S. Di Cosimo (MILANO, Italy)
Fondazione IRCCS Istituto Nazionale dei TumoriAuthor Of 2 Presentations
12P - The RODILIA pilot study for molecular screening of patients with metaplastic breast cancer
Abstract
Background
Metaplastic breast cancer (MPBC) is a rare disease characterized by aggressive features and dismal prognosis after standard therapy. Herein, we report the molecular screening of the Milan National Cancer Institute case series for the evaluation of potentially druggable alterations.
Methods
A total of 49 MPBC cases treated with curative intent were identified. Primary tumors were profiled using Oncomine Comprehensive Assay Plus panel (Thermo Fisher Scientific) for copy number alteration (CNA), mutation, tumor mutational burden (TMB), and microsatellite instability (MSI) analyses, according to the manufacturer instructions.
Results
Sequencing results are presented for the first 34 pathological reviewed cases. Quality control metrics were met in 33 cases. In total, 94 unique genes harbored at least one mutation representing 24% of the panel. The median number of mutations indexed per patient was 3.5 (range 0-29). Notably, 25 cases showed actionable mutated genes, including PTEN, mTOR, FGFR3, FGFR4. Most of the cases showed low TMB, the median value being 4.5 (range 0-28). MSI status was high only in 2 cases. Common CNAs included 13q (10%), 5q (9%) and 17p (6%). Eight out of ten canonical cancer pathways (cell cycle, Hippo, MYC, NOTCH, PI3K, RTK-RAS, TGFβ and β-catenin/WNT) were altered by both mutational and CNA events occurring at different proportions, with mutational events involving up to 33%, and CNA involving up to 42% of genes of the altered pathway. In the Hippo and RTK-RAS pathways the two types of alterations were instead equally represented whereas the remaining pathways (β-catenin/WNT, TGFβ, PI3K, NOTCH, MYC and Cell cycle) were more affected by CNA than mutations. NRF2 and TP53 signaling pathways were instead activated by mutational events only.
Conclusions
Mutational and copy number alterations conveyed complementary information in MPBC cooperating in activation of cancer pathways.These findings suggest to further study the value of CNAs in MPBC biological processes, especially immunogenicity, which cannot be explained by the low TMB and MSI found. Extended data with matched immune profile will be presented at the meeting.
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Funding
Italian Ministry of Health.
Disclosure
All authors have declared no conflicts of interest.
64P - Mammographic density to predict response to neoadjuvant chemotherapy for breast cancer.
Abstract
Background
Mammographic density (MD) has been strongly associated with increased risk of breast cancer (BC). In view of this, we aimed to investigate the predictive value of MD in a large consecutive cohort of BC patients (pts) treated with neoadjuvant chemotherapy (NAC).
Methods
Data on NAC treated pts prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (May 2009-Aprill 2020) were identified. Diagnostic mammograms were used to evaluate MD, which was categorized by the Breast Imaging-Reporting and Data System (BI-RADS). BI-RADS identify 4 categories of MD in keeping with the masking effect of fibroglandular tissue, as following: A (almost entirely fat), B (scattered areas of fibroglandular density), C (heterogeneously dense), and D (extremely dense). Multivariable logistic regression was used to assess the odds ratios (OR) for pathological complete response (pCR), ie absence of invasive tumor in breast and node surgical specimens, comparing BI-RADS categories with adjustment for patient age, BMI, and tumor characteristics.
Results
A total of 442 pts were analyzed, of which 120 (27.1%) attained a pCR. BI-RADS categories A, B, C, and D accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases, respectively, with corresponding pCR rates of 20.5%, 26.9%, 30.5%, 23.9%. At multivariable analysis cases classified as BI-RADS C showed an increased likelihood of pCR as compared to A (odds ratio [OR]=2.79), B (OR=1.70), and D (OR=1.47) independently of age, BMI (OR underweight vs normal=3.76), clinical N and T (OR T1/Tx vs T4=3.87), molecular subtype (HER2 vs luminal=10.74; triple negative vs luminal=8.19). In subgroup analyses, the strongest association of MD with pCR was observed in triple negative (ORs of B, C and D versus A: 1.85, 2.49 and 1.55, respectively) and HER2 positive cases (ORs 2.70, 3.23, and 1.16). Notably, no significant differential effect of MD with respect to pCR was observed in luminal BC (ORs of B, C and D versus A: 0.88, 2.01 and 1.58).
Conclusions
Patients with dense breast are more likely to attain a pCR after NAC at net of other current clinical and pathological predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Presenter Of 1 Presentation
64P - Mammographic density to predict response to neoadjuvant chemotherapy for breast cancer.
Abstract
Background
Mammographic density (MD) has been strongly associated with increased risk of breast cancer (BC). In view of this, we aimed to investigate the predictive value of MD in a large consecutive cohort of BC patients (pts) treated with neoadjuvant chemotherapy (NAC).
Methods
Data on NAC treated pts prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (May 2009-Aprill 2020) were identified. Diagnostic mammograms were used to evaluate MD, which was categorized by the Breast Imaging-Reporting and Data System (BI-RADS). BI-RADS identify 4 categories of MD in keeping with the masking effect of fibroglandular tissue, as following: A (almost entirely fat), B (scattered areas of fibroglandular density), C (heterogeneously dense), and D (extremely dense). Multivariable logistic regression was used to assess the odds ratios (OR) for pathological complete response (pCR), ie absence of invasive tumor in breast and node surgical specimens, comparing BI-RADS categories with adjustment for patient age, BMI, and tumor characteristics.
Results
A total of 442 pts were analyzed, of which 120 (27.1%) attained a pCR. BI-RADS categories A, B, C, and D accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases, respectively, with corresponding pCR rates of 20.5%, 26.9%, 30.5%, 23.9%. At multivariable analysis cases classified as BI-RADS C showed an increased likelihood of pCR as compared to A (odds ratio [OR]=2.79), B (OR=1.70), and D (OR=1.47) independently of age, BMI (OR underweight vs normal=3.76), clinical N and T (OR T1/Tx vs T4=3.87), molecular subtype (HER2 vs luminal=10.74; triple negative vs luminal=8.19). In subgroup analyses, the strongest association of MD with pCR was observed in triple negative (ORs of B, C and D versus A: 1.85, 2.49 and 1.55, respectively) and HER2 positive cases (ORs 2.70, 3.23, and 1.16). Notably, no significant differential effect of MD with respect to pCR was observed in luminal BC (ORs of B, C and D versus A: 0.88, 2.01 and 1.58).
Conclusions
Patients with dense breast are more likely to attain a pCR after NAC at net of other current clinical and pathological predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.