Introduction: Real-world data on the feasibility and potential interaction of concurrent immunotherapy with radiation therapy (RT) remains limited. Herein, we investigated the safety profile of adjuvant pembrolizumab with concomitant RT given with curative intent in operable triple negative breast cancer (TNBC) patients.
Materials And Methods: We conducted the INT 54/24 study to prospectively collect data from patients with operable TNBC treated with neoadjuvant chemotherapy plus pembrolizumab followed by surgery and adjuvant pembrolizumab with concomitant RT.
Advances in cancer biology and drug development now enable treatments tailored to individual tumor profile. Targeting specific molecular alterations marked a significant step forward in cancer care, including breast cancer. Access to these therapies is improving thanks to the implementation of molecular tumor boards and efforts to provide molecular diagnostics at sustainable costs for all.
View Article and Find Full Text PDFBackground: Body mass index (BMI) may affect prognosis in patients with breast cancer (BC). We assessed the association of BMI and weight changes with outcomes of patients with HER2-positive early BC included in the APHINITY trial.
Methods: This is an exploratory analysis of APHINITY (NCT01358877), randomized trial testing adjuvant dual vs.
In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial (NCT00490139), we identify and characterize five molecular subtypes associated with the risk of distant recurrence: immune-enriched, proliferative/metabolic-enriched, mesenchymal/stroma-enriched, luminal, and ERBB2-dependent.
View Article and Find Full Text PDFUp to 90 % of death from solid tumors are caused by metastases. By 2040, breast cancer (BC) is predicted to increase to over 3 million new cases. Additionally, with the personalization and intensification of BC follow-up, many patients will relapse with oligometastatic disease (OMD).
View Article and Find Full Text PDFThe Flood is the first pictorial scene that Michelangelo Buonarroti painted on the ceiling of the Sistine Chapel in the Vatican. On the right side of the fresco a woman with abnormal breast morphology is presented and the nature of her disease is considered using the Guidelines for Iconodiagnosis. A team of experts covering art history, art expertise, medicine, genetics, and pathology undertook the process and concluded that the pathology shown is probably breast cancer, most likely linked to the symbolic significance of an inevitable death as expressed in the Book of Genesis.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
December 2024
Male breast cancer (MaBC) is an uncommon disease. It is generally assimilated to post-menopausal female breast cancer and treated accordingly. However, the real impact of radiation therapy, after both mastectomy and breast conservation, has yet to be established.
View Article and Find Full Text PDFBackground: Multicenter precision oncology real-world evidence requires a substantial long-term investment by hospitals to prepare their data and align on common Clinical Research processes and medical definitions. Our team has developed a self-assessment framework to support hospitals and hospital networks to measure their digital maturity and better plan and coordinate those investments. From that framework, we developed PRISM for Cancer Outcomes: PR: agmatic I: nstitutional S: urvey and benchM: arking.
View Article and Find Full Text PDFChromosomal Instability (CIN) is a common and evolving feature in breast cancer. Large-scale Transitions (LSTs), defined as chromosomal breakages leading to gains or losses of at least 10 Mb, have recently emerged as a metric of CIN due to their standardized definition across platforms. Herein, we report the feasibility of using low-pass Whole Genome Sequencing to assess LSTs, copy number alterations (CNAs) and their relationship in individual circulating tumor cells (CTCs) of triple-negative breast cancer (TNBC) patients.
View Article and Find Full Text PDFClin Breast Cancer
January 2025
Background: Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer, with 5-10% of cases progressing into invasive disease. Herein, we investigated the association between HER2-low and clinico-pathological characteristics in DCIS and subsequent ipsilateral loco-regional relapse (LRR).
Materials And Methods: We accessed our prospectively maintained institutional database.
Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
July 2024
Background: The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [Fluorine]fluorodeoxyglucose-positron emission tomography ([F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [F]FDG-PET disease detection were evaluated.
Methods: A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.
Lancet
April 2024
Background: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy.
Methods: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries.
JAMA Oncol
May 2024
Importance: Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2-positive early breast cancer (EBC).
Objective: To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41.
Design, Setting, And Participants: In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.
The identification of prognostic markers in patients receiving neoadjuvant therapy is crucial for treatment optimization in HER2-positive breast cancer, with the immune microenvironment being a key factor. Here, we investigate the complexity of B and T cell receptor (BCR and TCR) repertoires in the context of two phase III trials, NeoALTTO and CALGB 40601, evaluating neoadjuvant paclitaxel with trastuzumab and/or lapatinib in women with HER2-positive breast cancer. BCR features, particularly the number of reads and clones, evenness and Gini index, are heterogeneous according to hormone receptor status and PAM50 subtypes.
View Article and Find Full Text PDFHuman Epidermal growth factor Receptor 2 (HER2) assessment is crucial for breast cancer treatment. Therapeutic decisions for recurrent cases often rely on primary tumor status. However, mounting evidence suggests that tumors show dynamic changes and up to 10% of breast cancer modify their initial status during progression.
View Article and Find Full Text PDFIntroduction: Clinical trials confirmed the beneficial effects of adding pertuzumab (P) to the combination of trastuzumab-chemotherapy (TC) in the (neo)adjuvant setting of high-risk HER2-positive early breast cancer (HER2+BC). We evaluated the clinical, economic and societal impact of adding pertuzumab to neoadjuvant TC combination (TPC) in Italy.
Methods: A cost-consequence analysis comparing TPC vs.
We studied the COVID-19 impact in newly-diagnosed breast cancer (7,349 patients in 2019, and 5,563 in 2020). In 2020 there were two diagnostic drops: -37.2% (March-May), -15.
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