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.

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.