Positive Axillary Lymph Nodes Research Articles

Hypofractionated radiotherapy with simultaneous tumor bed boost (Hi-RISE) in breast cancer patients receiving upfront breast-conserving surgery: study protocol for a phase III randomized controlled trial.

The effectiveness and safety of moderately hypofractionated radiotherapy (HFRT) in patients undergoing breast-conserving surgery (BCS) has been demonstrated in several pivotal randomized trials. However, the feasibility of applying simultaneous integrated boost (SIB) to the tumor bed and regional node irradiation (RNI) using modern radiotherapy techniques with HFRT needs further evaluation. This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to determine the non-inferiority of HFRT combined with SIB (HFRTsib) compared with conventional fractionated radiotherapy with sequential boost (CFRTseq) in terms of five-year locoregional control rate in breast cancer patients undergoing upfront BCS. A total of 2904 participants will be recruited and randomized in a 1:1 ratio into the HFRTsib and CFRTseq groups. All patients will receive whole breast irradiation, and those with positive axillary nodes will receive additional RNI, including internal mammary irradiation. The prescribed dose for the HFRTsib group will be 40Gy in 15 fractions, combined with a SIB of 48Gy in 15 fractions to the tumor bed. The CFRTseq group will receive 50Gy in 25 fractions, with a sequential boost of 10Gy in 5 fractions to the tumor bed. This trial intends to assess the effectiveness and safety of SIB combined with HFRT in early breast cancer patients following BCS. The primary endpoint is locoregional control, and the results of this trial are expected to offer crucial evidence for utilizing HFRT in breast cancer patients after BCS. This trial was registered at ClincalTrials.gov (NCT04025164) on July 18, 2019.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.

The prognostic value of preoperative neoindices consisting of lymphocytes, neutrophils and albumin (LANR) in operable breast cancer: a retrospective study.

Preoperative inflammatory factors and nutritional status are strongly associated with the prognosis of a variety of cancers. We explored the relationship between preoperative lymphocytes, neutrophils and albumin (LANR) and progression-free survival in breast cancer patients. The clinical and follow-up data of 200 breast cancer patients were retrospectively analyzed in this study, and the value of LANR was determined as follows: LANR, lymphocytes × albumin/neutrophils. ROC curves, COX proportional risk regression analysis and subgroup analysis were used to assess the prognostic value of LANR in progression-free survival of breast cancer patients. The median age of the patients was 55.5 years (range 50-62 years). The median follow-up time was 46 months (range 33-55 months). In progression-free survival, the area under the LANR curve was 0.748 and the HR (95% CI) was 0.035 (0.679-0.817). LANR was associated with age (p=0.02), positive axillary lymph nodes (p<0.001), TNM stage (p<0.001) and human epidermal growth factor receptor 2(p=0.004). The results indicated that preoperative LANR may be a reliable predictor of progression-free survival in patients with operable breast cancer. LANR may be an essential predictor for breast cancer patients and provides a therapeutic basis for clinicians and patients.

Abstract PO3-02-13: Breast Cancer in Very Young Adult Women At or Under the Age of 35 Years: Characteristics and Outcomes

Abstract Background: Breast cancer (BC) is the most common malignancy among women in Saudi Arabia. Noticeably, it shows a higher incidence in younger age groups than what is reported from Western countries. Age 35 years and less is an applied cut-off age for clinically defining BC in very young women (BCVY). This study describes characteristics, survival and risk of death associated factors in this rare subset of patients. Methods: A retrospective cohort study included females &amp;gt; 18 and &amp;lt; 35 years with histologically confirmed primary non-metastatic breast cancer from an academic hospital in Jeddah, Saudi Arabia between the years 2009-2019. Demographic data, tumor clinicopathological features, and outcomes were obtained. Survival and potential associated factors were examined. A p-value of less than 0.05 was regarded as statistically significant. Results: 204 female patients with a confirmed breast cancer diagnosis were included. The mean age at diagnosis was 31.43 ± 2.94 years. Fifty-three percent of the patients had a left-sided tumor with the majority being IDC (92%) and one-third with positive axillary lymph nodes (N+) and multifocal disease in 17%. One-quarter of the tumors showed LVI, 45% revealed associated DCIS and 26% showed tumor necrosis on histopathology examination. The presence of tumor-infiltrating lymphocytes (TILs) was reported in 23% of TNBC cases. Tubular differentiation score 3 was reported in 79.4%, nuclear pleomorphism score 3 in 79% and mitosis activity score 3 in 19% while the most reported overall grade was II in 48.5% followed by grade III in 34%. HER2-positive in 33.8 %, HR-positive in 34.3 %, TNBC in 24% and unknown in 8% of the patients. Thirty percent had a distant recurrence and 15% were deceased. The mean survival time was 4.61 years with a maximum of 6.54 years and a minimum of 3.67 years. Table 1 shows the multivariate logistic regression analysis of factors influencing the risk of death in very young patients with breast cancer. Conclusions: The current study describes the clinicopathological characteristic, survival and related factors of breast cancer in very young patients &amp;lt; 35 years, which is considered an uncommon presentation. Large, high-grade tumors and a high frequency of HER2 and TNBC were observed in BCVY patients. Involvement of the regional lymph nodes and the development of distant recurrence were associated significantly with an increased risk of death. The presence or absence of TILs, LVI and tumor necrosis on histopathological examination did not influence the risk of recurrence or death in this cohort. Table 1. The multivariate logistic regression analysis of factors influencing the risk of death in very young patients with breast cancer. Citation Format: Atlal Abusanad, Rana Ajabnoor, Aydah Al-Awadhi, Omalkhair Abualkhair. Breast Cancer in Very Young Adult Women At or Under the Age of 35 Years: Characteristics and Outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-13.

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-08.

Abstract PO5-02-01: Concerning Discrepancies in Estradiol Levels in Premenopausal Women Receiving Abemaciclib and Ovarian Function Suppression

Abstract Background: Adjuvant abemaciclib in combination with endocrine therapy improves outcomes for patients with high-risk, hormone receptor-positive (HR+), HER2-negative early-stage breast cancer. In premenopausal women, the use of an aromatase inhibitor (AI) requires chemical or surgical ovarian function suppression (OFS). Our published case report of a premenopausal woman receiving adjuvant abemaciclib with elevated estradiol levels measured by the Abbott Alinity chemiluminescent microparticle immunoassay (CMIA) despite bilateral salpingo-oophorectomy (BSO) but low estradiol levels using liquid chromatography-mass spectrometry (LC-MS/MS) suggested an interference of abemaciclib with the immunoassay (PMID: 37124155). The aim of this study was to determine discrepancies in estradiol levels using CMIA compared to LC-MS/MS and subsequent treatment changes in a larger patient population. Methods: We conducted an IRB-approved retrospective review of premenopausal women with early-stage HR+ breast cancer treated with adjuvant OFS and abemaciclib at our institution from October 2021 to April 2023 who had at least 1 CMIA estradiol level drawn during abemaciclib therapy. Pathology, treatment plans, and lab data were abstracted from medical records. Postmenopausal estradiol levels were based on reference ranges of &amp;lt; 41 pg/mL using CMIA or &amp;lt; 15 pg/mL using LC-MS/MS. We utilized descriptive statistics to describe the population and management. Results: We identified 22 patients who met criteria for our review. The average age was 42.3 years, all had positive axillary nodes, 6 (27%) received neoadjuvant chemotherapy, and 15 (68%) received adjuvant chemotherapy. There were 14 (64%) patients who received leuprolide and 8 (36%) received goserelin, whereas 19 (86%) received AI and 3 (14%) received tamoxifen as their initial oral antiestrogen therapy. The majority of patients did not have baseline estradiol levels when starting OFS though after starting abemaciclib, 20 patients had CMIA estradiol levels in the premenopausal range, 9 of which had estradiol monitored by both CMIA and LC-MS/MS (Table 1). The average length of time from starting OFS to starting abemaciclib was 144.6 days with 1 patient switching from tamoxifen to OFS and AI after starting abemaciclib. Due to elevated CMIA estradiol, treatment changes included increased OFS dosage (5 patients), change of OFS (2 patients), and change to tamoxifen (3 patients). There were 6 patients who underwent BSO, 3 due to persistently elevated CMIA estradiol levels, 2 due to patient preference, and 1 due to a BRCA mutation. Following surgery, 2 patients had persistently elevated CMIA estradiol but low LC-MS/MS estradiol. The remainder of these patients did not have estradiol levels measured by CMIA. Conclusions: Our retrospective review demonstrated the likely interference of abemaciclib with the Abbott Alinity immunoassay as shown by 9 patients treated with OFS and abemaciclib with simultaneous premenopausal range CMIA estradiol levels and postmenopausal range LC-MS/MS estradiol levels. As up to 91% of patients in our study may have had a false positive estradiol level erroneously suggesting inadequate OFS, monitoring of estradiol levels using the CMIA assay in patients receiving adjuvant abemaciclib in addition to OFS could lead to changes in therapy that may be unnecessary. It is recommended that the LC-MS/MS assay be used when monitoring of estradiol levels is indicated in patients receiving abemaciclib concurrently with OFS. Table 1: Estradiol levels in patients receiving OFS and abemaciclib who had both CMIA and LC-MS/MS assays Citation Format: Alaina Kessler, Rima Patel, Emily Gallagher, Tianxiang Sheng, Damodara Rao Mendu, Amy Tiersten, Paula Klein, Aarti Bhardwaj, Anupama Goel, Joseph Sparano, Theresa Shao, Julie Fasano. Concerning Discrepancies in Estradiol Levels in Premenopausal Women Receiving Abemaciclib and Ovarian Function Suppression [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-01.

Abstract PO2-23-04: Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment

Abstract Background: Axillary management in clinically node-positive patients who converted to ycN0 after neoadjuvant chemotherapy (NAC) for breast cancer (BC) remains under research with the aim of de-escalation of axillary lymph node dissection (ALND). A magnetic seed is one of the several positive lymph nodes marking techniques used in targeted axillary dissection (TAD) for patients with cN1 breast cancer undergoing neoadjuvant systemic therapy. It has been criticized for its potential masking effect due to the artefact it produces in the MRI sequences used to assess a proper breast response. This study evaluates if the magnetic seeds placed before NAC for guided TAD have influenced in the breast MRI response assessments. Methods: From October 2021 to June 2023, patients with cT0-4 cN1 breast cancer who were candidates for primary systemic treatment were prospectively recruited. Once a breast lesion and axillary node positivity were confirmed, a based hydrogel marker and a magnetic seed, respectively, were placed prior NAC. Once systemic treatment was completed, imaging techniques were used to assess the response, with MRI being the imaging technique of choice to assess breast response and axillary ultrasound the imaging technique of choice to assess axillary response. Surgical pathological confirmation of response in the axilla was by TAD, including sentinel lymph node and magnetic clipped node resection. Results: A total of 43 patients were included and their characteristics are shown in Table 1. In 16 patients (37%) the tumour was located in the upper outer quadrant (UOQ). In this group, the susceptibility artefact produced by the magnetic seed in the MRI created a black hole obscuring the axilla with a mean diameter of 69 mm (range: 57-76 mm). In no case did the halo interfere with the correct MRI visualisation of the breast marker. By MRI, the mean distance of the artifact halo from the breast marker or residual breast lesion was 40 mm (range: 13-79 mm). Overall, complete radiological response (ycCR) was reported in 20 patients (46%), breast only in 21 (49%) and axilla only in 38 (88%) patients. In 5 patients, preoperative axillary ultrasound revealed residual axillary disease, confirmed by FNA, lead to direct ALND. In the remaining 38 patients the axillary TAD assessment was completed. In all cases, the magnetic clipped node was successfully surgically removed. Pathological complete response (pCR) was confirmed in 9 (21%), breast only in 11 (26%) and axilla only in 13 (30%) patients. MRI diagnostic performance in detecting residual breast disease after NAC was not altered by the magnetic clipped node artifact when comparing the tumour location in the UOQ to the other quadrants (AUC 0.764 vs. 0.702; p=0.698). Conclusions: Surgical axillary staging remains the most reliable method for assessing the axillary response after NAC. Target axillary dissection guided by magnetic seed placed before NAC is an effective and accurate technique. The artifact generated in the MRI does not interfere with the pre-surgical breast response assessment after neoadjuvant systemic treatment. Table 1: Patients and tumor characteristics Citation Format: Martin Espinosa-Bravo, Joaquin Rivero Deniz, Clara Morales Comas, Javier de la Torre Fernandez de Vega, Irene Vives Rosello, Enrica Esposito, Vicente Peg Camara, María De Les Neus Rus Calafell, Ignacio Miranda Gomez, Christian Siso Raber. Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-04.

Abstract PO5-26-07: Surgery for Invasive Lobular Carcinoma: A Patient Experience Survey from the Lobular Breast Cancer Alliance

Abstract The Lobular Breast Cancer Alliance (LBCA) is a nonprofit, patient advocacy organization committed to raising awareness and promoting research into invasive lobular carcinoma (ILC). While ILC accounts for 15% of breast cancers, knowledge about ILC remains limited. ILC’s hallmark is lack of E-cadherin, which results in non-cohesive formation and impacts accuracy of imaging tests and staging. Consequently, patients with ILC have higher rates of positive surgical margins, mastectomies, and axillary lymph node (LN) dissections. To understand the surgery experience of individuals with ILC, LBCA conducted an anonymous online survey from 6/21-7/2/23, distributed via the LBCA newsletter, social media, and partner organizations. Questions addressed pre-operative imaging, type of surgery, surgical margins, LN status, decision making about and patient experience with surgery. Analyses were limited to those respondents who had surgery. Study limitations include potential recall and selection bias. Results 1,482 individuals with a diagnosis of ILC completed the survey and 1,426 had undergone surgery. 76% were from North America, 11% from England, and 4% from Australia. Average age at diagnosis was 56 (range 31-86). At diagnosis, 38% were clinically stage 1; 37% stage 2; 17% stage 3; and 4% de novo metastatic. 75% had a mammogram that indicated dense breasts. Of 1,426 surgery respondents (SR), 95% reported that ILC was identified in only one breast at diagnosis. 80% had a pre-surgical MRI. MRI revealed larger tumors than seen on other imaging for 43% and revealed previously unseen contralateral ILC for 3%. 375 (26%) of SRs were diagnosed with ipsilateral disease and had a pre-surgical MRI that did not reveal new information about their ILC. Of these, post-surgical pathology reports indicated 16% had additional ipsilateral foci, 2% contralateral disease, and 40% had larger tumors than seen on pre-surgical imaging. 614 (43%) of SRs had one or more lumpectomy (L), 560 (39%) of SRs had a double mastectomy (DM), and 451 (32%) of SRs had a single mastectomy (SM). 123 (20%) of SRs who had one or more Ls, had a subsequent SM or DM. For those undergoing L (614), reasons for this choice included: recommendation from their care team (83%), wanted to keep their breast (25%), thought it was better for their overall survival (OS) (14%), and 13% indicated they wanted breasts but did not want reconstruction. Of the 560 women who had a DM, 60% indicated that they thought a DM would improve their OS, 50% were concerned about the risk of local recurrence, 47% doubted that imaging would detect future ILC tumors, and 45% noted concern that ILC is more likely to be bilateral. Of note, only 9% had ILC or ILC and another invasive breast cancer in both breasts at initial diagnosis and 31% who had a pre-surgical MRI changed their initial surgical treatment plan. Post surgery, pathology for DM group revealed larger tumors than seen on imaging (57%), and 6% had tumors found in a second breast that were not seen on imaging. For those 451 who had an SM, reasons for this choice included: 75% said it was what their care team recommended, 35% thought it would improve OS, 20% feared risk for local recurrence, and 15% doubted imaging would detect future ILC. Of 614 respondents who had L, 33% had positive margins at first surgery. Of those, 17% reported multiple Ls and M; and 24% reported clear margins were never achieved. Of the 1011 SM or DMs reported, 10% did not achieve clear margins after these surgeries. Conclusion The survey demonstrates the experience of a large cohort of women with ILC, reporting high rates of uncertainty about accuracy of imaging, high rates of repeat surgery, bilateral mastectomies, and positive margins. Patients are factoring concerns about potential extent of disease and future recurrence in their surgical decision making. These results support the need for improved pre-operative staging and imaging modalities specific to ILC. Citation Format: Laurie Hutcheson, Janice Axelrod, Tracy Cushing, Colleen Fitzwater, Rinath Jeselsohn, Gitte Joergensen, Maria Karsten, Miranda Kimm, Megan Kruse, Theresa Langdon, Julia Levine, Mason Mitchell-Daniels, Rita Mukhtar, Barbara Neilsen, Shani Paluch-Shimon, Therese Pross. Surgery for Invasive Lobular Carcinoma: A Patient Experience Survey from the Lobular Breast Cancer Alliance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-07.

Abstract PO5-23-02: Targeted Axillary Dissection with Paramagnetic Marker Localization

Abstract Background: Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of SLNB alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NACT). However optimal methods for TAD are still under investigation. A paramagnetic marker Magseed® was used for the identification of the TLN in this study. Methods: 80 patients eligible to receive NACT were included. All patients had positive axillary lymph nodes verified by core biopsy. Six patients did not receive NACT for any reason. After NACT the targeted lymph nodes (TLNs) were marked with Magseed®, a non-radioactive paramagnetic marker. The SLNs were marked with dual tracer method. The SLNB and the selective TLNB were performed in 74 patients. The Magseed® marked TLNs were identified with the Sentimag® probe and excised. Specimen x-ray was performed to confirm the Magseed® within the prior to NACT biopsied and clipped lymph node. The identification rates of TLNs and SLNs, and the concordance rates were calculated. Results: The TLN identification rate was 100% (74/74), the SLN identification rate was 81.1% (60/74), the concordance rate of TLN and SLN was 58.1% (43/74). In 66.2% (49/74) of the patients the TLN converted to negative, and no ALND was performed. When the TLN converted to negative, a SLN could not be identified in 18.4% (9/49) of the patients. In 33.8% (25/74) of the patients the TLN remained positive after NACT and ALND was performed. When the TLN remained positive, a SLN could not be identified in 40% (10/25) of the patients. Complications according Magseed® deployment or identification could not be observed. Conclusion: Magseed® is a reliable and feasible marker for the identification of TLNs after NACT. Citation Format: Roland Reitsamer, Andreas Sir, Ernst Forsthuber, Florentia Peintinger. Targeted Axillary Dissection with Paramagnetic Marker Localization [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-02.

Abstract PO2-23-06: Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph node positive breast cancer

Abstract Background The probability of axillary lymph node converting from positive to negative after neoadjuvant systemic therapy (NST) for breast cancer patients is approximately 40%. A variety of axillary lymph node biopsy surgeries based on sentinel lymph node biopsy (SLNB) can help to omit axillary lymph node dissection (ALND). The common disadvantages, however, are mainly the restrictions, such as the need for strict regulation of the use of radiotracers, the high number of retrieved lymph nodes required, and the need to purchase ancillary equipment. The more restrictions there are, the more they limit the spread and availability of the technique and, more importantly, reduce the number of patients who will benefit. In fact, for patients with metastatic lymph nodes, the sentinel lymph nodes must be included in the lymph nodes that have metastasized. If these metastatic lymph nodes can be accurately marked and precisely retrieved after NST, it is possible to assess whether the axillary lymph nodes are converted from positive to negative without the need for SLNB. Materials and methods Breast cancer patients with pathologically confirmed axillary lymph node metastases who were receiving NST were recruited for this study. Before NST, carbon nanoparticles suspension injections were injected into the cortex of the pathologically confirmed metastatic lymph node to stain the region where the metastatic lymph node was located. The lymph nodes in the stained region were retrieved by stained region lymph node biopsy (SrLNB) during the axillary surgery, followed by ALND, without the use of SLNB. Finally, the identification rate and false-negative rate (FNR) of SrLNB were statistically analyzed according to pathology data. Results A total of 159 patients were successfully enrolled in this study between September 24, 2020 and December 2, 2022, with an axillary pCR rate of 40.9% (65/159). The identification rate of SrLNB was 100% (159/159), with an overall FNR of 5.3% (5/94). Subgroup analysis revealed that in the subgroups of 1, 2, 3 and ≥4 SrLN, the FNR was 0%, 0%, 0% and 8.9% (5/56), respectively, whereas in the cN1, cN2 and cN3 subgroups the FNR was 7.7% (3/39), 2.6% (1/38) and 5.9% (1/17), respectively. The FNR indexes were within the safety threshold of 10% in all subgroups. Conclusion SrLNB has a high identification rate and a low FNR and is useful for screening patients with positive to negative axillary lymph nodes for omitting ALND. srLNB requires only the use of an affordable and radiation-free carbon nanoparticles suspension injection for marking, making the whole technique simpler and easier to disseminate. The data from this study also suggest that SLNB may not be mandatory for axillary biopsy in patients with positive axillary lymph nodes undergoing NST. Table 1. General characteristics of enrolled patients. Table 2. Analysis of factors affecting axillary pCR rates. Table 3. Analysis for the FNR of SrLNB. Citation Format: Jue Wang, Rui Chen, Cuiying Li, Hailing Zha, Qiannan Zhu, Lifeng Huang, Xiaoming Zha. Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph node positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-06.

Abstract PO3-22-09: Implementation of nanoparticle-assisted axillary staging: reduced axillary intervention for patients with node-positive breast cancer following neoadjuvant therapy

Abstract Background: Nanoparticle-assisted axillary staging (NAAS), which combines carbon nanoparticles with standard dual-tracer (radioisotope and blue dye) sentinel lymph node biopsy (SLNB), has shown excellent results in patients undergoing neoadjuvant therapy (NAC) for pre-NAC node-positive breast cancer. This pilot study aimed to explore the possible expansion of indications (pre-NAC cN2, and cN3 stages; ycN+ stage) for NAAS, which was the first attempt till now for patients undergoing NAC, and to select specific post-NAC individuals who might be exempt from axillary lymph node dissection (ALND), especially those with relatively low tumor burdens, such as ITCs and micrometastases. Method: The medical records of all consecutive patients with breast cancer were prospectively collected from the Breast Center, West China Hospital. Patients with invasive, pre-NAC node-positive breast cancer who underwent NAAS followed by ALND between April 2021 and February 2023 were included. The detection rate (DR), average number of sentinel or NAAS nodes, false negative rate (FNR), negative predictive value (NPV), and NAAS accuracy were assessed. Subgroup analyses according to different pre- and post-NAC cN stages, especially the pre-NAC cN2-3 stages and the post-NAC cN+ stages, which were not the focus of previous studies, were conducted using crosstabs. To screen possible patients who might exempt ALND, we focus on relationships between the status of axillary lymph nodes and the number or tumor burden of NAAS nodes. Results: A total of 241 eligible patients were included in the study. There were 153 (63.49%), 40 (16.60%), and 48 (19.92%) patients in pre-NAC cN1, cN2, and cN3 stages, respectively. The post-NAC stages of patients were not restricted, 38.17% (92/241) of them converted to ycN0 stages, while 61.83% (149/241) were still in ycN+ stages. A total of 232 (96.27%) eligible patients successfully underwent NAAS; the DR, NPV, accuracy, and FNR of NAAS were 96.27%, 95.97%, 97.84%, and 4.42%, respectively. Additionally, NAAS showed accuracies of 97.30% and 93.02% and FNRs of 7.14% and 9.09% in patients with pre-NAC cN2 and cN3 breast cancers, respectively. There was no statistical difference among the FNRs of NAAS in the pre-NAC cN1, cN2, and cN3 stages (p=0.134). Moreover, NAAS yielded FNRs of 0.00% in the ycN0 population and 6.02% in the ycN+ population, respectively (p=0.323). Accuracies reached 100.00% and 96.48% in ycN0 and ycN+ patients, respectively (p=0.159). Notably, patients with one NAAS node with ITC or micrometastasis in the entire population showed no further positive disease at ALND. Conclusion: NAAS showed excellent and stable performance with a low FNR and high accuracy, indicating valuable application prospects in patients with breast cancer who received NAC. Patients with pre-NAC cN2-3 stages also have a chance to undergo NAAS, and the application of NAAS appears to be feasible regardless of the ycN stage. Especially for ycN0 population, there is no chance for NAAS to miss positive axillary lymph nodes. In addition, patients who had one NAAS node with ITC or micrometastasis might avoid ALND. Diagnostic performance of nanoparticle-assisted axillary staging in pre-neoadjuvant chemotherapy cN1, cN2 and cN3 patients Diagnostic performance of nanoparticle-assisted axillary staging in ycN0 and ycN+ patients Additional axillary disease at axillary lymph node dissection in patients with positive NAAS nodes after neoadjuvant chemotherapy XX- XX XX- XX XX- XX Citation Format: Ruixian Chen, Tao He, Jiqiao Yang, Shan Lu, Yunhao Wu, Chihua Wu, Ruoning Yang, Weijing Liu, Ya Huang, Xiangyue Meng, Xin Zhao, Qintong Li, Xin Sun, Jing Jing, Jie Chen. Implementation of nanoparticle-assisted axillary staging: reduced axillary intervention for patients with node-positive breast cancer following neoadjuvant therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-09.

Abstract PO1-06-11: Exosomal HMGB1 induce PD-L1+-tumor associated macrophages through glycometabolic reprogramming to promote lung-tropic metastasis of triple negative breast cancer

Abstract Background: Lung metastasis occurs in 30% of triple negative breast cancer (TNBC), the detailed molecular mechanism remains largely unexplored. Accumulating evidence suggests that PD-L1+-tumor associated macrophages (PD-L1+-TAMs) are closely related to immune suppression, invasion, and metastasis. Tumor-derived exosomes have been reported to remodel tumor microenvironment and accelerate metastasis via packing and delivering a variety of biologically active molecules. Our previous studies found that exosomes from breast cancer cells polarized macrophages toward TAMs within the primary tumor nest. The aim of this study was to reveal whether TNBC-derived exosomes were able to polarize lung macrophages towards PD-L1+-TAMs and generate a pre-metastatic immunosuppressive niche, therefore discovering the underlying mechanism of lung-tropic metastasis. Methods: Exosomes isolated from EO771 TNBC cell line (EO771/exo) and HC11 normal breast epithelial cell line (HC11/exo) were characterized. Uptake of exosomes by macrophages was visualized by confocal microscopy. Mass spectrometry was applied to identify the significantly highly expressed HMGB1 protein in EO771/exo, and ligands of HMGB1 on lung macrophages were detected by co-immunoprecipitation. Functions of EO771/exo and HMGB1 in inducing PD-L1+-TAMs and generating a pre-metastatic immunosuppressive niche were confirmed by both in vitro and in vivo studies. Roles of EO771/exo and HMGB1 on glycolysis and lactate production were evaluated by metabolism assays. Associations between PD-L1+-TAMs and CD3+CD8+ T lymphocytes within TNBC axillary lymph nodes and lung metastasis specimens were analyzed by immunofluorescence and immunohistochemistry. Results: Confocal microscopy showed constant internalization and absorption of EO771/exo by macrophages. EO771/exo could polarize macrophages toward PD-L1+-TAMs and generate a pre-metastatic immunosuppressive niche, with respect to HC11/exo. Mass spectrometry, clinical samples, and bioinformatics analysis revealed that HMGB1 was highly expressed in EO771/exo and was involved in cellular communication and metabolism processes. Co-immunoprecipitation and 3-dimensional modeling indicated a strong binding of HMGB1 with Tim-3 ligand on lung macrophages. Macrophages treated with EO771/exo displayed an enhanced glycolysis and lactate production. Flow cytometry demonstrated that green fluorescent protein (GFP)-EO771 tumor-bearing mice had more lung micro-metastases than brain and liver. Immunofluorescence and laser confocal microscopy confirmed that EO771/exo, with respect to HC11/exo, were able to increase lung micro-metastases and escalate PD-L1 expression on lung macrophages. Moreover, elevated PD-L1+-TAMs and reduced CD3+CD8+ T lymphocytes were found in TNBC positive axillary lymph nodes and lung metastasis specimens than TNBC negative axillary lymph nodes. Conclusions: Exosomal HMGB1 from TNBC could target Tim-3 ligand on lung macrophages and accelerate glycolysis and lactate production to induce PD-L1+-TAMs, thereby suppressing CD3+CD8+ T lymphocytes immunity and generating a pre-metastasis immune-suppressive niche. Our research would uncover a novel mechanism of lung-tropic metastasis and provide a new therapeutic approach for TNBC treatment. Keywords: breast cancer; lung metastasis; exosomes; tumor-associated macrophages; metabolic reprogramming Citation Format: Wei-Xian Chen, Jia-Hao Wu, Tian-Cheng Cheng, Sujin Yang. Exosomal HMGB1 induce PD-L1+-tumor associated macrophages through glycometabolic reprogramming to promote lung-tropic metastasis of triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-11.

Abstract GS02-07: Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304

Abstract Background: The benefit of adjuvant regional nodal irradiation including the chest wall after mastectomy (CWI+RNI) and with whole breast irradiation (WBI+RNI) after breast conserving surgery (BCS) is well established in pts with pathologically positive axillary nodes (pN+). Pts who present with axillary node involvement (cN+), receive neoadjuvant chemotherapy (NC), and are found to be pathologically node-negative at surgery (ypN0), have lower loco-regional recurrence (LRR) rates compared to those who remain pathologically node-positive (ypN+). This phase III, randomized trial aimed to evaluate whether CWI+RNI after mastectomy or addition of RNI to WBI after BCS significantly improves invasive breast cancer recurrence-free interval (IBC-RFI) in cN+ pts found to be ypN0 after NC. Methods: Eligible pts had clinical cT1-3, N1, M0 invasive breast cancer (biopsy-proven N+ by FNA/core needle bx), completed ≥8 wks of NC (and anti-HER2 therapy if HER2+), and were ypN0 after mastectomy or BCS and sentinel node biopsy (SLNB, ≥2 nodes), axillary lymph node dissection (ALND), or both. Pts were randomized to “No RNI” (i.e., observation after mastectomy or WBI after BCS) vs. “RNI” (i.e., CWI+RNI after mastectomy or WBI+RNI after BCS). Primary endpoint was IBC-RFI. Secondary endpoints reported here: LRR-free interval (LRRFI), distant recurrence-free interval (DRFI), disease-free survival (DFS), and overall survival (OS). Study was designed to have 80% power to detect 35% reduction in annual rate of IBC-RFI for an absolute risk reduction of 4.6% (5-yr cumulative rate). Per protocol, final analysis was to occur after 172 events or 10 yrs after study initiation.Here we report the time-driven analysis prespecified in the protocol. Results: From 9/13-12/20, 1,641 pts were enrolled; 1,556 pts were available for primary event analysis; median f/u time 59.5 mos (IQR 40.7-74.1). Pt/tumor characteristics were well balanced between groups. Median age 52 yrs (range 21-84); 31% non-white; 21% cT1, 60% cT2, 19% cT3; 23% triple-negative, 21% HR+/HER2-, 56% HER2+; 58% BCS; 55% SLNB, 45% ALND+/-SLNB; and 78% had breast pathologic complete response. At the time of the analysis, 109 IBC-RFI events (63% of the planned 172) were confirmed (“No RNI”: 59, “RNI”: 50). There was no statistically significant difference between groups for IBC-RFI (HR=0.88, 95%CI 0.60-1.29; p=0.51), 5-yr point estimates: 91.8% for “No RNI” and 92.7% for “RNI.” There were no statistically significant differences between the treatment groups for secondary endpoints. There were no study-related deaths and no unexpected toxicities.Grade 4 toxicity was rare (0.1% with “No RNI”, 0.5% with “RNI”); 6.5% of pts developed grade 3 toxicity in “No RNI” and 10% in “RNI” group. Most common grade 3 toxicity was radiation dermatitis (3.3% in “No RNI,” 5.7% in “RNI”). Conclusion: In pts who present with biopsy-proven axillary node involvement and convert their axillary nodes to ypN0 after NC, CWI+RNI after mastectomy, or WBI+RNI after BCS, did not significantly improve IBC-RFI, LRRFI, DRFI, DFS, or OS. These findings suggest that downstaging involved axillary nodes with NC can result in optimization of adjuvant radiotherapy without adversely affecting oncologic outcomes. Follow-up of pts for long-term outcomes continues. NCT01872975 *EPM and JW are co-first authors. Table 1 Citation Format: Eleftherios Mamounas, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres, Frank Vicini, Patricia Ganz, Susan McCloskey, Nilendu Gupta, X. Allen Li, Peter Lucas, Nadeem Abu-Rustum, Saumil Gandhi, Rahul Tendulkar, Robert Coleman, Keiichi Fujiwara, Samantha Seaward, William Irvin, Kristin Higgins, Robert Mutter, Jean-Francois Boileau, Andrew Muskovitz, Reshma Jagsi, Anna Weiss, Curran Walter Jr., Norman Wolmark. Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-07.

Abstract PO3-03-03: Prospective non-randomized study to compare accuracy of clinical examination under anesthesia, axillary ultrasound and histo-pathological evaluation for axillary nodal staging in women with clinically N0 early breast cancer

Abstract Introduction: Accurate assessment of axillary lymph nodes is crucial in the management of early breast cancer (EBC), especially in clinically node negative (cN0) axilla to avoid extensive axillary surgery. Clinical examination alone underestimates nodal disease in nearly 30% women with cN0 axilla. The current study compares, in cN0 axilla, the benefit of axillary ultrasonography (USG) and clinical axillary examination under anesthesia (EUA) to predict involvement of axillary lymph nodes. The gold standard in these patients however remains pathological evaluation after sentinel node biopsy/low axillary sampling (SNB/LAS) and a complete axillary lymph node dissection (ALND) if node positive. Methodology: Prospectively, 500 women with cN0 EBC were enrolled from Aug 2015 to April 2023 in a study approved by Institutional Ethics Committee. After informed consenting, a preoperative axillary USG was carried out in addition to standard breast imaging to determine number of axillary node(s) and its architecture. The USG assessment was labeled as suspicious or not and the result was blinded to the surgeons. A USG-guided FNAC was not performed as it would then be difficult to blind the surgeon and pathologist preoperatively. During surgery, an initial axillary EUA was performed before starting and any suspicious node was documented. This was followed by axillary staging by standard dual tracer SNB/LAS. A complete axillary dissection was done (level 1-3) if any node was positive on frozen section evaluation or final histopathology. Axillary node histopathology was the gold standard for comparison of effectiveness of clinical exam, USG, EUA, and SNB/LAS for prediction of axilla. Standard diagnostic tests such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used. Results: Thirty-six patients were excluded in the final analysis (disease progression, chemotherapy first, or had a surgery elsewhere). Of the eligible 464 cN0 patients, 129 were detected to have axillary metastases (27.8%) in final histopathology. The 2 interventions namely USG axilla, EUA were compared to final axillary nodal histopathology. Axillary USG reported suspicious/indeterminate node(s) in 129 (27.8%) patients. USG had a low sensitivity of 46.5% and a low PPV of 46.5% to identify a positive node. However, the specificity and NPV both were 79.4%. Axillary USG was 70.2% accurate in predicting axillary nodal involvement. EUA also had sensitivity of 60% and low PPV of 14.8%. However, the specificity of EUA was 73.4%, NPV of 95.9%; higher than that of USG. EUA was 72.4% accurate. SNB/LAS had the sensitivity of 93.3%, specificity 79.2%, NPV 82.9%, PPV 91.6% and accuracy rate 89.2% in predicting a positive axilla. Conclusions: While the fallacy of clinical exam remains at 27.8%, both USG alone (without FNAC) and EUA failed in predicting a positive axillary node. EUA fared better at predicting a negative axilla. USG guided FNAC would perhaps improve the sensitivity of USG, however additional investigations are difficult in resource constraint and high-volume center, especially, when surgical interventions like SNB or LAS remain standard of care. Table 1 Citation Format: Vani Parmar, Zeal Sanghvi, Shalaka Joshi, Nita Nair, Palak Popat, Seema Kembhavi, Souwmyashree KN, Soujanya Mynalli, Purvi Thakkar, Garvit Chitkara, Sangeeta Desai, Tanuja Shet, Rajendra Badwe. Prospective non-randomized study to compare accuracy of clinical examination under anesthesia, axillary ultrasound and histo-pathological evaluation for axillary nodal staging in women with clinically N0 early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-03.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

Predictors of positive axillary node clearance following positive sentinel node biopsy: A retrospective analysis at royal Glamorgan hospital

Predictors of positive axillary node clearance following positive sentinel node biopsy: A retrospective analysis at royal Glamorgan hospital

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.

The Impact of Neoadjuvant Chemotherapy on Axillary Surgical Management of Patients With Breast Cancer and Positive Axillary Lymph Nodes.

Sentinel lymph node biopsy (SLNB) is effective in patients with breast cancer (BC) and positive axillary lymph nodes undergoing neoadjuvant chemotherapy (NAC). However, the frequency with which axillary lymphadenectomy (ALND) can be avoided remains debated. This study aimed to identify patient populations that can benefit from this approach. The data of 195 consecutive patients with BC and positive axillary lymph nodes at diagnosis who underwent NAC were retrospectively analyzed. In all cases, the positivity of the lymph nodes was confirmed by cytological examination. Patients converted to ycN0 after NAC were considered eligible for SLNB. Indications for ALND were failed mapping, fewer than three SLNs recovered, and positive SLNs. Of 195 cN1 patients potentially eligible for SLNB, 71 (36.4%) remained clinically ycN+ after NAC and underwent elective ALND, while 124 (83.7%) converted to ycN0 after NAC and SLNB. The lymph node identification rate was 95.9% (119/124 patients) with three or more SLNs recovered in 83 cases (89.8%). One or two lymph nodes were recovered in 36 cases (30.2%). Nodal pathologic complete response (pCR) was found in 34/83 (40.9%) patients with three or more SLNs recovered. Considering all 195 patients initially included in the study, 55 patients (28.2%) achieved lymph node pCR after NAC. Nodal pCR varied based on hormone receptor and HER2 status, with rates ranging from 20.7% for ER+/HER2- patients to 95.3% for ER-/HER2+ patients (p<0.001). More than 80% of cN1 patients in our study were eligible for SLNB after NAC. ALND could be avoided in approximately 30% of cases, supporting the role of NAC in reducing the need for ALND among patients with lymph node metastases.

Interferon-Gamma Secretion Is Significantly Decreased in Stage III Breast Cancer Patients.

Even though some studies have shown possible clinical relationship between molecular subtypes and tumor infiltrating natural killer (NK) cells around tumors, there are few studies showing the clinical relevance of peripheral NK cell activity at diagnosis in female patients with invasive breast cancer. A total of 396 female invasive breast cancer patients who received curative surgical treatment from March 2017 to July 2021 were retrospectively analyzed. NK cell activation-induced interferon-gamma (IFN-γ) secretion measured by enzyme-linked immunosorbent assay was used to measure the activity of peripheral NK cells. Statistical analyses were performed to determine clinical relationships with major clinicopathologic parameters. Quadripartite NK cell activity measured by induced interferon-gamma showed significant relevance with staging and body mass index, and some of the inflammatory serological markers, namely N/L (neutrophil/lymphocyte), P/N (platelet/neutrophil), and P/L (platelet/lymphocyte), showed significantly different NK activity in each interval by univariate analysis. A binary subgroup analysis, setting the IFN-γ secretion cut-off at 100 pg/mL, showed that stage III was significantly increased and axillary lymph node metastasis positivity was increased in the group of IFN-γ < 100 pg/mL, and IFN-γ secretion decreased with an increasing N stage, increased BMI (body mass index), and decreased production of IFN-γ. Following this, the same binary analysis, but with the IFN-γ secretion cut-off at 250 pg/mL, also showed that secretion in stage III was increased in those concentrations with <250 pg/mL, axillary lymph node positivity appeared to be correlated, and BMI ≥ 30 increased in prevalence. Additional ANOVA post hoc tests (Bonferroni) were performed on some serological markers that tended to be somewhat inconsistent. By subgroup analysis with Bonferroni adjustment between the IFN-γ secretion and TNM stage, no significant difference in IFN-γ secretion could be identified at stages I, II, and IV, but at stage III, the IFN-γ secretion < 100 pg/mL was significantly higher than 250 ≤ IFN-γ secretion < 500 pg/mL or IFN-γ secretion ≥ 500 pg/mL. According to this study, stage III was significantly associated with the lowest IFN-γ secretion. Compared to a higher level of IFN-γ secretion, a lower level of IFN-γ secretion seemed to be associated with increased body mass index. Unlike when IFN-γ secretion was analyzed in quartiles, as the IFN-γ secretion fell below 100 pg/mL, the correlation between axillary lymph node positivity and increased N stage, increased BMI, and increased N/L and P/L, which are suggested poor prognostic factors, became more pronounced. We think a peripheral IFN-γ secretion test might be convenient and useful tool for pretreatment risk assessment and selecting probable candidates for further treatment such as immunotherapy in some curable but high-risk invasive breast cancer patients, compared to other costly assaying of tissue NK cell activity at diagnosis.

Implementation of the Targeted Axillary Dissection Procedure in Clinically Node-Positive Breast Cancer: A Retrospective Analysis.

The targeted axillary dissection (TAD) procedure is used in clinically positive lymph node (cN+) breast cancer to assess whether pathological complete response (pCR) is achieved after neoadjuvant systemic therapy (NST) to decide on de-escalation of axillary lymph node dissection (ALND). In this study, we review the implementation of the TAD procedure in a large regional breast cancer center. All TAD procedures between 2016 and 2022 were reviewed. The TAD procedure consists of marking pre-NST the largest suspected metastatic lymph node(s) using a radioactive I-125 seed. During surgery, the marked node was excised together with a sentinel node procedure. Axillary therapy (ALND, axillary radiotherapy, or nothing) recommendations were based on the amount of suspected positive axillary lymph nodes (ALNs < 4 or ≥ 4) pre-NST and if pCR was achieved after NST. A total of 312 TAD procedures were successfully performed in 309 patients. In 134 (43%) cases, pCR of the TAD lymph nodes were achieved. Per treatment protocol, 43 cases (14%) did not receive any axillary treatment, 218 cases (70%) received adjuvant axillary radiotherapy, and 51 cases (16%) underwent an ALND. During a median follow-up of 2.8 years, 46 patients (14%) developed recurrence, of which 11 patients (3.5%) had axillary recurrence. Introduction of the TAD procedure has resulted in a reduction of 84% of previously indicated ALNDs. Moreover, 18% of cases did not receive adjuvant axillary radiotherapy. These data show that implementation of de-escalation axillary treatment with the TAD procedure appeared to be successful.