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Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), after NAC, is aimed to select patient who should be safely spared of an axillary lymphadenectomy (ALND).GANEA 2 is a French prospective multi institutional trial, aimed to assess SLND after NAC. Objective To assess the risk of relapse for patients without previous axillary node involvement treated with NAC followed with a SLND without a systematic lymphadenectomy. Patients and Method Inclusion: FIGO stage T1-T3 infiltrating breast carcinoma, indication of NAC. Exclusion: inflammatory cancer, local relapse, contra-indication to NAC, NAC interrupted due to progressive disease. Design: indication to plan a NAC, axillary sonography with fine needle cytology before NAC to select patients without lymph node involvement, SLND after NAC. ALND was mandatory in case of SLN involvement (macro or micro-metastasis) or SLND failure. Follow-up was scheduled with a medical visit / 6 months with axillary assessment and a mammography each year. Follow-up results are updated every 6 months. Pathological analysis were carried out according to standard methods and classified according to the last American Joint Committee staging system. Studied parameters were SLND detection rate, pathological results on breast specimen and nodes, rate of relapse (axilla, breast, metastasis), and survival. Results From July 2010 to February 2014, 587 patients were enrolled, from 17 institutions, and experienced breast tumor surgery and a SLND after NAC. Each patient experienced breast surgery. A breast tumour pathological complete response was found in 21.3% (125/587). SLND rate was 97% (570/587), with a median number of 2 sentinel nodes (1-9). Patients with a sentinel detection failure (n=17) experienced a systematic lymphadenectomy, without any involvement (n=13), a micro-metastasis (n=2) and a macro-metastasis (n=2). A total of 140 patients had at least one sentinel node involved: macro-metastasis (n=86), micro-metastasis (n=54). A lymphadenectomy was performed in 128 cases: metastasis free (n=100), macro-metastasis (n=17), micro-metastasis (n=11). A total of 430 patients had a SLN metastasis free (75% ;430/570). A not mandatory lymphadenectomy was performed (n=14): metastasis free (n=11), macro-metastasis (n=2) and micro-metastasis (n=1). 17 patients were lost to follow-up. A total of 399 patients without sentinel node involvement were followed 2.3 years (from 0.5 to 5.6 yrs). At 3 years overall survival was 97.8% [94.9-99.1], disease free survival was 94.8% [91.0-97.1%]. Six patients died. Fifteen patients experienced a relapse: 8 metastasis, 4 homolateral breast, 2 controlateral breast, 1 homolateral axillary relapse. Conclusion This is the most important series of patients followed 2.3 years after SLND without axillary lymphadenectomy after NAC for an advanced breast cancer, showing acceptable results. The current series validate the safety of this conservative strategies avoiding systematic lymphadenectomy to patients without initially involved axillary node treated with NAC. Citation Format: Classe J-M, Loaec C, Alran S, Paillocher N, Tunon-Lara C, Gimbergues P, Faure-Virelizier C, Chauvet M-P, Lasry S, Dupre P-F, Verhaeghe J-L, De Blaye P, Gutowski M, Barranger E, Lecuru F, Lefevre Lacoeuille C, Loussert L, Lambaudie E, Ferron G, Campion L. Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S2-07.

Two thirds of node-positive breast cancer patients have limited pN1 disease and could benefit from a less extensive axillary lymph node dissection (ALND).172 breast cancers patients requiring an ALND were prospectively enrolled in the Sentibras Protocol of Axillary Reverse Mapping (ARM). Radioisotope was injected in the ipsilateral hand the day before surgery. ALND was standard. Removed lymph nodes were classified into non radioactive nodes and radioactive nodes (ARM nodes). Among ARM nodes, nodes located in the upper outer part of the axilla, above the second intercostal brachial nerve and lateral to the lateral thoracic vein were identified as "zone D ARM nodes". The main objective was: feasibility of identification of the zone D ARM nodes. Secondary objectives were: metastatic involvement and lymphedema rate.100% of patients had ARM nodes identified. The "zone D ARM nodes" were identified in 92% of cases. The rate of metastatic nodes was 60% in the all cohort, 31% in ARM nodes and 9% in zone D ARM nodes. Among those, metastatic rate was 6% in patients undergoing ALND for a positive sentinel node biopsy, 6% in case of primary ALND versus 14% after neo-adjuvant chemotherapy (p 0.05). After 34 months of median follow up, 27% of interviewed patients had a lymphedema.The ARM technique reliably identifies the "zone D ARM nodes". These nodes can also easily be identified using knowledge of axillary anatomy. In selected patients, a selective ALND sparing the zone D ARM nodes could be performed.

Background: The risk for developing breast cancer before the age of 40 is less than 1% and is similar worldwide. Breast cancer in young women is different from that of older women in terms of clinical and pathological characteristics and prognosis. We reviewed the evolution of breast cancer in young women aged < 40 years between 1980 and 2008 in the large database of the René Huguenin Hospital in France. Patients and Methods: Women diagnosed with a first breast cancer were prospectively included in the institution database. The analysis population included all women treated and followed between 1980 and 2008 for new breast cancer. The data were grouped into three periods: 1980-1990 (systematic pre-screening), 1991-2003 (first pilot screening experiences) and 2004-2008 (generalized systematic screening) and per age group comparing women Results: From 1980-2008, there were 20838 new breast cancers diagnosed, including 1431 (6.9%) in women Conclusion: Results of the retrospective analysis of a very large cohort of women less than 40 years diagnosed with breast cancer show that woman Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-19.

BACKGROUND: A prognostic index, the MD Anderson Prognostic Index (MDAPI), has been developed to help refine selection criteria for breast-conserving therapy after neoadjuvant chemotherapy. This score is based on initial nodal status N2/3, residual pathologic tumor size>2cm, a multifocal pattern of residual disease, and lymphovascular space invasion and ranged from 0 to 4. The objective of the current study was to validate the MDAPI for ipsilateral breast tumor recurrence. METHODS: Our study was a single-center retrospective analysis of a large prospectively collected breast cancer database. We identified data from 355 patients who received neoadjuvant chemotherapy and underwent breast-conserving therapy between 2002 and 2010. Predictive factors of ipsilateral breast tumor recurrence and the usefulness of the MDAPI were analyzed. Discrimitaion of models was also calculated. RESULTS: The median follow-up was 65 months, and the 5-year ipsilateral breast tumor recurrence-free survival rate was 90.7%. 5-year IBTR-free survival were 91.3% and 87.4% in MDAPI 0/1 and MDAPI 2+ categories (p = 0.07). (Multivariate analysis demonstrated that MDAPI (p = 0.01), Ki67 (p = 0.0004) and HER2 status (p = 0.0006) were associated significantly with ipsilateral breast tumor recurrence-free survival. Concordance index of the MDAPI was fair (0.6) but adding HER2 and ki67 status in the model improved concordance index : 0.75. CONCLUSIONS: The MDAPI was barely adaptable to the study patients in terms of predicting ipsilateral breast tumor recurrence. Biological factors such as ki67 and HER2 status should be included in the prognostic model. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-21.

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted.

Background: The major factor influencing the prognosis of cutaneous malignant melanoma (MMs) is the maximum thickness of the tumor as measured by Breslow's method. However, it has been reported that thin melanomas, which should have an excellent prognosis, may have the potential to metastasize, some with an unusually rapid course. Objective: Our purpose was to examine prognostic indicators in relation to unusually rapid aggressive behavior in patients with thin MMs ( Methods: We describe nine cases of thin MM ( Results: The particular aggressiveness of these thin melanomas was reflected by the short disease-free interval (3 years or less) in all nine patients. The recurring thin MM more frequently involved head and neck sites, occurred in male patients, and showed Clark's level III and IV. Conclusion: Our review suggests that the head and neck area is particularly involved by unusually rapidly recurring thin MM. Possible explanations are the specific problems of surgical management and the greater sun exposure of this location.

Background To evaluate whether predictive factors of axillary lymph node metastasis in female breast cancer (BC) are similar in male BC. Patients and methods From January 1994 to May 2011, we recorded 80 non-metastatic male BC treated at Institut Curie (IC). We analysed the calibration and discrimination performance of two nomograms [IC, Memorian Sloan-Kettering Cancer Center (MSKCC)] originally designed to predict axillary lymph node metastases in female BC. Results About 55% and 24% of the tumours were pT1 and pT4, respectively. Nearly 46% demonstrated axillary lymph node metastasis. About 99% were oestrogen receptor positive and 94% HER2 negative. Lymph node status was the only significant prognostic factor of overall survival (P = 0.012). The area under curve (AUC) of IC and MSKCC nomograms were 0.66 (95% CI 0.54–0.79) and 0.64 (95% CI 0.52–0.76), respectively. The calibration of these two models was inadequate. Conclusions Multi-variate models designed to predict axillary lymph node metastases for female BC were not effective in our male BC series. Our results may be explained by (i) small sample size (ii) different biological determinants influencing axillary metastasis in male BC compared with female BC.

Our objective was to assess the global cost of the sentinel lymph node detection [axillary sentinel lymph node detection (ASLND)] compared with standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for early breast cancer patients.We conducted a prospective, multi-institutional, observational, cost comparative analysis. Cost calculations were realized with the micro-costing method from the diagnosis until 1 month after the last surgery.Eight hundred and thirty nine patients were included in the ASLND group and 146 in the ALND group. The cost generated for a patient with an ASLND, with one preoperative scintigraphy, a combined method for sentinel node detection, an intraoperative pathological analysis without lymphadenectomy, was lower than the cost generated for a patient with lymphadenectomy [€ 2947 (σ = 580) versus € 3331 (σ = 902); P = 0.0001].ASLND, involving expensive techniques, was finally less expensive than ALND. The length of hospital stay was the cost driver of these procedures. The current observational study points the heterogeneous practices for this validated and largely diffused technique. Several technical choices have an impact on the cost of ASLND, as intraoperative analysis allowing to reduce rehospitalization rate for secondary lymphadenectomy or preoperative scintigraphy, suggesting possible savings on hospital resources.

Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), performed after NAC, must select patient who should be spared of an axillary lymph node dissection (ALND). The application of SLND for staging the axilla after NAC for patient who initially had a proven axillary lymph node involvement remains controversial because of a low detection rate (DR) and a high false negative rate (FNR). Objective The aim of GANEA 2 trial was to assess the DR and the FNR of SLND after NAC in the particular case of patients with a proven axillary lymph node involvement. Patients and Method GANEA 2 was validated by scientific and ethical national boards. Inclusion criteria: FIGO stage T2-T3 infiltrating breast carcinoma, indication of NAC, surgery (radical or conservative) after NAC and signed consent form, Exclusion criteria: inflammatory cancer, local relapse, previous surgical removal of the tumour, mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NAC interrupted due to progressive disease. Design: Diagnosis and indication to plan a NAC, control of inclusion and exclusion criteria, consent form signature, axillary sonography with fine needle cytology before NAC to select patients with a proven lymph node involvement. After NAC patients underwent both SLND, with the combined technique Blue dye and radiolabeled colloid, and complementary ALND. Pathological procedure: Pathological analysis, of sentinel and non sentinel nodes, carried out according to standard methods and classified according the last American Joint Committee staging system and Sataloff classification. Studied parameters were detection rate, false negative rate and Sataloff grading on tumor and lymph nodes. We evaluated particularly the likelihood that the FNR in patients with one or more SLN examined was greater than 10%. Patients with no lymph node involvement before NAC underwent only a SLND with an ALND only in the case of SLN macro-metastasis with a rigorous follow up. They are not part of this abstract. Results From July 2010, to February 2014, 242 patients from 19 institutions were enrolled, with a proven axillary lymph node involvement before NAC. After NAC, 1/3 had metastasis free axillary lymph node (80/142). Detection rate was 83.1% (201/242). Half of the patients with a detection failure had an involved ALND. The false negative rate was 14.2% in the whole series but 24.5% in the case of only 1 SLN resected, and 8% in case of more than 1 SLN resected. In case of involved SLN, half of the patients had involved ALND. Considering the node Sataloff scoring, 18 of the 20 false negative cases were grade C or D (n=15 grade C, metastatic disease and therapeutic effect; n = 3 grade D, metastasis and no therapeutic effect). Conclusion Among patients treated by NAC for a large operable breast cancer with proven involved lymph node before NAC, who had only 1 SLN examined, the false negative rate was 24.5%. SLND with the combined technique, provides a FNR of less than 10% only in the case of 2 or more SLN resected. Citation Format: Jean-Marc Classe, Loic Campion, Severine Alran, Christine Tunon de Lara, Pierre Francois Dupre, Christelle Faure, Nicolas Paillocher, Serge Lasry, Marie Pierre Chauvet, Gilles Houvenaeghel, Marian Gutowski, Pascaline De Blaye, Charlotte Ngo, Emmanuel Barranger, Jean Luc Veraeghe, Celine Lefebvre, Jean Francois Rodier, Virginie Bordes, Helene Charitansky, Gwenael Ferron, Pierre Gimbergues. Sentinel node surgery after neoadjuvant chemotherapy in patient with axillary node involvement: The French GANEA 2 prospective multi-institutional trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-01.

We compared the impact of neoadjuvant chemotherapy on pathologic response and outcome in operable invasive lobular breast carcinoma (ILC) and invasive ductal breast carcinoma (IDC).We extracted from our database all patients with pure invasive lobular (n=118, 14%) or pure invasive ductal carcinomas (n=742, 86%). Their treatment included neoadjuvant chemotherapy, adapted surgery, radiotherapy and adjuvant hormonal treatment.Compared with IDC, ILC presented with larger tumors (T3: 38.1% versus 21.4%, P=0.0007), more N0 nodes status (55.9% versus 43.3%, P=0.01), less inflammatory tumors (5.9% versus 11.8%, P=0.01), more hormone receptor positivity (65.5% versus 38.8%), lower histological grade (P0.0001). Final surgery was a mastectomy in 70% of patients with ILC (34% were reoperated after initial partial mastectomy) and in 52% of IDC after 8% of reoperation (P=0.006). A pathological complete response (pCR) was achieved in 1% of ILC and 9% of IDC (P=0.002). The outcome at 60 months was significantly better for ILC, but histologic type was not an independent factor for survival in multivariate analysis.ILC appeared less responsive to chemotherapy but presented a better outcome than IDC. While new information on biological features of ILC is needed, we consider that neoadjuvant endocrine therapy in hormone receptor-positive ILC may be a more adapted approach than neoadjuvant chemotherapy.

Tamoxifen has been used for two decades as adjuvant therapy for breast cancer. It is also now being used to try and prevent this disease in women at high risk. A series of 89 patients who developed endometrial cancer on adjuvant has been identified from nine French cancer institutes. Although there was a high frequency of superficial, generally well-differentiated forms, some patients did have aggressive disease with a relatively poor outcome and there were 10 deaths from endometrial carcinoma. These data support gynaecological surveillance of women receiving tamoxifen therapy.

Background: To evaluate whether predictive factors of axillary lymph node metastasis in female breast cancer (BC) are similar in male BC. Patients and methods: From January 1994 to May 2011, we recorded 80 non-metastatic male BC treated at Institut Curie. We analysed the calibration and discrimination performance of two nomograms (Institut Curie (IC), Memorian Sloan-Kettering Cancer Center (MSKCC)) originally designed to predict axillary lymph node metastases in female BC. Results: 55% and 24% of the tumours were pT1 and pT4 respectively. 46% demonstrated axillary lymph node metastasis. 99% were estrogen receptor positive and 94% HER2 negative. Lymph node status was the only significant prognostic factor of overall survival (p = 0.012). The area under curve (AUC) of IC and MSKCC nomograms were 0.66 (95%CI, 0.54–0.79) and 0.64 (95% CI, 0.52–0.76) respectively. The calibration of these two models was inadequate (Table 1). Conclusion: Multivariate models designed to predict axillary lymph node metastases for female BC weren't effective in our male BC series. Our results may be explained by a) small sample size b) different biological determinants influencing axillary metastasis in male BC compared to female BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-19.

To evaluate the possible involvement of obstructive sleep apnea (OSA) in retinal vein occlusion (RVO).From the medical records of 63 consecutive patients with RVO, 30 patients with 2 of the 3 following risk factors for OSA were selected for further screening from February 1, 2008, through March 31, 2009: associated cardiovascular disease, snoring, or daytime sleepiness.Of the 30 selected patients, 23 (77%) had OSA. If all 33 of the unscreened patients did not have OSA, the OSA prevalence would have been 37%. Among the patients with OSA, the mean apnea-hypopnea index (AHI) was 21; OSA was mild (AHI15) in 13 patients, moderate in 5 patients (AHI 15-30), and severe (AHI30) in 5 patients. The AHI was correlated with body mass index (P = .02).We found a higher than expected prevalence of OSA in a series of patients with RVO. Our findings suggest that OSA could be an additional risk factor that plays an important role in the pathogenesis of RVO or at least that it is a frequently associated condition that could be a triggering factor. This association may explain why most patients discover visual loss on awakening. It is too early to assess whether OSA treatment could improve visual outcome of RVO, but it seems vital to recognize OSA in RVO for the general health of the patient.

e11539 Background: The increased use of neoadjuvant chemotherapy (CT) in breast cancer (BC) management has raised new questions regarding the optimal locoregional treatment. The aim of this retrospective study was to compare the outcomes of BC patients (pts) with pathological N0 status (pN0) following primary CT and conservative surgery who received breast radiotherapy with or without lymph node irradiation. Methods: Between 1990 and 2004, 1054 patients received preoperative CT for locally advanced BC. Data from 248 pts (23.5%) with clinical N0 (164 pts) or N1-N2 (84 pts) lymph node status at diagnosis and pN0 status after primary CT were studied. Among them, 93 pts (37.5%) received breast irradiation alone and 155 pts (62.5%) underwent locoregional irradiation. Outcome was assessed in relation to lymph node recurrence, disease-free survival (DFS) and overall survival (OS). Results: Both groups were comparable in terms of baseline characteristics. With a median follow-up of 88 months, 3 pts experienced nodal recurrence in the breast irradiation alone group compared with 2 pts in the locoregional irradiation group (p>.05). Among the 164 N0 pN0 pts, the 5-year DFS and OS rates were respectively 84% and 89% vs 84% and 95%, according to whether they received (n=87) or not (n=77) lymph node irradiation(p>.05). Among the 84 N1-N2 pN0 pts, same outcome values did not show any significant difference according to group of treatment: 72% and 88% in 68 pts treated with locoregional irradiation vs 81% and 81% in 16 pts treated with breast irradiation alone (p>.05). Conclusions: Our results suggest that breast irradiation alone is not associated with a higher risk of regional recurrence in locally advanced BC pts with pN0 status after neoadjuvant chemotherapy. Whether this allows the omission of lymph node irradiation for such strategy should be addressed prospectively. No significant financial relationships to disclose.