Juan Lucas Bayo Calero

BACKGROUND: Trastuzumab improves survival outcomes in patients with HER2+ metastatic breast cancer. The Long-Her study was designed to identify clinical and molecular markers that could differentiate long-term survivors from patients having early progression after trastuzumab treatment. METHODS: Data were collected from women with HER2-positive metastatic breast cancer treated with trastuzumab that experienced a response or stable disease during at least 3 years. Patients having a progression in the first year of therapy with trastuzumab were used as a control. Genes related with trastuzumab resistance were identified and investigated for network and gene functional interrelation. Models predicting poor response to trastuzumab were constructed and evaluated. Finally, a mutational status analysis of selected genes was performed in HER2 positive breast cancer samples. RESULTS: 103 patients were registered in the Long-HER study, of whom 71 had obtained a durable complete response. Median age was 58 years. Metastatic disease was diagnosed after a median of 24.7 months since primary diagnosis. Metastases were present in the liver (25%), lungs (25%), bones (23%) and soft tissues (23%), with 20% of patients having multiple locations of metastases. Median duration of response was 55 months. The molecular analysis included 35 patients from the group with complete response and 18 patients in a control poor-response group. Absence of trastuzumab as part of adjuvant therapy was the only clinical factor associated with long-term survival. Gene ontology analysis demonstrated that PI3K pathway was associated with poor response to trastuzumab-based therapy: tumours in the control group usually had four or five alterations in this pathway, whereas tumours in the Long-HER group had two alterations at most. CONCLUSIONS: Trastuzumab may provide a substantial long-term survival benefit in a selected group of patients. Whole genome expression analysis comparing long-term survivors vs. a control group predicted early progression after trastuzumab-based therapy. Multiple alterations in genes related to the PI3K-mTOR pathway seem to be required to confer resistance to this therapy.

"Fundamentos: La implementación de la Toma de Decisiones Compartidas (TDC) en oncología es escasa. El objetivo del estudio fue determinar el conocimiento de la TDC que tienen los médicos que tratan a pacientes con cáncer, la utilidad que le conceden, el rol que desempeñan, la evaluación que hacen, y las barreras y facilitadores que encuentran para su uso.Métodos: Se realizó una encuesta a oncólogos médicos, oncólogos radioterápicos y cirujanos generales que ejercían en Andalucía (España). Se recogieron variables sociodemográficas, clínico-asistenciales y de aspectos de la TDC. La TDC se evaluó mediante el cuestionario SDM-Q-Doc. Se emplearon contrastes no paramétricos para determinar las posibles diferencias entre especialidades médicas.Resultados: El cuestionario se envió a 351 médicos y la tasa de respuesta fue del 37,04%. Respondieron 63 mujeres y 67 hombres, con un promedio de 45,6 años de edad y 18,04 años de experiencia. El 33,08% eran oncólogos médicos, el 34,61% oncólogos radioterápicos y el 29,23% cirujanos generales. El 82,3% no tenía formación en TDC y el 33,8% reconocía saber bastante y utilizarla en su práctica habitual. El 80% consideró que era muy útil. El 60% respondió que la decisión sobre el tratamiento la tomaban mayormente ellos. Al evaluar la TDC con la escala SDM-Q-Doc, todas las especialidades obtuvieron más de 80 puntos sobre 100. Las principales barreras para aplicar la TDC fueron la dificultad del paciente para entender lo que necesitaba saber, la falta de instrumentos de apoyo, así como la falta de tiempo. Conclusiones: Un 82% de los médicos no tiene formación en TDC y un 66% no la utiliza en su práctica habitual, tomando la decisión sobre el tratamiento mayoritariamente ellos. Es importante adoptar estrategias para aumentar la formación en TDC e implementarla en la práctica clínica diaria."

e11081 Background: Trastuzumab has shown an improvement in survival outcomes among patients with HER2+ metastatic breast cancer (MBC). Identification of factors and tumor molecular profiles that may predict long-term remission has become a key-issue. Methods: Multicenter, observational, cross-sectional study. Data were collected from women with HER2+ MBC treated with a trastuzumab-based regimen that experienced CR, PR or SD during at least 3 years. FFPE samples(at least 70% tumor cells)for Microarray Analysis were obtained. L2 Boosting for classification with classical Akaike Information criterion based on the binomial log-likelihood for stopping the boosting iterations algorithm was applied to RNA expression data, to identify variables related to clinical information. Predictive models of long term response were built using a Binary Logistic Regression with the Fisher's scoring. Results: 103 patients.Median age: 58(51-68) years. Metastatic disease diagnosed after a median of 24.7(1.8-51.9) months since primary diagnosis. Predominant type: ductal carcinoma(91.9%) and 59% histological grade III. Hormonal status: Progesterone receptor positive 39.2% and estrogen receptor positive 41.2%. Most common metastatic sites: multiple locations(31.4%), lung(23.5%), bone(14.7%) and liver(13.7%). Overexpression of HER2 assessed by IHC in 98.1% of patients, 91.1% were HER2+(3+) and 18.4% had FISH+ HER2 status. Tumor was positive for p53 (>30%) and Ki67(>20%) in 47.3% and 73.6%. Surgery: 87.4% of patients, 77.5% radical mastectomy. Surgery of metastases was performed on 16.8%. Trastuzumab used in combination in 88.3% with a median number of cycles of 35.5(7.0-46). 68.9% of patients achieved a CR, 20.4% PR and 10.7% had SD, during an overall median time of 55 (43-79) months. 4 patients discontinued trastuzumab due to toxicity. Conclusions: Trastuzumab may provide a substantial long-term survival benefit with a manageable safety profile in these patients. Molecular analysis will be presented in the forthcoming Congress.

Pertuzumab (P) has been approved in neoadjuvant setting for HER2-positive early breast cancer patients (pts) in association with Trastuzumab (T) and chemotherapy. Diverse studies support this treatment. The pathologic complete response (pCR) showed achieve percentages from 45.8 % to 66.6% depending on chemotherapy combination. This is a retrospective and multicentric study. We have collected all HER2-positive early breast cancer pts treated with P in neoadjuvant setting in our hospitals between 2015 and 2018. The effect of adding P on pCR was analyzed, as well as other predictive factors of response using logistic regression analyses. Kaplan Meier analysis has been used for survival analysis. A total of 310 pts met the selection criteria. The median age was 51 years (22-88 years), 54,5% were premenopausal. 4 pts were stage I, 204 pts stage II, 101 pts were stage III. The majority of the patient received anthracyclines and taxanes with P and T regimen (77,1%), 16,5% received carboplatin-docetaxel-P-T combination and 6,5% received taxane-P-T. 307 pts were analysed for response. pCR was seen in 62,2 % of the pts, dividing by hormonal receptor (HR) status, pCR was 53,8% in HR-positive and 71,1% in HR-negative. Treatment was well tolerated with only 14.8 % G3-4 adverse events related to chemotherapy and 1.9% related to antiHER2 therapy. Different adjuvant treatments patterns were seen between hospitals. After a follow-up of 7,5 years, 43 pts (13,9%) had a distant relapse, 16 of them (37,2%) had achieved a previous pCR. 38,5% had CNS recurrence and 61,5% non-CNS recurrence. In multivariate analysis non-pCR pts have 3.9 relative risk of experience disease relapse event (p 0.0001; 1.84-8.88), and patients with stage III at diagnosis have 4.3 relative risk (p 0.00004; 2.15-8.75). Disease free-survival (DFS) rates at 7.5 years is 86.4 %. After separating between pCR outcomes, results were statistical significative (p < 0.0001) with DFS rates of 89.4% in pCR pts and 70.6% in non-pCR pts. In our knowledge, this is the first real-world study that shows survival results for adding Pertuzumab in the neoadjuvant setting of HER2-positive breast cancer patients. Our results are consistent with those previously published.