Neoadjuvant Hormonal Therapy Research Articles

Long-term clinical outcomes of cancers diagnosed following detection by a blood-based multi-cancer early detection (MCED) test.

3037 Background: Less than 20% of cancers are diagnosed as a result of standard-of-care (SOC) screening in the US. MCED tests may expand screening to more cancers, but the long-term outcomes of MCED test-detected cancers are unknown. DETECT-A was the first large prospective interventional clinical trial to evaluate an MCED blood test. The test used was an early version of CancerSEEK and was evaluated in 9,911 women without history of cancer ( Science 369:6499, 2020). CancerSEEK, coupled with diagnostic PET-CT, safely identified cancers including those not detected by SOC screening, the majority of which were localized or regional. This follow-up observational study evaluated longitudinal clinical outcomes of cancers diagnosed as a result of an abnormal CancerSEEK test with a median follow up of 4.4 (IQR:4.1-4.6) years from initial CancerSEEK testing. Methods: Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnosis, treatment, treatment response, remission status, recurrence, secondary cancer diagnoses, and mortality (cancer-related and all-cause) was extracted from electronic medical records through November 2022. Data collection for living participants took place a median of 3.7 years following cancer diagnosis (IQR: 3.3-3.9) and a median of 4.3 years (IQR: 4.1-4.7) following initial CancerSEEK screen. Results: Fourteen (53.8%) participants underwent surgery; 5 had surgery alone, 9 had surgery with adjuvant and/or neoadjuvant chemotherapy, radiation, or hormone therapy. Twelve of 14 (85.7%) surgically treated participants were in remission as of November 2022, including 10 with localized or regional disease at diagnosis. Among patients whose treatment was non-surgical (11) or unknown (1), 1 (8.3%) was in remission (stage I at diagnosis), 9 (75.0%) were deceased (all stage III or IV at diagnosis), and 2 (16.7%) were in surveillance or ongoing treatment (stage II and stage III at diagnosis). Overall, 13 of 26 (50%) participants were in remission [ovarian (4), thyroid (1), uterus (2), breast (1), colorectal (2), and lung (3)]; 7 of these 13 (54%) had cancers without recommended SOC screening modalities. Eleven of 17 (64.7%) participants with localized or regional disease (stage I, II, or III) were in remission, whereas 2 of 9 (22.2%) with stage IV disease at diagnosis were in remission. Conclusions: CancerSEEK detected cancers earlier in patients who, when treated subsequently with conventional methods, achieved long-term survival. Half of all patients with a CancerSEEK-detected cancer remain cancer-free after treatment >4 years (median) after their initial CancerSEEK test. This includes 7 patients with cancer types for which no SOC screening option exists. Additional biomarkers, new analytic methods and algorithms are being incorporated in the development of the next generation of the MCED test.

Gene expression signatures, stromal tumor infiltrating lymphocytes (sTILs), and change in tumor cellularity to predict pathological complete response (pCR) after 12 week de-escalated neoadjuvant endocrine therapy (ET) vs paclitaxel + dual HER2 blockade in the WSG-TP-II trial.

519 Background: There are limited data on predictive biomarkers for de-escalated ET or chemotherapy with dual anti-HER2 blockade in HR+/HER2+ early breast cancer (BC). In this translational pre-planned project of the WSG-TP-II phase II-trial (NCT03272477), we aimed to identify associations of gene expression signatures and sTILs with pCR. Methods: Patients with cT1c-cT4c, cN0-3 centrally confirmed HR+/HER2+ BC were randomized to 12 weeks of standard ET (n = 100) or paclitaxel (Pac; n = 107). All patients received trastuzumab + pertuzumab (T+P) q3w as neoadjuvant and adjuvant treatment. Gene expression signatures were analyzed using NanoString BC360 panel in baseline biopsies (T+P+ET: n = 72; T+P+Pac: n = 78). sTILs were analyzed in 93 (T+P+ET) and 97 patients (T+P+Pac) at baseline and in 65 (T+P+ET) and 57 patients (T+P+Pac) at week 3. Impacts of standardized BC360 gene expression signatures and sTILs on pCR (ypT0/is ypN0; primary endpoint) expressed in odds ratios (OR) were estimated by logistic regression analysis. Results: pCR rate in patients with BC360 analysis was 39.3% (T+P+ET: 23.6%; T+P+Pac: 53.9%). Overall, ERBB2 (OR 2.37; 95%CI 1.55, 3.62) and cytotoxic cells signature (OR 1.42; 95%CI 1.02, 1.99) were favorable for pCR, while apoptosis (OR 0.64; 95%CI 0.44, 0.92), estrogen receptor 1 (OR 0.60; 95%CI 0.42, 0.85), estrogen receptor signaling (OR 0.64; 95%CI 0.45, 0.91), and progesterone receptor (OR 0.67; 95%CI 0.47, 0.94) signatures were unfavorable. Analyzing by treatment arm, a similar pattern was observed in the T+P+Pac arm (ERBB2: OR 2.01; apoptosis: OR 0.59; estrogen- and progesterone-related signatures: OR 0.41-0.58), but not in the T+P+ET arm where only ERBB2 was prognostic for pCR (OR 7.24; 95%CI 2.12, 24.05). Baseline ≥30% sTIL levels (vs < 30% sTILs; n = 16 vs n = 174) were associated with pCR (OR 5.16; 95%CI 1.60, 16.66); significance was not achieved in either trial arm. Compared to < 30% sTILs (n = 90), low tumor cellularity at week 3 precluding sTILs analysis ( < 500 invasive tumor cells, n = 22), but not ≥30% sTILs (n = 10), was prognostic for pCR in all patients (OR 9.47; 95%CI 2.94, 30.50) and in individual trial arms (OR 6.00-11.79). Conclusions: This hypothesis-generating translational results suggest that gene expression signatures (particularly ERBB2), baseline sTILs, and low tumor cellularity at week 3 predict pCR after ET + double HER2 blockade. Future neoadjuvant trials are needed to prospectively test the use of baseline gene expression and sTILs analysis, and early on-treatment cellularity measurement to select patients with HR+/HER2+ tumors for de-escalated endocrine-therapy-based approaches. Clinical trial information: NCT03272477 .

Clinical Efficacy of Neoadjuvant Endocrine Therapy in Non-Metastatic Prostate Cancer and Preliminary Experiences of Bone Metastasis Patients

Objective To explore the short-term efficacy of neoadjuvant endocrine therapy (NET) for localized prostate cancer and preliminary exploration of NET in patients with bone metastases. Methods Analyze clinical data of patients undergoing radical prostatectomy (RP) in the First Affiliated Hospital of Chongqing Medical University from January 2017 to January 2021 retrospectively. Patients with localized prostate cancer undergoing NET+RP were selected as the experimental group. The ones who only received RP were chosen as the control group, and the peri- and post-operative outcomes such as down-staging, pathological complete response, positive margin, intraoperative blood loss, and operation time were compared between the two groups. In addition, collect the information of patients with bone metastatic prostate cancer, excluding organ metastases, who received NET+RP over the same time-period and analyzed the short-term efficacy and quality of life. Results In the experimental group, there were more down-staging (13.08% vs. 4.67%, P=0.031), more pathological complete response (12.15% vs. 0.93%, P=0.001), less positive margin (9.35% vs. 29.91%, P< 0.001) and less blood loss (171.45±16.19 vs. 177.76±23.28, P=0.022). NET+RP also showed a satisfying short-term efficacy in patients with bone metastases, with well quality of life. Conclusion NET combined with RP can provide good short-term prognosis and patient satisfaction in patients with prostate cancer, and it is a potential option for patients with bone metastases without organ metastases.

Combined treatment of high and very high risk prostate cancer: results of neoadjuvant treatment

Purpose of the study. Assessment of safety and short‑term effectiveness of high and very high‑risk prostate cancer neoadjuvant chemo‑ hormonal treatment without distant metastases.Patients and methods. Combined hormone chemo‑ radiation treatment of 33 patients with prostate cancer of high and very high risk of progression without distant metastases was performed. Metastases to regional lymph nodes were found in 9 patients according to the examination data (MRI, MSCT), no metastases were detected in 24 patients. All patients underwent combined chemohormonal therapy in the amount of 4 courses of docetaxel intravenously at a dose of 75 mg/m2 every 3 weeks as the first stage of treatment. in combination with androgen deprivation therapy with agonists or antagonists of GnRH before performing radical radiation therapy (combined or remote). All patients underwent neoadjuvant hormone therapy: 16 patients – with the use of GnRH antagonists (Degarelix), 17 – with the use of GnRH agonists (Gozerelin/Leuprorelin/Triptorelin). The toxicity of the presented treatment regimen and its immediate effectiveness – the effect on the level of prostate‑s pecific antigen (PSA), prostate volume, and the quality of urination – were evaluated.Results. Treatment regimen was highly effective concerning PSA decrease (from initial median level 79,67 ng/ml to 1,45 ng/ml after neoadjuvant treatment), all subjects responded well, no non‑responders observed. Median prostate volume decreased from 44 cm3 to 25 cm3 after treatment, which guaranteed availability and safety of further radical radiation treatment. Urinary function was restored in all subject with initial urinary retention.Conclusion. Neoadjuvant chemo‑h ormonal treatment was highly effective in PSA level, prostate volume decrease and functional results improvement which secured further radical radiation treatment in one of its types. Toxicity was acceptable, adverse events did not exceed grade II in most cases and did not lead to treatment discontinuation in any cases, while quality of life remained high enough.

Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits.

Patients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT, raising the necessity for potential biomarker assessment. The transcriptomic profiling offers a unique opportunity to interrogate the accurate response to NCHT and NHT treatment and to identify the predictive biomarkers for neoadjuvant therapy. The whole transcriptomic profiling was performed on baseline biopsies and surgical tissue specimens from 64 patients with LAPCa at Renji Hospital between 2014 and 2018. Biochemical progression-free survival (bPFS)-based gene-by-treatment interaction effects were used to identify predictive biomarkers for guiding treatment selection. Comparing the transcriptome profiling of pre- and post-treatment LAPCa specimens, NHT and NCHT shared 1917 up- and 670 down-regulated DEGs at least 2-fold. Pathway enrichment analysis showed up-regulated pathways in response to NHT and NCHT were both enriched in cytokine receptor interaction pathways, and down-regulated pathways in response to NCHT were enriched in cell cycle pathways. By comprehensive transcriptome profiling of 64 baseline specimens, ten predictive markers were identified. We integrated them into the signature to evaluate the relative benefits of neoadjuvant therapy, which categorizes patients into two subgroups with relative bPFS benefits from either NHCT or NHT. In the high-score (≥ -95.798) group (n = 37), NCHT treatment led to significantly longer bPFS (P< 0.0001), with a clear and early separation of the Kaplan-Meier curves. In the low-score (< -95.798) group (n = 27), NHT also led to significantly longer bPFS (P=0.0025). In this study, we proposed the first predictive transcriptomic signature might potentially guide the effective selection of neoadjuvant therapy in LAPCa and might provide precise guidance toward future personalized adjuvant therapy. The study was approved by the Ethics Committee of Renji Hospital affiliated to Shanghai Jiao Tong University (Ky2019-087).

64P Baseline characteristics associated with Ki67 drop after neoadjuvant endocrine therapy in patients with HR+/HER2- early breast cancer: A systematic review

64P Baseline characteristics associated with Ki67 drop after neoadjuvant endocrine therapy in patients with HR+/HER2- early breast cancer: A systematic review

132P Neoadjuvant zanidatamab for stage I node-negative HER2- positive breast cancer (BC)

Outcome of patients (pts) w/ stage I node neg HER2+ treated w/ wkly paclitaxel x 12 doses and trastuzumab x 1yr is excellent (10yr RFS 96%). Therefore, trials to de-escalate chemo and use targeted therapy alone are underway. Zanidatamab is a novel, humanized, bispecific, immunoglobulin G isotype 1-like, monoclonal antibody directed against the juxtamembrane extracellular domain (ECD4) and the dimerization domain (ECD2) of HER2. This results in HER2 clustering that modulates signaling and leads to immune activation. Zanidatamab demonstrated antitumor activity in heavily pre-treated HER2+ metastatic BC with acceptable safety profile. We hypothesized that zanidatamab would be a safe and effective regimen for women w/ node neg stage I HER2+ BC. Pts w/ 1-3cm, clinically node neg HER2+ BC were enrolled in this investigator-initiated clinical trial. Pts had HER2+ BC: HER2 3+ by IHC or IHC 2+ and ISH +. Pts received 2-wkly zani x6 prior to surgery. Pts with ER+ tumors also received neoadjuvant endocrine therapy: postmenopausal pts received letrozole 2.5mg daily, and premenopausal pts received tamoxifen 20mg daily or GNRH and letrozole 2.5mg on treating physician preference. The primary objective was to evaluate efficacy as determined by pathologic complete response (pCR). Secondary objectives included pathologic response by residual cancer burden (RCB), radiological response, and safety profile of zanidatamab. Eleven pts w/ HER2+ BC were enrolled. Median age was 61yrs old (range 30-72). Median tumor size was 2.2cm (range 1-3cm). Four pts were pre-menopausal. Six pts had tumors >2cm tumors. Three received tamoxifen and 3 letrozole. All pts completed 6 cycles of zanidatamab and had Sx. Four (36%) had pCR, 3 RCB1 (28%) and 4 RCB2 (36%). This met the success criterion of Simon’s design (>=3/17 pts with pCR) of targeting a 25% pCR rate against a 5% null rate. Treatment was tolerated well. There were no grade 3 or 4 toxicities. One pt had minor infusion-related reaction and grade 2 acne, and 1 grade 2 diarrhea. Neoadjuvant zanidatamab for 3 months showed significant efficacy, (pCR/RCB-1 64%) w/ acceptable safety profile in pts w/ stage I node neg HER2+ BC. The trial is ongoing and has been modified to increase treatment duration to 5mths (10 cycles).

141P Concurrent neoadjuvant endocrine therapy with chemotherapy in HR+HER2- breast cancer: A systematic review and meta-analysis

141P Concurrent neoadjuvant endocrine therapy with chemotherapy in HR+HER2- breast cancer: A systematic review and meta-analysis

An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers

BackgroundThe reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)− breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined.MethodsWe recruited 170 patients with ER + /HER2− breast cancer who were treated with preoperative endocrine monotherapy. TILs were evaluated before and after NET, and their changes were noted. Furthermore, T cell subtypes were examined using CD8 and FOXP3 immunohistochemical analyses. Neutrophil and lymphocyte counts in the peripheral blood were analyzed with reference to TIL levels or changes. Responders were defined as Ki67 expression levels ≤ 2.7% after treatment.ResultsPost-treatment (p = 0.016), but not pre-treatment (p = 0.464), TIL levels were significantly associated with the response to NET. TIL levels increased significantly after treatment among non-responders (p = 0.001). FOXP3 + T cell counts increased significantly after treatment in patients with increased TILs (p = 0.035), but not in those without increased TILs (p = 0.281). Neutrophil counts decreased significantly after treatment in patients without increased TILs (p = 0.026), but not in patients with increased TILs (p = 0.312).ConclusionAn increase in TILs after NET was significantly associated with a poor response to NET. Given that FOXP3 + T-cell counts increased, and neutrophil counts did not decrease in patients with increased TILs after NET, the induction of an immunosuppressive microenvironment was speculated to play a role in the inferior efficacy. These data might partially indicate the involvement of the immune response in the efficacy of endocrine therapy.

The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients

BackgroundThere is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients.MethodsPostmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed.ResultsAmong 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p < 0.05).ConclusionsPIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.

Completeness of recording of neoadjuvant chemotherapy and endocrine therapy on the pathology form

Completeness of recording of neoadjuvant chemotherapy and endocrine therapy on the pathology form

Effect of Neoadjuvant Hormonal Therapy on the Postoperative Course for Patients Undergoing Robot-Assisted Radical Prostatectomy.

Neoadjuvant hormonal therapy (NHT) preceding robot-assisted radical prostatectomy (RARP) may be beneficial in high-risk cases to facilitate surgical resection. Yet, its improvement in local tumor control is not obvious. Its benefit regarding overall cancer survival is also not evident, and it may worsen sexual and hormonal functions. This study explores the effect of NHT on the perioperative course after RARP. In this study, 500 patients from a tertiary referral center who underwent RARP by a specialized surgeon were retrospectively included. Patients were divided into two groups: the NHT (n = 55, 11%) group, which included patients who received NHT (median: 1 month prior to RARP), and the standard non-NHT (NNHT) group (n = 445, 89%). Demographic and perioperative data were analyzed. Postoperative results, complications, and readmission rates were compared between the groups. NHT patients were heterogeneous from the rest regarding cancer parameters such as PSA (25 vs. 7.8 ng/mL) and tumor risk stratification, and they were more comorbid (p = 0.006 for the ASA score). They also received fewer nerve-sparing procedures (14.5% vs. 80.4%), while the operation time was similar. Positive surgical margins (PSM) (21.8% vs. 5.4%) and positive lymph nodes (PLN) (56.4% vs. 12.7%) were significantly higher in the NHT group compared to the non-NHT (NNHT) group. Hospital stay was equal, whereas catheter days were 3 days longer in the NHT group. NHT patients also suffered more minor vesicourethral-anastomosis-related complications. Major complications (p = 0.825) and readmissions (p = 0.070) did not differ between groups. Patients receiving NHT before RARP did not experience more major complications or readmissions within 90 days after surgery. Patients with unfavorable, high-risk tumors may benefit from NHT since it facilitates surgical resection. Randomized controlled trials are necessary to measure the advantages and disadvantages of NHT.

Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact.

To evaluate the differences in nodal positivity if the sentinel lymph node biopsy (SLNB) is performed before or after neoadjuvant endocrine therapy (NET) in breast cancer patients, and its impact on prognosis. A retrospective cohort study was performed in a single center including 91 postmenopausal cases with clinically node-negative and hormone receptor-positive/HER2-negative (HR + /HER2-) breast cancer, treated with NET and SLNB. SLNB was done pre-NET until 2014, and post-NET thereafter. Axillary lymph node dissection (ALND) was indicated only in SLNB macrometastasis, although in selected elderly patients, it was omitted. Kaplan-Meier survival curves were estimated in relation to the status of the axilla, and the differences assessed using the log-rank test. Between December 2006 and March 2022, SLNB was performed pre-NET in 14 cases and post-NET in 77. Both groups were similar in baseline tumor and patient characteristics. SLNB positivity was similar regardless of whether SLNB was performed before (5/14, 35.7%) or after NET (27/77, 37%), with 2/14 SLN macrometastases in the pre-NET cohort and 17/77 in the post-NET cohort. Only three patients (18.7%) with SLN macrometastasis had > 3 positive nodes following ALND. The 5-year overall survival and distant disease-free survival were 92.4% and 94.8%, respectively, with no significant differences according to SLNB status (p 0.5 and 0.8, respectively). SLN positivity did not differ according to its timing (before or after NET). Therefore, NET has no effect on lymph node clearance. Furthermore, the prognosis is good regardless of the axillary involvement. Therefore, factors other than axillary involvement may affect the prognosis in these patients.

Efficacy and safety of concomitant chemo-endocrine therapy in neoadjuvant treatment of hormone-positive HER2-negative breast cancer: a systemic review and meta-analysis

ABSTRACT Background The rate of pathological complete response (pCR) with both chemotherapy alone (CT) and endocrine therapy (ET) in the neoadjuvant (Na) treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) is unsatisfactory. Limited data on neoadjuvant concomitant chemotherapy and endocrine therapy (NaCET) are available. Research design and methods In this meta-analysis analyzed the efficacy and safety of randomized controlled trials (RCT) comparing the use of NaCET in HR-positive/HER2-negative BC. A comprehensive search was performed on PubMed, Cochrane Library and EMBASE databases, and congress paper lists for studies published/presented until 1 December 2022. Results Five RCTs involving a total of 630 patients were included. A pooled analysis of the five studies demonstrated that the pCR ratio was numerically higher in the NaCET arm than in the NaCT arm, but the difference was not statistically significant (6.5% vs. 3.8%; OR:1.72, 95% CI 0.82–3.62). Nonetheless, the NaCET arm exhibited a significantly higher objective response rate (ORR) (82% vs. 72.7%; OR:1.77, 95% CI 1.20–2.62). There was no difference between the arms in terms of grade 3–5 adverse events. Conclusions In HR-positive/HER2-negative BC, NaCET significantly increases ORR without an increase in serious adverse events. Although the pCR rate increased numerically, it was not statistically significant.

Neoadjuvant Endocrine Therapy: A Potential Way to Make Cold Hormone Receptor-Rich Breast Cancer Hot.

Turning the "cold" tumor immune microenvironment into "hot" is a critical issue in cancer treatment today. Hormone receptor-rich breast cancer (HR+ BC) was previously considered immunologically quiescent. This study aims to explore the immunomodulatory effects of endocrine therapy on HR+ BCs. The infiltrations and alterations of the tumor immune microenvironment in HR+ BCs before, after 10-14 days, and after three months of neoadjuvant endocrine therapy were computationally analyzed according to MCP-counter, CIBERSORT, xCell algorithms, and gene-set enrichment analysis (GSEA). The primary microarray data were obtained from three HR+ BC gene expression datasets (GSE20181, GSE55374, and GSE59515). Single-sample GSEA of hallmark and immune response gene sets was performed to evaluate the correlation between suspected treatment response and activated immune pathways in tumors. Both immune and stromal cells were specifically recruited into the HR+ BCs who responded to the neoadjuvant endocrine therapy by letrozole. Besides the enhanced infiltrations of immunosurveillance-related cells such as CD8+ T cells, dendritic cells, and the activation of immune response-related signals, the immunosuppressive M2-like macrophages, as well as the expression of immune checkpoint genes like PDCD1, SIRPA, and some HLA genes, were also stimulated in responders. We identified four pretreatment indicators (the intrinsic luminal subtype, the estrogen response early/late pathway, and the epithelial-mesenchymal transition pathway) as potential predictors of both clinical response and the activation of the tumor immune microenvironment post letrozole. Neoadjuvant endocrine therapy showed a promising way to convert the immunologically "cold" HR+ BCs into "hot" tumors. This study provides new insights into the application of immunotherapy for HR+ BCs, especially those who respond to endocrine therapy.

P113 MRI Patterns in the evaluation of pathological response after Neoadjuvant Endocrine therapy in ER+/HER2- Breast Cancer and Implications on Surgical Planning

P113 MRI Patterns in the evaluation of pathological response after Neoadjuvant Endocrine therapy in ER+/HER2- Breast Cancer and Implications on Surgical Planning

Comparing outcomes between neoadjuvant hormonal therapy followed by prostatectomy versus upfront prostatectomy in high-risk prostate cancer: The road ahead.

Comparing outcomes between neoadjuvant hormonal therapy followed by prostatectomy versus upfront prostatectomy in high-risk prostate cancer: The road ahead.

Phase III study of long-term prognosis of estrogen receptor-positive early breast cancer treated with neoadjuvant endocrine therapy with/without adjuvant chemotherapy

PurposeNeoadjuvant endocrine therapy (NET) is a treatment option for estrogen receptor-positive (ER+) postmenopausal early breast cancer (EBC). This phase III trial evaluated the prognosis of EBC patients treated with/without chemotherapy (CT) following NET.MethodsER+/HER2−, T1c-2, and clinically node-negative EBC patients were enrolled in 2008–2013 and treated with endocrine therapy (ET) in weeks 24–28. All patients, excluding those with progressive disease (PD) during NET or ≥ 4 positive lymph nodes after surgery, were randomized to ET for 4.5–5 years with/without CT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included distant DFS (DDFS), overall survival (OS), and DFS/DDFS/OS according to clinical response to NET.ResultsOf 904 patients, 669 were randomized to CT+ET (n = 333) or ET alone (n = 336). The median follow-up was 7.8 years. DFS (CT+ET, 47 events; ET alone, 70 events) and DDFS did not reach the planned numbers of events. Eight-year DFS/DDFS rates were 86%/93% and 83%/92%, respectively. DFS was significantly better in CT+ET than ET alone in subgroups aged < 60 years (P = 0.016), T2 (P = 0.013), or Ki67 > 20% (P = 0.026). Progesterone receptor and histological grade were predictive markers for clinical responses to NET.ConclusionNET may be used as standard treatment for patients with ER+EBC. Although it is difficult to decide whether to administer adjuvant CT based solely on the effect of NET, the response to NET may help to inform this decision.Trial registrationThis study was registered at the UMIN Clinical Trials Registry under UMIN000001090 (registered 20 March 2008).

Using Oncotype DX breast recurrence score® assay to define the role of neoadjuvant endocrine therapy in early-stage hormone receptor-positive breast cancer

PurposeThe role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need.MethodsWe assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay.ResultsWe observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0–25 may omit chemotherapy without compromising outcomes.ConclusionThese data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting.

Abstract P1-07-01: Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with HR+/HER2- early breast cancer: a systematic review and meta-analysis

Abstract Background: Neoadjuvant treatment allows to better distinguish responders from non-responders, and to tailor post-neoadjuvant treatment according to tumor response in patients with HER2+ and triple-negative early breast cancer. For HR+/HER2- tumors, the pathologic complete response is less likely to occur, and residual disease is predictive of inferior recurrence-free or overall survival. Therefore, Ki-67 index, a prognostic biomarker in early breast cancer, is often used in clinical trials as an endpoint for evaluating response to neoadjuvant endocrine therapy (NET). In this systematic review and meta-analysis, we aim to assess if Ki-67 level after NET is associated with disease recurrence and/or survival. Methods: We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings (ASCO and ESMO annual meetings, ESMO Breast, and SABCS) up to June 28, 2022, to identify clinical trials or observational studies reporting Ki-67 index after NET in patients with HR+/HER2- early breast cancer treated with NET (PROSPERO number CRD42021282338). We excluded studies in which all patients received neoadjuvant chemotherapy, or from which separate data from patients receiving only NET was not retrieved. Here we report data from studies screened for the availability of the primary endpoint - recurrence-free survival (RFS), and the secondary endpoint - overall survival (OS), comparing patients with low Ki-67 versus high Ki-67 index after NET, as defined per each study. We performed a sensitivity analysis of the studies measuring the post-NET Ki-67 index in a pre-planned core biopsy. We used the Higgins I2 index to evaluate the heterogeneity between included studies, which did not reach statistical significance. Therefore, we used a fixed effects model to combine RFS and OS hazard ratios (HR) with 95% confidence intervals (CI). Results: We included 11 studies reporting data from 4,231 patients: nine clinical trials (n=3,926), one pooled analysis of two clinical trials (n=217), and one retrospective cohort study (n=88). Nine studies included only post-menopausal women (n=4,069), one included both post- and premenopausal women (n=88), and one included only premenopausal women (n=74). NET was aromatase inhibitor (AI) in four studies (n=3,359), tamoxifen or AI in four (n=465), tamoxifen in two (n=190), and one study with AI or fulvestrant (n=217). There were no studies with targeted agents combined with NET. No study restricted the use of adjuvant chemotherapy in high-risk patients. Three studies evaluated post-NET Ki-67 in a pre-planned core biopsy after a window of treatment of two to four weeks (n=3,348), while the other eight evaluated KI67 in the surgery specimen (n=883). The timing of post-NET evaluation ranged from 2 to 24 weeks. The median follow-up for RFS ranged between 37 and 95 months, and between 62 to 84 months for OS. We found a statistically significant association of adverse RFS (HR 2.43, 95% CI 1.99-2.98) and OS (2.66, 95% CI 1.65-4.28) with higher Ki-67 after NET. The sensitivity analysis of the three studies evaluating post-NET Ki-67 in a pre-planned core biopsy showed the same association with RFS (HR 2.41, 95% CI 1.77-3.30). These three studies did not report OS data. Conclusion: Our data reinforce the role of Ki-67 index after NET as a valuable biomarker of response or resistance to endocrine therapy in women with HR+/HER2- early breast cancer. Despite the use of adjuvant chemotherapy in most of the high-risk patients included in this analysis, the reduction of Ki-67 after NET is strongly associated with survival outcomes (RFS/OS), even after a short course of two to four weeks NET. Ki-67 index post-NET might be a useful tool to help tailoring the use of adjuvant chemotherapy in HR+/HER2-negative breast cancer patients, particularly in low-resource settings where the access to genomic assays is limited. Citation Format: Diogo Martins-Branco, Chiara Molinelli, Guilherme Nader Marta, Lieveke Ameye, Marianne Paesmans, Roberto Salgado, Philippe Aftimos, Evandro de Azambuja. Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with HR+/HER2- early breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-07-01.