have been proposed and demonstrated to be predictive of survival outcomes in breast cancer. In the present article, we assessed whether three of these models are comparable at an individual level.Methods:We used a large data set (n=965) of women with hormone receptor-positive and HER2-negative early breast cancer from the public data set of the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study. We compared the overall performance of three validated web-based models: Adjuvant!, CancerMath.net and PREDICT, and we assessed concordance of these models in 10-year survival prediction.Results:Discrimination performances of the three calculators to predict 10-year survival were similar for the Adjuvant! Model, 0.74 (95% CI 0.71–0.77) for the Cancermath.net model and 0.72 (95% CI 0.69–0.75) for the PREDICT model). Calibration performances, assessed graphically, were satisfactory. Predictions were concordant and stable in the subgroup, with a predicted survival higher than 90% with a median score dispersion at 0.08 (range 0.06–0.10). Dispersion, however, reached 30% for the subgroups with a predicted survival between 10 and 50%.Conclusion:This study revealed that the three web-based predictors equally perform well at the population level, but exhibit a high degree of discordance in the intermediate and poor prognosis groups.

Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma

PurposeFew studies evaluated the prognostic value of the presence of lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast cancer (BC).MethodsThe association between LVI and survival was evaluated in a cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC prognostic scores (ypAJCC, RCB, CPS, CPSxa0+xa0EG and Neo-Bioscore) were evaluated and compared with or without the addition of LVI.ResultsOut of 1033 tumors, LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases. Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54; 95% CI 1.96–3.31; Pxa0<xa00.001), and the magnitude of this effect depended on BC subtype (Pinteractionxa0=xa00.003), (luminal BC: HR 1.83; Pxa0=xa00.003; triple negative BC: HR 3.73; Pxa0<xa00.001; HER2-positive BC: HR 6.21; Pxa0<xa00.001). Post-NAC LVI was an independent predictor of local relapse, distant metastasis, and overall survival; and increased the accuracy of all five post-NAC prognostic scoring systems.ConclusionsPost-NAC LVI is a strong independent prognostic factor that: (i) should be systematically reported in pathology reports; (ii) should be used as stratification factor after NAC to propose inclusion in second-line trials or adjuvant treatment; (iii) should be included in post-NAC scoring systems.

Cellules tumorales circulantes en oncologie digestive

Les cellules tumorales circulantes (CTC) correspondent a l’une des etapes du processus de dissemination metastatique. Le developpement recent des techniques de detection des CTC dans le sang des patients a genere de nombreux resultats, obtenus par techniques heterogenes d’isolement et, tres souvent, dans de petites cohortes. Nous faisons ici la revue de ces donnees et de leur impact clinique dans les cancers digestifs (œsophage, estomac, pancreas, colon-rectum et foie), et discutons la possible utilisation des CTC comme nouveaux biomarqueurs.