Neoadjuvant Systemic Therapy Research Articles

Emerging Indications for Neoadjuvant Systemic Therapies in Cutaneous Malignancies.

Patients with cutaneous malignancies and locoregional involvement represent a high-risk population for disease recurrence, even if they receive optimal surgery and adjuvant treatment. Here, we discuss how neoadjuvant therapy has the potential to offer significant advantages over adjuvant treatment, further improving outcomes in some patients with skin cancers, including melanoma, Merkel cell carcinoma, and cutaneous squamous-cell carcinoma. Both preclinical studies and in vivo trials have demonstrated that exposure to immunotherapy prior to surgical resection can trigger a broader and more robust immune response, resulting in increased tumor cell antigen presentation and improved targeting by immune cells, potentially resulting in superior outcomes. In addition, neoadjuvant approaches hold the possibility of providing a platform for evaluating pathological responses in the resected lesion, optimizing the prognosis and enabling personalized adaptive management, in addition to expedited drug development. However, more data are still needed to determine the ideal patient selection and the best treatment framework and to identify reliable biomarkers of treatment responses. Although there are ongoing questions regarding neoadjuvant treatment, current data support a paradigm shift toward considering neoadjuvant therapy as the standard approach for selecting patients with high-risk skin tumors.

Intraoperative evaluation of sentinel lymph nodes in patients with breast cancer treated with systemic neoadjuvant therapy

AimsTouch preparation (TP) and frozen section (FS) are the two methods routinely used in the intraoperative evaluation (IOE) of sentinel lymph nodes (SLNs) to detect metastases in patients with breast...

Non-Invasive 3D Breast Tumor Localization: A Viable Alternative to Invasive Tumor Marking.

Background: We present a detailed description and the preliminary results of our original technique for non-invasive three-dimensional tumor localization in the breast, which was created as an alternative to standard invasive tumor marking before neoadjuvant systemic therapy (NAST), aiming to enable adequate surgery after complete tumor regression. Methods: A detailed description of the technique is provided in the main text. The technique's feasibility and precision were assessed in a single-arm, prospective study based on the histological parameters of the adequacy and rationality of the excision of completely regressed tumor beds. Results: Out of 94 recruited patients, 15 (16%) were deemed unsuitable, mainly due to the tumors' inadequate ultrasound visibility. Among the 79 processed patients, 31 (39%) had complete clinical regression after NAST and were operated on using our technique. The histological parameters of surgical precision (signs of tumor regression: 24/31; microscopic cancer residues: 7/31) were verified in all excised specimens (100% precision). There were no positive margins in seven cases with microscopic residues, indicating our technique's capacity to enable oncologically safe post-NAST surgery. Conclusions: The proposed technique is feasible and satisfactorily accurate in determining the location of regressed tumors, thus representing an alternative to invasive tumor marking, especially in surgical centers lacking trained staff and equipment for invasive marking. The technique's limitations are mainly related to the inadequate ultrasound visibility of the tumor.

Initial MRI findings predictive of a pathological complete response to neoadjuvant treatments in HER2-positive breast cancers

PurposeThis study aimed to determine if initial MRI findings could predict a pathological complete response (pCR) following neoadjuvant systemic therapy (NST) in HER2-positive breast cancers. MethodsThe study retrospectively included 111 patients (Center 1, training set) and 71 patients (Center 2, validation set) with HER2-positive cancer who underwent NST. Initial clinicopathological data and MRI findings were recorded. Continuous variables were analyzed using the Mann–Whitney and Student’s t-tests, while categorical variables were analyzed using the χ2 or Fisher’s exact test. Univariate analysis was conducted to determine the associations between these variables and pathological complete response (pCR), defined as the absence of invasive malignant cells in the breast and lymph nodes. Interobserver reproducibility was assessed for associated non-mass enhancement (NME) parameter by analyzing 50 MR studies (intraclass correlation coefficient). ResultspCR was achieved in 67 patients, 51 (46 %) from Center 1 and 16 (23%) from Center 2 (p = 0.003), with significant differences between Centers 1 and 2 in tumor-infiltrating lymphocyte levels and lymphovascular invasion (p < 0.001). The initial presence of suspicious associated NME was the only significant parameter predictive of pCR (p < 0.001 for Center 1 and 0.04 for Center 2). The inter-observer reproducibility for this MRI feature was good, with an intraclass correlation coefficient of 0.872 (95 % CI: 0.73–1.00). ConclusionThe presence of suspicious associated NME in HER2-positive cancers on the initial MRI study was predictive of achieving pCR after NST. This significant preliminary finding warrants confirmation through prospective multicenter studies.

Multiparametric MRI–based radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

Tailoring neoadjuvant systemic therapy in breast cancer: "The advent of a personalized approach"-The Breast-Gynecological and Immuno-Oncology International Cancer Conference (BGICC) consensus and recommendations.

The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus. During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer. The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

Treatment and Staging Intensification Strategies Associated with Radical Prostatectomy for High-Risk Prostate Cancer: Efficacy Evaluation and Exploration of Novel Approaches.

The management of high-risk prostate cancer (PCa) presents a significant clinical challenge, often necessitating treatment intensification due to the potential presence of micrometastases. While radical prostatectomy (RP) constitutes one of the primary treatment modalities, the integration of neoadjuvant and adjuvant therapies suggests a paradigm shift towards more aggressive treatment strategies, also guided by new imaging modalities like positron emission tomography using prostate-specific membrane antigen (PSMA-PET). Despite the benefits, treatment intensification raises concerns regarding increased side effects. This review synthesizes the latest evidence on perioperative treatment intensification and de-escalation for high-risk localized and locally advanced PCa patients eligible for surgery. Through a non-systematic literature review conducted via PubMed, Scopus, Web of Science, and ClinicalTrials.gov, we explored various dimensions of perioperative treatments, including neoadjuvant systemic therapies, adjuvant therapies, and the role of novel diagnostic technologies. Emerging evidence provides more support for neoadjuvant systemic therapies. Preliminary results from studies suggest the potential for treatments traditionally reserved for metastatic PCa to show apparent benefit in a non-metastatic setting. The role of adjuvant treatments remains debated, particularly the use of androgen deprivation therapy (ADT) and adjuvant radiotherapy in patients at higher risk of biochemical recurrence. The potential role of radio-guided PSMA lymph node dissection emerges as a cutting-edge approach, offering a targeted method for eradicating disease with greater precision. Innovations such as artificial intelligence and machine learning are potential game-changers, offering new avenues for personalized treatment and improved prognostication. The intensification of surgical treatment in high-risk PCa patients is a dynamic and evolving field, underscored by the integration of traditional and novel therapeutic approaches. As evidence continues to emerge, these strategies will refine patient selection, enhance treatment efficacy, and mitigate the risk of progression, although with an attentive consideration of the associated side effects.

Diffusion-weighted imaging in addition to contrast-enhanced MRI in identifying complete response in HER2-positive breast cancer.

The aim of this study is to investigate the added value of diffusion-weighted imaging (DWI) to dynamic-contrast enhanced (DCE)-MRI to identify a pathological complete response (pCR) in patients with HER2-positive breast cancer and radiological complete response (rCR). This is a single-center observational study of 102 patients with stage I-III HER2-positive breast cancer and real-world documented rCR on DCE-MRI. Patients were treated between 2015 and 2019. Both 1.5 T/3.0 T single-shot diffusion-weighted echo-planar sequence were used. Post neoadjuvant systemic treatment (NST) diffusion-weighted images were reviewed by two readers for visual evaluation and ADCmean. Discordant cases were resolved in a consensus meeting. pCR of the breast (ypT0/is) was used to calculate the negative predictive value (NPV). Breast pCR-percentages were tested with Fisher's exact test. ADCmean and ∆ADCmean(%) for patients with and without pCR were compared using a Mann-Whitney U-test. The NPV for DWI added to DCE is 86% compared to 87% for DCE alone in hormone receptor (HR)-/HER2-positive and 67% compared to 64% in HR-positive/HER2-positive breast cancer. Twenty-seven of 39 non-rCR DWI cases were false positives. In HR-positive/HER2-positive breast cancer the NPV for DCE MRI differs between MRI field strength (1.5 T:50% vs. 3 T:81% [p = 0.02]). ADCmean at baseline, post-NST, and ∆ADCmean were similar between patients with and without pCR. DWI has no clinically relevant effect on the NPV of DCE alone to identify a pCR in early HER2-positive breast cancer. The added value of DWI in HR-positive/HER2-positive breast cancer should be further investigated taken MRI field strength into account. The residual signal on DWI after neoadjuvant systemic therapy in cases with early HER2-positive breast cancer and no residual pathologic enhancement on DCE-MRI breast should not (yet) be considered in assessing a complete radiologic response. Radiologic complete response is associated with a pathologic complete response (pCR) in HER2+ breast cancerbut further improvement is warranted. No relevant increase in negative predictive value was observed when DWI was added to DCE. Residualsignalon DW-images without pathologic enhancement on DCE-MRI, does not indicate a lower chance of pCR.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

Reliability of Magseed® marking before neoadjuvant systemic therapy with subsequent contrast-enhanced mammography in patients with non-palpable breast cancer lesions after treatment: the MAGMA study

PurposeTo assess the reliability of excising residual breast cancer lesions after neoadjuvant systemic therapy (NAST) using a previously localized paramagnetic seed (Magseed®) and the subsequent use of contrast-enhanced spectral mammography (CESM) to evaluate response.MethodsObservational, prospective, multicenter study including adult women (> 18 years) with invasive breast carcinoma undergoing NAST between January 2022 and February 2023 with non-palpable tumor lesions at surgery. Radiologists marked tumors with Magseed® during biopsy before NAST, and surgeons excised tumors guided by the Sentimag® magnetometer. CESMs were performed before and after NAST to evaluate tumor response (Response Evaluation Criteria for Solid Tumors [RECIST]). We considered intraoperative, surgical, and CESM-related variables and histological response.ResultsWe analyzed 109 patients (median [IQR] age of 55.0 [46.0, 65.0] years). Magseed® was retrieved from breast tumors in all surgeries (100%; 95% CI 95.47–100.0%) with no displacement and was identified by radiology in 106 patients (97.24%), a median (IQR) of 176.5 (150.0, 216.3) days after marking. Most surgeries (94.49%) were conservative; they lasted a median (IQR) of 22.5 (14.75, 40.0) min (95% CI 23.59–30.11 min). Most dissected tumor margins (93.57%) were negative, and few patients (5.51%) needed reintervention. Magseed® was identified using CESM in all patients (100%); RECIST responses correlated with histopathological evaluations of dissected tumors using the Miller–Payne response grade (p < 0.0001) and residual lesion diameter (p < 0.0001). Also 69 patients (63.3%) answered a patient’s satisfaction survey and 98.8% of them felt very satisfied with the entire procedure.ConclusionLong-term marking of breast cancer lesions with Magseed® is a reliable and feasible method in patients undergoing NAST and may be used with subsequent CESM.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design

BackgroundDisease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial.MethodsThis randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the “Trials within Cohorts” (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19–9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment.DiscussionThe RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients’ quality of life will be obtained.Trial registrationClinicaltrials.gov, NCT04875325. Registered on May 6, 2021.

Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence.

In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation. A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995-2010 and 2010-2020). Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar. Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation.

Wire-Free Targeted Axillary Dissection: A Pooled Analysis of 1300+ Cases Post-Neoadjuvant Systemic Therapy in Node-Positive Early Breast Cancer.

Recent advances in neoadjuvant systemic therapy (NST) have significantly improved pathologic complete response rates in early breast cancer, challenging the role of axillary lymph node dissection in nose-positive patients. Targeted axillary dissection (TAD) integrates marked lymph node biopsy (MLNB) and tracer-guided sentinel lymph node biopsy (SLNB). The introduction of new wire-free localisation markers (LMs) has streamlined TAD and increased its adoption. The primary endpoints include the successful localisation and retrieval rates of LMs. The secondary endpoints include the pathological complete response (pCR), SLNB, and MLNB concordance, as well as false-negative rates. Seventeen studies encompassing 1358 TAD procedures in 1355 met the inclusion criteria. The localisation and retrieval rate of LMs were 97% and 99%. A concordance rate of 67% (95% CI: 64-70) between SLNB and MLNB was demonstrated. Notably, 49 days (range: 0-272) was the average LM deployment time to surgery. pCR was observed in 46% (95% CI: 43-49) of cases, with no significant procedure-related complications. Omitting MLNB or SLNB would have under-staged the axilla in 15.2% or 5.4% (p = 0.0001) of cases, respectively. MLNB inclusion in axillary staging post-NST for initially node-positive patients is crucial. The radiation-free Savi Scout, with its minimal MRI artefacts, is the preferred technology for TAD.

Oncologic outcomes of de-escalating axillary treatment in clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy – A two center cohort study

BackgroundThe aim of the present study was to report the 5-year axillary recurrence-free interval (aRFI) in clinically node-positive breast cancer patients treated according to a de-escalating axillary treatment protocol after neoadjuvant systemic therapy (NST). MethodsAll patients diagnosed in two hospitals between October 2014 and March 2021 were identified retrospectively. Data on diagnostic workup, treatment and follow-up was collected. Adjuvant axillary treatment was considered based on the initial staging using 18F-FDG PET/CT and the results of axillary lymph node marking with a radioactive-iodine seed protocol or a targeted axillary dissection procedure. Follow-up was updated until 27th April 2024. Kaplan-Meier curves were calculated to report the 5-year aRFI with corresponding 95 % confident intervals (95%-CI). ResultsA total of 199 patients were included. Axillary pathological complete response was reported in 66 (33.2 %). Based on the treatment protocol and initial clinical staging, no adjuvant axillary treatment was indicated in 30 patients (15 %), while 139 (70 %) received axillary radiotherapy without performance of an axillary lymph node dissection (ALND). The remaining 30 patients (15 %) underwent an ALND with additional locoregional radiotherapy. A median follow-up of 62 months (30–106) showed that 4 (2 %) patients experienced an axillary recurrence after 7, 8, 36 and 36 months, respectively. In all 4 patients, synchronous distant metastases were diagnosed. The estimated 5-year aRFI was 97.8 % (95%-CI 95.6–99.9 %) ConclusionAlthough longer follow-up should be awaited before final conclusions can be drawn regarding the oncological safety of this approach, the implementation of a de-escalating axillary treatment protocol appears to be safe since the estimated 5-year aRFI is 97.8 %.

Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.

Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, 125I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; p = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from 125I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.

Trends in the management of small HER2-positive breast cancers.

e12523 Background: Small HER2 positive breast cancers have not been well studied in randomized trials. The treatment landscape for this population aims to optimize efficacy while minimizing potential over-treatment and associated toxicities. Due to the potential for post-neoadjuvant therapy optimization, use of neoadjuvant systemic therapy (NAT) increased in recent years. However, this approach can often lead to overtreatment of patients with small tumors. This study aims to evaluate recent trends in treatment patterns of patients with T1 HER2 positive tumors. Methods: Patients diagnosed with HER2 positive, T1, any N, breast cancer treated at a single institution from January 2018 to December 2022 were included. Clinicopathological data, treatment data, and survival data were collected and analyzed. Results: 326 patients were included. Mean age was 62 (±12.2) years. T category included 3 (0.9%) cT0, 17 (5.2%) cTmi, 28 (8.6%) cT1a, 94 (28.8%) cT1b, 178 (54.6%) cT1c tumors, and 6 patients (1.8%) had clinical T1 stage without further specification. 41 patients (12.6%) had cN+ disease and 243 (74.5%) were hormone receptor positive. Systemic therapy data was available for 288 patients; 7 (2.4%) received Herceptin monotherapy, 105 (36.5%) Taxol + Herceptin, 41 (14.2%) Taxol + Carboplatin + Herceptin, and 74 (25.7%) Taxol + Carboplatin + Herceptin + Pertuzumab (TCHP), 12 (4.2%) other. 49 patients (17%) did not receive any systemic therapy. 58 patients (17.8%) were treated with NAT and a pathologic complete response rate was noted in 39 patients (67.2%) undergoing NAT. Overall, in patients who received systemic therapy, NAT increased from 2018 (17.6%) to 2021 (37.5%) and decreased in 2022 (23.5%). Similar patterns were observed in patients with T1a/b (2021: 17.4%; 2022: 0%), as well as T1c (2021: 51.4%; 2022: 36.4%). TCHP was the most commonly administered NAT regimen (86.2%). Discontinuation or dose reduction occurred in a total of 57 patients (18.8%). Conclusions: The primary treatment for T1 HER2 positive breast cancers is surgery with adjuvant HER2 targeted therapy in combination with chemotherapy. Although NAT witnessed an upward trend from 2018 to its peak in 2021, its utilization declined again in 2022. A balance between the most effective treatment and minimizing toxicities should be ensured.

Impact of extent of disease at presentation on oncologic outcomes according to pathologic response to neoadjuvant systemic therapy among participants of the I-SPY2 clinical trial.

594 Background: Recent analyses in HER2+ and triple negative (TN) breast cancer (BC) treated with neoadjuvant systemic therapy (NAST) suggest that extent of disease at presentation (tumor [T] size and nodal [N] involvement) influences outcomes independently of response to NAST, even in the context of pathologic complete response (pCR). Given this, we evaluated the association of clinical T and N status prior to NAST with long-term outcomes in I-SPY2. Methods: We identified patients (pts) with TN and HER2+ BC who received NAST on the I-SPY2 trial with available clinical T size and N status prior to NAST, pathologic response after NAST, and follow up for recurrence and survival. We conducted univariable and multivariable (MV) Cox proportional models for Event Free (EFS), Distant Recurrence Free (DRFS), and Overall Survival (OS) in TN and HER2+ BC according to response after NAST, adjusting for residual cancer burden (RCB) category. Results: Of 1,170 pts with TN or HER2+ BC, 1,013 were eligible (TN: 623 and HER2+: 390), after 157 pts were excluded due to missing critical variables. Median follow up was 4.4 years (range 0.3-10.2). Median age was 48 for TN and 49 for HER2+ BC. Following NAST, pCR was achieved in 277 (45%) pts with TN and 197 (51%) pts with HER2+ BC. Among pts with pCR, separate MV analyses for TN and HER2+ BC showed no independent association between clinical T and N category with EFS, DRFS or OS (p values all &gt; 0.05). However, among pts with residual disease, clinical T category (but not clinical N status) prior to NAST retained independent prognostic information in both TN and HER2+ BC in a MV model adjusting for age, RCB class, and hormone receptor status (for HER2+ BC). Compared to cT1-2, cT3-4 stage at diagnosis was associated with worse EFS, DRFS, and OS in TNBC, and with worse EFS, DRFS (but not OS) in HER2+ BC (Table). Additionally, hormone receptor status was independently associated with outcomes in HER2+ BC with residual disease (data not shown). The 5y EFS for cT1-2 vs cT3-4 according to RCB class in TNBC were: RCB0: 94% vs 95%, RCB1: 90% vs 65%, RCB2: 74% vs 44% and RCB3: 45% vs 20%. The 5y EFS for cT1-2 vs cT3-4 according to RCB class in HER2+ were: RCB0: 95% vs 88%, RCB1: 89% vs 84%, RCB2: 85% vs 64% and RCB3: 56% vs 50%. Conclusions: Tumor size (but not N involvement) prior to NAST was independently associated with outcomes in TN and HER2+ BC with residual disease, independently of RCB class. TN and HER2+ BC achieving pCR exhibited favorable outcomes regardless of extent of disease prior to NAST. These data are consistent with prior findings of the Neobioscore contributing only in the context of residual disease. Clinical trial information: NCT01042379 . [Table: see text]

Pathologic examination of specimen after vacuum-assisted biopsy (VAB) in patients with breast cancer after neoadjuvant systemic therapy (NST).

e12589 Background: VAB of the tumor bed in the breast has shown promising results as a minimally invasive method for determining pathologic complete response (pCR). A significant disadvantage of VAB is the fragmentation of the obtained material and the lack of methods for determining generally accepted predictive and prognostic factors such as RCB index in case if residual tumor is detected. Here we present a description of the accumulated experience of histological examination of specimens obtained using VAB in patients with breast cancer after NST. Methods: A single-center, prospective, non-randomized study included patients with unifocal breast cancer (cT1–2N0–1M0). Patients who achieved a complete clinical response (cCR) underwent VAB. VAB specimen intraoperatively was divided into «inner contour» (first 6-12 samples) and «outer contour» (latter 6-12 samples). Patients without signs of residual tumor (pCR, ypT0N0) did not undergo further surgical intervention. In case if residual tumor cells (RTC) were detected, standard breast surgery was performed. To assess an extent of tumor response to NST instead of RCB we used Miller-Payne system which has correlation with RCB. Results: 35 patients with a mean age of 48.3 (31–67) years were included in the analysis. Examination of VAB samples showed that 11 (31.4%) patients had a residual tumor, and in 24 (68.6%) patients no tumor cells were detected (ypT0N0). According to the Miller-Payne system, 28 patients had a complete pathological response, which corresponds to Miller-Payne = 5 and pathological stage ypT0/ypTis (24 patients ypT0N0, 3 patients ypTisN0 and 1 patient ypT0N1). In 7 patients with residual invasive tumor, the tumor response according to the Miller-Payne scale corresponded to grades 3 and 4. There was a statistically significant correlation between presence of RTC in the «outer contour» of VAB and presence of RTC in the postoperative histology after standard surgery (Х2 p=0.01, Fisher exact test p=0.048). In case when RTC were found in the «inner contour» no correlation with the presence of RTC in the postoperative histology after standard surgery was observed (Х2 p=0.292, Fisher exact test p=1.0). Radiologic-pathologic discordance was 25% for mammolymphoscintigraphy, 35.5% for US and 39.4% for mammography. In case if 3 of 3 studies after NST described cCR radiologic-pathologic discordance was 16.7%, in case if 2 of 3 studies described cCR it was 22.2% and in case if only 1 of 3 studies described cCR it was 27.3%. Conclusions: The method used to evaluate histological material allows us to obtain predictive and prognostic information necessary to clarify further treatment tactics in accordance with modern standards. It is necessary to conduct large-scale studies in this area to answer the question if this method can be used in routine clinical practice. Clinical trial information: NCT04293796 .

Presence of molecular residual disease after pathologic complete response among patients with inflammatory breast cancer.

3044 Background: Inflammatory breast cancer (IBC) is known to recur more frequently than non-IBC after pathologic complete response (pCR). The presence of circulating tumor cells (CTCs), a marker of molecular residual disease (MRD), has been associated with higher likelihood of metastasis. We sought to characterize CTCs and its relationship with pCR in IBC patients. Methods: Patients diagnosed with IBC were enrolled in a prospective registry from 2005-2022. Serial blood draws were performed before, during, and after neoadjuvant systemic therapy (NST), and 6-months and 1-year post-surgery. CTCs were enumerated using CellSearch™. Patients with ≥ 1 CTC at any timepoint in the post-operative period were included in the positive CTC cohort. T-tests, one-way ANOVA, and chi-squared tests were used to compare differences between groups. Kaplan-Meier analysis was used for survival outcomes. Results: A total of 112 patients were included. The median age of diagnosis was 50.5 years (IQR 17) and BMI was 29.3 kg/m2 (IQR 11.3). Patients were predominantly White (85, 75.9%) with clinical stage IIIB-C (94, 84.9%), node-positive (107, 95.5%), and HER2-negative (66, 59.0%) disease. Almost all patients (109, 97.3%) received trimodality therapy – NST, modified radical mastectomy, and adjuvant radiation. At a median follow-up period of 7.1 years (95% CI: 4.7-9.4), the overall survival (OS) rate was 72.3%. Baseline CTC positivity rate was 61.8% (42/68). More than half of the patients (61, 54.5%) had a positive CTC at some point in the post-operative surveillance period. Among the 39 patients who achieved pCR (34.8%), 15 (38.5%) had positive CTCs during follow-up. There were no differences in age, BMI, menopause status, clinical stage, nodal status, grade, presence of LVI, and number of lymph nodes (LNs) removed by CTC status. However, patients with positive CTCs had a significantly higher number of positive LNs at resection (p = 0.01), were more likely to be HER2-negative (p = 0.001), and were less likely to achieve pCR (p = 0.01). Triple negative disease (p &lt; 0.0001), lack of pCR (p = 0.006), and positive CTCs (0.007) were associated with poor prognosis. When pCR was combined with CTC status, patients with positive CTCs demonstrated significantly worse survival, despite having achieved pCR, compared to those with pCR and negative CTC status (5-year OS: 35.0% vs. 83.1%, respectively, p = 0.016). Conclusions: A high proportion of IBC patients who achieved pCR had MRD, as demonstrated by persistent CTCs. CTCs portended worse prognosis in patients with IBC, even after pCR. Future incorporation of longitudinal CTC monitoring may be helpful in identifying patients at risk for relapse despite having achieved a pCR. [Table: see text]

De-escalation of breast cancer surgery using vacuum-assisted biopsy (VAB): Interim results.

e12590 Background: Currently, there is a point of view according to which, in patients diagnosed with breast cancer (BC), surgical intervention when achieving a complete pathological response (pCR) after neoadjuvant systemic therapy (NST) is diagnostic, not therapeutic, and does not affect long-term treatment outcomes. Vacuum-assisted biopsy (VAB) of the tumor bed in breast cancer has shown promising results as a minimally invasive method for diagnosing pCR. This work presents a prospective analysis of treatment of patients with triple-negative and HER2-positive breast cancer who achieved pCR after NST and who underwent VAB alone without subsequent breast surgery. Methods: Women aged 18 years old and older with unicentric (cT1-2N0-1M0) triple-negative or HER2-positive breast cancer were included. Primary lesions were marked with a single clip before NST. In cases with nodal involvement (cN1) the affected lymph nodes were also clipped. Patients with TNBC received 4 cycles of AC q21d followed by 12 cycles of weekly paclitaxel and carboplatin AUC 2.0. HER2+ patients received dual anti-HER2 blockade with chemotherapy (TCHP or AC-DHP regimen). Breast US, mammography and mammolymphoscintigraphy were used at baseline and at response evaluation. Patients with complete clinical response after NST underwent VAB with 7G needle and US-guidance simultaneously with the sentinel lymph node biopsy and/or targeted axillary dissection. In case if no invasive or in situ residual tumor cells were detected (ypT0N0), no further breast surgery was performed and patients underwent subsequent radiation therapy. Primary endpoint was 2-year ipsilateral breast tumour recurrence-free survival [IBTR-FS]. Secondary endpoints included 2-year disease-free survival (DFS) and complication rates. The study is registered on сlinicaltrials.gov, NCT04293796. Results: 35 patients with a mean age of 48.3 (31–67) years were included in the trial. Examination of VAB samples showed that 11 (31.4%) patients had a residual tumor, and in 24 (68.6%) patients no tumor cells were detected (ypT0N0). This 24 patients were included in the analysis. Median follow-up was 26 months. Median survival was not reached for any endpoint. 2-year IBTR-FS was 91.7% in the VAB group. 2-year DFS was 83.3% in the VAB group. We registered 4 events: in 2 patients biopsy-proven de novo breast cancer occurred in contralateral breast, in 1 patient recurrence occurred in the postoperative zone and in 1 patient recurrence occurred in another quadrant of the ipsilateral breast. Conclusions: Additional observation and large randomized prospective studies are needed to determine the safety of VAB use. Clinical trial information: NCT04293796 .