Discussing the safety and effectiveness of transcatheter arterial embolization combined with intravenous chemotherapy in treating locally advanced breast cancer.

To investigate the efficacy and safety of drug-eluting bead-transarterial chemoembolization (DEB-TACE) combined with systemic chemotherapy in HR+/Her2- locally advanced breast cancer (LABC) patients. A controlled study was conducted on LABC patients treated at Jianyang People's Hospital and the First Affiliated Hospital of Chengdu Medical College from December 2020 to June 2022. The patients were randomly divided into the experimental group and the control group. The experimental group received DEB-TACE combined with the TAC regimen (175 mg/m2 paclitaxel-loaded albumin, 50 mg/m2 Doxorubicin, and 500 mg/m2 cyclophosphamide), while the control group received the TAC regimen intravenously. The therapeutic efficacy was evaluated using the mRECIST criteria. Statistical analysis was performed using SPSS 22.0 software, and baseline characteristics, overall response rate (ORR), pathological complete response (PCR), adverse reactions, and complications were compared between the two groups using paired t-test and chi-square test. A total of 60 patients were included, with 30 patients in the experimental group (50%) and 30 patients in the control group (50%). After the first treatment, the ORR was 90% in the experimental group and 60% in the control group (P < 0.05). The overall ORR was 100% in the experimental group and 83% in the control group (P < 0.05). PCR was achieved in 14 patients (47%) in the experimental group and 4 patients (13%) in the control group. The main adverse reactions in the experimental group were skin blistering, pigmentation, and pain. There was no statistically significant difference in vomiting and grade II or above bone marrow suppression between the two groups. No grade III or above adverse events occurred in either group. The comparison of tumor shrinkage between the two groups was P = 0.051, and axillary lymph node shrinkage was P < 0.05. The use of drug-eluting beads in combination with neoadjuvant chemotherapy is a feasible and safe treatment option for locally advanced breast cancer patients.

Multidisciplinary and Tailored Treatment of Locally Advanced Breast Cancer in Progression during Neoadjuvant Chemotherapy: Case Report.

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Surgical Planning after Neoadjuvant Treatment in Breast Cancer: A Multimodality Imaging-Based Approach Focused on MRI.

Neoadjuvant chemotherapy (NACT) today represents a cornerstone in the treatment of locally advanced breast cancer and highly chemo-sensitive tumors at early stages, increasing the possibilities of performing more conservative treatments and improving long term outcomes. Imaging has a fundamental role in the staging and prediction of the response to NACT, thus aiding surgical planning and avoiding overtreatment. In this review, we first examine and compare the role of conventional and advanced imaging techniques in preoperative T Staging after NACT and in the evaluation of lymph node involvement. In the second part, we analyze the different surgical approaches, discussing the role of axillary surgery, as well as the possibility of non-operative management after-NACT, which has been the subject of recent trials. Finally, we focus on emerging techniques that will change the diagnostic assessment of breast cancer in the near future.

The Role of the CDK4/6 Inhibitor Ribociclib in Locally Advanced and Oligometastatic Hormone Receptor Positive, Her2 Negative, Advanced Breast Cancer: Case Series and Review of the Literature.

The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors to endocrine therapy has remarkably improved the outcome of patients affected with hormone receptor positive (HR+), human epidermal grow factor receptor 2 negative (HER2 -) advanced breast cancer (ABC). Ribociclib showed to be effective across most subgroups, regardless of the number and the site of metastasis. Up to 10% of patients with ABC, reported an oligometastatic condition, recently defined as a slow-volume metastatic disease with limited number and size of metastatic lesions (up to 5 and not necessarily in the same organ), potentially amenable for local treatment, aimed at achieving a complete remission status. Despite the wide use of CDK4/6 inhibitors in HR+, HER2-, ABC treatment, data regarding both locally advanced, inoperable disease and oligometastatic conditions are still poor. We reported a review and case series of HR+, HER2-, ABC patients treated with ribociclib as first-line therapy, for a locally advanced and oligometastatic conditions, reporting an impressive response and good safety profile.

Implementation of Non-Invasive Quantitative Ultrasound in Clinical Cancer Imaging.

Quantitative ultrasound (QUS) is a non-invasive novel technique that allows treatment response monitoring. Studies have shown that QUS backscatter variables strongly correlate with changes observed microscopically. Increases in cell death result in significant alterations in ultrasound backscatter parameters. In particular, the parameters related to scatterer size and scatterer concentration tend to increase in relation to cell death. The use of QUS in monitoring tumor response has been discussed in several preclinical and clinical studies. Most of the preclinical studies have utilized QUS for evaluating cell death response by differentiating between viable cells and dead cells. In addition, clinical studies have incorporated QUS mostly for tissue characterization, including classifying benign versus malignant breast lesions, as well as responder versus non-responder patients. In this review, we highlight some of the important findings of previous preclinical and clinical studies and expand the applicability and therapeutic benefits of QUS in clinical settings. We summarized some recent clinical research advances in ultrasound-based radiomics analysis for monitoring and predicting treatment response and characterizing benign and malignant breast lesions. We also discuss current challenges, limitations, and future prospects of QUS-radiomics.

A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer.

INTRODUCTION: Neoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC. METHODS: We conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m2 IV weekly ×12 followed by doxorubicin 24 mg/m2 IV weekly + cyclophosphamide 60 mg/m2 PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade). RESULTS: Seventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER+ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue. CONCLUSIONS: Neoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.

Transarterial chemoembolization as a part of multi-modality treatment with drug-eluting beads for locally advanced breast cancer: A case report.

Locally advanced breast cancer (LABC) is generally treated with combined-modality therapy including systemic chemotherapy, surgery, radiotherapy, and targeted therapy due to its nature of rapid onset of metastatic disease and poor prognosis. In this case report, we present a 61-year-old female who suffered from a huge protruding breast mass (16.2cm) with superficial ulcerative wound noted for three months. LABC was diagnosed via core needle biopsy and PET-CT examination. Initially, she received combined systemic chemotherapy, hormone therapy and radiation therapy; however, severe necrosis caused rupture in part of the breast mass and extensive wound discharge resulting in difficulty in wound care and prolonged disease course. Trans-arterial chemoembolization with drug-eluting beads (DEB-TACE) was applied as a part of combined-modality therapy for shortening the time before surgery. HepaSphere (as one of the DEB) loaded with high dose of epirubicin (total 80mg) was infused intra-arterially due to the nature of slow-releasing effect and longer duration of ischemic effect. Shortly after DEB-TACE following in about 40 days, surgery was smoothly performed. Post-operative adjuvant target therapy and adjuvant chemotherapy with taxane were administered. There was no evidence of local recurrence or distal metastases after 9 months of follow-up. It is suggested that performing DEB-TACE prior to surgery becomes a part of multimodality treatment of LABC to achieve better local control, better wound care and shortened treatment course.

Prediction of chemotherapy response in breast cancer patients at pre-treatment using second derivative texture of CT images and machine learning.

Although neoadjuvant chemotherapy (NAC) is a crucial component of treatment for locally advanced breast cancer (LABC), only about 70% of patients respond to it. Effective adjustment of NAC for individual patients can significantly improve survival rates of those resistant to standard regimens. Thus, the early prediction of NAC outcome is of great importance in facilitating a personalized paradigm for breast cancer therapeutics. In this study, quantitative computed tomography (qCT) parametric imaging in conjunction with machine learning techniques were investigated to predict LABC tumor response to NAC. Textural and second derivative textural (SDT) features of CT images of 72 patients diagnosed with LABC were analysed before the initiation of NAC to quantify intra-tumor heterogeneity. These quantitative features were processed through a correlation-based feature reduction followed by a sequential feature selection with a bootstrap 0.632+ area under the receiver operating characteristic (ROC) curve (AUC0.632+) criterion. The best feature subset consisted of a combination of one textural and three SDT features. Using these features, an AdaBoost decision tree could predict the patient response with a cross-validated AUC0.632+ accuracy, sensitivity and specificity of 0.88, 85%, 88% and 75%, respectively. This study demonstrates, for the first time, that a combination of textural and SDT features of CT images can be used to predict breast cancer response NAC prior to the start of treatment which can potentially facilitate early therapy adjustments.

Superselective arterial embolization with drug-loaded microspheres for the treatment of unresectable breast cancer.

BACKGROUND: To investigate the short-term efficacy and safety of drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) using CalliSpheres® microspheres in the treatment of unresectable locally advanced breast cancer (LABC). METHODS: DEB-TACE using CSM was performed in 15 patients with LABC after failure of medical treatment. The efficacy was evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The postoperative adverse reactions and complications were analyzed. The changes of white blood cell (WBC) count, creatine kinase isoenzyme-MB (CK-MB), B-type natriuretic peptide (BNP), and carbohydrate antigen15-3 (CA15-3) before and after treatment were compared by using Wilcoxon signed-rank test. RESULTS: The surgeries were successful in all patients. The subjects were followed up for 2-60 months (median: 10 months). According to the mRECIST, no patient achieved complete remission (CR) 1, 3, and 5 months after surgery, and partial response (PR) was achieved in 9, 11, and 11 cases; also, there were 6, 4, and 2 stable disease (SD) cases, and 0, 0, and 2 progressive disease (PD) cases. The postoperative WBC count, CK-MB level, and BNP level were not significantly different from those before surgery, whereas the CA15-3 level significantly decreased. The main postoperative adverse reactions were pain, fever, and gastrointestinal reactions. No severe adverse reactions were observed. CONCLUSIONS: DEB-TACE with CalliSpheres® microspheres is a safe and feasible treatment for LABC. However, more multi-center studies with larger sample sizes are still warranted.

Polymorphisms in microRNA let-7 binding sites of the HIF1AN and CLDN12 genes can predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Germline genetic polymorphisms in certain genes are associated with response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer (BC). Recent evidence has indicated that microRNA (miRNA) let-7 expression is associated with response to chemotherapeutics. This study aims to evaluate the potential role of let-7 miRNA-related single nucleotide polymorphisms (mirSNPs) in the prediction of pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in locally advanced breast cancer (LABC). METHODS: We genotyped the SNPs that reside in and around miRNA let-7 binding sites of two target genes: hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) and claudin 12 (CLDN12). The distribution frequencies of the SNPs were genotyped in LABC patients who received taxane- and platinum-based neoadjuvant chemotherapy. Associations among tumour-relevant biomarkers, genotype and pathological complete response (pCR) were evaluated using Student's t-test for continuous variables and the chi-square or Fisher's exact tests for non-categorical variables. The modified odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated by a multivariate logistic regression analysis to explore the association of genotype with pCR. RESULTS: For rs11292, which is located in the 3'-untranslated region (UTR) of HIF1AN, significant differences were detected in codominant, dominant and overdominant models between the patients who achieved pCR and those who did not (non-pCR) (P<0.05) in a multivariate analysis. For rs1017105, which is located in the 3'-UTR of CLDN12, significant differences were observed in the recessive model between the pCR and non-pCR patients with luminal-type BC. CONCLUSIONS: Let-7-related mirSNPs could predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in LABC, which suggests the potential role of variants of miRNA let-7-related gene networks as predictive markers in a clinical setting.

Radiotherapy for patients with unresected locally advanced breast cancer.

BACKGROUND: Management of locally-advanced breast cancer is determined by multiple factors, but in patients without distant metastases often involves neoadjuvant systemic therapy, surgery and radiation. If the primary tumour remains unresectable following systemic therapy, radiotherapy may be used for tumour shrinkage prior to surgery. When metastatic disease is present, locoregional radiotherapy is generally reserved for management of tumour-related symptoms. We reviewed our experience of high-dose radiotherapy for unresected locally-advanced breast cancer. METHODS: A retrospective chart review was conducted of patients with unresected locally advanced breast cancer (LABC) receiving external beam radiotherapy to the breast, chest wall and/or regional lymph nodes. Patients were stratified based on the presence of metastatic disease at presentation. Patient demographics, disease characteristics, and treatment outcomes were recorded. RESULTS: Forty-three cases were analyzed between 2004 and 2016. Median follow-up was 25 months from diagnosis and 14 months from completion of radiotherapy. There were 24 cases (56%) with metastatic disease on presentation, and 19 (44%) without. Tumour shrinkage occurred within 3 months of completing radiotherapy in 36 cases (84%). Ulceration and bleeding improved following radiotherapy in 13 (54%) of the 24 applicable cases. Twenty-six patients (60%) developed moist desquamation but none experienced grade 4 or 5 radiation dermatitis. Median locoregional progression-free survival for all patients was 12 months from completion of radiotherapy. Locoregional progression-free survival (P=0.2) and overall survival (OS) (P=0.4) were not significantly different between patients with and without distant metastases at presentation. CONCLUSIONS: Radiotherapy provided good response and symptom control in most patients in this study; there is a role for palliative radiotherapy in patients with LABC.

Pathologic complete response rates in triple-negative, HER2-positive, and hormone receptor-positive breast cancers after anthracycline-free neoadjuvant chemotherapy with carboplatin and paclitaxel with or without trastuzumab.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) is considered a surrogate for improved survival. Platinum-containing NCT, particularly in patients with HER2+ and triple-negative breast cancers (TNBC) may increase pCR rates. METHODS: Tumor characteristics, pCR rates (no invasive disease in breast and lymph nodes), toxicities, and survival in patients who received carboplatin, a taxane, and trastuzumab (HER2+ disease) between April 2009 and December 2011, were reviewed. RESULTS: Thirty eight patients (39 tumors) completed a median of 4 cycles of NCT. Eighteen of 39 (46%) tumors were HER2+, 8/18 (44%) responded with pCR; 13/18 HER2+ tumors were HR+ (72%) and 4/13 (31%) had a pCR. Ten of 39 (26%) tumors were TNBC; 6/10 (60%) had a pCR. At a median of 25-months no recurrences were observed in patients with pCR. CONCLUSIONS: Prospective studies of anthracycline-free platinum-containing NCT are warranted in LABC patients with HER2+ and TNBC.

Oncoplastic technique in breast conservative surgery for locally advanced breast cancer.

Locally advanced breast cancer (LABC) should be taken into decision making when planning breast conservative surgery, but this procedure should be done on the principle of oncologic safety in order to achieve negative surgical margin and maintain aesthetic result. This procedure should be offered as the choice of treatment in selected patients.