4089 Background: Overexpression of HER2 is an important biomarker in gastroesophageal junction (GEJ) and gastric cancer (GC) and a predictive factor for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit in overall survival of adding trastuzumab to chemotherapy inHER2-positive advanced GEJ/GC patients, following validated scoring criteria by a central laboratory. This study examines the incidence of HER2 positivity (local laboratories) in GEJ/GC according to EMA Herceptin label. Methods: HER-EAGLE was an epidemiological, non–interventional, international study assessing HER2 status by IHC/ISH in tumor samples from any stage GEJ/GC patients. Neutral buffered 10% formalin embedded tissues (surgical excision specimens or minimum 6-8 biopsies) analyzed via validated Ventana and Dako methods and scoring criteria used in ToGA: HER2-positive if IHC 3+ or IHC 2+ (FISH/SISH confirmed; HER2/CEP17 ratio ≥ 2.0); HER2-negative if IHC 0 or IHC 1+. Overall and subgroup estimates calculated with 95%CI. Data from the Spanish cohort are presented. Results: The Spanish cohort of HER-EAGLE included 1,954 participants (63.7% males) from 33 hospitals (Dec2010 to Aug2011), with 469 biopsies (24.0%) and 1,479 excisions (75.7%). Samples were 13.7% GEJ and 86.3% GC, and the adenocarcinomas were 1,137 intestinal (58.2%), 510 diffused (26.1%), 163 mixed (8.3%; Laureen classification), and 144 not available (7.3%). Median time from sampling to HER2 analysis of 5.1 years (range from days to 12 years). Total of 210 cases tested IHC 3+ (10.7%), 215 IHC 2+ (11.0%), 308 IHC 1+ (15.8%), and 1,221 IHC 0 (62.5%). Overall, HER2 positivity (IHC 3+ or IHC2+/ISH+) was 14.1% (95%CI 12.61 – 15.75). HER2 positivity by histological type was higher in intestinal adenocarcinomas (19.5%) compared to diffused (4.5%) or in mixed (9.2%). Conclusions: HER-EAGLE confirmed the feasibility of community based HER2 testing in GC as the first study with a high number of samples analyzed by local laboratories. The incidence of HER2-positivity (EMA label definition) was similar to the ToGA screening population, and it was again higher in adenocarcinomas of intestinal type (19.5%).
Evidence on relative treatment effects concerning OS, progression-free survival (PFS) and discontinuation due to any reason (treatment persistence) and adverse events (tolerability) was estimated using a mixed treatment comparison following a systematic review of randomized clinical trials enrolling post-menopausal women with hormone-sensitive ABC. Health service costs were included and a lifetime perspective adopted (5% annual discount rate). Results: Everolimus+exemestane is estimated to significantly delay progression or death (HR PFS = 0.53; 95% CI: [0.37; 0.76]) and to increment life expectancy by 6.8 months in comparison to fulvestrant (HR OS = 0.82; 95% CI: [0.50; 1.36]), resulting in a 0.45 discounted life year (LY) gain. Corresponding incremental health service costs amount to 16,544€ /patient starting everolimus+exemestane. This results in an incremental cost-effectiveness ratio of 36,703€ /LY gained with everolimus+exemestane. Probabilistic sensitivity analysis showed a greater than 60% probability of everolimus+exemestane being costeffective against fulvestrant, at a willingness to pay of 50,000€ /LY. ConClusions: We evidence how valuable information from clinical trials can be pooled and used to inform about the therapeutic and economic value of guideline recommended therapies for advanced breast cancer.
BACKGROUND: Factors by which breast cancer cells invade blood and lymphatic capillaries and metastasize regional lymph nodes and distant sites are not well understood. Genetics, molecular subtype, epidemiological, mechanical and pathological factors are being considered. Once breast cancer cells invade lymphatic or blood vessels the route of spread is still unclear. Cells could access the systemic circulation through the sentinel lymph node or directly avoiding the lymph node step. Molecular subtype is one of the most important factors associated with the risk of metastases. Our objective is to determine the influence of immunophenotype and the sentinel lymph node (SLN) status to predict the risk of locoregional relapses and distant metastases in early breast cancer. In our center we are using a molecular technique (OSNA) to ascertain if there is sentinel lymph node involvement, this technique creates a new continuous variable, Total Tumor Load (TTL), defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL), indicating the total tumor volume of axillary tumor involvement. METHODS: Clinicopathological and follow up data were obtained from all patients with early breast cancer treated with Tumorectomy (Tx) and Sentinel Lymph Node (SLN) assessed by OSNA with the decision to proceed to ALND based on Z0011 criteria and systemic therapy between 2011 and 2018 at our center (J Clin Oncol 37, 2019 (suppl; abstr 564)) RESULTS: 304 breast cancer patients underwent Tx and SLN assessed by OSNA followed by systemic therapy with an average follow-up of 64.9 months. SLN was positive in 122 cases and negative in 182. SLN negative patients were Luminal A (LA) 58%, Luminal B (LB) 14%, HER2 10% and Triple-Negative (TN) 7%. SLN positive patients were LA 52%, LB 35%, HER2 7% and TN 5%. Mean TTL was 136,244 copies (see table). As of now, 11 patients have had recurrence (locoregional relapse and distant disease): 6 of them with positive SLN (54,54%) and 5 with negative SLN (45,45%). A total of 4 patients have had locoregional relapse, two of them with negative SLN (50%) both non luminal tumors (1 HER2, 1 TN), and 7 have had distant disease, three of them with negative SLN (43%). Only one patient has died from metastatic breast cancer (HER2 positive, SLN negative). CONCLUSIONS: 1. In our series, almost half of the patients (45%) with recurrence were negative SLN. 2. The probability of recurrence when the sentinel lymph node is negative is higher in HER2 and TN tumors (60%). 3. The probability of recurrence when the SLN is positive is higher in luminal tumors (66,6%). 4. Luminal tumors with positive SLN and large volume axillary involvement (median 1.419.450 copies) have a higher probability of recurrence (statistically significant) than luminal tumors with positive SLN and small volume axillary involvement (median 131.479 copies). PATIENTS AND OUTCOMES VARIABLE N=304Number of cases (n,%)Median age, range (years)LOCOREGIONAL RELAPSEMETASTASIC BREAST CANCEREXITUSMean TTL with NO recurrenceMean TTL with recurrencePOSITIVE SLN122 (40%)59,8 (33-87)2 (1,63%)4 (3,27%)0By ImmunophenotypeLuminal A64 (52,4%)59,3 (36-87)1 (1,5%)2 (3,1%)0371.5592.838.333Luminal B43 (35,2%)59,5 (36-84)1 (2,32%)00258.6221600HER29 (7,3%)61 (33-80)01 (11,1%)021.582640Triple Negative6 (5%)59,6 (50-80)01 (16,6%)0108.181184.000NEGATIVE SLN182 (60%)59,3 (27-89)2 (1,09%)3 (1,64%)1 (0,5%)By ImmunophenotypeLuminal A106 (58%)59,3 (33-82)000Luminal B43 (14,1%)59,5 (36-89)1 (2,32%)1 (2,32%)0HER219 (10,4%)59,3 (40-82)01 (5,2%)1 (5,2%)Triple Negative14 (7,7%)59,4 (27-85)1 (7,14%)1 (7,14%)0 Citation Format: José Enrique Alés-Martínez, Raquel Tur, Juan Parra, Ana De Castro, Jaime Ceballos, Rocío Martín, Rosa Ana Marcos, Paz Blanco, MJose Velasco. Cancer phenotype is the key factor in axillary involvement and distant recurrence in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-03.
564 Background: The study of sentinel lymph nodes (SLN) assessed by One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) creates a new variable, Total Tumor Load (TTL). This variable is defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL). The latest edition of the Spanish Oncological Gynecology Society (SEGO) Guideline (2017) proposes a complete axillary lymph node dissection (ALND) when TTL is 15,000 copies or more in early breast cancer. In our center we are using OSNA to ascertain if there is axillary node involvement but the decision to proceed to ALND is based on Z0011 criteria. We want to determine if there is a correlation between clinical outcomes and TTL values, between TTL and pathological variables and if TTL is a useful tool to decide when to complete an ALND. Methods: Clinicopathological and follow up data were obtained from all patients with invasive breast cancer and SLN assessed by OSNA between 2011 and 2017 at our center. Results: A total of 321 patients underwent SNB assessed by OSNA with an average follow-up of 56 months. 320 were female and 1 male. Age range 27-89 years (mean 58.9). 85 % were ductal, 10 % lobular and 5 % other. 53.5% were luminal A, 28.66% luminal B, 7.78%, triple negative, 4.3%, Her2 positive and 4.3%. luminal B-Her2 positive.TTL was equal to 0 in 183 cases and greater than zero in 138 cases.71 cases showed a TTL higher than 15,000 copies. Only 21 cases met Z0011 criteria and had ALND. As of now, 3 patients have had locoregional relapse and 8 metastatic disease. 12 have died, only two from metastatic breast cancer. Conclusions: Using Z0011 criteria, we have adequate clinical outcomes with a low rate of ALND; If we had based the axillary management on TTL values we would have multiplied the number of ALND by a factor of 3.3 (from 21 to 71); We have observed a tendency to higher TTL in luminal phenotypes and to lower TTL in HER2 positive and triple negative subtypes; Work is in progress to increase our sample size.
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