M. Albiter

Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen.

Background:Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers.Methods:We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features.Results:Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07–0.86), P=0.028).Conclusions:AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.

Risque IRM : règles de sécurité, incidents et accidents

It is now accepted that MR imaging does not present any biological risk for humans, even in cases of repeated exposure. However, several of the MR components (magnetic field, gradients, RF pulses, electrodes...) may cause some inconveniences to patients, most of them being reversible. However, severe accidents have been reported. Even though screening of patients for MR imaging eligibility is performed to identify patients with contra-indications to MRI, the lack of vigilance or the ignorance of certain basic safety requirements could lead to serious adverse effects, including death. The goal of this article is to review the various accidents reported with MRI, to explain their mechanism, and to describe means of prevention.

Diagnostic strategy for the assessment of axillary lymph node status in breast cancer

The nodal status in breast cancer is a major prognostic factor in terms of survival. It also plays a role in the therapeutic decision-making process. Therefore, the evaluation of lymph node involvement in breast cancer is imperative in establishing a personalized treatment scheme. The sentinel lymph node procedure has proved successful for small breast tumors (T1-T2), limiting axillary lymphadenectomy and its side effects without changing overall survival. Even so, a substantial number of women must undergo axillary lymphadenectomy during a second surgery when the analysis of the sentinel node discloses major nodal involvement. Imaging can improve patient selection, especially those who appear eligible for immediate axillary lymphadenectomy. Ultrasound is able to depict morphological abnormalities in the lymph nodes such as cortical thickening, peripheral vascularization, hilar infiltration and loss of the kidney-shaped appearance of a normal node. When ultrasound is negative, the risk of massive nodal involvement is limited, thus allowing the oncologist to take an approach with the sentinel lymph node procedure. Magnetic resonance imaging (MRI) can also be useful in detecting pathological lymph nodes, particularly with diffusion-weighted MRI sequence.

Diffusion en IRM mammaire

Objectifs Connaitre les indications de la diffusion en IRM mammaire. Savoir identifier les aspects suspects et les pieges. Savoir quand et comment utiliser l’ADC. Messages a retenir La mesure de l’ADC sert a caracteriser les lesions en hypersignal T2. La fusion d’image est utile pour localiser les lesions sur les cartes ADC. L’hyposignal en diffusion et l’hypersignal en ADC sont rassurants. Un hypersignal en diffusion et un hyposignal en ADC sont en faveur d’une hypercellularite suspecte. Resume La diffusion sert a caracteriser des anomalies equivoques apres analyse morphologique et dynamique. Les lesions suspectes sont en hypersignal en diffusion et en hyposignal en ADC temoignant d’une diffusion restreinte et d’une hypercellularite. Les lesions benignes et les tumeurs repondant au traitement presentent generalement une diffusion libre. Les cartes ADC sont utiles en cas de lesions en hypersignal T2, pouvant masquer une diffusion restreinte. La fusion d’image est parfois indispensable pour localiser precisement les prises de contraste sur les cartes ADC. En cas d’hesitation, un aspect hypo-cellulaire plaide pour un ACR inferieur, une diffusion restreinte oriente vers une categorie superieure.

Abstract P1-14-08: Prediction of pathological response (pCR) to neoadjuvant dose dense and intense cyclophosphamide and anthracycline in a prospective series of triple negative locally advanced breast cancers (TNLABC)

Background : Stage II-III TNBC retains a poor outcome despite high chemosensitivity. Patients (pts) with pCR after neoadjuvant chemotherapy have a good prognosis whereas non-responding pts have a 25-40% risk of distant relapse at 5 years. pCR is thus a major goal in TNBC. We previously reported that TNLABC benefit the most of dose dense dose intense cyclophosphamide (C)-epirubicin (E) ( S.Giacchetti; BJC, 2014 ) Aim : To confirm these results prospectively and analyze the predictive factors of response to high dose chemotherapy in TNBC. Patients and methods : From january 2009 to april 2015 non inflammatory TNLABC received high dose C (1200 mg/m2 d1 qw 2) with E (75 mg/m2/ d1 qw2) for 6 cycles. The pts had a breast biopsy with frozen tissue. We performed molecular studies: qRT-PCR for AR, FOXA1, PI3K and FASAY technic for p53 mutation.The percentage of stromal Tumor-infiltrating lymphocytes (TILs) was also evaluated by two independent pathologists and assessed as a continuous variable. A18F-FDG PET/CT was performed initially and after 2 courses of chemotherapy and the metabolic answer assessed as a variation of the tumor uptake (ΔSUVmax). We report here the pathological complete response (pCR) (absence of infiltrative carcinomas in the breast and in the lymph nodes) and the factors associated with pCR. Results : The characteristics of the 74 pts are listed in table 1. The median age is 48 years old, 48 pts (65.8%) are premenopausal and 79% did not have any family history of breast cancers. TIL was divided in 3 groups 50% (9 pts, 14 %). Pathological response was assessed in 66 pts, one pt progressed during chemotherapy and 6 pts did not undergo surgery yet. 28 pts were in pCR (42.4 %). With a median follow up of 25 months, 13 pts (17.8 %) progressed and 8 (11%) died. Tumor size, tumor grade, percentage of TILs, the change in 18F-fluorodeoxyglucose tumor uptake (ΔSUVmax) were significantly associated with pCR at univariate analysis. Only one factor remained significant at multivariate analysis, the ΔSUVmax, OR: 0.04 [0.007- 0.27], p = 0.0008. Conclusion : In this prospective phase III trial we confirm the efficacy of a dose dense EC in TNBC. The metabolic response evaluated with 18 F-FDG PET/CT is a strong and reliable predictor of pCR and could allow an early change of treatment for the non responders. A clinical trial is planned to test this strategy. Citation Format: Giacchetti S, De Roquancourt A, Groheux D, Piron P, Lehmann-che J, Cuvier C, Resche-rigon M, Albiter M, Roche B, Frank S, Hamy A-S, Teixeira L, Marty M, Lalloum M, Espie M. Prediction of pathological response (pCR) to neoadjuvant dose dense and intense cyclophosphamide and anthracycline in a prospective series of triple negative locally advanced breast cancers (TNLABC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-08.

Abstract P4-13-03: Hormone replacement therapy, is there an increased risk of in situ breast cancer ? data from a french cohort

Background: Use of hormone replacement therapy (HRT) has been associated with an increased risk of breast cancer. Few studies focus on correlation between HRT and in situ breast cancer A large cohort study, the Million Women Study ( Reeves GK et al. Lancet Oncol. 2006 ) have shown that the use of HRT has been associated with an increased incidence of in situ breast cancer (RR = 1, 55, IC=1, 4–1,72, p = 0,03). Purpose: We investigated the association between HRT use and duration and in situ breast cancer incidence from a data base of infraclinic breast lesions. Materials & Methods: From 2007 to 2011, 2708 patients (pts) with a non palpable breast lesion were referred to our breast disease unit for exploration (Saint Louis Hospital, Paris). Radiological abnormalities were screened by mammography and/or breast ultrasound, and/or MRI. Out of 2708 pts, 1668 had a biopsy. All biopsies were seen by an anatomopathologist dedicated to breast. Here, we focus on the 1017 postmenopausal women (61%). Results: Biopsies revaled invasive breast cancers in 222 pts (22%), in situ breast cancers in 164 pts (16%) [10 lobular in situ carcinoma and 154 ductal in situ carcinoma], high risk breast lesions in 103 pts (10%) and benign breast lesions in 528 patients (52%). Characteristics of the 164 patients with in situ breast cancer: median age 62 [IQR: 57 to 68], at least one pregnancy (mean number of pregnancies per woman, 1.6) 75,6%, family history of breast cancer:30,2%. Among these 164 patients, 42.6 % had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 7 years. The HRT use was not significantly associated with in situ breast cancer (p = 0.66) as well as the duration of HRT. Discussion: In this study of postmenopausal women, HRT use, whatever is the duration, was not associated with in situ breast cancer. Although a lack of statistical power may be invoked to explain these results, these findings suggest that the type of the HRT could be important to explain the difference between our study and the Million Women Study. In our study, the HRT used is in the majority of the pts, percutaneous oestrogens and natural progesterone as it is the most commun HRT used in France ( Fournier A, Int J Cancer. 2005 ) during this period of time. Use and type of HRT are different in USA where conjugated estrogens and medroxy progestogerone acetate were commonly used. Conclusion: We therefore encourage further studies to better appreciate the links between type of HRTs and in situ breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-03.

Value of whole-body CTA in the management of brain-dead patients [in French]

PURPOSE To assess the value of whole body CTA, as a complement to head CTA, in the management of brain-dead patients as potential organ donors. Materials and Methods. A total of 27 consecutive brain-dead patients admitted in a center authorized in the harvesting of organs between October 2006 and January 2008 were included. The imaging protocol used was the protocol recommended by the French Society of Neuroradiology, with additional arterial phase helical acquisition of the chest, abdomen and pelvis, and parenchymal phase helical acquisition of the abdomen and pelvis. The imaging findings were then correlated to the surgical reports after organ harvesting. RESULTS CTA readily demonstrates tissue lesions, a contraindication to harvesting (14 cases, including one false positive), and anatomical variants of the vascular system (7 arterial variants and 3 venous variants) and liver (8 patients). CONCLUSION CTA, the gold standard paraclinical examination for brain death assessment, allows, in a single examination, the identification of contraindications to organ harvesting that may modify the surgical approach and even avoid unnecessary mobilisation of the transplant team. It may also provide valuable preoperative evaluation by detecting anatomical variants of the liver and kidneys.

IRM de diffusion et cancer du sein : resultats preliminaires

Objectifs Connaitre les indications de la diffusion en IRM mammaire. Savoir identifier les aspects suspects et les pieges. Savoir quand et comment utiliser l’ADC. Messages a retenir La mesure de l’ADC sert a caracteriser les lesions en hypersignal T2. La fusion d’image est utile pour localiser les lesions sur les cartes ADC. L’hyposignal en diffusion et l’hypersignal en ADC sont rassurants. Un hypersignal en diffusion et un hyposignal en ADC sont en faveur d’une hypercellularite suspecte. Resume La diffusion sert a caracteriser des anomalies equivoques apres analyse morphologique et dynamique. Les lesions suspectes sont en hypersignal en diffusion et en hyposignal en ADC temoignant d’une diffusion restreinte et d’une hypercellularite. Les lesions benignes et les tumeurs repondant au traitement presentent generalement une diffusion libre. Les cartes ADC sont utiles en cas de lesions en hypersignal T2, pouvant masquer une diffusion restreinte. La fusion d’image est parfois indispensable pour localiser precisement les prises de contraste sur les cartes ADC. En cas d’hesitation, un aspect hypocellulaire plaide pour un ACR inferieur, une diffusion restreinte oriente vers une categorie superieure.

Correlation between 18F Fluorodeoxyglucose (FDG) Uptake and Tumor Characteristics in Locally Advanced Breast Cancers.

Background: This study analysed the correlation between [ 18 F]fluorodeoxyglucose (FDG) uptake, assessed by positron emission tomography (PET), and prognostic factors in locally advanced breast cancers Material and Methods: All locally advanced breast cancers seen at Saint Louis hospital and treated with neo-adjuvant chemotherapy (NAC) have a FDG PET after core needle biopsy and before chemotherapy. We correlated the tumor characteristics: T-stage, histological grade, estrogen and progesterone receptors, c-erbB2 over-expression (immuno-histochemistry determination) and P53 (determinate on frozen biopsies by the FASAYmethod) to FDG standardized uptake value (SUV max). The statistics tests used are student test (comparison of 2 means) and kendall correlation. Results: From June 2006 to April 2009, 91 patients with locally advanced breast tumors have both PET scan and frozen tissue before NAC. Median age at diagnosis is 48 (26-81) and 45 % are post menopausal. Conclusion: This study indicates that FDG-PET uptake is correlated with the phenotype of breast tumours. Over-expression of c-erbB2 does not influence FDG uptake. Triple negative tumours and p53 mutated tumors have a high initial SUV which can reflect their aggressiveness and their chemotherapy sensitivity. The knowledge of SUV uptake according to tumor characteristics allows a better understanding of the role of FDG-PET in the prediction of neoadjuvant chemotherapy response. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5010.

Nonpalpable Breast Lesions in a Breast Care Unit: Prospective Analysis on 2708 Consecutive Cases.

Background: Breast cancer screening increases the detection of nonpalpable breast lesions, These lesions raise specific concerns, involving radiological imaging, biopsy techniques, and pathological analysis. The objective of the study is to evaluate the management of nonpalpable breast lesions in a breast disease unit.Material and Methods: From 2001 to 2007, 2708 nonpalpable breast lesions were prospectively evaluated by a multidisciplinary team. Radiologic lesions were detected by mammography alone (71,5%), ultrasonography (27,90%), MRI (0,20%). All lesions were classified according to the BI RADS classification. Three hundred and nine (309) core needle biopsies were performed, 807 vacuum assisted biopsies, and 521 open breast biopsies. The pathologic results were correlated with surgery, rebiopsy or long-term imaging follow up.Results: The pathologic results showed 33 % of malignant lesions (DCIS, invasive carcinoma), 9 % of high risk lesions (atypical ductal or lobular hyperplasia, lobular carcinoma in situ) and 58 % of benign lesions. The prevalence of cancer as a function of BI-RADS was: BI-RADS 0 : 2,6% (4/152), BI-RADS 2: 0% (0/55), BI-RADS 3: 2,3% (17/740), BI-RADS 4: 23,4% (352/1502) et BI-RADS 5 : 78,7% (185/235). Twelve of 152 (7,9 %) high risk lesions were upgraded to malignant lesions and 34/211 DCIS (16,1%) were upgraded to invasive carcinoma after surgery. Diagnostic performance rates exhibited the following results: agreement rate=96,6%, sensibility=96,2%, overall underestimation rate=12,6%, and false-negative rate=1,6%.After vacuum assisted biopsy, one-step surgery was performed in 82,9% and after core needle biopsy in 68,4%.Conclusion: This kind of quality evaluation in community practice should be encouraged. Management of those lesions continuously evolves with the widespread of RMI and new biopsy techniques. Efforts should be made in exploring imaging-pathologic discrepancies, and in identifying predictive factors of invasion on biopsies. We currently perform a focused analysis on lesions that required two surgical steps despite a prior biopsy, in order to point out new ways to improve our practices. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6020.