Breast Cancer Patient's Outcomes after Neoadjuvant Chemotherapy and Surgery at 5 and 10 Years for Stage II-III Disease.

Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. Material and Methods: A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years. Kaplan-Meier curves with a log-rank test were calculated for differences according to age, BRCA status, menopausal status, TNM, pathological and molecular surrogate subtype, 20% TIL cut-off, surgical procedure, response to chemotherapy and the presence of vascular invasion. Results: The pCR rate was 25.3% and was greater in HER2 (51.3%) and TNBC (31.7%) and in BRCA carriers (41.9%). The factors independently related to patient survival were pathology and molecular surrogate subtype, type of surgery, response to NACT and vascular invasion. BRCA status was a protective prognostic factor without reaching statistical significance, with an HR 0.5 (95%CI 0.1-1.4). Mastectomy presented a double risk of distant recurrence compared to breast-conservative surgery (BCS), supporting BCS as a safe option after NACT. After a mean follow-up of 126 (SD 43) months, luminal tumors presented a substantial difference in survival rates calculated at 5 or 10 years (81.2% compared to 74.7%), whereas that for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to the response in patients with pCR, who exhibited a 10 years DDFS of 95.5% vs. 72.4% for those patients without pCR, p < 0001. This difference was especially meaningful in TNBC: the 10 years DDFS according to an RCB of 0 to 3 was 100%, 80.6%, 69% and 49.2%, respectively, p < 0001. Patients with a particularly poor prognosis were those with lobular carcinomas, with a 10 years DDFS of 42.9% vs. 79.7% for ductal carcinomas, p = 0.001, and patients with vascular invasion at the surgical specimen, with a 10 years DDFS of 59.2% vs. 83.6% for those patients without vascular invasion, p < 0.001. Remarkably, BRCA carriers presented a longer survival, with an estimated 10 years DDFS of 89.6% vs. 77.2% for non-carriers, p = 0.054. Conclusions: Long-term outcomes after neoadjuvant chemotherapy can help patients and clinicians make well-informed decisions.

Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients.

Uveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (amino acid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and does not suffer immunoediting. Therefore, we hypothesize that driver mutations in GNAQ/11 genes could be recognized by the immune system. Genomic and transcriptomic data from primary uveal tumors were collected from the TCGA-UM dataset (n = 80) and used to assess the immunogenic potential for GNAQ/GNA11 Q209L/Q209P mutations using a variety of tools and HLA type information. All prediction tools showed stronger GNAQ/11 Q209L binding to HLA than GNAQ/11 Q209P. The immunogenicity analysis revealed that Q209L is likely to be presented by more than 73% of individuals in 1000 G databases whereas Q209P is only predicted to be presented in 24% of individuals. GNAQ/11 Q209L showed a higher likelihood to be presented by HLA-I molecules than almost all driver mutations analyzed. Finally, samples carrying Q209L had a higher immune-reactive phenotype. Regarding cancer risk, seven HLA genotypes with low Q209L affinity show higher frequency in uveal melanoma patients than in the general population. However, no clear association was found between any HLA genotype and survival. Results suggest a high potential immunogenicity of the GNAQ/11 Q209L variant that could allow the generation of novel therapeutic tools to treat UM like neoantigen vaccinations.

Estudio comparativo entre el método One step nucleic acid amplification y el método convencional en la estadificación en cáncer de mama: un aumento en la detección de micrometástasis / Comparative study of the One step nucleic acid amplification method and the conventional method in axillary staging in breast cancer: an increase in the detection of micrometastases

Objetivos. El método One step nucleic acid amplification (OSNA) se ha incorporado para el estudio del ganglio centinela (GC) en cáncer de mama como alternativa al estudio convencional histológico (MC). El propósito de nuestro estudio fue comparar la estadificación por ganglio centinela (EGC) obtenida por el método OSNA con la obtenida mediante MC. Material y métodos. Se seleccionaron pacientes con cáncer de mama y EGC recogidas durante los años 2009-2010 y 2012-2013, estudiadas con MC y método OSNA. Se analizaron diferentes parámetros clínico-patológicos. Resultados. Se incluyó a 1.124 pacientes, 590 estudiadas por MC y 534 por método OSNA. La EGC inicial fue: pN0: MC 349 (59,2%) y OSNA 335 (62,7%); pN0(i+): MC 74 (12,5%) y OSNA 14 (2,6%); pN1mi: MC 59 (10%) y OSNA 77 (14,4%); pN1: MC 108 (18,3%) y OSNA 108 (20,3%). Se encontraron diferencias estadísticamente significativas entre la EGC por método OSNA y MC (p<0,001), a expensas de las tasas de pN1mi y pN0(i+). Se seleccionó a 224 pacientes con EGC pN1mi y pN0(i+) para determinar si las diferencias encontradas podrían atribuirse a distintas características clínico-patológicas. El método OSNA detecta el doble de micrometástasis (84,6%). Conclusiones. En nuestra casuística, por el método OSNA se observa un incremento significativo de pN1mi (84,6% vs. 44,4%) y una disminución de pN0(i+) respecto al estudio convencional, diferencias que no están condicionadas por los parámetros clínico-patológicos. El 75% de casos con pN1mi por OSNA muestra un número de copias inferior a 1.000 (AU)

Objetives. The One Step Nucleic Acid Amplification (OSNA) method has been incorporated in the study of the sentinel lymph node (SLN) in breast cancer as an alternative to conventional histological study. The aim of our study was to compare sentinel lymph node staging (SLNS) obtained by the OSNA method with that obtained by the conventional method (CM). Material and methods. We identified patients with breast cancer and SLN study during the periods 2009-2010 and 2012-2013, who underwent the CM and by OSNA. We analysed different clinicopathological parameters. Results. A total of 1124 patients were studied, 590 by CM and 534 by OSNA. SLNS was: pN0: CM 349 (59.2%) and OSNA 335 (62.7%); pN0(i+): CM 74 (12.5%) and OSNA 14 (2.6%); pN1mi: CM 59 (10%) and OSNA 77 (14.4%); pN1: CM 108 (18.3%) and OSNA 108 (20.3%). Statistically significant differences were found between the SLNS by OSNA and CM (p <0.001), due to the rates of pN1mi and pN0(i+). To determine whether this statistical significance could be attributed to different clinicopathological features, 224 patients were selected from the initial series with SLN pN1mi and pN0(i+). In this subgroup, the OSNA method detected twice as many micrometastases (pN1mi) (84.6%). Conclusions. In our series, the OSNA method resulted in a significant increase in pN1mi (84.6% vs 44.4%) and a decrease in pN0(i+) compared with the conventional method. Those differences were not affected by clinicopathological parameters. Most cases (75%) with pN1mi by OSNA showed less than 1000 copies (AU)