Preoperative axillary nodal staging of invasive lobular breast cancer with ultrasound guided fine needle aspiration in patients with suspicious ultrasound findings versus aspiration in all patients - A retrospective single institutional analysis.

INTRODUCTION: - At present, surgical strategies for breast cancer patients with >2 lymph nodes (LN) involved differ from those with no or lower degree of nodal involvement. Preoperative assessment of the axilla is less sensitive in patients with lobular carcinoma (ILC) than patients with other histological tumour types. MATERIALS AND METHODS: - A retrospective analysis of axillary staging by palpation, axillary ultrasound (AXUS) and AXUS-guided fine-needle aspiration cytology (FNAC) of 153 patients with ILC diagnosed and operated on between January 2013 and December 2020 was performed. Patients had either sentinel node biopsy or axillary lymph node dissection according to current practice. In period 1, patients had FNAC only when AXUS suggested nodal involvement (n = 106), and in period 2, all ILC patients had axillary FNAC (n = 47). RESULTS: - Of the factors associated with >2LNs involvement, logistic regression suggested only AXUS/FNAC based staging as independent variable for all patients. Patients with AXUS-guided FNAC had a significantly higher proportion of true negative and lower proportion of true positive cases in the P2 period (0 vs 55% and 72% vs 11% for >2 LNs involvement, respectively; both p < 0.0001). CONCLUSIONS: - AXUS-guided FNAC of all ILC patients did not result in improved preoperative identification of patients with >2 metastatic LNs but increased the false-negative rate of the assessment by producing false-negative results in patients who would not have undergone a biopsy due to negative AXUS findings.

Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors.

Background: Based on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor. Patients and methods: We used a previously published next generation sequencing dataset of 21 matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also carried out the myChoice HRD analysis on an independent cohort of 17 breast cancer patients with matched primary/brain metastasis pairs. Results: All of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort, the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria. Conclusions: The consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.