Neoadjuvant Hormonal Treatment Research Articles

Abstract 5185: A multimodal, spatially defined, nanomechanical signature as predictive biomarker for breast cancer outcome: A 20 year survival study

Abstract Background: With the recent advancement in perioperative treatment protocols, the search for clinical biomarkers that can predict overall response and long-term cancer outcome independent from treatment acquires even more importance. Recently, it has become clear that mechanical properties of the tumor microenvironment in solid tumors play a key role in driving outcome, mediating immune infiltration and activation, and response to therapy. Moreover, a growing body of evidence supports the understanding that mechanical changes induced by a plethora of therapeutic regimens should be leveraged to elicit favorable outcome. Methods: In this work we propose a dual approach to reveal mechanical biomarkers predictive of long-term outcome in solid cancers. Our first approach is based on a newly developed, 60 channel, biomechanical imaging mass cytometry panel to elucidate biomechanical cues that drive tumor aggressiveness and immune infiltration. Our second approach utilizes the AFM-based Automated and Reliable Tissue Diagnostics (ARTIDIS) investigational device to measure mechanical properties of fresh clinical biopsy samples at a nanoscale resolution. Our analysis was performed on over 300 clinical samples, from routine baseline clinical biopsies collected from both the Breast Clinic, University Hospital Basel, and the University of Dundee, in the UK. Patients in these two cohorts were treated with either adjuvant or neoadjuvant approaches, including radiation, chemotherapy, hormonal, and surgical treatment regimens, with individual patient follow up as long as 20 years. Results: We demonstrated with two complimentary technologies that biomechanical spatial patterns drive outcome in breast cancer. Our results include a multi-platform elucidation of the biomechanical phenotypes of epithelial to mesenchymal transitions driven by hypoxic environments. Furthermore, we identified several biomechanical subpopulations of cancer associated fibroblasts, and their role in mediating cancer outcome, in relationship with survival time and several clinical variables (e.g. metastasis, nodes, grade). We mechanistically corroborated these results by evaluating the immune modulatory effect of the identified biomechanical microenvironments in breast cancer. Lastly, we correlated the identified biomechanical microenvironments with the ARTIDIS nanomechanical signature as a clinically integrated, rapid, single biomechanics signature at the nanoscale. Conclusion: Our results further validate the importance of biomechanics in driving tumor response and immune infiltration across a variety of clinical treatment setting. These result support the integration of ARTIDIS nanomechanical signature in clinical settings as a single predictive biomarker able to rapidly and accurately capture biomechanical alterations that drive cancer outcome. Citation Format: Sara Nizzero, Maria Pelaez Soni, Gregory Zaugg, Yitian Xu, Licheng Zhang, Junjun Zheng, Lee B. Jordan, Colin A. Purdie, Philip R. Quinlan, Chandandeep Nagi, Karla A. Sepulveda, Philipp Oertle, Tobias A. Appenzeller, Marko Loparic, Shu-Hsia Chen, Vittorio Cristini, Marija Plodinec, Alastair M. Thompson. A multimodal, spatially defined, nanomechanical signature as predictive biomarker for breast cancer outcome: A 20 year survival study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5185.

Baseline PSMA-PET/CT as a predictor of PSA persistence following radical prostatectomy in high-risk nonmetastatic prostate cancer patients receiving neoadjuvant therapy.

The precise staging and proper management of high-risk prostate cancer (PCa) continues to be a challenge. We aimed to demonstrate the prognostic value of baseline prostate-specific membrane antigen-ligand positron emission tomography/computed tomography (PSMA-PET/CT) in high-risk, nonmetastatic PCa patients who received neoadjuvant hormonal or chemohormonal treatment followed by radical prostatectomy (RP). We performed retrospective analyses of 70 patients with high-risk, nonmetastatic PCa confirmed by biopsy between 2018 and 2021. All patients underwent neoadjuvant therapy followed by RP and pelvic lymph node dissection (PLND); PSMA-PET/CT was performed before initiation of neoadjuvant therapy. Acquired image information and clinical characteristics/outcomes were examined for possible associations. Among 70 high-risk PCa patients, median age was 69 years old and median prostate specific antigen (PSA) at presentation was 58.5 ng/mL. Thirty (42.9%) patients had uptake of the PSMA tracer only in the primary PCa lesions and 40 (57.1%) patients had PSMA-positive lesions in regional or distant sites. Sixteen (32%) localized PCa patients defined by pre-PET magnetic resonance imaging were found to have locally advanced PCa based on PSMA-PET/CT. Fifteen (30%) localized PCa patients and 7 (35%) locally advanced PCa patients were upstaged to metastatic PCa. The sensitivity and specificity of PSMA-PET/CT for the detection of lymph node involvement were 90.9% and 69.5%, respectively, with a positive prediction value of 35.7% and negative prediction value of 97.6%. The diagnostic accuracy was 72.9%. Univariate analysis showed upstaging, tumor stage, and metastasis location based on PSMA-PET/CT are predictors to PSA persistence after surgery, while multivariate logistic regression analysis showed only the tumor stage based on PSMA-PET/CT remained an independent predictor of the outcome. This study further highlights the accuracy and necessity of PSMA-PET/CT in newly diagnosed, high-risk, nonmetastatic PCa patients.

Neoadjuvant hormonal treatment in infants with undescended testis – A prospective case control study

Neoadjuvant hormonal treatment in infants with undescended testis – A prospective case control study

Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. Of the 354 patients enrolled, 253 initiallyresponded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

The safety of neoadjuvant hormonal treatment in infants with cryptorchidism

The standard treatment for boys with non-syndromic cryptorchidism is an early orchidopexy. It is unclear if surgical intervention alone is enough for future fertility. Recent studies show benefit of neoadjuvant or adjuvant hormonal treatment with gonadorelin (GnRH) for spermatogonia maturation based on testicular biopsy. The aim of this prospective study was to assess the safety of this treatment in infants with undescended testis at the recommended timing of early gonadorelin administration and timing of orchidopexy. Unilateral cryptorchid full term boys were initially examined (including hormonal, physical and ultrasound examination) at the age of 2.5-3.5 months. At 6 months of age, cryptorchidism was confirmed. Those with non-syndromic cryptorchidism and palpable or sonographically detected testis were randomly assigned into two groups: with and without intranasal gonadorelin treatment. Inclusion criteria were met by 36 boys (21 in GNRH and 15 in the control groups). The following orchidopexy was performed before 12 months of age with repeated examination at time of surgery. Penile size and testicular volume (using ultrasound) and basal serum levels of LH, FSH, testosterone, Inhibin B and AMH were recorded at age of 3.0 (mean) months and 11.0 (mean) months (date of surgery). The stimulation hormonal levels were checked during GnRH administration. Between minipuberty (mean 3 months) and time of orchidopexy (mean 11 months of age) the penile size increased significantly and similarly in both groups. There was no significant difference in the change of the volume of descended testis between the groups nor of the volume of undescended testis. In addition, we did not find any significant difference in the change (drop) of hormonal levels of LH, FSH, Testosterone, Inhibin B and AMH (Table 1a) CONCLUSION: The neoadjuvant gonadorelin stimulation in infants with unilateral undescended testis has not shown any specific effect on the development of penile size, testicular volume and hormonal levels at time of orchidopexy in comparison with boys without stimulation, and in the mid-term, this treatment can be considered safe. Further follow-up is necessary to evaluate the long-term effect of this early treatment.

Prediction of recurrence from metabolites and expression of TOP2A and EZH2 in prostate cancer patients treated with radiotherapy.

The dual upregulation of TOP2A and EZH2 gene expression has been proposed as a biomarker for recurrence in prostate cancer patients to be treated with radical prostatectomy. A low tissue level of the metabolite citrate has additionally been connected to aggressive disease and recurrence in this patient group. However, for radiotherapy prostate cancer patients, few prognostic biomarkers have been suggested. The main aim of this study was to use an integrated tissue analysis to evaluate metabolites and expression of TOP2A and EZH2 as predictors for recurrence among radiotherapy patients. From 90 prostate cancer patients (56 received neoadjuvant hormonal treatment), 172 transrectal ultrasound-guided (TRUS) biopsies were collected prior to radiotherapy. Metabolic profiles were acquired from fresh frozen TRUS biopsies using high resolution-magic angle spinning MRS. Histopathology and immunohistochemistry staining for TOP2A and EZH2 were performed on TRUS biopsies containing cancer cells (n = 65) from 46 patients, where 24 of these patients (n = 31 samples) received hormonal treatment. Eleven radical prostatectomy cohorts of a total of 2059 patients were used for validation in a meta-analysis. Among radiotherapy patients with up to 11 years of follow-up, a low level of citrate was found to predict recurrence, p = 0.001 (C-index = 0.74). Citrate had a higher predictive ability compared with individual clinical variables, highlighting its strength as a potential biomarker for recurrence. The dual upregulation of TOP2A and EZH2 was suggested as a biomarker for recurrence, particularly for patients not receiving neoadjuvant hormonal treatment, p = 0.001 (C-index = 0.84). While citrate was a statistically significant biomarker independent of hormonal treatment status, the current study indicated a potential of glutamine, glutamate and choline as biomarkers for recurrence among patients receiving neoadjuvant hormonal treatment, and glucose among patients not receiving neoadjuvant hormonal treatment. Using an integrated approach, our study shows the potential of citrate and the dual upregulation of TOP2A and EZH2 as biomarkers for recurrence among radiotherapy patients.

Effect of Neoadjuvant Hormonal Treatment on the Necessity of Secondary Radiotherapy in Patients Undergoing Radical Prostatectomy for High-Risk Prostate Cancer

Effect of Neoadjuvant Hormonal Treatment on the Necessity of Secondary Radiotherapy in Patients Undergoing Radical Prostatectomy for High-Risk Prostate Cancer

Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.

Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens. However, despite results from these studies demonstrating a reduction in positive surgical margins and tumour volume, no benefit has been observed in hard oncological end points, such as cancer-related death. The introduction of potent androgen receptor signalling inhibitors (ARSIs), such as abiraterone, apalutamide, enzalutamide and darolutamide, has led to a renewed interest in using neoadjuvant hormonal treatment in high-risk prostate cancer. The addition of ARSIs to androgen deprivation therapy has demonstrated substantial survival benefits in the metastatic castration-resistant, non-metastatic castration-resistant and metastatic hormone-sensitive settings. Intuitively, a similar survival effect can be expected when applying ARSIs as a neoadjuvant strategy in high-risk prostate cancer. Most studies on neoadjuvant ARSIs use a pathological end point as a surrogate for long-term oncological outcome. However, no consensus yet exists regarding the ideal definition of pathological response following neoadjuvant hormonal therapy and pathologists might encounter difficulties in determining pathological response in hormonally treated prostate specimens. The neoadjuvant setting also provides opportunities to gain insight into resistance mechanisms against neoadjuvant hormonal therapy and, consequently, to guide personalized therapy.

Similar decrease of proliferation employing Ki-67 after brief neoadjuvant hormonal treatment on invasive ductal carcinoma versus invasive lobular carcinoma.

e12606 Background: Invasive lobular carcinoma (ILC) differs from the more prevalent invasive ductal carcinoma (IDC) in histology, molecular underpinning, and biological responsiveness to cytotoxics. Patients diagnosed with IDC or ILC were evaluated in the clinical setting to determine if they differ in responsiveness to neoadjuvant hormone treatment. Methods: This is a retrospective observational study of an underserved, low income, rural population in Oroville, California. The data for this study was collected over ten years (2011-2021) from 58 estrogen receptor positive (ER+) breast cancer patients. The majority of these patients (48/58) were diagnosed with IDC with ages ranging from 35 to 91 (mean age is 66) and the remaining 10 were diagnosed with ILC with ages ranging from 58 to 85 (mean age is 64). Patients were given neoadjuvant hormone treatment starting after their initial biopsy confirming ER+ status until scheduled surgical removal by lumpectomy or mastectomy. Ki-67 was measured prior to treatment and then measured again after a minimum of 14 days on hormone therapy. The initial Ki-67 range for patients with IDC was 2%-75% (median of 15%). Ki-67 initial range for patients with ILC was 2%-30% (median of 11%). Positive response to treatment was set at &gt; 50% reduction in Ki-67, with no response set at &lt; 50% reduction in Ki-67. We compared the response rates of ILC and IDC patients using a chi-square test. Results: Chi-square analysis found no statistically significant difference between IDC and ILC response to hormone therapy. 34/48 (71%) patients with IDC responded to treatment, and 8/10 (80%) of ILC patients showed response. Incidentally, we noticed a higher prevalence of ILC in our community compared to expected numbers. Conclusions: When evaluating hormone therapy responsiveness in the neoadjuvant setting, there is no observable statistical difference in response rates between IDC and ILC. Neoadjuvant hormone testing employing Ki-67 response identifies subgroups of patients who benefit from the addition of new biologics (-ciclibs, mTOR inhibitors) in addition to hormone treatment. Our experience supports testing in this way to further individualize the care of patients unable to participate in clinical trials.

Abstract 340: ABI1 and androgen dependence in prostate cancer

Abstract Background: Androgen independence is the most challenging problem in the treatment of advanced prostate cancer. Although most patients with early-stage prostate cancer can be cured with surgical and/or radiation treatment, the remainder of patients ultimately recur with metastatic disease upon development of resistance to anti-androgen therapy. Epithelial mesenchymal transition (EMT) and lineage plasticity has been proposed as key mechanisms underlying resistance in treatment-induced prostate cancer with neuroendocrine features (NEPC). There has been a rise in treatment-induced NEPC with increased use of anti-androgen therapies. ABI1 regulates EMT by suppressing FYN-STAT3 activation downstream from noncanonical WNT pathway, but the interaction of ABI1 with androgen pathway is not known. We sought to determine the effect of neoadjuvant hormone treatment (NHT) on ABI1 expression levels in different tumor types. Methods: Here we analyzed ABI1 expression (IHC) in tissue microarray containing 75 tumors with no prior treatment, 198 patients subjected to NHT prior to surgery and 39 castration resistant tumors (total n=307). Androgen-induced ABI1 expression was determined upon R1881 treatment by Western blotting and immunofluorescence in hormone- sensitive LNCaP cells. Results: ABI1 expression was significantly downregulated in tumors from patients undergoing NHT(p&amp;lt;0.05). ABI1 expression was significantly increased in CRPC tumors developed while on hormone therapy compared to ABI1 expression in tumors undergoing NHT (p&amp;lt;0.001), or with NEPC (p&amp;lt;0.001). Consistently with these observations, ABI1 expression was upregulated upon treatment of LNCaP cells with R1881 and downregulated by treatment of cells with enzalutamide. Conclusion: ABI1 is an androgen sensitive gene. ABI1 expression is increased in CRPC, most likely secondary to androgen receptor reactivation. It is subsequently downregulated in NEPC, hence, we hypothesize that this may be a key mechanism driving the NEPC phenotype through promoting EMT. Further understanding of the role ABI1 may play in this transformation will provide a more mechanistic understanding of prostate cancer progression and maylead to improved targeted treatment options. Citation Format: Leszek Kotula, Baylee A. Porter, Xiang Li, Maria A. Ortiz, Rakesh Khanna, Fan Zhang, Sonia H. Kung, Ladan Fazli, Martin E. Gleave, Gennady Bratslavsky, Jeffrey S. Ross. ABI1 and androgen dependence in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 340.

PT264 - Neoadjuvant hormonal treatment in cryptorchid boys has no effect on normal hypothalamopituitary axis hormone levels – preliminary results

PT264 - Neoadjuvant hormonal treatment in cryptorchid boys has no effect on normal hypothalamopituitary axis hormone levels – preliminary results

Clinical Experience with the Use of Neoadjuvant Hormone Therapy for Breast Cancer in a Latin American Cancer Center

Introduction: The most frequent subtype of breast cancer is the luminal one, in 70 to 80% of cases; the poor response to neoadjuvant chemotherapy of these tumors positions neoadjuvant hormone therapy as a treatment option. Materials and Methods: An observational, descriptive, historical cohort study was conducted in patients with hormone receptor (HR positive and HER2-positive breast cancer, managed with neoadjuvant hormone therapy in the INC (National Cancer Institute, for its initials in Spanish), with the aim of evaluating their clinical and pathological response. Results: 57 patients were managed with neoadjuvant hormone therapy. Most stage IIA patients (40.3%, n = 23). 86% (n = 49) had luminal A tumors. Letrozole was the most widely used drug, in 78.9% (n = 45). The overall response rate (ORR) was reached in 94.6% (n = 53); and 10.7% of the patients (n = 6) achieved complete clinical response (cCR). Complete pathological response (pCR) was achieved only in one patient. Conservative surgery was possible in 56.9% (n = 29) of the patients. There was no difference between the type of aromatase inhibitor (AI) and the duration of neoadjuvant hormonal treatment with the clinical response. With a median follow-up of 3 years (0.6 and 6 years), no disease progression was reported in any of the patients in the study. Conclusion: The results of this study support the neoadjuvant hormone therapy recommendations for postmenopausal patients older than 65 years with luminal breast cancer, with well or moderately differentiated tumors, strongly HR positive and low Ki 67.

MP62-12 PREDICTIVE ABILITY OF PREBIOPSY MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING FOR NEGATIVE LYMPH NODE METASTASIS OF THE SIDE IN RADICAL PROSTATECTOMY: FEASIBILITY OF UNILATERAL LYMPH NODE DISSECTION

You have accessJournal of UrologyProstate Cancer: Staging I (MP62)1 Apr 2020MP62-12 PREDICTIVE ABILITY OF PREBIOPSY MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING FOR NEGATIVE LYMPH NODE METASTASIS OF THE SIDE IN RADICAL PROSTATECTOMY: FEASIBILITY OF UNILATERAL LYMPH NODE DISSECTION Noboru Numao*, Yudai Ishikawa, Shinya Yamamoto, Motohiro Fujiwara, Shotaro Yasuoka, Ryo Fujiwara, Yoshinobu Komai, Takeshi Yuasa, Iwao Fukui, and Junji Yonese Noboru Numao*Noboru Numao* More articles by this author , Yudai IshikawaYudai Ishikawa More articles by this author , Shinya YamamotoShinya Yamamoto More articles by this author , Motohiro FujiwaraMotohiro Fujiwara More articles by this author , Shotaro YasuokaShotaro Yasuoka More articles by this author , Ryo FujiwaraRyo Fujiwara More articles by this author , Yoshinobu KomaiYoshinobu Komai More articles by this author , Takeshi YuasaTakeshi Yuasa More articles by this author , Iwao FukuiIwao Fukui More articles by this author , and Junji YoneseJunji Yonese More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000937.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Localization of cancer lesion in the prostate is reported to be associated with difference between right and left in frequency of lymph node metastasis (LNM). However, preoperatively it is difficult to evaluate detailed cancer lesions in the prostate. Therefore, pelvic lymph node dissection (PLND) is recommended to perform bilaterally in radical prostatectomy (RP). Previous studies have demonstrated that side-specific negative biopsy cannot predict negative LNM of the side in patients undergoing PLND in RP. In this study, we investigated whether prebiopsy multiparametric magnetic resonance imaging (mpMRI) findings can predict negative LNM of the side to explore feasibility of unilateral PLND in RP. METHODS: A total of 1980 prostate cancer patients underwent RP in our institution Between January 2005 and August 2018. Of these, we selected 344 patients who underwent prebiopsy mpMRI, a combination of mpMRI-targeted biopsy and the median 14-core systematic biopsy, and RP with extended PLND without neoadjuvant hormonal treatment. We defined extended PLND as fulfilling the following criteria: 1) 10 or more dissected lymph nodes; 2) dissection of the nodes overlying the external iliac artery and vein, the nodes within the obturator fossa located cranially and caudally to the obturator nerve, and the nodes medial and lateral to the internal iliac artery in principle. PLND area was somewhat modified by each surgeon. MRI, biopsy findings and LNM were assessed for each side. The negative predictive value (NPV) of biopsy and MRI for ipsilateral LNM was examined. RESULTS: LNM were found in 6.4% of all patients. The rate of LNM according to risk category was 0%(0/8), 3.8%(8/208) and 11%(14/128) in low, intermediate, high risk, respectively. Number of side with biopsy-positive/mpMRI-positive, biopsy-positive/mpMRI-negative, biopsy-negative/mpMRI-positive and biopsy-negative/mpMRI-negative were 340, 176, 21 and 151, respectively. In side-specific analysis, the NPV of biopsy and mpMRI 98.8 and 98.6 for ipsilateral LNM, respectively. The positive predictive value of biopsy, mpMRI was 5.8 and 6.4 for ipsilateral LNM, respectively. CONCLUSIONS: Prebiopsy mpMRI and subsequent biopsy based on mpMRI was useful for prediction of side-specific negative LNM in RP. Our findings suggest feasibility of unilateral PLND according to side-specific risk of LNM using prebiopsy mpMRI. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e950-e950 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Noboru Numao* More articles by this author Yudai Ishikawa More articles by this author Shinya Yamamoto More articles by this author Motohiro Fujiwara More articles by this author Shotaro Yasuoka More articles by this author Ryo Fujiwara More articles by this author Yoshinobu Komai More articles by this author Takeshi Yuasa More articles by this author Iwao Fukui More articles by this author Junji Yonese More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract P5-13-05: Gene expression changes with neoadjuvant hormonal treatment

Abstract Breast cancers (BC) expressing estrogen and/or progesterone receptors, referred to as hormone receptor (HR)-positive represent the largest molecular subset of breast tumors. Fortunately, estrogen receptor expression on the cell surface serves as a drug target for endocrine therapy. In HR+, human epidermal growth factor receptor-2 (HER2) negative BC, neoadjuvant endocrine therapy (NET) is being increasingly used. While NET has been shown to reduce tumor cell proliferation causing apoptosis, up to 20% of tumors do not respond. Currently there are no validated predictive gene signatures distinguishing responders from non-responders to NET. Furthermore, there are limited data on the effects of different NET regimens in vivo and how they vary between responders and non-responders. Methods: We conducted a retrospective translational study in patients who were treated with NET at our institution. This study was approved by our institutional review board. Paired pre-treatment and surgical samples were collected from 24 patients along with clinico-pathological information. Responders were defined as those with a preoperative endocrine prognostic index (PEPI) score of 0. RNA isolation was performed using the Roche HighPure FFPET RNA Isolation spin-column kit. Purified RNA was hybridized with the PanCancer Code Set and finally the cartridge was scanned on the nCounter Digital Analyzer. Raw counts from each gene were imported into the nSolver Analysis. Log2 normalized data obtained from Nanostring nCounter analysis was analyzed for differentially expressed genes between pre- and post-treatment samples. The bioinformatics analysis was carried out using nCounter analysis software. Results: The median age at diagnosis was 64 years and NET used was anastrozole alone or in combination with fulvestrant. At baseline the majority of tumors were invasive ductal carcinomas (n=18), grade II (n=18), with a Ki67% &amp;gt;15% (n=16). Median duration of treatment with NET was 5 months (range 2-10 months). Nine tumors were defined as responders to NET and 15 were non-responders. In all of the 24 paired samples, we found 123 genes with a statistically significant change in expression (defined by greater than two-fold change and a false discovery rate adjusted p-value &amp;lt;0.05) in the surgical specimen compared to pre-treatment biopsy. Genes in the Janus kinase-signal transducers and activators of transcription (Jak-STAT) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, RAS signaling, cytosine-cytosine receptor interaction and the Phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K-Akt) signaling pathway were found to be upregulated whereas genes in cell cycle pathway were downregulated in the surgical specimens after NET. Comparing pre-treatment samples of responders to non-responders 25 genes involving PI3K-Akt, Notch signaling and Fanconi anemia pathway were differentially expressed. Conclusions: In our retrospective translational study we found that NET upregulates genes in the Jak-STAT, MAPK, RAS, cytosine-cytosine receptor interaction and PI3K-Akt signaling pathways and downregulates cell cycle pathway genes independent of type or duration of NET. We also found multiple genes involving the PI3K-Akt and Notch pathway were differentially expressed in pre-treatment specimens among responders compared to non-responders. While the sample size comparing responders versus non-responders was inadequate, our results suggest some early trends which warrant further investigation. Citation Format: Darien E Reed, Ritu Pandey, Jennifer M Segar, Michele Chu, Lauren LeBeau, Pavani Chalasani. Gene expression changes with neoadjuvant hormonal treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-13-05.

36TiP - A prospective study to assess response to neoadjuvant hormonal therapy in postmenopausal women with hormone-receptor positive breast cancer at a regional cancer centre in South India

BackgroundHormonal receptor-positive breast carcinoma constitutes the most common subtype of the disease. Neoadjuvant chemotherapy is the current standard of treatment for any locally advanced breast carcinoma. However, the hormone receptor-positive, Her-2 negative cancers are less likely to respond to neoadjuvant chemotherapy than other biologic subtypes. Studies have explored the efficacy of neoadjuvant hormone treatment in this cohort of patients and efforts are ongoing to identify the subgroup of patients who can be treated with hormonal therapy alone, hence avoiding the unnecessary toxicity of chemotherapy. Our study aims to assess the response to neoadjuvant hormonal therapy (NAHT) in the postmenopausal women who are considered to be low-risk subgroup and for whom chemotherapy can be safely avoided. Trial designObjectives Primary objective: To determine the clinical tumor response rate to NAHT. Secondary Objective: To assess the number of patients undergoing surgery and pCR rates. To assess biologic changes in the tumor, including hormonal receptor status and proliferation by Ki67 staining. Methods Type of study: Phase II Prospective single-center study. Patients: Postmenopausal women diagnosed with biopsy-proven, non-metastatic and potentially operable breast cancer. Inclusion Criteria: Clinical stage T3-T4c with node-negative or clinical stage T2-T4c with node-positive disease (N1, N2) ER-positive with Allred score 6-8, Her 2 negative and Ki67 < 14%. Exclusion Criteria: Past history of treatment for any other cancer, history of having received chemotherapy or use of hormone replacement therapy previously. Sample size: 35 patients. Study site and duration: Kidwai Cancer Institute, 1.5 years. Eligible patients will receive Neoadjuvant hormonal therapy with Aromatase inhibitor and will undergo regular monitoring of objective response rate using calipers at the time of diagnosis and monthly once. The response will be noted as per the WHO criteria. Progressive disease recorded at any time will lead to exclusion from the study and the patient will be started on chemotherapy. Toxicity assessment will be done regularly. Legal entity responsible for the studyDepartment of Medical Oncology, Kidwai Cancer Institute, Bengaluru. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Abstract P4-13-01: Oncoplastic breast conservations – The Scottish Audit: Surgical techniques, oncological outcomes, complication rates and variations in practice across the country based on the analysis of 589 patients

Abstract Introduction: current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. We studied the outcomes of OBC practice in Scotland and compare individual breast units. Methods: a predefined database of patients treated with OBC was completed retrospectively in 11 breast units in Scotland. Patients were treated with OBC from 2005 onwards were included. For statistical calculations Chi-test, ANOVA and Pearson correlation analysis were used. Results: Altogether 589 patients were included. Median age was 56 years [21-86]. Patients were diagnosed between September 2005 and March 2017. Number of patients treated with OBC per unit ranged between 4 and 145. High volume units were doing a mean of 19.3 OBCs per year [17.3 – 26.5] vs. low volume units doing 11.1 OBCs per year [7 .7– 14.4] (p=0.012). 23 different oncoplastic surgical techniques were applied. Range of oncoplastic techniques used was associated with case-loads: high volume units used a wider range (8 – 14 different techniques) compared to low volume units (3 – 6) (p=0.004). Volume displacement was done in 515 patients (91.3%), volume replacement in 49 patients (8.7%). OBC was carried out as a joint operation between a breast and a plastic surgeon in 66.3% (389 patients). Immediate contralateral symmetrisation rate was significantly higher when the procedure was carried out as a joint operation (70.7% vs. not joint operations: 29.8%; p&amp;lt;0.001). Incomplete excision rate was 10.4% (60 of 578). Incomplete excision was significantly higher after invasive lobular carcinoma (18.9%; 10 of 43; p=0.0292). After neoadjuvant chemotherapy incomplete excision rate was significantly lower (3%; 2 of 66 vs. no neoadjuvant chemotherapy: 11%; 35 of 319; p=0.031). Neodjuvant systemic treatment rate was 28.6% (142 of 496 patients). Of those 68 patients received neoadjuvant chemotherapy (13.7%) and 74 patients had neoadjuvant hormonal treatment (14.9%). Neoadjuvant systemic treatment rate varied amongst the units from 9.7% to 57.2% for patients with invasive carcinoma. 259 patients diagnosed with (non)invasive carcinoma had a median follow-up time of 5 years [35-124]. Of these 7 patients (2.7%) developed isolated local recurrence. 5-year local recurrence rate after DCIS was higher than after pure invasive ductal carcinoma (DCIS: 8.3%; 3 of 36 vs. ductal: 1.6%; 3 of 181; p=0.02567). 5-year disease-free survival of these patients was 91.7%, overall survival was 93.8%, and cancer-specific survival was 96.1%. 145 of 510 patients developed complications, which is 28.4% overall complication rate. 71 patients had major complications (13.9%) and 74 patients had minor complications (14.5%). Overall complication rate was significantly lower after neoadjuvant chemotherapy (15.9%; 11 of 69) compared to patients who did not receive neoadjuvant chemotherapy (27.9%; 127 of 455 patients) (p=0.035). Conclusion: this national audit demonstrated similar outcomes overall compared to relevant published data. Units should be urged to build stronger collaboration in order to reduce variability in OBC practices. None of the authors have conflict of interest to declare. Citation Format: Romics L, Macaskill J, Fernandez T, Morrow E, Simpson L, Pitsinis V, Barber M, Tovey S, Masannat Y, Young O, Mansell J, Stallard S, Doughty J, Dixon M. Oncoplastic breast conservations – The Scottish Audit: Surgical techniques, oncological outcomes, complication rates and variations in practice across the country based on the analysis of 589 patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-01.

Prediction of organ-confined disease after robot-assisted radical prostatectomy in patients with clinically locally-advanced prostate cancer

Little is known about the preoperative predictive factors that could identify subsets of favorable patients who can be possibly cured with robot-assisted radical prostatectomy (RARP) alone in locally advanced prostate cancer (LAPCa). Our study was designed to identify clinical predictors of pathologic organ-confined disease (pOCD) in RARP setting. Between 2007 and 2013, clinicopathological and oncological data from 273 consecutive men undergoing robot-assisted RP with extended PLND for clinically LAPCa were reviewed in a single-institution, retrospectively. After exclusion of patients who received neoadjuvant hormone treatment before surgery, 186 subjects satisfied the final inclusion criteria. Fourty-three patients (23.1% of total cohort) with preoperative clinically LAPCa patients were down-staged to pOCD following RARP. Preoperative prostate-specific antigen (PSA) level, preoperative PSAD, positive core percent, maximal tumor volume in any core, and biopsy Gleason score were significantly associated with down-staging into pOCD following RARP. Multivariate logistic regression analysis revealed that lower preoperative PSA (≤10ng/mL) and maximal tumor volume in any core (≤70%) were independent predictors of pOCD following RARP. Approximately 23% of preoperative clinically LAPCa patients were down-staged to pOCD following RARP. Preoperative PSA and maximal tumor volume in any biopsy core might be useful clinical predictors of pOCD in clinically LAPCa patients in RARP setting.

Effect on prostate volume following neoadjuvant treatment with an androgen receptor inhibitor monotherapy versus castration plus an androgen receptor inhibitor in prostate cancer patients intended for curative radiation therapy: A randomised study.

To avoid pubic arch interference, prostate cancer patients are treated with neoadjuvant androgen deprivation therapy (ADT) to achieve prostate volume (PV) reduction prior to radiation treatment. The aim of the present randomised study was to compare the effects on PV of two regimens of ADT, an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. Consecutive patients with non-metastatic prostate cancer were included in a randomised neoadjuvant study, comparing an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. PV was assessed prior to the start of endocrine neoadjuvant treatment and prior to the start of radiation therapy (RT). PV assessment was performed by transrectal ultrasound. A total of 110 patients were included. Final sample constituted 88 (80%) patients due to lack of PV information. Castration plus an androgen receptor inhibitor was more effective in PV reduction compared with an androgen receptor inhibitor alone (P<0.001). Planning target volume decreased in the combination arm. There was no significant difference in clinical or demographic or length of neoadjuvant hormonal treatment between the groups. Overall, a significantly larger PV reduction was achieved by castration plus androgen receptor inhibitor, as compared with androgen receptor inhibitor monotherapy. The PV reduction, however, appeared not to translate into better health associated quality of life during the subsequently given curative intended combined EBRT and HDR-brachytherapy. Potential differences between these two treatments regarding anti-tumor effects on micro metastatic disease and radiation potentiating effect remains to be addressed in future prospective trials.

Abstract P1-09-17: EndoPredict multigene test in the prediction of response and outcome after neoadjuvant hormonal treatment with letrozole adn palbociclib (OOTR-N007)

Abstract Background: The EndoPredict [EP] is a multi-gene expression assay designed to predict the replapse-free survival of patients with estrogen receptor [ER] positive, HER2 negative breast cancer treated with adjuvant endocrine therapy alone. Relative expression levels of the eight prognostic genes [AZGP1, BIRC5, DHCR7, IL6ST, MGP, RBBP8, STC2, UBE2C] and 3 reference genes were analyzed by real-time PCR system. EP low-risk patients have a better RFS when treated with endocrine therapy. One study indicated that EP high-risk patients are more sensitive to anathracycline-based neoadjuvant chemotherapy than low-risk patient. Palbociclib is an orally active potent and highly selective reversible inhibitor of CDK4/6. N007 study aims to evaluate the efficacy of the pre-operative use of letrozole plus palbociclib for ER positive, HER2 negative post-menopausal breast cancer. Whether EP could predict for response and outcome to such treatment will be evaluated. Method: Twenty patients were treated. EP assays were intended to be tested for all patients. RNA were extracted from paired FFPE tumour blocks [core biopsies and corresponding surgical sections]. EP score were calculated for the first 7 paired samples. Also the EP Clin Score which integrate both mRNA of prognostic genes expression and their pathological parameters, including tumor size and nodal status, were also evaluated. The change in EP score were compared with that of Ki67 and also with the pathologic tumor response. Results: The results of the first 7 patients were presented. The overall pCR rate rate was 14.3%[1/7]. 85.7% [6/7] samples were classified as low risk group. Paired T-test showed EP score is significantly lower [P=0.0014] after neoadjuvant hormonal treatment [NHT]. The change of EP score before and after treatment corresponds to the change in Ki67. Both have a similar prediction of response. EP scores either remained high or showed minimal change for patients with stable disease [SD]. The subsequent EP Clin score was high for one of such patients, indicating high clinical risk. The corresponding Ki67 did not show any change and was low after treatment. ResultsSubjectEP (before)EP (after)Ki67 (before)Ki67 (after)Change in EPChange in Ki67EP CLin0014.93.75%1%-1.2.4%2.70028.24.750%3%-3.5.47%2.3003107.113%13%-2.90%4.30045.6-10%--5.6-100%-0057.75.39%1%-2.4-8%2.80063.72.220%8%-1.5-12%2.60074.43.710%5%-0.7-5%3.4 Conclusion: pCR has been used as an endpoint for neoadjuvant chemotherapy trial. Our data suggest that the EP score can be reliably determined in core biopsy specimens and can be applied as endpoint on NHT trials. Changes in EP score correlated with that of Ki67 and also with response. However, changes in EP score may have a better prediction of response than Ki67. EP Clin score, which integrates clinical parameters, may predict subsequent risk and clinical outcome after treatment. The data of all the 20 patients will be presented at the meeting. Citation Format: Chow LWC, Toi M. EndoPredict multigene test in the prediction of response and outcome after neoadjuvant hormonal treatment with letrozole adn palbociclib (OOTR-N007) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-17.

24 - Safety and efficacy of neoadjuvant chemohormonal and hormonal treatment followed by radical prostatectomy for patients with high- and very high risk prostate cancer: Initial results of prospective, randomized, phase III clinical trial

24 - Safety and efficacy of neoadjuvant chemohormonal and hormonal treatment followed by radical prostatectomy for patients with high- and very high risk prostate cancer: Initial results of prospective, randomized, phase III clinical trial