Breast cancer is a heterogeneous disease characterized by variant pathological features, disparate response to therapeutics, and substantial differences in long-term patient survival. Over the years, several histopathological features have been recognized as strong independent prognostic factors in early breast cancer, including tumour size, lymph node status and histological grade. Today, breast cancer management is already changing considering the new molecular analysis that is becoming more accessible in daily clinical practice thanks to commercially available genetic prognostic tests, such as PAM50/PROSIGNA®. The integration of clinical features of the patient, such as tumour size and nodal status, with genomic profiling of individual breast cancer can help clinicians better estimate disease outcome and safely tailor adjuvant treatments. Lymphovascular invasion (LVI), the presence of malignant cells within lymphovascular channels, is a crucial step in the invasion-metastasis cascade. LVI, when identified morphologically in the peritumoural area, is regarded as an indicator of metastatic potential, and is strongly associated with a poor prognosis in many solid tumours, but its prognostic role in breast cancer remains controversial. Data from 82 patients who underwent surgery and subsequent PAM50 PROSIGNA® genomic test at Campus Bio-Medico of Rome were retrospectively analysed to determine LVI occurrence in luminal breast cancer and to explore the correlation between LVI status and genomic risk of relapse based on PAM50 ROR score in a LUMINAL breast cancer population. After systematic pathological revision of tumour specimens, the proportion of patients with evidence of LVI was 54%, slightly higher than rates reported in the literature (21–42%). Extensive LVI (defined as the presence of multiple foci of LVI in more than 1 tumour block) was significantly associated with larger tumour size (p = 0.04) in both node-negative and node-positive patients, while no statistically significant associations were found with all the other traditional clinicopathological parameters (age, grading, KI67, ER and PR expression). When compared to prognostic results from PROSIGNA, the rate of LVI positivity was higher among node-positive patients with a higher Risk of Recurrence (ROR), but the association did not reach statistical significance. Nevertheless, an association with 10-year recurrence rate calculated by PROSIGNA was found in node-negative population (p = 0.004) against node-positive cases (p = 0.501). These findings are consistent with most previous studies which reported LVI prognostic value confined to node-negative disease. In multivariate linear regression analysis, the presence of LVI (score 0 versus 1-2) nor extensive LVI status itself provided independent prognostic information for PROSIGNA 10-year recurrence score besides node status, grading, KI67 and tumour dimensions. When chemotherapy benefit calculated by PREDICT online was investigated, extensive LVI correlated with higher percentage of 10-year survival rate gain from third-generation therapy in node-negative population (p = 0.022). By the way, when tested in univariate regression analysis, LVI status did not provide additional prognostic information besides 10-year PREDICT overall survival. Taken together, these results suggested that the analysis of LVI might provide independent prognostic information beyond advanced molecular testing, but it remains controversial. Due to favourable prognosis of the included population (early-stage, hormone receptor-positive, HER2-negative disease, 60% node-negative) and short follow-time time (five years), few DFS events were registered and the impact of LVI on survival outcomes could not be analysed. In conclusion, the present work confirmed that the presence of extensive lymphovascular invasion is associated with larger tumour dimension and worse recurrence rate in node-negative luminal breast cancer. As a marker that has the strength to upgrade apparently low-risk cases to a higher category, more convincing data from large series studies and real-world experiences including molecular analysis, are needed to test its potential additional prognostic value beyond genomic tests.

Prognostic value of Lymphovascular invasion (LVI) in early breast cancer: pathological definition and comparison with PROSIGNA gene test results / Loretta D'onofrio , 2021 Jun 16. 33. ciclo

Prognostic value of Lymphovascular invasion (LVI) in early breast cancer: pathological definition and comparison with PROSIGNA gene test results

2021-06-16

Abstract

Breast cancer is a heterogeneous disease characterized by variant pathological features, disparate response to therapeutics, and substantial differences in long-term patient survival. Over the years, several histopathological features have been recognized as strong independent prognostic factors in early breast cancer, including tumour size, lymph node status and histological grade. Today, breast cancer management is already changing considering the new molecular analysis that is becoming more accessible in daily clinical practice thanks to commercially available genetic prognostic tests, such as PAM50/PROSIGNA®. The integration of clinical features of the patient, such as tumour size and nodal status, with genomic profiling of individual breast cancer can help clinicians better estimate disease outcome and safely tailor adjuvant treatments. Lymphovascular invasion (LVI), the presence of malignant cells within lymphovascular channels, is a crucial step in the invasion-metastasis cascade. LVI, when identified morphologically in the peritumoural area, is regarded as an indicator of metastatic potential, and is strongly associated with a poor prognosis in many solid tumours, but its prognostic role in breast cancer remains controversial. Data from 82 patients who underwent surgery and subsequent PAM50 PROSIGNA® genomic test at Campus Bio-Medico of Rome were retrospectively analysed to determine LVI occurrence in luminal breast cancer and to explore the correlation between LVI status and genomic risk of relapse based on PAM50 ROR score in a LUMINAL breast cancer population. After systematic pathological revision of tumour specimens, the proportion of patients with evidence of LVI was 54%, slightly higher than rates reported in the literature (21–42%). Extensive LVI (defined as the presence of multiple foci of LVI in more than 1 tumour block) was significantly associated with larger tumour size (p = 0.04) in both node-negative and node-positive patients, while no statistically significant associations were found with all the other traditional clinicopathological parameters (age, grading, KI67, ER and PR expression). When compared to prognostic results from PROSIGNA, the rate of LVI positivity was higher among node-positive patients with a higher Risk of Recurrence (ROR), but the association did not reach statistical significance. Nevertheless, an association with 10-year recurrence rate calculated by PROSIGNA was found in node-negative population (p = 0.004) against node-positive cases (p = 0.501). These findings are consistent with most previous studies which reported LVI prognostic value confined to node-negative disease. In multivariate linear regression analysis, the presence of LVI (score 0 versus 1-2) nor extensive LVI status itself provided independent prognostic information for PROSIGNA 10-year recurrence score besides node status, grading, KI67 and tumour dimensions. When chemotherapy benefit calculated by PREDICT online was investigated, extensive LVI correlated with higher percentage of 10-year survival rate gain from third-generation therapy in node-negative population (p = 0.022). By the way, when tested in univariate regression analysis, LVI status did not provide additional prognostic information besides 10-year PREDICT overall survival. Taken together, these results suggested that the analysis of LVI might provide independent prognostic information beyond advanced molecular testing, but it remains controversial. Due to favourable prognosis of the included population (early-stage, hormone receptor-positive, HER2-negative disease, 60% node-negative) and short follow-time time (five years), few DFS events were registered and the impact of LVI on survival outcomes could not be analysed. In conclusion, the present work confirmed that the presence of extensive lymphovascular invasion is associated with larger tumour dimension and worse recurrence rate in node-negative luminal breast cancer. As a marker that has the strength to upgrade apparently low-risk cases to a higher category, more convincing data from large series studies and real-world experiences including molecular analysis, are needed to test its potential additional prognostic value beyond genomic tests.
16-giu-2021
breast cancer; LVI
Prognostic value of Lymphovascular invasion (LVI) in early breast cancer: pathological definition and comparison with PROSIGNA gene test results / Loretta D'onofrio , 2021 Jun 16. 33. ciclo
File in questo prodotto:
File Dimensione Formato  
DT_271_DOnofrioLoretta.pdf

accesso aperto

Tipologia: Tesi di dottorato
Licenza: Creative commons
Dimensione 2.75 MB
Formato Adobe PDF
2.75 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/68644
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact