Coexpression of androgen receptor and FOXA1 in nonmetastatic triple-negative breast cancer: ancillary study from PACS08 trial.

AIM: Microarray studies identified a subgroup of molecular apocrine tumors (estrogen receptor [ER] negative/androgen receptor [AR] positive) that express luminal genes including FOXA1. FOXA1 may direct AR to sites normally occupied by ER in luminal tumors, inducing an estrogen-like gene program that stimulated proliferation. MATERIALS & METHODS: Expression of AR and FOXA1 was evaluated by immunohistochemistry in 592 patients with nonmetastatic triple-negative breast cancer (TNBC). RESULTS: Coexpression of AR and FOXA1 was found in 15.2% of patients. These tumors were more frequently lobular, found in older patients and exhibited a lower nuclear grade and a greater degree of node involvement. They less often exhibited lymphocytic infiltrate, pushing margins, syncytial architecture, central fibrosis or necrosis. CONCLUSION: TNBC with coexpression of AR and FOXA1 seems to behave like luminal tumors with a morphological profile distinct from other TNBC. These biomarkers could be useful to identify a subgroup of TNBC and could have future therapeutic implications.

Relations between arthralgia and fear of recurrence: results of a cross-sectional study of breast cancer patients treated with adjuvant aromatase inhibitors therapy.

PURPOSE: The aim of this study was to explore associations between arthralgia and fear of recurrence in breast cancer patients treated by aromatase inhibitors (AI). METHOD: We sent a set of questionnaires to 100 patients examining their pain characteristics, anxiety (STAI), depression (BDI-SF), quality of life (SF-36), fear of recurrence (FCRI), and representations of AI treatment (ad hoc questionnaire). Nonparametric tests were used to investigate between-group comparisons (arthralgia vs. nonarthralgia) in these domains as well as the associations between arthralgia and fear of recurrence. RESULTS: Of the 77 patients who returned the questionnaires (response rate = 77%), 60 (78%) reported arthralgia. The mean score of fear of recurrence exceeded the pathological threshold in the arthralgia group and was significantly higher than that in the nonarthralgia group (14.8 vs. 10.7, p < 0.01). Significant associations were observed between fear of recurrence and pain intensity (r = 0.274, p < 0.05) and pain relief (r = -0.409, p < 0.05). More than 80% of the total sample declared that they were well informed about the aim of AI, their side effects, and the risk of developing arthralgia. Fear of recurrence did not appear to be associated with representations of AI. CONCLUSION: The study revealed a close relationship between pain intensity and fear of recurrence. In particular, it showed that effective pain management was accompanied by a reduced fear of recurrence. Information, although essential, appeared insufficient to overcome patients' concerns about pain. Therefore, the implement of a systematic screening for arthralgia and the improvement of analgesic treatment are essential issues. New strategies for pharmacological and nonpharmacological treatment must be developed.

Correlation of HER2, FCGR2A, and FCGR3A gene polymorphisms with trastuzumab related cardiac toxicity and efficacy in a subgroup of patients from UNICANCER-PACS 04 trial.

The purpose of this study was to investigate, in the context of a prospective node-positive-breast cancer trial HER2 containing-regimen (UNICANCER-PACS 04 trial), the predictive value of HER2, FCGRIIA, and FCGRIIIA gene polymorphisms for cardiac toxicity and efficacy of trastuzumab. We analyzed HER2-I655V, FCGR2A-H131R, and FCGR3A-V158F single nucleotide polymorphisms in patients in adjuvant setting treated by six courses of either fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2), or epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2) every 3 weeks then randomly assigned, in case of HER2 overexpressing tumor, to either trastuzumab for 1 year or nothing. Left ventricular ejection fraction and clinical examination were monitored in each patient, seven times throughout the study to detect congestive heart failure or asymptomatic subclinical cardiac toxicity. All genotypes were analyzed in relation to cardiac toxicity, EFS, and OS. One hundred and thirty-two HER2-positive breast cancer patients were analyzed. The HER2-I655V genotype was significantly associated with cardiac toxicity (p = 0.025). The FCGR2A-131 H/H genotype was significantly correlated with a shorter EFS (p = 0.027). The FCGR3A-158 V/V genotype was not correlated with EFS nor OS. These results might be useful in making a treatment choice of HER2 blockers in adjuvant setting by with an increase in efficacy and decrease in toxicity.

Recommandations francophones pour la pratique clinique concernant la prise en charge des cancers du sein de Saint-Paul-de-Vence 2022-2023.

With more than 60,000 new cases of breast cancer in mainland France in 2023 and 8% of all cancer deaths, breast cancer is the leading cancer in women in terms of incidence and mortality. While the number of new cases has almost doubled in 30 years, the percentage of patients at all stages alive at 5 years (87%) and 10 years (76%) testifies to the major progress made in terms of screening, characterisation and treatment. However, this progress, rapid as it is, needs to be evaluated and integrated into an overall strategy, taking into account the characteristics of the disease (stage and biology), as well as those of the patients being treated. These are the objectives of the St Paul-de-Vence recommendations for clinical practice. We report here the summary of the votes, discussions and conclusions of the Saint-Paul-de-Vence 2022-2023 RPCs.

Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial.

PURPOSE: The initial report from the Programme Action Concertée Sein (PACS) PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS) and overall survival (OS) rates with the sequential administration of docetaxel after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast cancer. We evaluate here the impact of this regimen at 8 years. PATIENTS AND METHODS: Between June 1997 and March 2000, a total of 1,999 patients (age <65) with localized, resectable, non-pretreated, unilateral breast cancer were randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21 days. Radiotherapy was mandatory after conservative surgery and tamoxifen was given for 5 years to hormone receptor (HR)-positive patients. Five-year DFS was the trial's main endpoint. Updated 8-year survival data are presented. RESULTS: With a median follow-up of 92.8 months, 639 patients experienced at least one event. A total number of 383 deaths were registered. Eight-year DFS rates were 65.8% with FEC alone and 70.2% with FEC-D. OS rates at 8 years were 78% with FEC alone and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse and a 25% reduction in the relative risk of death in favor of FEC-D. Significant relative risk reductions were observed in the HR-positive, HER2-positive, and Ki67 ≥20% subpopulations. CONCLUSION: Benefits for DFS and OS rates with the sequential FEC-D regimen are fully confirmed at 8 years.

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review.

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.

Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study.

BACKGROUND: The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP). PATIENTS AND METHODS: The study observed 623 patients for > or = 2 years. Treatment was given according to oncologists' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for > or = 30 days following progression or stopped at or before progression. RESULTS: The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months). CONCLUSION: The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab.

A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients.

To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients. From May 2004 till October 2007, 340 patients with stage II and III breast adenocarcinoma, ineligible for breast conserving surgery, received eight sequential three weekly cycles of EC-D [epirubicin (75 mg/m(2))-cyclophosphamide (750 mg/m(2)) for four cycles followed by docetaxel (100 mg/m(2)) for four cycles]. HER2-negative patients (N = 220) were randomized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5-8 or no additional treatment, while HER2-positive patients confirmed by FISH (N = 120) were randomized to trastuzumab concomitant to docetaxel (8 mg/kg then 6 mg/kg IV every 3 weeks) or no additional preoperative treatment. In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5 and 13% of patients treated without and with neoadjuvant Celecoxib, respectively. In the HER2 positive group, pCR rate reached 26% in those who received neoadjuvant trastuzumab versus 19% in the others. There was no unexpected toxicity, no cardiac toxicity, and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%. Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor. In HER2-positive tumor patients, trastuzumab added to ECD leads to increased pCR rates. It was the only combination to deserve further study according to the two-stage Fleming's design used in this trial.

Exonic expression profiling of breast cancer and benign lesions: a retrospective analysis.

BACKGROUND: Gene-expression arrays have generated molecular predictors of relapse and drug sensitivity in breast cancer. We aimed to identify exons differently expressed in malignant and benign breast lesions and to generate a molecular classifier for breast-cancer diagnosis. METHODS: 165 breast samples were obtained by fine-needle aspiration. Complementary DNA was hybridised on splice array. A nearest centroid prediction rule was developed to classify lesions as malignant or benign on a training set, and its performance was assessed on an independent validation set. A two-way ANOVA model identified probe sets with differential expression in malignant and benign lesions while adjusting for scan dates. FINDINGS: 120 breast cancers and 45 benign lesions were included in the study. A molecular classifier for breast-cancer diagnosis with 1228 probe sets was generated from the training set (n=94). This signature accurately classified all samples (100% accuracy, 95% CI 96-100%). In the validation set (n=71), the molecular predictor accurately classified 68 of 71 tumours (96%, 88-99%). When the 165 samples were taken into account, 37 858 exon probe sets (5.4%) and 3733 genes (7.0%) were differently expressed in malignant and benign lesions (threshold: adjusted p<0.05). Genes involved in spliceosome assembly were significantly overexpressed in malignant disease (permutation p=0.002). In the same population of 165 samples, 956 exon probe sets presented both higher intensity and higher splice index in breast cancer than in benign lesions, although located on unchanged genes. INTERPRETATION: Many exons are differently expressed by breast cancer and benign lesions, and alternative transcripts contribute to the molecular characteristics of breast malignancy. Development of molecular classifiers for breast-cancer diagnosis with fine-needle aspiration should be possible.

CXCR4 expression in early breast cancer and risk of distant recurrence.

BACKGROUND: Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to evaluate the prognostic value of CXCR4 expression in primary breast tumors and describe correlations with the occurrence of metastasis in organs expressing the CXCR4 ligand stromal cell-derived factor 1 (i.e., liver, lung, brain, and bone). PATIENTS AND METHODS: CXCR4 expression in primary breast tumors was evaluated by immunohistochemistry in 823 patients included in two prospective clinical trials. CXCR4 expression was considered positive when >1% of tumor cells were stained. The prognostic value of CXCR4 expression was assessed by a Cox regression model adjusted for clinical characteristics. We assessed the association of CXCR4 expression with the rate of distant metastasis to specific organ sites. RESULTS: CXCR4 was expressed in 92 of 794 primary tumors (12%). CXCR4 expression was not associated with clinical characteristics. CXCR4 was not prognostic for overall survival and showed a nonsignificant trend toward a higher risk for distant metastasis. CXCR4(+) tumors showed a significantly higher risk for bone metastasis. The 10-year incidences of bone metastases were 23% (13.6%-32.6%) and 12% (9.7%-15%) in CXCR4(+) and CXCR4(-) tumors, respectively. CONCLUSION: This study suggests that expression of CXCR4 in primary breast tumors is associated with a higher likelihood of developing bone metastases. This finding could open new avenues for the development of novel adjuvant strategies, including bone-targeting agents.

Individualized Prediction of Menses Recovery After Chemotherapy for Early-stage Breast Cancer: A Nomogram Developed From UNICANCER PACS04 and PACS05 Trials.

BACKGROUND: The likelihood of menses recovery varies greatly in premenopausal patients receiving adjuvant chemotherapy for breast cancer. Quantifying this probability for each patient could better inform the chemotherapy discussion and individualize fertility counseling. We performed a pooled analysis of the PACS04 and PACS05 adjuvant randomized trials to develop a nomogram to estimate the probability of menses recovery at 3, 6, and 18 months after the end of adjuvant chemotherapy. PATIENTS AND METHODS: Women who were premenopausal and aged ≤ 50 years at randomization in the PACS04 and PACS05 trials were included in the present analysis. The primary endpoint was the probability of menses recovery within 18 months of chemotherapy completion. Multivariable Cox proportional hazards regression was used to estimate the association of each variable with the likelihood of menses resumption. A nomogram was developed to predict menses recovery at different intervals. RESULTS: The factors associated with menses recovery were assessed for 1210 patients. At a median follow-up of 90 months (range, 3-189 months), 342 of 1210 patients (28.2%) had recovered menses. The probability of menses recovery at 18 months was 25.5% (range, 23.0%-27.9%). After backward elimination, age, final body mass index, type of chemotherapy, and hormone therapy were selected to build the nomogram to predict the probability of menstrual resumption at 3, 6, and 18 months after chemotherapy. CONCLUSION: An accurate and individualized prediction of menses recovery is feasible for premenopausal patients eligible for adjuvant chemotherapy for early-stage breast cancer. Our nomogram will be externally validated in a large prospective cohort.

UCBG 2-08: 5-year efficacy results from the UNICANCER-PACS08 randomised phase III trial of adjuvant treatment with FEC100 and then either docetaxel or ixabepilone in patients with early-stage, poor prognosis breast cancer.

PURPOSE: UNICANCER-PACS08 compared adjuvant FEC (5-FU; epirubicin; cyclophosphamide) then docetaxel to FEC then ixabepilone in poor prognosis early breast cancer (BC). We evaluated whether replacing docetaxel with ixabepilone would increase 5-year disease-free survival (DFS). PATIENTS AND METHODS: Triple-negative breast cancer (TNBC) or oestrogen receptor (ER)+/progesterone receptor (PR)-/HER2- BC patients were randomised to receive standard FEC (3 cycles) followed by 3 cycles of either docetaxel (100 mg/m2) or ixabepilone (40 mg/m2). Radiotherapy was mandatory after conservative surgery; ER+ patients received endocrine therapy. RESULTS: Seven hundred sixty-two patients were enrolled between October 2007 and September 2010. Baseline characteristics were balanced between arms. Median follow-up was 66.7 months. Median DFS was not reached; 5-year DFS rate was 76% with docetaxel and 79% with ixabepilone (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.58-1.10; p = 0.175). Median overall survival (OS) was not reached; 5-year OS rate was 86% versus 84% (HR = 0.97; 95% CI = 0.66-1.42; p = 0.897). TNBC patients treated with ixabepilone had a 23% lower risk of relapse compared to docetaxel (HR for DFS = 0.77; 95% CI = 0.53-1.11; p = 0.168). DFS was longer with ixabepilone than docetaxel in patients with grade II-III lymphocytic infiltration (HR = 0.55; 95% CI = 0.29-1.05; p = 0.063). All patients experienced ≥1 adverse events (AEs): 75% reported grade III-IV AEs and two (<1%) had grade V AEs (both with neutropenia and infection receiving ixabepilone). CONCLUSION: After adjuvant FEC, ixabepilone was comparable to docetaxel for treating poor prognosis early BC patients. The benefit of ixabepilone in subgroups (patients with TNBC and grade II-III lymphocytic infiltration) requires further evaluation.

Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations.

In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients' representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the "actionability" of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.

Differential immunohistochemical and biological profile of squamous cell carcinoma of the breast.

BACKGROUND: Pure or metaplastic squamous cell carcinoma (SCC) of the breast is a rare entity with an unclear pathogeny and aggressive clinical behaviour. An attempt was made to characterize its differential immunohistochemical and biological profile. PATIENTS AND METHODS: Twenty-seven cases of SCC (pure or not) of the breast were matched with 27 ductal invasive carcinomas (IDC) for age, tumour size, nodal involvement and year of diagnosis. The expression levels of oestrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), HER2, Cyclin Bl, hTERT, cytokeratins (CK) 5/6 and p63 were determined immunohistochemically in both cohorts. The presence of the human papilloma virus (HPV) genome was investigated by polymerase chain reaction (PCR). RESULTS: Pure and metaplastic SCC displayed common profiles typifying a basal origin: they never expressed ER or PR, were HER2-negative in 93% of cases, exhibited positivity for CK5/6 or EGF-R in 75% and 85%, and for p63 in 70% of cases and were highly proliferative. These profiles were markedly different from those of matched controls (p<0.001 for five markers) except for HER2 and hTERT. The HPVgenome was detected in 2 out of 14 cases (14%) of SCC. CONCLUSION: The expression profile of SCC of the breast was markedly different from that of IDC. A typical "basal-like" phenotype was displayed that may explain part of their behaviour and justify specific therapeutic approaches. HPV infection was not a leading oncogenic event in SCC of the breast.

Mitotic index and benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer.

PURPOSE: We have evaluated whether the mitotic index could predict the benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer who are eligible for adjuvant chemotherapy according to Saint Gallen guidelines. PATIENTS AND METHODS: A total of 937 patients from a single institution were included in two randomized trials that compared adjuvant anthracycline-based chemotherapy with no chemotherapy. These patients account for 83% of the overall population included in these trials. The first trial included premenopausal patients with node-negative disease, and the second one included postmenopausal patients, regardless of lymph node status. The treatment benefit was assessed according to the number of mitoses per field (x400). RESULTS: The mitotic index was assessable in 888 patients (94%). All the patients presented as either node-positive or an average-risk breast cancer according to 2003 Saint Gallen consensus conference guidelines. The 5-year overall survival rates were 91% and 87% for patients treated or not with adjuvant chemotherapy (P = .09). In patients with low/medium mitotic index (< three mitoses/field; n = 450), the 5-year overall survival rate was 95% for patients treated or not with adjuvant chemotherapy (P = .56). In patients with high mitotic index (>/= three mitoses/field; n = 438), the 5-year overall survival rates were 86% and 79% for patients treated or not treated with adjuvant chemotherapy, respectively (P = .02). CONCLUSION: A high mitotic index is associated with the efficacy of adjuvant anthracycline-based chemotherapy in patients eligible for adjuvant chemotherapy in daily practice.

Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer.

PURPOSE: To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis-free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram. PATIENTS AND METHODS: Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model. RESULTS: The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of > or = 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02). CONCLUSION: Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.

[Perception of pT1a,b pN0 breast tumor prognosis by the French oncology community: Results of the EURISTIC national survey]. / Perception du pronostic des tumeurs mammaires pT1a,b pN0 par la communauté oncologique française : résultats de l'enquête nationale EURISTIC.

The prognosis of infracentimetric breast cancers (BC) is heterogeneous. The EURISTIC survey describes how French oncology specialists perceive the prognosis of pT1a,b pN0 BCs. A self-administered questionnaire has been sent to over 2000 French BC specialists. Six hundred and sixty-three physicians responded. Fifty-eight percent do not consider tumor size as a key prognostic criterion. They consider that the cutoff for poor prognosis is 22mm, 10mm and 7mm for hormone receptors (HRs)+, HER2+ and triple-negative (TN) tumors respectively. Eighty-three percent of respondents consider that a HR+ pT1a,b tumor has a good prognosis (21% and 8% for HER2+ and TN respectively). Factors perceived as most detrimental are: HER2 overexpression (29% of respondents); HR- (20%); high grade (20%); TN status (14%); high KI67 (5%); presence of lymphovascular invasion (3%); young age (2%) and high mitotic index (1%). For French specialists, immunohistochemical characteristics, in particular hormone and HER2 status, are strong prognostic factors in BCs below 1cm.

Breast cancer with synchronous metastases: trends in survival during a 14-year period.

PURPOSE: Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. PATIENTS AND METHODS: A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by chi(2) test, log-rank test, and Cox regression analysis. RESULTS: Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P <.001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P <.001). CONCLUSION: The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.

Dermal lymphatic emboli in inflammatory and noninflammatory breast cancer: a French-Tunisian joint study in 337 patients.

BACKGROUND: We studied whether dermal lymphatic emboli (DLE) add independent prognostic information to the clinical definition of inflammatory breast cancer (IBC). PATIENTS AND METHODS: The study was performed in 2 centers, one each in France and Tunisia. For every patient with IBC, 1-3 patients with noninflammatory breast cancer (non-IBC) were included. All patients were to have a surgical tumor biopsy, including a sample of the skin surrounding the tumor. The endpoint was the risk of a relapse at 2 years, which was estimated using univariate and multivariate Cox models. RESULTS: Three hundred thirty-seven patients were included (150 in France and 187 in Tunisia). The IBC status was divided into 2 clinical categories according to the extent of inflammation in the breast (localized IBC, which was defined as clinical inflammation in the tumor area, vs. diffuse IBC, which was defined as inflammation of at least two thirds of the breast). In total, 57 patients presented with localized IBC, 71 with diffuse IBC, and 209 with non-IBC. Dermal lymphatic emboli were found in 7% of non-IBC cases, in 25% of localized IBC cases, and in 45% of diffuse IBC cases. We found a significant interaction between the presence of DLE and diffuse IBC (P = 0.01). In patients with diffuse IBC, the presence of DLE increased the risk of relapse 3-fold. Conversely, DLE were not associated with the risk of relapse in patients with non-IBC, nor in patients with localized IBC. In patients with diffuse IBC and no DLE, the risk of relapse was similar to that of patients with localized IBC. CONCLUSION: A DLE status might be a useful prognostic indicator exclusively in patients with diffuse IBC. However, because all patients with localized and diffuse IBC generally receive similar types of treatment, additional information on the presence or absence of DLE will not have an impact on treatment practice.

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer.

In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B(+) puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B(+) puncta reflects increased autophagic flux. After setting optimal thresholds in the test cohort, cytoplasmic LC3B(+) puncta and nuclear HMGB1 were scored as positive in 27.2% and 28.6% of the tumors, respectively, in the validation cohort, while 8.7% were considered as double positive. LC3B(+) puncta or HMGB1 expression alone did not constitute independent prognostic factors for metastasis-free survival (MFS) in multivariate analyses. However, the combined positivity for LC3B(+) puncta and nuclear HMGB1 constituted an independent prognostic factor significantly associated with prolonged MFS (hazard ratio: 0.49 95% confidence interval [0.26-0.89]; P = 0.02), and improved breast cancer specific survival (hazard ratio: 0.21 95% confidence interval [0.05-0.85]; P = 0.029). Subgroup analyses revealed that within patients with poor-prognosis BC, HMGB1(+) LC3B(+) double-positive tumors had a better prognosis than BC that lacked one or both of these markers. Altogether, these results suggest that the combined positivity for LC3B(+) puncta and nuclear HMGB1 is a positive predictor for longer BC survival.