Gene Expression Assays to Tailor Adjuvant Endocrine Therapy for HR+/HER2- Breast Cancer.

Adjuvant endocrine therapy (ET) represents the standard of care for almost all hormone receptor (HR)+/HER2- breast cancers, and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is therefore a significant need for the integration of biological biomarkers in the choice of adjuvant ET beyond currently used clinicopathological characteristics. Several gene expression assays have been developed to identify patients with HR+/HER2- breast cancer who will not derive benefit from the addition of adjuvant chemotherapy. By enhancing risk stratification and predicting therapeutic response, genomic assays have also shown to be a promising tool for optimizing endocrine treatment decisions. In this study, we review evidence supporting the use of most common commercially available gene expression assays [Oncotype DX, MammaPrint, Breast Cancer Index (BCI), Prosigna, and EndoPredict] in tailoring adjuvant ET. Available data on the use of genomic tests to inform extended adjuvant treatment choice based on the risk of late relapse and on the estimated benefit of a prolonged ET are discussed. Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low-risk patients is reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

Clinical Applications of Radiomics and Deep Learning in Breast and Lung cancer: a Narrative Literature Review on Current Evidence and Future Perspectives.

Radiomics, analysing quantitative features from medical imaging, has rapidly become an emerging field in translational oncology. Radiomics has been investigated in several neoplastic malignancies as it might allow for a non-invasive tumour characterization and for the identification of predictive and prognostic biomarkers. Over the last few years, evidence has been accumulating regarding potential clinical applications of machine learning in many crucial moments of cancer patients' history. However, the incorporation of radiomics in clinical decision-making process is still limited by low data reproducibility and study variability. Moreover, the need for prospective validations and standardizations is emerging. In this narrative review, we summarize current evidence regarding radiomic applications in high-incidence cancers (breast and lung) for screening, diagnosis, staging, treatment choice, response, and clinical outcome evaluation. We also discuss pro and cons of the radiomic approach, suggesting possible solutions to critical issues which might invalidate radiomics studies and propose future perspectives.

Efficacy and Safety of Immune Checkpoint Blockade in Patients With Li-Fraumeni Syndrome.

A case series evaluating efficacy and safety of immune checkpoint blockade in Li-Fraumeni syndrome.

TP53-associated early breast cancer: new observations from a large cohort.

BACKGROUND: A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. METHODS: This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. RESULTS: Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor-positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. CONCLUSION: We observed high rates of ductal carcinoma in situ, hormone receptor-positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor-positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.