Performance of MRI for standardized lymph nodes assessment in breast cancer: are we ready for Node-RADS?

OBJECTIVES: The Node-RADS score was recently introduced to offer a standardized assessment of lymph node invasion (LNI). We tested its diagnostic performance in accurately predicting LNI in breast cancer (BC) patients with magnetic resonance imaging. The study also explores the consistency of the score across three readers. MATERIALS AND METHODS: A retrospective study was conducted on BC patients who underwent preoperative breast contrast-enhanced magnetic resonance imaging and lymph node dissection between January 2020 and January 2023. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for different Node-RADS cut-off values. Pathologic results were considered the gold standard. The overall diagnostic performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). A logistic regression analysis was performed. Cohen's Kappa analysis was used for inter-reader agreement. RESULTS: The final population includes 192 patients and a total of 1134 lymph nodes analyzed (372 metastatic and 762 benign). Increasing the Node-RADS cut-off values, specificity and PPV rose from 71.4% to 100% and 76.7% to 100%, respectively, for Reader 1, 69.4% to 100% and 74.6% to 100% for Reader 2, and from 64.3% to 100% and 72% to 100% for Reader 3. Node-RADS > 2 could be considered the best cut-off value due to its balanced performance. Node-RADS exhibited a similar AUC for the three readers (0.97, 0.93, and 0.93). An excellent inter-reader agreement was found (Kappa values between 0.71 and 0.83). CONCLUSIONS: The Node-RADS score demonstrated moderate-to-high overall accuracy in identifying LNI in patients with BC, suggesting that the scoring system can aid in the identification of suspicious lymph nodes and facilitate appropriate treatment decisions. CLINICAL RELEVANCE STATEMENT: Node-RADS > 2 can be considered the best cut-off for discriminating malignant nodes, suggesting that the scoring system can effectively help identify suspicious lymph nodes by staging the disease and providing a global standardized language for clear communication. KEY POINTS: Axillary lymphadenopathies in breast cancer are crucial for determining the disease stage. Node-RADS was introduced to provide a standardized evaluation of breast cancer lymph nodes. RADS > 2 can be considered the best cut-off for discriminating malignant nodes.

Cryoablation for the treatment of breast cancer: immunological implications and future perspectives. Utopia or reality?

Cryoablation is a minimally invasive technique currently employed in breast cancer care, that uses freeze and thaw cycles to treat benign breast lesions, small breast cancers or focal sites of metastatic disease in patients not eligible for surgery. The final goal of this procedure is to destroy breast cancer cells using extreme cold. In addition, several studies have shown that this technique seems to have an enhancing effect on the immune response, especially by increasing the expression of tumor neoantigens specific to tumor cells, which are then attacked and destroyed. Exploiting this effect, cryoablation in combination with immunotherapy could be the key to treating early-stage breast cancers or patients who are unsuitable for surgery. According to some recent studies, there are other potential tools that could be used to enhance the therapeutic effect of cryoablation, such as FE3O4 nanoparticles or the manipulation of aquaporin expression. The aim of this narrative review is to summarize the current evidence regarding the use, indications, advantages and disadvantages of cryoablation in the treatment of breast cancer.

Could breast multiparametric MRI discriminate between pure ductal carcinoma in situ and microinvasive carcinoma?

BACKGROUND: Ductal carcinoma in situ (DCIS) is often reclassified as invasive cancer in the final pathology report of the surgical specimen. It is of significant clinical relevance to acknowledge the possibility of underestimating invasive disease when utilizing preoperative biopsies for a DCIS diagnosis. In cases where such histologic upgrades occur, it is imperative to consider them in the preoperative planning process, including the potential inclusion of sentinel lymph node biopsy due to the risk of axillary lymph node metastasis. PURPOSE: To assess the capability of breast multiparametric magnetic resonance imaging (MP-MRI) in differentiating between pure DCIS and microinvasive carcinoma (MIC). MATERIAL AND METHODS: Between January 2018 and November 2022, this retrospective study enrolled patients with biopsy-proven DCIS who had undergone preoperative breast MP-MRI. We assessed various MP-MRI features, including size, morphology, margins, internal enhancement pattern, extent of disease, presence of peritumoral edema, time-intensity curve value, diffusion restriction, and ADC value. Subsequently, a logistic regression analysis was conducted to explore the association of these features with the pathological outcome. RESULTS: Of 129 patients with biopsy-proven DCIS, 36 had foci of micro-infiltration on surgical specimens and eight were diagnosed with invasive ductal carcinoma (IDC). The presence of micro-infiltration foci was significantly associated with several MP-MRI features, including tumor size (P <0.001), clustered ring enhancement (P <0.001), segmental distribution (P <0.001), diffusion restriction (P = 0.005), and ADC values <1.3 × 10-3 mm2/s (P = 0.004). CONCLUSION: Breast MP-MRI has the potential to predict the presence of micro-infiltration foci in biopsy-proven DCIS and may serve as a valuable tool for guiding therapeutic planning.

Diagnostic Performance of Contrast-Enhanced Digital Mammography versus Conventional Imaging in Women with Dense Breasts.

The aim of this prospective study was to compare the diagnostic performance of contrast-enhanced mammography (CEM) versus digital mammography (DM) combined with breast ultrasound (BUS) in women with dense breasts. Between March 2021 and February 2022, patients eligible for CEM with the breast composition category ACR BI-RADS c-d at DM and an abnormal finding (BI-RADS 3-4-5) at DM and/or BUS were considered. During CEM, a nonionic iodinated contrast agent (Iohexol 350 mg I/mL, 1.5 mL/kg) was power-injected intravenously. Images were evaluated independently by two breast radiologists. Findings classified as BI-RADS 1-3 were considered benign, while BI-RADS 4-5 were considered malignant. In case of discrepancies, the higher category was considered for DM+BUS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated, using histology/≥12-month follow-up as gold standards. In total, 51 patients with 65 breast lesions were included. 59 (90.7%) abnormal findings were detected at DM+BUS, and 65 (100%) at CEM. The inter-reader agreement was excellent (Cohen's k = 0.87 for DM+BUS and 0.97 for CEM). CEM showed a 93.5% sensitivity (vs. 90.3% for DM+BUS), a 79.4-82.4% specificity (vs. 32.4-35.5% for DM+BUS) (McNemar p = 0.006), a 80.6-82.9% PPV (vs. 54.9-56.0% for DM+BUS), a 93.1-93.3% NPV (vs. 78.6-80.0% for DM+BUS), and a 86.1-87.7% accuracy (vs. 60.0-61.5% for DM+BUS). The AUC was higher for CEM than for DM+BUS (0.865 vs. 0.613 for Reader 1, and 0.880 vs. 0.628, for Reader 2) (p < 0.001). In conclusion, CEM had a better diagnostic performance than DM and BUS alone and combined together in patients with dense breasts.

Pregnancy-Associated Breast Cancer: A Diagnostic and Therapeutic Challenge.

Pregnancy-associated breast cancer (PABC) is commonly defined as a breast cancer occurring during pregnancy, throughout 1 year postpartum, or during lactation. Despite being a rare circumstance, PABC is one of the most common types of malignancies occurring during pregnancy and lactation, with growing incidence in developed countries, due both to decreasing age at onset of breast cancer and to increasing maternal age. Diagnosis and management of malignancy in the prenatal and postnatal settings are challenging for practitioners, as the structural and functional changes that the breast undergoes may be misleading for both the radiologist and the clinician. Furthermore, safety concerns for the mother and child, as well as psychological aspects in this unique and delicate condition, need to be constantly considered. In this comprehensive review, clinical, diagnostic, and therapeutic aspects of PABC (including surgery, chemotherapy and other systemic treatments, and radiotherapy) are presented and fully discussed, based on medical literature, current international clinical guidelines, and systematic practice.

Precision Medicine in Breast Cancer: Do MRI Biomarkers Identify Patients Who Truly Benefit from the Oncotype DX Recurrence Score® Test?

The aim of this study was to combine breast MRI-derived biomarkers with clinical-pathological parameters to identify patients who truly need an Oncotype DX Breast Recurrence Score® (ODXRS) genomic assay, currently used to predict the benefit of adjuvant chemotherapy in ER-positive/HER2-negative early breast cancer, with the ultimate goal of customizing therapeutic decisions while reducing healthcare costs. Patients who underwent a preoperative multiparametric MRI of the breast and ODXRS tumor profiling were retrospectively included in this study. Imaging sets were evaluated independently by two breast radiologists and classified according to the 2013 American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) lexicon. In a second step of the study, a combined oncologic and radiologic assessment based on clinical-pathological and radiological data was performed, in order to identify patients who may need adjuvant chemotherapy. Results were correlated with risk levels expressed by ODXRS, using the decision made on the basis of the ODXRS test as a gold standard. The χ2 test was used to evaluate associations between categorical variables, and significant ones were further investigated using logistic regression analyses. A total of 58 luminal-like, early-stage breast cancers were included. A positive correlation was found between ODXRS and tumor size (p = 0.003), staging (p = 0.001) and grading (p = 0.005), and between BI-RADS categories and ODXRS (p < 0.05 for both readers), the latter being confirmed at multivariate regression analysis. Moreover, BI-RADS categories proved to be positive predictors of the therapeutic decision taken after performing an ODXRS assay. A statistically significant association was also found between the therapeutic decision based on the ODXRS and the results of combined onco-radiologic assessment (p < 0.001). Our study suggests that there is a correlation between BI-RADS categories at MRI and ODXRS and that a combined onco-radiological assessment may predict the decision made on the basis of the results of ODXRS genomic test.

Do body composition parameters correlate with response to targeted therapy in ER+/HER2- metastatic breast cancer patients? Role of sarcopenia and obesity.

Purpose: To investigate the association between body composition parameters, sarcopenia, obesity and prognosis in patients with metastatic ER+/HER2- breast cancer under therapy with cyclin-dependent kinase (CDK) 4/6 inhibitors. Methods: 92 patients with biopsy-proven metastatic ER+/HER2- breast cancer, treated with CDK 4/6 inhibitors between 2018 and 2021 at our center, were included in this retrospective analysis. Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT) and Skeletal Muscle Index (SMI) were measured before starting therapy with CDK 4/6 inhibitors (Palbociclib, Abemaciclib or Ribociclib). Measurements were performed on a computed tomography-derived abdominal image at third lumbar vertebra (L3) level by an automatic dedicated software (Quantib body composition®, Rotterdam, Netherlands). Visceral obesity was defined as a VAT area > 130 cm2. Sarcopenia was defined as SMI < 40 cm2/m2. Changes in breast lesion size were evaluated after 6 months of treatment. Response to therapy was assessed according to RECIST 1.1 criteria. Spearman's correlation and χ2 analyses were performed. Results: Out of 92 patients, 30 were included in the evaluation. Of the 30 patients (mean age 53 ± 12 years), 7 patients were sarcopenic, 16 were obese, while 7 patients were neither sarcopenic nor obese. Statistical analyses showed that good response to therapy was correlated to higher SMI values (p < 0.001), higher VAT values (p = 0.008) and obesity (p = 0.007); poor response to therapy was correlated to sarcopenia (p < 0.001). Moreover, there was a significant association between sarcopenia and menopause (p = 0.021) and between sarcopenia and the persistence of axillary lymphadenopathies after treatment (p = 0.003), while the disappearance of axillary lymphadenopathies was associated with obesity (p = 0.028). Conclusions: There is a growing interest in body composition, especially in the field of breast cancer. Our results showed an interesting correlation between sarcopenia and progression of disease, and demonstrated that VAT can positively influence the response to targeted therapy with CDK 4/6 inhibitors. Larger-scale studies are needed to confirm these preliminary results. Clinical Relevance: Sarcopenia and obesity seem to predict negative outcomes in many oncologic entities. Their prevalence and impact in current breast cancer care are promising but still controversial.

Radiologic-pathologic correlation in breast cancer: do MRI biomarkers correlate with pathologic features and molecular subtypes?

BACKGROUND: Breast cancer (BC) includes different pathological and molecular subtypes. This study aimed to investigate whether multiparametric magnetic resonance imaging (mpMRI) could reliably predict the molecular status of BC, comparing mpMRI features with pathological and immunohistochemical results. METHODS: This retrospective study included 156 patients with an ultrasound-guided biopsy-proven BC, who underwent breast mpMRI (including diffusion-weighted imaging) on a 3-T scanner from 2017 to 2020. Histopathological analyses were performed on the surgical specimens. Kolmogorov-Smirnov Z, χ2, and univariate and multivariate logistic regression analyses were performed. RESULTS: Fifteen patients were affected with ductal carcinoma in situ, 122 by invasive carcinoma of no special type, and 19 with invasive lobular carcinoma. Out of a total of 141 invasive cancers, 45 were luminal A-like, 54 luminal B-like, 5 human epidermal growth factor receptor 2 (HER2) positive, and 37 triple negative. The regression analyses showed that size < 2 cm predicted luminal A-like status (p = 0.025), while rim enhancement (p < 0.001), intralesional necrosis (p = 0.001), peritumoural oedema (p < 0.001), and axillary adenopathies (p = 0.012) were negative predictors. Oppositely, round shape (p = 0.001), rim enhancement (p < 0.001), intralesional necrosis (p < 0.001), and peritumoural oedema (p < 0.001) predicted triple-negative status. CONCLUSIONS: mpMRI has been confirmed to be a valid noninvasive predictor of BC subtypes, especially luminal A and triple negative. Considering the central role of pathology in BC diagnosis and immunohistochemical profiling in the current precision medicine era, a detailed radiologic-pathologic correlation seems vital to properly evaluate BC.

Breast imaging: Beyond the detection.

Breast cancer is a heterogeneous disease nowadays, including different biological subtypes with a variety of possible treatments, which aim to achieve the best outcome in terms of response to therapy and overall survival. In recent years breast imaging has evolved considerably, and the ultimate goal is to predict these strong phenotypic differences noninvasively. Indeed, breast cancer multiparametric studies can highlight not only qualitative imaging parameters, as the presence/absence of a likely malignant finding, but also quantitative parameters, suggesting clinical-pathological features through the evaluation of imaging biomarkers. A further step has been the introduction of artificial intelligence and in particular radiogenomics, that investigates the relationship between breast cancer imaging characteristics and tumor molecular, genomic and proliferation features. In this review, we discuss the main techniques currently in use for breast imaging, their respective fields of use and their technological and diagnostic innovations.

Gadoteridol-enhanced MRI of the breast: can contrast agent injection rate impact background parenchymal enhancement?

BACKGROUND: Normal background parenchymal enhancement (BPE) is a dynamic parameter affected by multiple factors. PURPOSE: To determine whether contrast agent injection rate affects the degree of BPE in women undergoing breast magnetic resonance imaging (MRI). MATERIAL AND METHODS: A total of 85 patients included in our prospective study randomly received 0.1 mmol/kg gadoteridol at a rate of 3 mL/s (group A; n = 46) or 2 mL/s (group B; n = 39). Breast MRI was performed at 3T using a standard protocol including postcontrast axial 3D GRE T1-weighted sequences. Two expert breast radiologists, blinded to clinical and radiological information, independently quantified BPE on early postcontrast subtracted images, assigning a score of 1-4. Mean comparison and regression analysis were performed to assess the influence of injection rate on BPE. RESULTS: Groups were homogeneous in terms of age and final BI-RADS score. The mean BPE score was significantly lower among patients in group A (mean of two readers: 1.36 vs. 1.90; P < 0.01) with 70%-72% of patients assigned a BPE score of 1, compared with 36%-38% of patients in group B. Lower BPE scores were noted with the higher flow rate in subgroup analyses of both pre- and postmenopausal women, although the effect was more evident in premenopausal women. Regression analysis confirmed that the likelihood of a BPE 1 score was significantly increased with a higher flow rate (P < 0.01). The inter-reader agreement was excellent (0.83). CONCLUSION: A higher contrast agent injection flow rate (3 mL/s) during breast MRI significantly reduces the degree of BPE, potentially allowing improved diagnostic accuracy by reducing false-positive and false-negative findings.

Ultrasound-guided 8-Gauge vacuum-assisted excision for selected B3 breast lesions: a preliminary experience.

PURPOSE: Nowadays, surgical excision is no longer justified for all B3 lesions and a minimally-invasive therapeutic treatment has been encouraged. The aim of this study was to evaluate the feasibility and the therapeutic efficacy of ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of selected breast lesions of uncertain malignant potential (B3). MATERIAL AND METHODS: From July 2018 to December 2019, 11/48 breast lesions classified as B3 after ultrasound-guided core needle biopsy were treated with US-VAE in our Institution. Inclusion criteria were: B3 nodules ultrasonographically detectable for which VAE is recommended by international guidelines2, size ranging between 5 and 25 mm, circumscribed margins, and lesion position at least 5 mm from the skin and the nipple. A radiological follow-up to evaluate the completeness of excision, the presence of post-procedural hematoma or of residual disease/recurrence was performed after 10 and 30 days and 6 and 12 months. 12-month ultrasound was considered the gold standard. All patients were asked to complete a satisfaction survey and a full assessment of the costs of US-VAE was performed. RESULTS: Complete excision was achieved in 81.8% of US-VAE. No lesions were upgraded to carcinoma and no patients had to undergo surgery. No complications occurred during or after US-VAE. All patients were satisfied with the procedure and the cosmetic result (100%). US-VAE cost approximately 422 Euros per procedure. CONCLUSION: US-VAE has proven to be an optimal tool for the therapeutic excision of selected B3 lesions, with high success rate, good patient compliance and considerable money savings compared to surgery. This technique has the potential to reduce unnecessary surgery and healthcare costs.

Preoperative Staging in Breast Cancer: Intraindividual Comparison of Unenhanced MRI Combined With Digital Breast Tomosynthesis and Dynamic Contrast Enhanced-MRI.

OBJECTIVES: To evaluate the accuracy in lesion detection and size assessment of Unenhanced Magnetic Resonance Imaging combined with Digital Breast Tomosynthesis (UE-MRI+DBT) and Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), in women with known breast cancer. METHODS: A retrospective analysis was performed on 84 patients with histological diagnosis of breast cancer, who underwent MRI on a 3T scanner and DBT over 2018-2019, in our Institution. Two radiologists, with 15 and 7 years of experience in breast imaging respectively, reviewed DCE-MRI and UE-MRI (including DWI and T2-w) + DBT images in separate reading sections, unaware of the final histological examination. DCE-MRI and UE-MRI+DBT sensitivity, positive predictive value (PPV) and accuracy were calculated, using histology as the gold standard. Spearman correlation and regression analyses were performed to evaluate lesion size agreement between DCE-MRI vs Histology, UE-MRI+DBT vs Histology, and DCE-MRI vs UE-MRI+DBT. Inter-reader agreement was evaluated using Cohen's κ coefficient. McNemar test was used to identify differences in terms of detection rate between the two methodological approaches. Spearman's correlation analysis was also performed to evaluate the correlation between ADC values and histological features. RESULTS: 109 lesions were confirmed on histological examination. DCE-MRI showed high sensitivity (100% Reader 1, 98% Reader 2), good PPV (89% Reader 1, 90% Reader 2) and accuracy (90% for both readers). UE-MRI+DBT showed 97% sensitivity, 91% PPV and 92% accuracy, for both readers. Lesion size Spearman coefficient were 0.94 (Reader 1) and 0.91 (Reader 2) for DCE-MRI vs Histology; 0.91 (Reader 1) and 0.90 (Reader 2) for UE-MRI+DBT vs Histology (p-value <0.001). DCE-MRI vs UE-MRI+DBT regression coefficient was 0.96 for Reader 1 and 0.94 for Reader 2. Inter-reader agreement was 0.79 for DCE-MRI and 0.94 for UE-MRI+DBT. McNemar test did not show a statistically significant difference between DCE-MRI and UE-MRI+DBT (McNemar test p-value >0.05). Spearman analyses showed an inverse correlation between ADC values and histological grade (p-value <0.001). CONCLUSIONS: DCE-MRI was the most sensitive imaging technique in breast cancer preoperative staging. However, UE-MRI+DBT demonstrated good sensitivity and accuracy in lesion detection and tumor size assessment. Thus, UE-MRI could be a valid alternative when patients have already performed DBT.

Can MRI Biomarkers Predict Triple-Negative Breast Cancer?

The purpose of this study was to investigate MRI features of triple-negative breast cancer (TNBC) compared with non-TNBC, to predict histopathological results. In the study, 26 patients with TNBC and 24 with non-TNBC who underwent multiparametric MRI of the breast on a 3 T magnet over a 10-months period were retrospectively recruited. MR imaging sets were evaluated by two experienced breast radiologists in consensus and classified according to the 2013 American College of Radiology (ACR) BI-RADS lexicon. The comparison between the two groups was performed using the Chi-square test and followed by logistic regression analyses. We found that 92% of tumors presented as mass enhancements (p = 0.192). 41.7% of TNBC and 86.4% of non-TNBC had irregular shape (p = 0.005); 58.3% of TNBC showed circumscribed margins, compared to 9.1% of non-TNBC masses (p = 0.001); 75% of TNBC and 9.1% of non-TNBC showed rim enhancement (p < 0.001). Intralesional necrosis was significantly associated with TNBC (p = 0.016). Rim enhancement and intralesional necrosis risulted to be positive predictors at univariate analysis (OR = 29.86, and 8.10, respectively) and the multivariate analysis confirmed that rim enhancement is independently associated with TNBC (OR = 33.08). The mean ADC values were significantly higher for TNBC (p = 0.011). In conclusion, TNBC is associated with specific MRI features that can be possible predictors of pathological results, with a consequent prognostic value.

Peritumoral edema as a biomarker of the aggressiveness of breast cancer: results of a retrospective study on a 3 T scanner.

PURPOSE: To determine whether there is a correlation between the presence of peritumoral edema detected on T2-weighted sequences and pathological prognostic factors and specific biological subtypes of breast cancer. METHODS: A retrospective study on 120 women with invasive breast cancer, who underwent breast MRI on a 3 T scanner over a period of 12 months, was performed. Peritumoral edema was assessed visually by two breast radiologist in consensus and patients were consequently divided into two groups. For each lesion dimensions, histology and molecular profiling were evaluated. The comparison between the two groups was performed using the χ2 test, subsequently carrying out a univariate and a multivariate logistic regression analysis. RESULTS: 41 (34.2%) invasive breast cancers with perilesional edema and 79 (65.8%) without edema were identified. A significant association between the presence of perilesional edema and a larger lesion size (p = 0.0001), grade 3 (p < 0.001) and a higher Ki-67 index (p < 0.001) was found. The multivariate analysis confirmed that a larger tumor size is independently associated with peritumoral edema. A total of 101 (84.2%) luminal-like, 8 (6.7%) HER2-positive, and 11 (9.2%) triple-negative tumors were included in the study. Peritumoral edema turned out to be less frequently associated with luminal-like lesions (p < 0.001), while the luminal A status was found to have a significant association with the absence of peritumoral edema in the univariate analysis. CONCLUSION: The detection of peritumoral edema on T2-weighted sequences should be considered as a valid additional prognostic tool in the evaluation of breast cancer, since it is associated with biologically aggressive non-luminal breast cancers, characterized by large dimension, high tumor grade, and high Ki-67 values.

Breast Magnetic Resonance Spectroscopy at 3 T in Biopsy-Proven Breast Cancers: Does Choline Peak Correlate With Prognostic Factors?

OBJECTIVES: The role of functional techniques, such as magnetic resonance spectroscopy (H-MRS), as noninvasive tools to increase breast MR imaging reliability has been widely investigated during the last 2 decades. Considering the growing interest in tumor biology and its influence on functional parameters, the aim of this study was to investigate the relationship between H-MRS parameters and breast cancer biomarkers and to evaluate whether the results of H-MRS at 3 T can correlate with established breast cancer prognostic factors in our clinical experience. MATERIALS AND METHODS: One hundred two patients with biopsy-proven breast cancer underwent 3 T breast MR imaging. Single-voxel H-MRS was performed after the T1-weighted sequence, using a PRESS water-suppressed sequence (BREASE). Data were collected from a single rectangular volume of interest that encompassed the lesion. Magnetic resonance images and spectra of 102 Breast Imaging Reporting and Data System 6 lesions were prospectively evaluated by 2 radiologists in consensus. H-MRS results were considered positive if the choline peak signal-to-noise ratio was 2 or higher. H-MRS findings were then compared with morphological features and to histological findings, such as lesion size, nuclear grade, Ki-67, hormone receptor status, and Her2 expression. RESULTS: Elevated levels of total choline were detectable in 68/102 cases (66.67%) and undetectable in 34/102 (33.33%). A statistically significant association between the presence of choline peak and higher tumor grading (P < 0.0001), greater Ki-67 value (P < 0.0001), and larger lesion size (P < 0.0001) was found. No statistically significant associations were observed between choline peak and the luminal subgroups, even if higher levels of choline were more frequent in nonluminal A lesions. CONCLUSIONS: Our study confirms that 3 T breast H-MRS can be a valid additional tool to obtain further information about breast cancer biology and to predict tumor aggressiveness, because the detection of elevated levels of total choline in the spectrum is associated with a biologically aggressive breast cancer phenotype (large dimensions, grade 3, high values of Ki-67). Our results need to be validated in standardized larger-scale studies.