Background: Multiple endocrine neoplasia type 2A (MEN2A) is a rare, hereditary syndrome resulting from a germline mutation in the RET proto-oncogene and characterized primarily by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and hyperparathyroidism. Types of RET mutation have been associated with age at onset, clinical outcomes of MTC, and the penetrance of other components. Patients classified as ‘high-risk’ by the American Thyroid Association (ATA), based on the aggressiveness of MTC and the penetrance of other components, are recommended to undergo early prophylactic thyroidectomy at age ≤ 5 years and to be screened for PHEO at age ≥ 11 years. Patients with RET codon C634R mutations have been classified as high-risk. Case presentation: The present study describes a 71-year-old woman newly diagnosed with hereditary MTC related to a RET C634R germline mutation. Her basal serum calcitonin level was high, but there was no evidence of distant metastases. Surgery revealed bilateral MTC with two metastatic lymph nodes. Because microscopic resection was incomplete and extranodal extension was observed, the patient underwent adjuvant external beam radiotherapy. Response to therapy was excellent. Follow-up after 1.5 years showed no evidence of disease or other manifestations of MEN2A. Conclusion: Despite RET C634R carriers being classified as high-risk by the ATA, this patient did not present with either distant MTC or PHEO until her seventies. To our knowledge, only one other patient has shown a similar late identification of a RET C634R mutation, but MTC could not be diagnosed because the patient was lost to follow-up. Further research is required to develop optimal protocols that could allow patients requiring prophylactic thyroidectomy to be differentiated from those who can be monitored closely without early surgery.

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a well-known oncogene with a high prevalence of mutation in breast cancer patients. The effect of the mutation is a deregulation in phosphatidylinositol 3-kinase-related pathways, and, consequently, in unrestricted cell growth and differentiation. With the advent of precision oncology, PIK3CA has emerged as a pivotal treatment target, culminating in the recent approval of alpelisib. Despite years of research on this genetic alteration, certain aspects of its influence on the prognosis of breast cancer remain ambiguous. The purpose of this analysis is to characterize the clinical picture of breast cancer patients with PIK3CA mutation in comparison to the PIK3CA-wild-type group. We examined 103 tumor samples from 100 breast cancer patients using a next-generation sequencing panel. Presence of the mutation was linked to an older age at diagnosis, a lower expression of Ki67 protein, a greater percentage of tumors expressing progesterone receptors, and a notably higher incidence of metastatic disease at presentation. No significant differences were identified in overall and progression-free survival between the two groups. Our findings enhance the understanding of how PIK3CA mutations shape the clinical and prognostic landscape for breast cancer patients.

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Objectives We evaluated the performance of mammography-based radiomics in prediction of clinical nodal status, clinical tumor stage, clinical disease stage, status of the PIK3CA mutation and concordance with the radiologist-assessed BI-RADS category. Mammography is often the first imaging modality performed in the screening or diagnostic workup of breast cancer. Materials & Methods In this single-center retrospective study, we included 102 histopathologically-confirmed cases of breast cancer from 100 patients. The tumor region and whole-breast parenchyma were contoured on 368 craniocaudal and mediolateral-oblique mammograms. Cases were temporally split into training and test sets by histopathological diagnosis date (training 70%, held-out test 30%). Six linear models were tuned by 5-fold x 3-repeat stratified cross-validation. The winning model per endpoint was applied once to the test set. We report AUC with 95% confidence intervals, permutation p-values and Benjamini-Hochberg false discovery rate (BH-FDR) correction across five endpoints. Results Three of the studied endpoints reached significance after BH-FDR correction: clinical nodal status (cN0 vs cN-positive; AUC 0.726 (95% CI: 0.501–0.886)), clinical tumor stage (cT1-2 vs cT3-4; AUC 0.792 (95% CI: 0.575–0.929)) and overall disease stage (I-II vs III-IV; AUC 0.778 (95% CI: 0.572–0.917)). Mammography-based radiomics failed to predict the presence of PIK3CA mutation and concordance with radiologist-assessed BI-RADS category. Conclusion Mammography-based radiomics can be used to discriminate between cN-negative and cN-positive disease, early from advanced clinical tumor stage and early from advanced overall disease stage in breast cancer. Mammography-based radiomics did not predict PIK3CA status and did not discriminate between radiologist-assessed BI-RADS 4 and 5 groups.

Objectives: We evaluated the performance of mammography-based radiomics in prediction of clinical nodal status, clinical tumor stage, clinical disease stage, status of the PIK3CA mutation and concordance with the radiologist-assessed BI-RADS category. Mammography is often the first imaging modality performed in the screening or diagnostic workup of breast cancer. Materials and Methods: In this single-center retrospective study, we included 102 histopathologically confirmed cases of breast cancer from 100 patients. The tumor region and whole-breast parenchyma were contoured on 368 craniocaudal and mediolateral-oblique mammograms. Cases were temporally split into training and test sets by histopathological diagnosis date (training: 70%, held-out test: 30%). Six linear models were tuned by 5-fold x 3-repeat stratified cross-validation. The winning model per endpoint was applied once to the test set. We report AUCs with 95% confidence intervals, permutation p-values and Benjamini–Hochberg false discovery rate (BH-FDR) correction across five endpoints. Results: Three of the studied endpoints reached significance after BH-FDR correction: clinical nodal status (cN0 vs. cN-positive; AUC: 0.726 (95% CI: 0.501–0.886)), clinical tumor stage (cT1-2 vs. cT3-4; AUC: 0.792 (95% CI: 0.575–0.929)) and overall disease stage (I–II vs. III–IV; AUC: 0.778 (95% CI: 0.572–0.917)). Mammography-based radiomics failed to predict the presence of PIK3CA mutation and concordance with radiologist-assessed BI-RADS category. Conclusions: Mammography-based radiomics has shown a hypothesis-generating discriminative value for differentiation between cN-negative and cN-positive disease, early from advanced clinical tumor stage, and early from advanced overall disease stage in breast cancer. Mammography-based radiomics did not predict PIK3CA status and did not discriminate between radiologist-assessed BI-RADS 4 and 5 groups.