Clinical experience of the Magseed® magnetic marker to localize non-palpable breast lesions: a cohort study of 100 consecutive cases.

Background: The aim of this study was to report on a cohort of 100 patients where the Magseed® paramagnetic marker was used to localize non-palpable breast lesions. Methods: Data were collected from a cohort of 100 patients with non-palpable breast lesions, who underwent localization using the Magseed® marker. This marker consists of a paramagnetic seed that can be seen on mammography or ultrasound and intraoperatively detected with the use of the Sentimag® probe. The data were collected over a period of 23 months (May 2019 to April 2021). Results: All 111 seeds were successfully placed in the breasts of 100 patients under ultrasound or via stereotactic guidance. Eighty-nine seeds were inserted in single lesions or small microcalcification clusters in a single breast, 12 seeds were deployed to a bracket microcalcification clusters and 10 to help localize two tumors within the same breast. Most Magseed® markers (88.3%) were placed in the center of the lesion (≤1 mm). The re-excision rate was 5%. All Magseed® markers were successfully retrieved and no surgical complications were observed. Conclusions: This study reports our experience in a Belgian breast unit using the Magseed® magnetic marker and it highlights the many advantages of the Magseed® marker system. With this system, we successfully identified subclinical breast lesions and extended microcalcification clusters, targeting multiple sites within the same breast.

A Randomized Prospective Non-Inferiority Trial of Sentinel Lymph Node Biopsy in Early Breast Cancer: Blue Dye Compared with Indocyanine Green Fluorescence Tracer.

BACKGROUND: Indocyanine green (ICG) is a promising tracer for sentinel lymph node biopsy in early breast cancer. This randomized study was conducted to evaluate sentinel lymph node biopsy with ICG compared with blue dye as a tracer in woman with early breast cancer without any sign of lymph node invasion. METHODS: Between January 2019 and November 2020, 240 consecutive women with early breast cancer were enrolled and randomized to sentinel lymph node biopsy using ICG or blue dye. The primary endpoint was the sentinel lymph node detection rate in both arms. RESULTS: ICG was used in 121 patients and detected sentinel lymph nodes in all patients (detection rate, 100%; 95% CI: 96.9-100.0) while blue dye was used in 119 patients and detected sentinel lymph nodes in 116 patients (detection rate: 97.5%, 95% CI: 92.9-99.1). This analysis indicated the non-inferiority of ICG vs. blue dye tracer (90%CI: -1.9-6.9; p = 0.0009). CONCLUSION: ICG represents a new promising tracer to detect sentinel lymph nodes in early breast cancer with a detection rate similar to other conventional tracers, and is associated with easy learning and low cost. Our result suggest that this technique is a good alternative to avoid radioactive isotope manipulation.

Sentinel lymph node mapping with patent blue dye in patients with breast cancer: a retrospective single institution study.

BACKGROUND: Since the end of the last century, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as standard of care for axillary staging in early breast cancer in patients without any clinical sign of axillary lymph node infiltration. The worldwide most frequently used mapping method consists in the injection of radioactive technetium-99 isotope alone or in combination with blue dye. As a specific infrastructure and dedicated personnel are needed for the use of a radioactive tracer, the CHC in Liege (Belgium) decided to test the use of patent blue dye alone to detect sentinel lymph nodes in a large consecutive cohort of patients and compared the results with radioactive mapping methods and guidelines recommendations. METHODS: Patent blue dye was used in 456 consecutive patients with early breast cancer who underwent conservative breast cancer surgery or radical mastectomy between 1/1/2000 and 31/12/2007 in a community hospital (CHC Liège, Belgium). After SLNB, an ALND was performed in each patient. RESULTS: Sentinel lymph nodes were identified in 444 patients among the 456 patients evaluated by this mapping method during this time period, which represents a detection rate of 97.4%. Infiltrated lymph nodes were detected in 32.7% of patients (149/456) while in the 444 patients with sentinel lymph nodes identified and resected, 137 patients have at last one positive lymph node (30.9%). The false negative rate was 4.9% and the predictive negative value was 97.7% with the blue dye mapping method. CONCLUSIONS: In addition of the simplicity of the method and the large economic advantage, SNLB using blue dye alone showed a quite acceptable performance in our retrospective analysis concerning its ability to find the SLN as well as its reliability to remove the good ones.

From modified radical mastectomy to infra-radical mastectomy: a phase I study for surgical de-escalation focusing on pathological analyses.

BACKGROUND: Despite that breast conservative therapy became the standard of care in breast cancer, modified radical mastectomy, a large mutilating surgery, is still required for an important number of patients. In order to improve the quality of life and the psychological aspects of a surgery involving the femininity of woman, we developed a new less invasive procedure called infra-radical mastectomy. It aims to save the neckline of patients by the maintenance of the peripheral skin-fatty flap that constitutes the base for implantation of the breast. This phase I study analyzed the feasibility of this procedure using outcome of anatomo-pathological analyses as primary endpoint. METHODS: Between March 2015 and July 2017, all women with operable breast cancer without signs of lymph node invasion were invited to participate in the study in the 2 participating institutions. After a water-assisted dissection of the peri-glandular space, an enucleation of the breast was performed by a cold knife which represents the infra-radical mastectomy. A peri-glandular re-excision (PGR) of the skin and the fat tissue surrounding the gland was then achieved to obtain an MRM. This PGR underwent a careful pathological examination (10 samples per patient). Moreover, the tissue volume and the skin surface of the PGR were quantified. RESULTS: A total of 53 patients (median age: 60 years) were prospectively recruited. The pathological analysis of peri-glandular biopsies revealed none residual invasive carcinoma, 1% of biopsies contained focal ductal carcinoma in situ (DCIS) and 0.4% atypical hyperplasia corresponding to 4 and 2 patients respectively. These 4 patients with residual DCIS were preoperatively diagnosed with extensive DCIS. On average after an infra-radical mastectomy, 37% of the volume and 53% of the skin surface of a complete modified radical mastectomy were sparred. CONCLUSIONS: The evaluation of biopsies from peri-glandular tissue suggests that infra-radical mastectomy should be further evaluated except for patients diagnosed with extensive DCIS which must be excluded of this infra-radical approach. Additional work is needed to evaluate cosmetic outcome and impact on quality of life, the need of radiotherapy and the oncological long-term outcome.

Description of Two Cases of Anaplastic Large Cell Lymphoma Associated with a Breast Implant.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized provisional entity in the 2017 revision of the World Health Organization classification of lymphoid neoplasms. Although the majority of the cases described in the literature demonstrate an effusion confined to the capsule of the breast implant, this rare pathology can also invade the capsule and adjacent tissues and/or involve lymph nodes. We hereby report two new cases of BIA-ALCL in a 58-year-old and a 47-year-old Caucasian female who received a silicone breast implant. The first patient showed a sudden and rapid right breast volume increase 6 years after the implantation surgery. As for the second patient, a left breast volume increase was observed also suddenly and quickly 11 years after surgery. In both cases, an uncompressed mammography was performed allowing a new approach to highlight periprosthetic fluid reaction. Pathologic examination of the fluid collection revealed atypical cells positive for CD30 and CD45 and negative for ALK and CK7. This allowed pathologists to diagnose a breast implant-associated anaplastic large cell lymphoma. Patients were treated with bilateral capsulectomy with no additional local or systemic therapy. The development of breast augmentation may come with an increase in the frequency of this pathology. Radiologists and senologists must therefore be careful when women with breast implants show an increase of breast volume and all cases of BIA-ALCL must be recorded and reported.

Expression of MT4-MMP, EGFR, and RB in Triple-Negative Breast Cancer Strongly Sensitizes Tumors to Erlotinib and Palbociclib Combination Therapy.

PURPOSE: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), and retinoblastoma protein (RB).Experimental Design: IHC analyses were conducted on human and PDX-TNBC samples to evaluate the production of the three biomarkers. The sensitivity of cancer cells expressing or not MT4-MMP to anti-EGFR (erlotinib) or anti-CDK4/6 inhibitor (palbociclib) was evaluated in vitro in 2D and 3D proliferation assays and in vivo using xenografts and PDX-TNBC displaying different RB, MT4-MMP, and EGFR status after single (erlotinib or palbociclib) or combined (erlotinib + palbociclib) treatments. RESULTS: EGFR and MT4-MMP were coexpressed in >70% of TNBC samples and PDX-TNBC, among which approximately 60% maintained RB expression. Notably, approximately 50% of all TNBC and PDX-TNBC expressed the three biomarkers. Single erlotinib and palbociclib treatments drastically reduced the in vitro proliferation of cells expressing EGFR and MT4-MMP when compared with control cells. Both TNBC xenografts and PDX expressing MT4-MMP, EGFR, and RB, but not PDX-TNBC with RB loss, were sensitive to erlotinib and palbociclib with an additive effect of combination therapy. Moreover, this combination was efficient in another PDX-TNBC expressing the three biomarkers and resistant to erlotinib alone. CONCLUSIONS: We defined a new association of three biomarkers (MT4-MMP/EGFR/RB) expressed together in 50% of TNBC and demonstrated its usefulness to predict the TNBC response to anti-EGFR and anti-CDK4/6 drugs used in single or combined therapy.

Transcriptome-wide analysis of natural antisense transcripts shows their potential role in breast cancer.

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts. Several ncNATs were described as regulating protein coding gene expression on the same loci, and they are expected to act more frequently in cis compared to other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired adjacent non-malignant tissues were analyzed by strand-specific RNA sequencing. To highlight ncNATs potentially playing a role in protein coding gene regulations that occur in breast cancer, three different data analysis methods were used: differential expression analysis of ncNATs between tumor and non-malignant tissues, differential correlation analysis of paired ncNAT/PCT between tumor and non-malignant tissues, and ncNAT/PCT read count ratio variation between tumor and non-malignant tissues. Each of these methods yielded lists of ncNAT/PCT pairs that were enriched in survival-associated genes. This work highlights ncNAT lists that display potential to affect the expression of protein-coding genes involved in breast cancer pathology.

Primary osteosarcoma of the breast: a case report.

We report a rare case of primary osteosarcoma of the breast in a patient who presented a calcified fibroadenoma one year before the appearance of the malignant lesion. We describe the follow-up of the patient and the discovery of a similar osteosarcoma in the other breast one year later.

Circulating microRNA-based screening tool for breast cancer.

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative screening procedure to mammography for breast cancer diagnosis.A plasma miRNA profile was determined by RT-qPCR in a cohort of 378 women. A diagnostic model was designed based on the expression of 8 miRNAs measured first in a profiling cohort composed of 41 primary breast cancers and 45 controls, and further validated in diverse cohorts composed of 108 primary breast cancers, 88 controls, 35 breast cancers in remission, 31 metastatic breast cancers and 30 gynecologic tumors.A receiver operating characteristic curve derived from the 8-miRNA random forest based diagnostic tool exhibited an area under the curve of 0.81. The accuracy of the diagnostic tool remained unchanged considering age and tumor stage. The miRNA signature correctly identified patients with metastatic breast cancer. The use of the classification model on cohorts of patients with breast cancers in remission and with gynecologic cancers yielded prediction distributions similar to that of the control group.Using a multivariate supervised learning method and a set of 8 circulating miRNAs, we designed an accurate, minimally invasive screening tool for breast cancer.

Genomic Grade Index (GGI): feasibility in routine practice and impact on treatment decisions in early breast cancer.

PURPOSE: Genomic Grade Index (GGI) is a 97-gene signature that improves histologic grade (HG) classification in invasive breast carcinoma. In this prospective study we sought to evaluate the feasibility of performing GGI in routine clinical practice and its impact on treatment recommendations. METHODS: Patients with pT1pT2 or operable pT3, N0-3 invasive breast carcinoma were recruited from 8 centers in Belgium. Fresh surgical samples were sent at room temperature in the MapQuant Dx™ PathKit for centralized genomic analysis. Genomic profiles were determined using Affymetrix U133 Plus 2.0 and GGI calculated using the MapQuant Dx® protocol, which defines tumors as low or high Genomic Grade (GG-1 and GG-3 respectively). RESULTS: 180 pts were recruited and 155 were eligible. The MapQuant test was performed in 142 cases and GGI was obtained in 78% of cases (n=111). Reasons for failures were 15 samples with <30% of invasive tumor cells (11%), 15 with insufficient RNA quality (10%), and 1 failed hybridization (<1%). For tumors with an available representative sample (≥ 30% inv. tumor cells) (n=127), the success rate was 87.5%. GGI reclassified 69% of the 54 HG2 tumors as GG-1 (54%) or GG-3 (46%). Changes in treatment recommendations occurred mainly in the subset of HG2 tumors reclassified into GG-3, with increased use of chemotherapy in this subset. CONCLUSION: The use of GGI is feasible in routine clinical practice and impacts treatment decisions in early-stage breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT01916837, http://clinicaltrials.gov/ct2/show/NCT01916837.