ABSTRACT
PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.
Subject(s)
Breast Neoplasms , Ovarian Neoplasms , Argentina/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Fanconi Anemia Complementation Group N Protein/genetics , Female , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/genetics , Retrospective StudiesABSTRACT
Introducción La variante pleomórfica del carcinoma lobulillar infiltrante es considerada más agresiva y con peor pronóstico que la variante clásica, según se ve reflejado en numerosos trabajos que muestran una menor sobrevida global en pacientes con carcinoma lobulillar infiltrante pleomórfico (CLP) en comparación con el carcinoma lobulillar infiltrante clásico (CLC). El objetivo del presente trabajo fue comparar las características clínicas, anatomo-patológicas, la sobrevida global y libre de enfermedad entre el carcinoma lobulillar infiltrante pleomórfico y el carcinoma lobulillar infiltrante clásico. Material y método Estudio comparativo, descriptivo, retrospectivo, llevado a cabo en el Instituto de Ginecología de Rosario, donde de un total de 562 pacientes con diagnóstico de cáncer de mama, se hallaron 112 pacientes con diagnóstico de cáncer lobulillar infiltrante, de las cuales un grupo de 94 pacientes tuvo diagnóstico de carcinoma lobulillar infiltrante clásico (19,9%) y 18 pacientes fueron diagnosticadas con carcinoma lobulillar infiltrante pleomórfico (3,2%), de acuerdo al informe anatomopatológico. Se compararon las características clínico-patológicas de presentación, el tratamiento quirúrgico y los resultados oncológicos a largo plazo. Resultados No hubo diferencias significativas en la edad de presentación entre el CLC y el CLP (Mediana: 55 años vs 55 años), tamaño tumoral (Promedio: 2,4 cm vs 3,1 cm), multicentricidad (17% vs 11.1%), receptores hormonales positivos (93,3% vs 97,1%), y tratamiento quirúrgico conservador (70.6% vs 79.4%). Se encontró diferencia estadísticamente significativa en cuanto a estadificación ganglionar (N3: 2.8% vs 44.5% p=0,004), Her2neu positivo (p=0,012) e indicación de quimioterapia en el grupo de carcinoma lobulillar infiltrante pleomórfico (43,2% vs 75% p=0,028). Con respecto al seguimiento, en el grupo CLP se observó menor sobrevida global (p=0,006) y libre de enfermedad (p=0,004) durante 151 meses de seguimiento promedio. Hallamos concordancia con las publicaciones que reportan al CLP como una variante con peor evolución en comparación al CLC. Conclusión Hallamos que el CLP tuvo mayor compromiso ganglionar, indicación de quimioterapia adyuvante, mayor porcentaje de Her2neu positivo y peor evolución, lo que se vio reflejado en una menor sobrevida global y libre de enfermedad.
Introduction According to what is reflected in numerous studies showing a lower global survival in patients with pleomorphic infiltrating lobular carcinoma (PLC) rather than in those with classical infiltrating lobular carcinoma (CLC), the pleomorphic variant of infiltrating lobular carcinoma is considered an aggressive tumor which has a worst prognosis than the classical type. The aim of the present study was to compare the clinical, pathological characteristics, the global and disease-free survival between the pleomorphic infiltrating lobular carcinoma and the classical infiltrating lobular carcinoma. Material and method Comparative, descriptive, retrospective study, conducted at the Instituto de Ginecología de Rosario, where a total of 562 patients diagnosed with breast cancer. 112 patients of them were found diagnosed with infiltrating lobular carcinoma, of which a group of 94 patients had a diagnosis of classic lobular carcinoma (19.9%) and 18 (3.2%) patients were diagnosed with pleomorphic infiltrating lobular carcinoma, according to the pathological report. The clinical-pathological characteristics of presentation, surgical treatment and long-term outcomes were compared. Results There were no significant differences in the age of presentation between the CLC and the CLP (Median: 55 years vs 55 years), tumor size (Mean: 2.4 cm vs. 3.1 cm), multicentricity (17% vs. 11.1%), positive hormonal receptors (93.3% vs. 97.1%), and surgical treatment (70.6% vs. 79.4% in conservative surgery). A statistically significant difference was found in terms of lymph node status (N3: 2.8% vs. 44.5% p=0.004), Her2neu positive (p=0.012) indication of chemotherapy in the group of pleomorphic infiltrating lobular carcinoma (43.2% vs. 75% p=0.028). Regarding the follow-up, in the CLP group, lower overall survival (p= 0.006) and disease-free (p=0.004) noticed during 151 months of average follow-up. We found ourselves in agreement with the publications that report to the CLP as a variant with worse evolution compared to the CLC. Conclusion We found that CLP had a greater lymph node involvement, an indication for adjuvant chemotherapy, a higher percentage of positive Her2 neu and worse evolution, which was reflected in a lower overall and disease-free survival.
