Search Results (105)

Background and Objectives: The Hippo pathway, via Yes-associated protein 1 (YAP1), regulates cell proliferation, apoptosis, and tissue regeneration. Aberrant YAP1 activation is linked to tumor progression and immune evasion in various cancers, including breast carcinoma, despite conflicting evidence on its prognostic value. Preclinical studies have explored drugs targeting YAP1–TEAD interactions, but therapeutic application is limited. Materials and Methods: This study included 50 patients with locally advanced breast cancer, who were assessed by a multidisciplinary tumor board and underwent neoadjuvant treatment per tumor subtype and clinical guidelines. Eligibility required both pre-treatment core biopsy and post-treatment surgical resection samples. Due to the absence of residual tumor in some patients achieving complete pathological response, post-treatment tissue was available and analyzable in 30 patients. YAP1 expression was evaluated immunohistochemically for nuclear and cytoplasmic staining patterns. ROC analysis identified a cutoff for YAP1 expression, defining tumors with ≥70% nuclear and ≥80% cytoplasmic staining. Results: YAP1 expression had a significant relationship with tumor subtype (p = 0.001), being most frequent in HER-2-positive tumors (55.6%) and least frequent in luminal tumors (11.1%). YAP1 positivity significantly predicted axillary pathological complete response (pCR) (p = 0.01). In YAP1-positive patients, 77.8% achieved axillary pCR compared to 31.7% in YAP1-negative patients, though the YAP1 status and breast pCR association were insignificant (p = 0.07). The Mann–Whitney U test indicated that higher Ki-67 values were significantly associated with positive YAP1 expression (p = 0.028). In contrast, there was no association between ER, PR status, age, and tumor size. Following treatment, there was a statistically significant change in YAP1 expression, with nuclear staining decreasing (p = 0.004) while cytoplasmic staining increased (p = 0.002). YAP1 was significantly linked to axillary pCR, HER-2 status, and Ki-67. Conclusions: Post treatment, nuclear YAP1 decreased, whereas cytoplasmic expression increased, showing a localization shift. These results suggest that YAP1 may predict treatment response and become a future therapeutic target. Full article

Purpose: Neoadjuvant endocrine therapy (NET) represents a valuable treatment option for hormone receptor-positive (HR+)/HER2-negative breast cancer, particularly in postmenopausal women. This study aimed to evaluate the clinical and histopathological efficacy of NET and to explore early and late changes in Ki-67 and progesterone receptor (PgR) expression as indicators of endocrine response. Methods: A prospective cohort of 127 postmenopausal patients with stage cT1–4N0–3M0 HR+/HER2− breast cancer was enrolled between 2019 and 2021. Patients received NET (mostly letrozole) for a mean of 7.7 months. In 80 cases, a second core biopsy was performed after four weeks. Tumor size, histological grade, and biomarkers (Ki-67, PgR) were assessed pre- and post-treatment. Results: NET led to a significant reduction in tumor size, with median shrinkage of 47.0% (from 32.0 mm to 17.0 mm, p < 0.0001). Breast-conserving surgery (BCS) was performed in 52.2% of patients and lymph node negativity (pN0) was observed in 50.4%. Median Ki-67 decreased from 20.0% at baseline to 5.0% after four weeks (p < 0.0001) and remained low in surgical specimens (median 5.0%, p < 0.0001). In 33.3% of patients, Ki-67 dropped below 2.7%, and 67.0% showed a concordant decrease in both Ki-67 and PgR. PgR expression declined significantly during treatment (p < 0.0001). HER2 status conversion was noted in 6.4% of patients during treatment. Pathological complete response (pCR) occurred in 3.5%, while minimal or moderate residual disease (RCB I–II) was identified in 71.3% of cases. Conclusions: NET effectively reduced tumor burden and histological aggressiveness, enabling higher rates of BCS. Early reduction in Ki-67 and PgR may serve as surrogate markers of endocrine responsiveness, supporting their use for treatment stratification and monitoring during NET in HR+/HER2− breast cancer. Full article

Background and Objectives: The accuracy of breast cancer diagnosis depends on the concordance between imaging features and pathological findings. While BI-RADS (Breast Imaging Reporting and Data System) provides standardized risk stratification, its correlation with histologic grade and immunohistochemical markers remains underexplored. This study assessed the diagnostic performance of BI-RADS 3, 4, and 5 classifications and their association with tumor grade and markers such as ER, PR, HER2, and Ki-67. Materials and Methods: In this prospective study, 67 women aged 33–82 years (mean 56.4) underwent both mammography and ultrasound. All lesions were biopsied using ultrasound-guided 14G core needles. Imaging characteristics (e.g., margins, echogenicity, calcifications), histopathological subtype, and immunohistochemical data were collected. Statistical methods included logistic regression, Chi-square tests, and Spearman’s correlation to assess associations between BI-RADS, histology, and immunohistochemical markers. Results: BI-RADS 5 lesions showed a 91% malignancy rate. Evaluated features included spiculated margins, pleomorphic microcalcifications, and hypoechoic masses with posterior shadowing, and were correlated with histological and immunohistochemical results. Invasive tumors typically appeared as irregular, hypoechoic masses with posterior shadowing, while mucinous carcinomas mimicked benign features. Higher BI-RADS scores correlated significantly with increased Ki-67 index (ρ = 0.76, p < 0.001). Logistic regression yielded an AUC of 0.877, with 93.8% sensitivity and 80.0% specificity. Conclusions: BI-RADS scoring effectively predicts malignancy and correlates with tumor proliferative markers. Integrating imaging, histopathology, and molecular profiling enhances diagnostic precision and supports risk-adapted clinical management in breast oncology. Full article

Introduction: A potential prognostic biomarker for predicting the response to immunotherapy in breast cancer (BC) is tumor-infiltrating lymphocytes (TILs). The purpose of this research is to examine if preoperative characteristics of breast magnetic resonance imaging (MRI) may be used to predict TIL levels in a group of BC patients. In addition, we aimed to assess any potential relationship between the various tumor biology subgroups and MR imaging characteristics. Materials and Methods: This retrospective analysis comprised 145 participants with histologically confirmed BC who had preoperative DCE MRI. We collected and examined patient information as well as tumor MRI features, such as size and shape, edema, necrosis, multifocality/multicentricity, background parenchymal enhancement (BPE), and apparent diffusion coefficient (ADC) values. We divided patients into two groups based on their TIL levels: low-TIL (<10%) and high-TIL groups (≥10%). Following core needle biopsy, tumors were categorized as Luminal A, Luminal B, HER2+, and Triple Negative using immunohistochemical analysis. TIL levels were correlated with tumor biological profiles and MRI features using both parametric and non-parametric tests. Results: Patients were categorized as having a high TIL level (≥10%; 54/145 patients) and a low TIL level (<10%; 91/145 patients) based on the median TIL level of 10%. Of the lesions, 13 were HER2-positive, 16 were Triple Negative, 49 were Luminal A, and 67 were Luminal B. Higher TIL levels were statistically correlated with TNBC (11/16 individuals, p: 0.007). ADC values (p = 0.01), BPE levels (p = 0.008), and TIL levels were all significantly negatively correlated. Significantly more homogenous enhancement was seen in tumors with elevated TIL levels (p = 0.001). The ADC values and the enhancing characteristics were the most important factors in predicting TIL levels, according to logistic regression analysis, and when combined, they demonstrated the strongest ability to distinguish between the two groups (AUC = 0.744). Conclusions: MRI features, particularly ADC values and enhancement characteristics, may play a pivotal role in the assessment of TIL levels in BC before surgery. This could help patients to better customize treatments to the features of their tumors. Full article

Luminal B breast cancer (LBBC) represents an aggressive, high-grade ER+ disease, associated with a high proliferation rate, higher mutation burden, and higher probability of eliciting the immune response. Clinical and pathological data from 89 patients of stage II-III, triple-negative (TN), and luminal B-like BC (LB-like BC) were included in the analysis. All patients were submitted to neoadjuvant chemotherapy (NACT). Quantitative and qualitative evaluations of TILs (Tumor-Infiltrating Lymphocytes) were performed on tissue microarrays constructed from pretreatment core-needle biopsy tumor specimens. The proportion of stromal TILs, CD8, CD4, and PD-L1 positive (+) immune cells (IC), as well as the number of FOXP3, CTLA4, and HSP-70+ IC, was observed concerning tumor immunophenotype, traditional clinicopathological prognostic factors, and tumor response to NACT. There was no statistically significant difference in the proportion of stromal TILs between the LB-like and TNBC (p = 0.344) cohorts. However, a higher CD4/CD8 ratio was associated with the TNBC biology (p = 0.018) and within the LB-like BC cohort with a high proliferation index and metastatic nodal involvement (p = 0.045, p = 0.015). Within the LB-like BC cohort, a higher expression of PD-L1 and HSP70+ IC was associated with a high proliferation index of tumor cells (p = 0.018, p = 0.040), massive metastatic nodal involvement (p = 0.002, p = 0.026), and higher stages of disease (p = 0.004, p = 0.042). Better response to NACT was associated with higher numbers of HSP70+ IC and higher proportions of CD8+ cells within the LB-like BC cohort (p = 0.045, p = 0.012). Routine evaluation of immune markers and HSP70 may help identify high-risk patients of LB-like breast cancer who would have a better response to NACT. Full article

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting. Full article

Metastases to the breast from non-mammary malignancies are rare, accounting for 0.1–5% of all breast malignancies. Neuroendocrine tumors (NETs) rarely metastasize to the breast. PET-CT somatostatin receptor imaging plays a pivotal role in the staging and follow-up of NETs, leveraging tracers like 68Ga-DOTATOC that bind to somatostatin receptors (SSTRs) expressed on tumor cells. While both primary and metastatic NETs express SSTRs, primary breast tumors may also exhibit an uptake of 68Ga-somatostatin analogs, making the differential diagnosis between primary breast tumors and neuroendocrine metastases challenging. Additionally, imaging characteristics of breast metastases from NETs are poorly documented in the literature, posing a diagnostic challenge that extends to pathology, particularly when in the absence of clinical suspicion. Misdiagnosis in such cases can lead to inappropriate therapeutic interventions. We report the case of a 75-year-old female patient with a history of pancreatic NET who presented to our breast clinic for further evaluation of a breast mass after a PET-CT scan revealed moderate 68Ga-DOTATOC uptake. Multimodality breast examination, including mammography and multiparametric US with B-mode, Color Doppler, Strain Elastography (SE), Shear Wave Elastography (SWE), and contrast-enhanced US (CEUS), was performed. Following a core biopsy, the lesion underwent surgical excision, revealing the diagnosis of NET metastasis. This case highlights a rare instance of neuroendocrine tumor metastasis to the breast, assessed using various ultrasound techniques, with detailed imaging and quantitative analysis. The comprehensive multimodal assessment contributes to the limited body of literature and provides elements for the differential diagnosis of a rare breast lesion that should always be considered in the presence of a known primary NET. Full article

Mammography is an essential tool in breast screening, often revealing lesions that appear as microcalcifications with or without an associated mass. Decisions about biopsy requirements are guided by the BI-RADS system, aiming to confirm the histopathology of suspicious lesions while avoiding unnecessary procedures. A vacuum-assisted breast biopsy (VABB) is a minimally invasive procedure for diagnosing breast abnormalities. Precise lesion targeting is ensured under stereotactic guidance, reducing the need for repeated procedures. Compared to traditional core needle biopsy (CNB) and fine-needle aspiration cytology (FNAC), it differs in using vacuum assistance to gather more tissue volume, increasing diagnostic accuracy and reducing the likelihood of histological underestimation. This is particularly crucial in cases where microcalcifications are the primary finding, as they are often the earliest signs of ductal carcinoma in situ (DCIS). Managing such findings requires precise diagnostic tools to differentiate benign from malignant lesions without subjecting patients to unnecessary surgical interventions. Building on several years of experience in our department, we have assembled a selection of ten interesting cases encountered in our clinical practice. Each case is documented with paired mammographic images and their corresponding image of histopathological findings, offering a comprehensive view of the diagnostic journey. These cases were selected for their educational value, highlighting the integration of imaging modalities, histopathological evaluation, and clinical decision-making. All cases underwent an extensive diagnostic workup at our facility. This compilation aims to provide valuable insights for both clinicians and researchers, offering a deeper understanding of advanced diagnostic techniques and their role in improving patient outcomes. Full article

Background: Functional tumor volume (FTV), measured from dynamic contrast-enhanced MRI, is an imaging biomarker that can predict treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The FTV-based predictive model, combined with core biopsy, informed treatment decisions of recommending patients with excellent responses to proceed to surgery early in a large NAC clinical trial. Methods: In this retrospective study, we constructed models using FTV measurements. We analyzed performance tradeoffs when a probability threshold was used to identify excellent responders through the prediction of pathology complete response (pCR). Individual models were developed within cohorts defined by the hormone receptor and human epidermal growth factor receptor 2 (HR/HER2) subtype. Results: A total of 814 patients enrolled in the I-SPY 2 trial between 2010 and 2016 were included with a mean age of 49 years (range: 24 to 77). Among these patients, 289 (36%) achieved pCR. The area under the ROC curve (AUC) ranged from 0.68 to 0.74 for individual HR/HER2 subtypes. When probability thresholds were chosen based on minimum positive predictive value (PPV) levels of 50%, 70%, and 90%, the PPV-sensitivity tradeoff varied among subtypes. The highest sensitivities (100%, 87%, 45%) were found in the HR−/HER2+ sub-cohort for probability thresholds of 0, 0.62, and 0.72; followed by the triple-negative sub-cohort (98%, 52%, 4%) at thresholds of 0.13, 0.58, and 0.67; and HR+/HER2+ (78%, 16%, 8%) at thresholds of 0.34, 0.57, and 0.60. The lowest sensitivities (20%, 0%, 0%) occurred in the HR+/HER2− sub-cohort. Conclusions: Predictive models developed using imaging biomarkers, alongside clinically validated probability thresholds, can be incorporated into decision-making for precision oncology. Full article

Background and clinical significance: Phyllodes tumors (PTs) are rare stromal neoplasms originating in the connective tissue of the breast, distinct from carcinomas that arise from the ducts or lobules. These tumors exhibit a broad spectrum of morphologic features and are traditionally classified as benign, borderline, or malignant. Case presentation: We present the case of a 71-year-old female diagnosed with a malignant PT and treated at our hospital. The patient noticed a gradually enlarging lump in her right breast over several months. Mammography was inconclusive, but an ultrasound later revealed a lobulated, firm mass, classified as BIRADS 5. Physical examination identified a 20 cm mass, and core needle biopsy suggested a borderline PT. Following lumpectomy, pathology confirmed a malignant tumor with narrow surgical margins (0.1 cm). Although mastectomy was recommended to achieve wider margins, the patient opted for adjuvant radiotherapy. She received 50 Gy in 25 fractions to the whole breast, followed by a 16 Gy boost to the tumor bed in 8 fractions. The treatment was well tolerated and completed successfully. Initially, the patient’s therapeutic management was delayed due to a combination of personal and organizational factors. However, the process was later streamlined through the use of a novel digital tool developed to facilitate the entire patient journey within our hospital system. Conclusions: This case highlights the diagnostic complexities of PTs, the critical need for effective collaboration between specialties, and the importance of timely treatment planning for optimal patient outcomes. Full article

B3 breast lesions, classified as lesions of uncertain malignant potential, present a significant diagnostic and therapeutic challenge due to their heterogeneous nature and variable risk of progression to malignancy. These lesions, which include atypical ductal hyperplasia (ADH), papillary lesions (PLs), flat epithelial atypia (FEA), radial scars (RSs), lobular neoplasia (LN), and phyllodes tumors (PTs), occupy a “grey zone” between benign and malignant pathologies, making their management complex and often controversial. This article explores the diagnostic difficulties associated with B3 lesions, focusing on the limitations of current imaging techniques, including mammography, ultrasound, and magnetic resonance imaging (MRI), as well as the challenges in histopathological interpretation. Core needle biopsy (CNB) and vacuum-assisted biopsy (VAB) are widely used for diagnosis, but both methods have inherent limitations, including sampling errors and the inability to determine malignancy in some cases definitively. The therapeutic approach to B3 lesions is nuanced, with treatment decisions strongly influenced by factors such as the lesion size, radiological findings, histopathological characteristics, and patient factors. While some lesions can be safely monitored with watchful waiting, others may require vacuum-assisted excision (VAE) or surgical excision to rule out malignancy. The decision-making process is further complicated by the discordance between the BI-RADS score and biopsy results, as well as the presence of additional risk factors, such as microcalcifications. This review provides an in-depth analysis of the current diagnostic challenges and treatment strategies for B3 lesions, emphasizing the importance of a multidisciplinary approach to management. By synthesizing the most recent research, this article aims to provide clinicians with a clearer understanding of the complexities involved in diagnosing and treating B3 breast lesions while highlighting areas for future research, such as artificial intelligence and genomics, to improve the diagnostic accuracy and patient outcomes. Full article

Background: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Accurate staging, including the detection of axillary metastases, is vital for treatment planning. This study evaluates the efficacy of MRI relaxometry as a diagnostic tool for axillary lymph node metastases in breast cancer patients. Methods: A prospective study was conducted on 67 consecutive breast cancer patients. Relaxometry parameters, including T2Max, T2Min, and 1HAv, were assessed using 1.5 Tesla MRI. All axillary metastases were histologically confirmed using core-needle biopsy or surgical specimens. Statistical analyses included ROC curves, chi-square tests, and multivariate analysis to determine correlations between imaging findings and pathological results. Results: Significant associations were found between T2Min-ipsilateral (p = 0.018), 1HAv-ipsilateral (p = 0.003), and axillary metastases. ROC analysis demonstrated that T2Min-ipsilateral and 1HAv-ipsilateral have modest to acceptable discriminatory abilities (AUC = 0.681 and AUC = 0.740, respectively). Combined clinical and imaging models enhanced diagnostic accuracy (AUC = 0.749). Conclusions: MRI relaxometry improves the detection of axillary metastases in breast cancer, particularly when integrated with clinical and pathological evaluations. Full article

Background and Objectives: Among breast cancer molecular types, HER2 positive and triple negative (TN) subtypes have the highest likelihood of pathological complete response (pCR), which is a surrogate marker for reduced recurrence and improved patient survival after neoadjuvant systemic treatment (NST). Preoperative pathological identification of these exceptional responders is a new era. Therefore, we aimed to determine the accuracy of trucut biopsy in identifying the exceptional responders in selected molecular subtypes of breast cancer patients. Materials and Methods: This two-centre, observational, single-arm, prospective, pilot study was conducted between January and September 2024. The patients with TN or HER2 positive breast cancer whose breast tumour had completely disappeared on the radiological assessment including MRI after neoadjuvant therapy were enrolled. To assess neoadjuvant treatment response, a standardised biopsy protocol was used, consisting of 10 samples from the marked tumour area per patient by 12 G core needle. Then, all patients underwent surgery. The pathological results of both postchemo-presurgical biopsy and surgical breast specimen were compared. Results: The study included 20 patients. The mean age of the patients was 47.3 years. The median tumour size at diagnosis was 23.1 mm. All biopsy results were concordant with the findings of surgical specimen. Seventeen patients had a complete response. The remaining 3 patients had residual disease. Conclusions: Along with thorough patient selection, post-chemo radiological assessment and the reliable biopsy technique are the key points in accurately predicting response to neoadjuvant treatment. If an image-guided core biopsy confirms elimination of tumour tissue at the marked tumour area with a radiological complete response on MRI after NST in breast cancer patients with selected molecular subtypes, these may be suitable patients as exceptional responders in whom we can omit breast surgery. Full article

Background/Objectives: B3 breast lesions, characterized by uncertain malignant potential, pose a significant challenge for clinicians. With the increasing use of preoperative biopsies, there is a need for careful management strategies, including watchful waiting, vacuum-assisted excision (VAE), and surgery. This study aims to assess the concordance between preoperative biopsy findings and postoperative histology, with a focus on evaluating the positive predictive value (PPV) for malignancy in B3 lesions. Methods: Over a seven-year period, 305 patients preoperatively diagnosed with B3 lesions were treated at the Multidisciplinary Breast Center of “Fondazione Policlinico Universitario Agostino Gemelli IRCCS” in Rome. All cases were reviewed at multidisciplinary meetings involving surgeons, radiologists, histopathologists, and oncologists. Preoperative diagnoses were obtained by ultrasound-guided core needle biopsies (CNBs) or stereotactic-guided vacuum-assisted biopsies (VABs). The radiological features were assessed using the Breast Imaging Reporting and Data System (BIRADS), and discrepancies between radiological and pathological findings were recorded. The biopsy results were compared with the postoperative histological findings to calculate the PPV for malignancy. Results: Of the 305 B3 lesions biopsied, 242 were confirmed as B3 on the final histological examination, resulting in a concordance rate of 79.3%. A total of 63 cases were upgraded to malignancy on postoperative histology, yielding a cumulative upgrade rate of 20.7%. The PPV for malignancy was 31.5% for atypical ductal hyperplasia (ADH), 27.6% for lobular neoplasia (LN), 22.9% for papillary lesions (PLs), 12.1% for flat epithelial atypia (FEA), 10.4% for radial scar (RS), and 10.3% for phyllodes tumors (PTs). Conclusions: Our findings demonstrate that the cumulative PPV for B3 lesions, as well as the PPV for each subtype, are consistent with the existing literature. The factors influencing the PPV include the use of CNB versus VAB, discordance between the BIRADS and biopsy results, the presence of atypia in the biopsy sample, the presence of microcalcifications on mammography, mass lesions identified on MRI, and the extent of the lesion. These factors should be considered in the personalized management of B3 lesions, potentially leading to more targeted and less invasive approaches in the future. Full article

Objectives: This study aimed to investigate whether the apparent diffusion coefficient (ADC) maps values of breast lesions presenting as non-mass enhancement (NME) on MRI could predict benign or malignant pathohistological findings. Materials and Methods: This retrospective single-center study included 136 female patients with NME and corresponding ultrasound correlate and a subsequent ultrasound-guided core needle biopsy. The patients were subdivided into benign or malignant subgroups based on pathology reports, which served as the gold standard. Blinded to the pathological results, two radiologists independently measured the ADC values of the depicted NME using punctate, 10 mm and whole tumor regions of interest (ROIs) wherever applicable. The mean of all measurements was also analyzed and compared with the pathologic subdivision. Results: The sensitivity of whole tumor ROI in detecting benign NME is 91% compared to 74% for 10 mm ROI and 78% for punctate ROI. No significant differences in ADC values were observed when comparing fatty breast tissue and dense breast tissue. Conclusions: There were differences in ADC values between benign and malignant findings using all types of measurements, where the whole tumor ROI was the most sensitive. Full article