Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer.

BACKGROUND: Chemokines and chemokine receptors are major actors of leukocytes trafficking and some have been shown to play an important role in cancer metastasis. Chemokines CCL19, CCL20 and CCL21 and their receptors CCR6 and CCR7, were assessed as potential biomarkers of metastatic dissemination in primary breast cancer. METHODS: Biomarker expression levels were evaluated using immunohistochemistry on paraffin-embedded tissue sections of breast cancer (n = 207). RESULTS: CCR6 was expressed by tumor cells in 35% of cases. CCR7 was expressed by spindle shaped stromal cells in 43% of cases but not by tumor cells in this series. CCL19 was the only chemokine found expressed in a significant number of breast cancers and was expressed by both tumor cells and dendritic cells (DC). CCR6, CCL19 and CCR7 expression correlated with histologic features of aggressive disease. CCR6 expression was associated with shorter relapse-free survival (RFS) in univariate and but not in multivariate analysis (p = 0.0316 and 0.055 respectively), and was not associated with shorter overall survival (OS). Expression of CCR7 was not significantly associated with shorter RFS or OS. The presence of CCL19-expressing DC was associated with shorter RFS in univariate and multivariate analysis (p = 0.042 and 0.020 respectively) but not with shorter OS. CONCLUSION: These results suggest a contribution of CCR6 expression on tumor cells and CCL19-expressing DC in breast cancer dissemination. In our series, unlike what was previously published, CCR7 was exclusively expressed on stromal cells and was not associated with survival.

Shared decision-making in the physician-patient encounter in France: a general overview.

In France, patients' claim for information and participation to medical decision-making was initiated in the eighties by AIDS associations, then reinforced by the tainted blood scandal and more recently by demands from cancer patients. The right to patient information was recognised on March 4th 2002 by the law pertaining to patients' rights and the quality of the healthcare system. The present article will explore this background by examining the bases, the current status and the development of shared decision-making in the physician-patient encounter in France. We will describe the evolution of the physician-patient relationship on the basis of legal and administrative documents, then show that patients' information, and more generally healthcare users' information, is a central concern for some national health institutions. Finally, we will demonstrate that even if the literature on shared decision-making is little developed in France as compared to other European countries, Northern America and Australia, some studies have nonetheless been conducted. Their results, combined with a legal context and national health institutions encouraging shared decision-making, should prompt otherwise reluctant healthcare professionals to implement this approach in everyday medical practice.

Cancer patients who experienced diagnostic genetic testing for cancer susceptibility: reactions and behavior after the disclosure of a positive test result.

The aim of this prospective study was to evaluate the consequences of the disclosure of a positive genetic test result to patients affected with cancer. Personal repercussions and patients' behavior with the transmission of their results to relatives were considered. We conducted semistructured interviews with 23 cancer patients identified as carriers of a cancer-predisposing mutation for hereditary breast ovarian or nonpolyposis colorectal cancers, 1 month after the disclosure of the test result. Eight patients spontaneously expressed distressed reactions ("you no longer feel cured"), and 14 patients reported at least one negative feeling (dissatisfied, discouraged, unhappy, or worried), despite expecting to be a carrier. Sixteen patients expressed concerns about the risk of developing another cancer, and 18 were concerned for their children's future, in that they may carry the mutation and develop a cancer. Although 8 patients found that disadvantages of knowing their genetic status outweighed the advantages, all but 1 did not regret having undergone genetic testing. All of the patients transmitted their results to at least one close relative. Although 6 of them expressed difficulties in being the only person who could transmit the information and 9 said it was a heavy responsibility, all except 1 did not want someone else to have to inform their families. Our results illustrate the potential negative impact of diagnostic genetic testing in patients with cancer. This includes distressed reactions and difficulties in transmitting their results to relatives. Future large-scale studies are warranted to confirm our findings.

Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience.

PURPOSE: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. METHODS AND MATERIALS: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. RESULTS: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p <0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged < or =40, 41-60, and > or =61 years (p <0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p = 0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p <0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p <0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p = 0.00012 and p = 0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group was 0.35 (95% CI 0.25-0.51, p = 0.0001). Subsequent contralateral breast cancer occurred in 7.1% and 7.5% of the patients in the CS+RT and CS groups, respectively. CONCLUSION: Despite the absence of randomization, our results are extremely consistent with the updated National Surgical Adjuvant Breast Project B17 and European Organization for Research and Treatment of Cancer 10853 trials. We also noted that the LR risk was very high in women <40 years and/or in the case of incomplete excision.

[Adjuvant treatments in breast cancer: interest of completion of axillary dissection in case of micrometastases or isolated tumor cells in sentinel lymph node]. / Traitements adjuvants dans le cancer du sein : impact du résultat du curage axillaire en cas de micrométastase ou de cellules tumorales isolées dans le ganglion sentinelle.

Prognostic signification of micrometastases ou isolated tumor cells (ITC) has not yet been clearly precised. Management of the axilla in case of micrometastases or ITC depends on the local pratices: no surgical completion or axillary lymph node dissection (ALND). Axillary lymph node status is the most important prognostic factor in patients with breast cancer; morbidity of ALND is now well known whereas its therapeutic benefit has not been demonstrated. This study is based on a retrospective database of 1375 patients who underwent sentinel node (SN) biopsy for breast cancer. In case of micrometastase or ITC in SN with completion axillary dissection, we examined if non-sentinel lymph node status has changed the indications of adjuvant treatments (chimiotherapy or radiotherapy). The results of our study show that non-sentinel lymph node status modify systemic therapy for a very few patients (less than 4% concerning chimiotherapy and less than 15% concerning radiotherapy).

Multidisciplinarity and medical decision, impact for patients with cancer: sociological assessment of two tumour committees' organization.

PURPOSE: Medical practices in oncology are expected to be multidisciplinary, yet few articles studied how this may be concretely applied. In the present study, we evaluated the organization of two multidisciplinary committees, one for breast cancer and one for sarcoma, in a French Comprehensive Cancer Centre. METHODS: Both tumours were specifically chosen so as to emphasise substantial differences in relation with incidence, histological subtypes, management strategy, and scientific evidence. Between 2003 and 2004, 404 decision processes were observed, 210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number of physicians who took part in the discussions and their medical specialties were systematically noted as well as the number of contradictory discussions, medical specialties represented in these contradictory discussions and the topics of contradiction. The last measured data was whether the final committee's decision was in conformity with the referent preferences or not. All these measures were related to the referent's medical speciality and working place, to the stage of the disease and to the disease management stage. RESULTS: Committees' specificities concerned their organization, referent's medical specialties, the number of participants in discussions and their medical specialties. Discussions in the sarcoma committee tended to be more multidisciplinary, involving more specialties. Initial strategy proposal for one patient was modified during the discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%) respectively for sarcoma and breast cancer. However, there was no significant difference in the rate of contradictory discussions between breast cancer and sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of contradictory discussions were similar for localized cancers, local relapse and metastasis disease (37%, 41% and 34% respectively; P = 0.86). CONCLUSIONS: The present study reports more than 30% of changes concerning strategy for patient with cancer due to multidisciplinary discussions. This indicates that, providing tumour committees are adapted to the pathologies' characteristics, they can promote a collective and multidisciplinary approach to oncology.

Non sentinel node involvement prediction for sentinel node micrometastases in breast cancer: nomogram validation and comparison with other models.

PURPOSE: The risk of non sentinel node (NSN) involvement varies in function of the characteristics of sentinel nodes (SN) and primary tumor. Our aim was to determine and validate a statistical tool (a nomogram) able to predict the risk of NSN involvement in case of SN micro or sub-micrometastasis of breast cancer. We have compared this monogram with other models described in the literature. METHODS: We have collected data on 905 patients, then 484 other patients, to build and validate the nomogram and compare it with other published scores and nomograms. RESULTS: Multivariate analysis conducted on the data of the first cohort allowed us to define a nomogram based on 5 criteria: the method of SN detection (immunohistochemistry or by standard coloration with HES); the ratio of positive SN out of total removed SN; the pathologic size of the tumor; the histological type; and the presence (or not) of lympho-vascular invasion. The nomogram developed here is the only one dedicated to micrometastasis and developed on the basis of two large cohorts. The results of this statistical tool in the calculation of the risk of NSN involvement is similar to those of the MSKCC (the similarly more effective nomogram according to the literature), with a lower rate of false negatives. CONCLUSION: this nomogram is dedicated specifically to cases of SN involvement by metastasis lower or equal to 2 mm. It could be used in clinical practice in the way to omit ALND when the risk of NSN involvement is low.

Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: results of Ganglion Sentinelle et Chimiotherapie Neoadjuvante, a French prospective multicentric study.

PURPOSE: To determine the detection rate, the false-negative rate, and the accuracy of sentinel lymph node (SLN) detection after neoadjuvant chemotherapy (NAC) for advanced breast cancer. PATIENTS AND METHODS: A prospective multicentric study was initiated to evaluate the results of SLN biopsy with the combined method after NAC for advanced large operable breast cancer. RESULTS: From September 2003 to March 2007, 195 patients enrolled from 12 institutions were found suitable for evaluation. The detection rate was 90% (176 of 195 patients), and the false-negative rate was 11.5% (six of 52 patients). Patients without axillary palpable nodes (N0) before NAC had a better detection rate compared with patients with axillary suspicious nodes (N1, 94.6% v 81.5%; P = .008). The false-negative rate was not correlated with clinical nodal status before NAC (9.4% v 15%; P = .66). CONCLUSION: This study confirms the feasibility of SLN biopsy after NAC in the case of large operable breast cancer. The detection rate, false-negative rate, and accuracy do not differ from those obtained in the case of early breast cancer without NAC, thus demonstrating the feasibility of SLN biopsy after NAC.

Is surgical biopsy mandatory in case of atypical ductal hyperplasia on 11-gauge core needle biopsy? A retrospective study of 300 patients.

BACKGROUND: Atypical ductal hyperplasia (ADH) is diagnosed in 4% to 10% of directional vacuum-assisted stereotactic biopsies (DVABs) performed for microcalcifications. Since the underestimation rate varies from 7% to 36%, surgical excision is still recommended, although some authors have tried to identify a subset of patients who can be spared surgery. METHODS AND RESULTS: In this study, we analyzed a retrospective series of 300 patients with ADH on 11-gauge DVAB. The only 4 events that occurred (3%) in 135 of 184 patients (61%) who were followed may not be due to underestimation. Comparing the diagnoses on DVAB and surgical excisions for 116 patients (39%), we identified 3 subsets of patients: no underestimation (size <6 mm and complete removal), low rate of 4% (< or =2 foci ADH in microcalcifications either <6 mm with incomplete removal or > or =6 mm and <21 mm), and high rate of 36% to 38% (>2 foci ADH in microcalcifications either <6 mm with incomplete removal or > or =6 mm and <21 mm, lesion size > or =21 mm). CONCLUSIONS: Our results suggest that strict follow-up can be a safe option for the first 2 groups of patients, but that surgical excision is mandatory for patients from the third group.

Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort and review.

PURPOSE: The debate concerning poorer survival for patients with breast cancer (BC) carrying a BRCA1 germline mutation is unresolved, and requires additional data from population-based studies. PATIENTS AND METHODS: We followed 232 women with invasive BC under age 46, ascertained prospectively through a French population-based BC registry and tested for BRCA1/2 mutations (median follow-up: 82 months). We compared tumour characteristics and survival rates between 21 BRCA1/2 deleterious mutation carriers and 211 non-carriers. RESULTS: As compared to sporadic tumours, BRCA1/2 tumours showed higher grade (P = 0.02), fewer ductal carcinoma in situ (P = 0.02), more frequent medullary histology (P = 0.02), more frequent negative oestrogen and progesterone receptors (P = 0.001 each). At 5 years, BC-specific survival, metastasis-free survival, ipsilateral recurrence-free survival and contralateral BC-free survival rates for BRCA1/2 mutation carriers were 95.0%, 94.7%, 100% and 90.0% respectively, compared with 89.6%, 78.2%, 88.8% and 94.4% respectively, for non-carriers (not significant). Rates for women carrying only a BRCA1 mutation were 93.3%, 93.3%, 100%, 86.7%, respectively. 76% of BRCA1/2 carriers received chemotherapy. CONCLUSION: Despite unfavourable tumour features, we found no evidence for poorer short-term survival in BRCA1 mutation carriers compared to non-carriers in this prospective population-based cohort. The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours.

Prospective multicentric randomized study comparing periareolar and peritumoral injection of radiotracer and blue dye for the detection of sentinel lymph node in breast sparing procedures: FRANSENODE trial.

PURPOSE: To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer. PATIENTS AND METHODS: A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients. RESULTS: The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001). CONCLUSION: This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.

[Neoadjuvant chemotherapy and ovarian cancer]. / Chimiothérapie néoadjuvante et cancer de l'ovaire.

Primary surgical cytoreduction followed by chemotherapy usually is the preferred management of advanced (stage III or IV) ovarian cancer. The presence of residual disease after surgery is one of the most important adverse prognostic factors for survival. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of improving surgical quality. Retrospective analyses suggest that a subgroup of patients with Stage III and IV ovarian carcinoma can be treated with neoadjuvant chemotherapy followed by interval debulking surgery. The absolute indications for neoadjuvant chemotherapy appear to be Stage IV disease (excluding pleural fluid) or metastases of more than 1 g at sites where resection is impossible. Interval debulking surgery in patients with suboptimal primary debulking surgery has been proven effective in increasing overall survival and progression-free survival in a large prospective, randomized trial of the European Organization for Research and Treatment of Cancer (EORTC). GOG evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy. Unfortunately in this study, for patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal, the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival. The strategy of neoadjuvant chemotherapy, followed by interval debulking surgery, should be confirmed in a prospective randomized trial. The EORTC55971 trial is currently addressing this issue.

Micrometastases in sentinel lymph node in a multicentric study: predictive factors of nonsentinel lymph node involvement--Groupe des Chirurgiens de la Federation des Centres de Lutte Contre le Cancer.

PURPOSE: To determine the rate of nonsentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) and predictive factors of this involvement following detection of micrometastasis in sentinel nodes (SN). METHODS: We analyzed 700 observations of SN micrometastases with additional ALND with the characteristics of the patients, tumors, and SN. RESULTS: Involvement of SN was diagnosed 388 times by serial sections (55.4%) with standard hemoxylin and eosin staining (HES) and 312 times solely on immunohistochemical analysis (IHC; 44.6%). The accurate size of the micrometastases was indicated in 488 cases: 301 larger than 0.2 mm (61.7%) and 187 < or = 0.2 mm (38.3%). Ninety-four patients (13.4%) presented an NSN involvement with only one NSN involved in 62 cases (66%). Predictive factors of NSN involvement were in univariate analysis (pT stage [P < .000], menopausal status [P = .048], T stage [P = .006], grade [P = .013], lymphovascular invasion [LVI; P = .013], histologic tumor type [P = .017], and method of micrometastasis detection, by HES or IHC [P = .015]) and in multivariate analysis (pT stage < or = or > 20 mm [odds ratio, 2.54], micrometastases detected by HES or IHC [odds ratio,1.734], presence or absence of LVI [odds ratio, 1.706]). Micrometastasis size < or = or greater than 0.2 mm was not predictive. CONCLUSION: This study confirms the value of serial sections and the vital role played by IHC in screening for small micrometastases. Omission of additional ALND may be envisaged with minimal risk for pT1a and pT1b tumors, and pT1a-b-c tumors corresponding to tubular, colloidal, or medullar cancers.

Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France.

The prevalence of BRCA1/2 germ-line mutations was assessed in a prospective population-based series of early-onset breast cancer (BC) patients in France, and the usefulness of a clinical assessment of hereditary BC risk, based on multiple criteria including pedigree structure, was evaluated. Through the Rhone region BC registry, 232 women diagnosed with BC before 46 years of age were included. They were tested for BRCA1/2 mutations an average of 10 months after diagnosis. All the women were classified according to their family history of cancer: high risk of hereditary breast cancer (HBC), low risk of HBC, isolated BC, and unknown HBC risk. Deleterious mutations were observed in 21 women (9.1%): 15 (6.5%) BRCA1 and 6 (2.6%) BRCA2. Mutations were more prevalent in women who developed BC before age 41 than in women who developed BC between ages 41 and 45 (12.8% versus 5.2%, respectively, P = 0.04). A high prevalence of BRCA1/2 mutations was found among women in the high-risk category with particular family features (i.e., small family size, predominantly male pedigree, specific cancers; 23.5%) and among women with isolated BC before age 41 and with five or fewer close adult female relatives (16.6%). According to the 10% probability level recommended by the American Society of Clinical Oncology guidelines for genetic testing of cancer, BRCA1/2 mutation screening should be considered for all women diagnosed before age 41, except for those with isolated BC in a large pedigree including multiple unaffected female relatives. The clinical assessment of HBC risk that we have developed should help in the decision to perform genetic testing.

Cost comparison of two surgical strategies in the treatment of breast cancer: sentinel lymph node biopsy versus axillary lymph node dissection.

OBJECTIVES: The feasibility and accuracy of sentinel lymph node biopsy (SLNB) in the treatment of breast cancer is widely acknowledged today. The aim of our study was to compare the hospital-related costs of this strategy with those of conventional axillary lymph node dissection (ALND). METHODS: A retrospective study was carried out to determine the total direct medical costs for each of the two medical strategies. Two patient samples (n = 43 for ALND; n = 48 for SLNB) were selected at random among breast cancer patients at the Centre Leon Bérard, a comprehensive cancer treatment center in Lyon, France. Costs related to ALND carried out after SLNB (either immediately or at a later date) were included in SLNB costs (n = 18 of 48 patients). RESULTS: Total direct medical costs were significantly different in the two groups (median 1965.86 Euro versus 1429.93 Euro, p = 0.0076, Mann-Whitney U-test). The total cost for SLNB decreased even further for patients who underwent SLNB alone (median, 1,301Euro). Despite the high cost of anatomic pathology examinations and nuclear medicine (both favorable to ALND), the difference in direct medical costs for the two strategies was primarily due to the length of hospitalization, which differs significantly depending on the technique used (9-day median for ALND versus 3 days for SLNB, p < 0.0001). CONCLUSIONS: A lower morbidity rate is favorable to the generalization of SLNB, when the patient's clinical state allows for it. From an economic point of view, SLNB also seems to be preferred, particularly because our results confirm those found in two published studies concerning the cost of SLNB.

Elaborating patient information with patients themselves: lessons from a cancer treatment focus group.

OBJECTIVE: To assess the significance of patients' input in the elaboration of a patient information booklet. DESIGN: Qualitative study based on focus group discussions. SETTING: Centre Léon Bérard, a comprehensive cancer centre in the Rhône-Alpes region of France. PARTICIPANTS: (1) A multidisciplinary working group (oncologists, health economists and one clinical psychologist) wrote up initial information documents concerning possible breast cancer treatments. (2) A focus group comprised of patients with a history of breast cancer and healthy volunteers discussed their reactions to these documents. MAIN OUTCOME MEASURE: Analysis of the focus group's reactions according to key themes predetermined by the working group and related themes introduced by the focus group itself. RESULTS: The focus group proposed numerous, significant modifications to answer requests for additional information, clarification and better readability in the information booklets. DISCUSSION/CONCLUSIONS: This qualitative analysis showed a significant input of patients' perspective in the elaboration of patient information. It is also an additional support to the feasibility and appropriateness of the focus group technique. The next stage will be to test whether information documents produced here conform to the needs of patients currently undergoing treatment.