Efficacy Of Neoadjuvant Endocrine Therapy Research Articles

Abstract PO1-18-10: ANNE: A phase II single-arm clinical trial to assess the feasibility and efficacy of neoadjuvant anastrozole in patients with luminal breast cancer and low proliferative index in TNM stages II and III

Abstract Background: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors (AIs) in this context. However, in clinical practice, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Ideally, after identifying suitable candidates for NET, patients undergo tumor re-biopsy after 2 to 4 weeks of treatment, and only those with Ki67 ≤ 10% proceed with NET. Limitations of this strategy include the standardization of re-biopsy and the reliability of Ki67 immunohistochemical analysis, as treatment decisions are based on these results. Objective: To evaluate the feasibility and efficacy of NET in postmenopausal patients with stage II and III luminal BC and to identify predictive biomarkers of therapeutic response. The efficacy will be measured by the rate of patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) score 0 on the surgical specimen. The feasibility of the study will be assessed by the acceptance rate of participating in the study (recruitment rate ≥ 50%) and the inclusion rate of >2 patients per month. Methods: This non-randomized phase II clinical trial includes postmenopausal women with invasive breast carcinoma, Scarf-Bloom-Richardson histological grades 1 or 2, Estrogen Receptor positive (Allred ≥ 6), progesterone receptor positive (any value), HER2 negative, Ki-67 antigen < 50% on immunohistochemistry, stages TNM II-III, with palpable tumor ≥ 2 cm, and ECOG 0-2. All eligible patients will receive anastrozole (1 mg/day) continuously until the day before the surgical procedure or exclusion from the study (in case of disease progression during endocrine therapy). After 2 to 4 weeks, a re-biopsy of the breast tumor will be performed. If Ki67 > 10%, endocrine therapy will be suspended, and the patient will be excluded from the study and redirected to neoadjuvant chemotherapy (routine care) or immediate surgery (as per attending clinical oncologist and surgeon). If Ki67 ≤ 10%, the patient will continue to receive NET. Extended NET will be administered for up to 10 months, with monthly physical examinations (using calipers) and bimonthly breast ultrasound. The presence of stable disease on ultrasound at 4, 6, and 8 months indicates scheduling surgery within 2 months thereafter, and disease progression at any time indicates surgery within one month. Patients will complete the EORTC QLQ-C30 and its supplemental module BR45 questionnaires every 2 months. Toxicity will be assessed using CTCAE version 4.0, and patients will respond to 11 specific items extracted from the Brazilian version of PRO-CTCAE. The radiological response will be evaluated by RECIST 1.1. Blood samples for molecular analyses will be collected at baseline and during re-biopsy. MicroRNA profiles will be evaluated using Nanostring, and extracellular vesicles will be examined using ATR-FTIR to identify predictive markers of therapeutic response (Ki67 < 10%) in re-biopsy. All cases will be evaluated using PAM50 at the initial biopsy and at surgery to determine the molecular phenotype (luminal A, B, or other) and molecular response (ROR score difference). Pathologic therapeutic response will be assessed using the PEPI score in all operated cases. The sample size was calculated to be 59 patients. The study was initiated in July 2022, and since then, a total of 26 patients have been enrolled. This study is registered with The Brazilian Registry of Clinical Trials (ReBEC): RBR-5pygzhj. Citation Format: Carlos Paiva, Izabella Oliveira, Vitor Guimarães, Alinne Faria, Domício Lacerda, Anapaula Uema, Nilton Onari, Bianca Paiva, Augusto Antoniazzi, Karina Oikawa, Maria Fernanda Machado, Matheus Godinho, Cristiano Souza, Chrissie Amirati, Gustavo Teixeira, Idam de Oliveira Jr, Márcia Marques, Yara Maia. ANNE: A phase II single-arm clinical trial to assess the feasibility and efficacy of neoadjuvant anastrozole in patients with luminal breast cancer and low proliferative index in TNM stages II and III [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-10.

Long-term outcomes of neoadjuvant endocrine therapy versus chemotherapy in luminal HER2-breast cancer

Introduction. Neoadjuvant endocrine therapy (NET) is an effective treatment modality that can downsize breast tumors in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. A lack of data regarding efficacy of NET vs neoadjuvant cytotoxic chemotherapy (NCT) leads to limited usage of NET despite its favorable toxicity profile. Perioperative endocrine therapy is mainly used for the elderly or patients with comorbidities that limit their access to NCT. The COVID-19 pandemic led to increased data of NET efficacy. Nevertheless, long-term outcomes of NET application are underrepresented in literature. Objective. Assessment of long-term outcomes in patients treated with neoadjuvant endocrine therapy (NAT) versus neoadjuvant cytotoxic chemotherapy in a cohort of postmenopausal women with HR-positive HER2-negative breast cancer. Materials and methods. We retrospectively evaluated the results of treatment of 154postmenopausal patients with luminal HER2-breast cancer who were treated with neoadjuvant systemic therapy (NET or NCT) at the State Medical Institution «St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)» from 01.01.2019 to 31.11.2020. We analyzed data on radiological, pathomorphological and long-term treatment outcomes (rate of locoregional and overall recurrence) in two groups.Results. 154 patients received neoadjuvant hormone therapy (n=78) or neoadjuvant chemotherapy (n=76). The clinical response was evaluated according to the RECIST criteria after 12 weeks and after study treatment using MMG. Partial or complete radiological response was achieved in 41.0% (n=32) in the NET group vs 69.7% (n=53) in the NCT group (p<0.001). All patients included in the study underwent surgery. A complete pathologic response was observed in 9.2% (n=7) of patients in the chemotherapy group, and in 0% of patients in the endocrine therapy group (p=0.006). Median follow-up was 46.2 months. Progression was recorded in 23.2% (n=29) of participants, with no significant benefit of NCT over NET in the frequency of locoregional relapses (NET n=8 (10.3%) vs NCT n=4 (5.3%)) (p= 0.369) or the occurrence of distant metastases NAT n=8 (10.3%) vs NCT n=13 (17.1%)) (p=0.216). Multivariate analysis showed that only pathologic lymph node status (ypN2–3) was an independent predictor of progression (p=0.007, OR=3.2; 95%CI: 1.380-7.422). Conclusions. Long-term outcomes after neoadjuvant hormone therapy are comparable with chemotherapy in the group of postmenopausal women with luminal HER2-breast cancer. The small sample size and limited follow-up period are significant limitations of our work.

Efficacy of neoadjuvant endocrine therapy in HR-positive/HER2-negative breast cancer: A review

IMPORTANCE. Neoadjuvant endocrine therapy (NET), despite demonstrating comparable data to neoadjuvant chemotherapy (NACT) in regard to ORR and being a less toxic alternative, is still used in clinical practice mainly for elderly patients or those who are not good candidates for chemotherapy. The COVID-19 pandemic led to increased application of NET for patients with HR-positive/HER2-negative breast cancer, that showed a growing need for data evaluating its efficacy in terms of long-term outcomes of treatment and for examining potential predictive biomarkers. OBSERVATIONS. We provide readers with a critical in-depth review on landmark trials comparing NET with NCT in HR-positive/ HER2-negative breast cancer. This also includes an overview of potential predictive biomarkers for identifying subsets of HR-positive breast cancer that could be safely spared neoadjuvant chemotherapy. CONCLUSIONS AND RELEVANCE. NET is an effective treatment modality for postmenopausal women diagnosed with HR-positive/ HER2-negative cancer that can downsize breast tumors. Due to the absence of large RCT comparing NET with NCT, little data on long-term outcomes, deep analysis of clinical practice treatment results is needed. Further research on potential predictive biomarkers and their validation is an important clinical issue.

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.

Abstract P2-03-19: The efficacy of neoadjuvant endocrine therapy during the waiting period for surgery in postmenopausal hormone receptor positive breast cancer

Abstract Background: Although neoadjuvant endocrine therapy has been used to improve breast conservation rate, its prognostic relevance is unknown. The search for a valid prognostic factor equivalent to pCR in neoadjuvant chemotherapy is a current challenge in neoadjuvant endocrine therapy. In this study, we investigated the efficacy of short term neoadjuvant endocrine therapy utilizing the waiting period for surgery and the prognostic factor including Preoperative Endocrine Prognostic Index (PEPI) score. Patients and Methods: A total of 269 postmenopausal women with hormone receptor-positive, HER2-negative breast cancer was treated with endocrine therapy with non-steroidal aromatase inhibitor during the waiting period for surgery between October 2012 and November 2021. Of the entire 269 patients, 92 and 177 patients had anastrozole and letrozole, respectively. The primary endpoint was change in tumor size by ultrasound and Ki67 before and after short-term endocrine therapy. The secondary endpoint was prognosis of patients divided by PEPI score which was calculated using tumor size, lymph node metastasis, Ki67, and ER Allred score. This study was approved by the institutional review board of Teikyo University. Results: Median age was 68 years old (range, 41-89). ER and PgR was positive in 266 (98%) and 232 (86%) of the entire 269 patients, respectively. Median tumor size was 1.65 cm (range, 0.4-7.5). Seventeen (6.3%) pts were clinically node-positive. Patients with histological grade I tumor were 190 (70.6%). The median duration of endocrine therapy was 39 days (range, 2-88). Average pretreatment Ki67 expression was 10% (range, 0-90). Tumor diameter was significantly decreased to 1.43cm (range,0.45-5.83) after short-term endocrine therapy (p=0.01). The Ki67 expression was significantly decreased to 3.0% (range, 0-85) after endocrine therapy (p< 0.01) and only five patients (1.9%) showed marked increase in Ki-67 expression. PEPI score 0, 1-3 and ≥ 4 was found in 83 (30.9%),147 (54.7%) and 39 patients (14.5%), respectively. After the median observation period of 928 days, patients with PEPI score ≥ 4 showed worse disease-free survival (Figure) compared with patients with PEPI score 0 and 1-3 (p=0.06). In terms of mortality, patients with PEPI score ≥ 4 had worse overall survival than patients with PEPI score 0 and 1-3 (p=0.07). Conclusions: These results suggested that neoadjuvant endocrine therapy during the waiting period for surgery might be effective in reducing the size and Ki67 expression level and PEPI score might be useful in predicting the prognosis of postmenopausal hormone receptor positive breast cancer patients. Citation Format: Yuka Maeda, Saki Naruse, Yuka Isono, Ayana Sato, Miki Yamada, Akiko Matsumoto, Tatsuhiko Ikeda, Hiromitsu Jinno. The efficacy of neoadjuvant endocrine therapy during the waiting period for surgery in postmenopausal hormone receptor positive breast cancer [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 P2-03-19.

Abstract P5-09-04: Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with hormone-responsive and HER2-negative, lymph node-negative breast cancer

Abstract Background: Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive and her2-negative breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal patients with hormone-responsive, her2-negative and lymph node-negative breast cancer. Materials and Methods: In this prospective, randomised study, pre-menopausal patients with hormone-responsive, her2-negative and lymph node-negative breast cancer were recruited. Enrolled patients were randomly assigned (1:1) to receive either NCT or NET with goserelin and tamoxifen, followed by goserelin and anastrozole. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by ultrasound. Results: A total of 68 patients were assigned to receive NCT (n = 31) or NET (n = 37). The clinical response rate was 16.1% for NCT and 35.1% for NET (estimated difference19%, 95%CI:-1.1%-39.1%, non-inferior p = 0.002). Rates of breast-conserving surgery were similar between NCT and NET (90.3% vs 83.8%, p=0.494). Conclusions: The clinical response rate of NET is non-inferior to NCT in pre-menopausal patients with hormone-responsive, HER2-negative, lymph node-negative breast cancer. Summary of ultrasound clinical response The breast surgery and MP grading system Citation Format: chongshan gu, yingjian he, jinfeng li, tianfeng wang, zhaoqing Fan, tao ouyang. Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with hormone-responsive and HER2-negative, lymph node-negative breast cancer [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 P5-09-04.

Gauging the efficacy of neoadjuvant endocrine therapy in breast cancer patients with known axillary disease.

Neoadjuvant endocrine therapy (NET) for ER+ breast cancer can downstage primary tumors. We evaluated NET efficacy in node-positive patients. Node-positive patients undergoing NET for ER+ breast cancer from 2012 to 2019 were reviewed. Primary endpoints included rates of axillary lymphadenectomy (ALND), pathologic complete response (pCR), and final nodal staging. Thirty-nine patients were included. Before NET, all were clinically node-positive (cN1 = 36, 94%; cN2 = 2, 5%; cN3 = 1, 3%; Stage II = 23, 59%, Stage III = 16, 41%). After NET, nine (23%) had clinically persistent axillary disease necessitating ALND. The remaining 30 (77%) underwent sentinel lymph node biopsy (SLNB). Of these, 25 (83%) were SLNB+ on frozen section, undergoing immediate ALND. Five patients were negative on frozen section: one had a confirmed axillary pCR, and four had residual nodal disease on permanent pathology. One underwent delayed ALND, and for the remaining three patients, decision was made to forgo ALND. Final overall axillary staging was: N0 (pCR) = 1, 3%, pN1mic = 1, 3%, pN1 = 20, 51%, pN2 = 12, 30%, pN3 = 5, 13%; Stage II = 16, 41%, Stage III = 23, 59%. While NET is reported to downstage primary tumors, downstaging of the axilla was unsuccessful in the majority of patients.

Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer

IntroductionNeoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer.Patients and methodsIn this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints.ResultsA total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6–44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4–24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group.ConclusionsBetter clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET.Trial registrationClinicaltrials.gov, NCT01622361. Registration June 19, 2012.

Response to neoadjuvant chemotherapy and the 21-gene breast recurrence score in young women with estrogen receptor-positive early breast cancer.

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% &gt; 25 and only 4 &lt; 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS &gt; 25 was 21% (8/38) vs. 5% in patients with RS &lt; 25 (2/38), with both pCRs in the &lt;25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.

Neoadjuvant Endocrine Therapy in Breast Cancer: Current Knowledge and Future Perspectives.

In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.

NEOADJUVANT ENDOCRINE THERAPY FOR PATIENTS WITH ESTROGEN-RECEPTOR-POSITIVE BREAST CANCER

More than 70 % of patients with breast cancer have estrogen-receptor-positive tumors (ER+) and are considered hormone- sensitive. That is why a vast majority of patients with early operable tumors receive adjuvant endocrine therapy. Patients with metastatic ER+ breast cancer also receive hormone therapy as first-line treatment. Patients with ER+/PR+ locally advanced breast cancer including potentially operable cases (cT2N1, cT3N0M0) are still a subject to neoadjuvant chemotherapy in most of the oncology centers in Russia and worldwide. More than 10 years ago, several trials evaluating the efficacy of neoadjuvant endocrine therapy were conducted in the Petrov Research Institute of Oncology (aromatase inhibitors vs tamoxifen, neoadjuvant endocrine therapy vs neoadjuvant chemotherapy, etc.) The primary endpoint was the evaluation of pathologic complete/partial response to therapy and the frequency of breast-conserving surgeries following neoadjuvant treatment. We now represent 10-year long-term follow-up data on comparison of neoadjuvant chemotherapy with neoadjuvant endocrine therapy after retrospective determination of IHC- phenotypes of 239 patients with ER+ breast cancer. The study results show tendency to better 10-year disease-free survival in patients with luminal-A breast cancer who received endocrine therapy compared to neoadjuvant chemotherapy (72.8 % vs 53.9 %, respectively, p=0.062) There were no statistically significant differences in DFS rates among patients with the luminal B breast cancer subtype (41 % vs 40 %) The discovery of biomarkers of potential resistance to endocrine therapy (cycline-dependant kinase activity [cdk 4/6], estrogenreceptor mutation [ESR1], mTOR signaling pathway activity, co-expression of the ER and HER2neu [ER+/ HER2neu3+]) and ways to inhibit the activity of the resistance pathways (palbocyclib, everolimus, etc.) have expanded the armamentarium of endocrine-therapy for not only metastatic and locally-advanced but also operable cases of ER+ breast cancer.

Utilization, trend and impact of neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy in postmenopausal breast cancer patients: Analysis of the National Cancer Data Base.

578 Background: Three small prospective trials that compared the efficacy of neoadjuvant endocrine therapy (NET) to neoadjuvant chemotherapy (NCT) showed no statistically significant difference. We report the differences in utilization of NET and NCT using National Cancer Data Base (NCDB) and their trend, response rates (RR) and breast conservation rates (BCR). Methods: A retrospective review of hormone receptor positive breast cancer patients ≥ 50 yrs without metastasis using NCDB was performed (2004-2014). Patients underwent NET or NCT prior to definitive surgery. Utilization pattern, practice trend, RR and BCR between NET and NCT was assessed using univariate and multivariate logistic analysis. Results: Out of 2,246,279 breast cancer patients reported in NCDB, 38,632 met our inclusion criteria. 9178 received NET and 29,454 received NCT. On multivariate analysis NET use was higher in academic vs community centers [Odds ratio (OR) 1.355, 95% CI 1.270-1.445], age &gt;70 vs &lt; 70 (OR 6.603, 95% CI 6.110-7.137) and high vs low Charlson Deyo comorbidity index (OR 1.817, 95% CI 1.548-2.133). NET use was lower in black vs white (OR 0.790, 95% CI 0.712- 0.875), tumors with higher vs lower grade (OR 0.153, 95% CI 0.138-0.169), higher vs lower T stage (OR 0.372, 95% CI 0.340-0.407), higher vs lower N stage (OR 0.274, 95% CI 0.243-0.310) and private vs no insurance (OR 0.600, 95% CI 0.509- 0.707), (all p&lt;0.0001). A significant upward trend in utilization of NET was observed from year 2011 (25.9%) compared to before (22.2%), p&lt;0.0001. RR was significantly higher for patients receiving NCT (90.5%) compared to NET (77.2%), with an [adjusted OR (aOR) 2.413; 95% CI 2.116-2.752], however the BCR was superior in the NET group (50.0%) compared to NCT group (31.1%) with (aOR 1.676; 95% CI 1.567-1.794). Conclusions: Our study is the first to compare NET and NCT utilization and their efficacy using NCDB database. Our results have shown striking differences in outcome among these two strategies as compared to other prospective trials. Despite high RR, more patients underwent mastectomy in the NCT group. We also see a steady upward trend in usage of NET from year 2011.

The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy.

Estrogen receptor (ER)/GATA3/Forkhead box A1 (FOXA1) network is necessary for the ERα functional signature. High FOXA1 expression indicates a good prognosis in ER-positive breast cancer. However, little is known about the significance of FOXA1 and GATA3 expression in neoadjuvant endocrine therapy (NAE). The aim of this study is to investigate their predictive potential for NAE and their expression changes after NAE. FOXA1 and GATA3 expression was evaluated using immunohistochemistry in 66 patients with ER-positive/HER2-negative breast cancer who had been treated with NAE. The association between biological marker expressions and the efficacy of NAE and their expression changes after NAE were analyzed. The median pre-treatment FOXA1 and GATA3 expressions were 94.6 and 90%. Pre-treatment FOXA1 expression was positively correlated with GATA3 (P=0.0003) and progesterone receptor (PgR) (P=0.0138). There was no correlation between pre- or post-treatment FOXA1 and GATA3 expressions and the efficacy of NAE. Post-treatment Ki67 expression was significantly lower in tumors with partial response (PR) (P=0.0007). In terms of the changes of the expression, PgR, Ki67, and FOXA1 expression significantly decreased after NAE (P<0.0001, P<0.0001, and P<0.0001, respectively). FOXA1 and GATA3 expression was not correlated with the efficacy of NAE, but FOXA1 expression was significantly reduced after NAE.

Abstract C48: Neoadjuvant endocrine therapy in locally advanced hormone receptor positive (HR+) breast cancer (BC) in a low-resource, middle-income setting (Guatemala)

Abstract Background: BC is the leading cause of cancer death in women in low- and middle-income countries (LMIC). For locally advanced BC, neoadjuvant treatment is often needed to downstage tumors prior to surgery, however many patients (pts) with BC in low-resource settings do not receive adequate therapy due to financial, social, and logistical barriers. This study evaluates the feasibility, adherence rates, and efficacy of neoadjuvant endocrine therapy with tamoxifen in a low-resource setting in Guatemala. Methods: This is a single arm, single center study of neoadjuvant tamoxifen in pts with locally advanced HR+ BC. Pts were treated with tamoxifen for 4-6 weeks then underwent a core biopsy of their primary tumor for Ki67 evaluation. If Ki67 was ≤ 10%, tamoxifen was continued for a total of 4 months. If Ki67 &amp;gt; 10%, pts were taken off study. The primary endpoint was assessing the proportion of pts who completed neoadjuvant treatment and received definitive surgery. Results: The median age was 59 years (range 35-78). Nine (25.7%) pts were pre-menopausal and 26 (74.3%) pts were post-menopausal. Ductal histology was present in 31 (88.6%) pts and lobular histology in 3 (8.6%) pts. Clinical stage was IIB in 5 (14.3%) pts, IIIA in 22 (62.9%) pts, IIIB in 7 (20%) pts, and IIIC in 1 (2.9%) pt. All pts were estrogen receptor positive (ER+), 29 (82.9%) pts were progesterone receptor positive (PR+), and 2 (5.7%) pts were HER2+. Of the 35 pts enrolled, 32 (91.4%) returned for a biopsy after 4 weeks of tamoxifen. Seventeen pts were taken off study; 8 pts had Ki67 &amp;gt; 10% and 9 pts had clinical progression. Fifteen (46.9%) pts continued on tamoxifen for 4 months. Of these, 13 pts (86.7%) underwent mastectomy. By exam, 6 pts had a complete response (CR) and 7 pts had a partial response. There was one pathologic CR. One pt was lost to follow-up and in one the tumor was still too large. The cost of neoadjuvant endocrine therapy with additional biopsy was 28% the cost of neoadjuvant chemotherapy in this setting. Conclusions: Neoadjuvant tamoxifen is a tolerable, acceptable, and less expensive option for pts with HR+ locally advanced BC in a middle-income, low-resource setting, with good rates of adherence and clinical response. This has implications for other LMIC, but further studies are needed to better define patient selection, applicability, and length of treatment of neoadjuvant tamoxifen Citation Format: Laila S. Agrawal, Mei-Ling Pereira, Ingrid A. Mayer, Eduardo Gharzouzi. Neoadjuvant endocrine therapy in locally advanced hormone receptor positive (HR+) breast cancer (BC) in a low-resource, middle-income setting (Guatemala). [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C48.

Abstract P5-13-05: The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy

Abstract Background. The estrogen receptor (ER)/ GATA3/ Forkhead box A1 (FOXA1) network is necessary for the ERα functional signature specific to luminal type breast cancers. High expression of FOXA1 indicates a good prognosis in ER-positive breast cancer. However, little is known about the association between the expression of FOXA1 and GATA3, and the efficacy of neoadjuvant endocrine therapy (NAE). This study investigated their predictive potential for NAE and the changes of their expression after NAE. Methods. The expression of ER, progesterone receptor (PgR), Ki67, FOXA1, and GATA3 were analyzed by immunohistochemistry in 66 patients with hormone receptor-positive/ human epidermal growth factor receptor 2 (HER2)-negative breast cancer who had been treated with NAE between March 2003 and December 2012 at Kyushu University Hospital, National Kyushu Cancer Center, and Sagara Hospital. The association between the expression of biological marker and the efficacy of NAE, and their expression changes after NAE were evaluated. Results. The median age of the patients was 60 years (range, 30–84 years). Pre- and post-menopausal patients were 24 (36.4%) and 42 (63.6%). Endocrine agents that were administered are as follows: aromatase inhibitors (AIs) for 42 patients (63.6%), luteinizing hormone-releasing hormone (LHRH) agonist plus AI for 10 patients (15.2%), LHRH agonist plus tamoxifen for 13 patients (19.7%). NAE yielded a partial response (PR) in 21 patients (31.8%) and stable disease (SD) in 45 patients (68.2%). Breast conserving surgery was performed in 56 patients (84.8%) and mastectomy was performed in 10 patients (15.2%). Preoperative Endocrine Prognostic Index (PEPI) score was 0 in 10 patients (15.2%) and 1 or greater (score 1 ≤) in 56 patients (84.8%). Pre-treatment FOXA1 expression was positively correlated with GATA3 (P = 0.0003) and PgR (P = 0.0138). Post-treatment Ki67 expression was significantly lower in tumors, which achieved PR compared with those with SD (P = 0.0007). The expression of PgR, Ki67, and FOXA1 was significantly lower in post-treatment tumors compared with those in pre-treatment samples (p &amp;lt; 0.0001, p &amp;lt; 0.0001 and p &amp;lt; 0.0001, respectively). The expression of PgR, Ki67, and FOXA1 was significantly reduced in both tumors with PR and those with SD (PR: P = 0.0004, P &amp;lt; 0.0001, and P = 0.0417, respectively; SD: P &amp;lt; 0.0001, P = 0.0001, and P &amp;lt; 0.0001, respectively). The expression of PgR, Ki67, and FOXA1 was significantly decreased in post-treatment tumors in both patients with the PEPI score 0 and those with score 1 ≤ (score 0: P = 0.0078, P = 0.0059, and P = 0.0098, respectively; score 1 ≤: P &amp;lt; 0.0001, P &amp;lt; 0.0001, and P = 0.0002, respectively). In tumors with PgR &amp;gt; 20%, the expression of Ki67 and FOXA1 were significantly lower in post-treatment tumors (P &amp;lt; 0.0001 and P &amp;lt; 0.0001, respectively). Conclusions. FOXA1 expression correlated with PgR expression, and was reduced significantly after NAE. These results suggest that blocking the effect of estrogen might reduce FOXA1 expression. Citation Format: Tanaka K, Tokunaga E, Inoue Y, Ueo H, Yamashita N, Sagara Y, Ohi Y, Taguchi K, Ohno S, Okano S, Kitao H, Oki E, Oda Y, Maehara Y. The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-05.

Abstract P1-11-11: Correlation between ER/PgR/Her-2/Ki67 Expression and Response to Neoadjuvant Endocrine Therapy for HR Positive Post-Menopausal Breast Cancer

Abstract Background: Endocrine therapy was standard adjuvant treatment for hormone receptor positive breast cancer. However, there were factors other than receptor status could influence endocrine responsiveness. Neoadjuvant therapy was an excellent platform for predictive factors research, but the standard for evaluating the efficacy of neoadjuvant endocrine therapy was controversy. The aim of this study was to investigate the correlation among the results of different response evaluation system, and the relationships between ER/PgR/Her-2/Ki67 expression and the responses to neoadjuvant endocrine therapy for postmenopausal breast cancer. Methods: Data of consecutive 133 core needle biopsy (CNB) confirmed hormone receptor strongly positive (more than 50% tumor cell stained ER or PgR) postmenopausal breast cancer treated with neoadjuvant endocrine therapy were analysis retrospectively. All pts. were planned to receive endocrine therapy alone as their adjuvant treatment and prescribed Anastrozole 1 mg per day for 16 weeks before surgery. Clinical response were evaluated by using documented ultrasound records,pathological response was evaluated by one senior pathologist with Miller &amp; Payne classification. Cell cycle complete response was defined as post-treatment Ki67 ≥1%. The new slides of pre-treatment and surgical specimens were made for ER/PgR (ER\PR DakoCytomation)/Her-2 (Her-2 Dako HercepTest TM)/Ki67 (Ki67 Ventana) immunohistochemical staining through Benchmark XT Staining Instrument (Ventana Medical Systems. Inc. Arizona. USA) and classified by using image analysis system Ariol (Applied Imaging Inc., San-Jose, California, USA). Results: Clinical response were CR:0.8% PR:33.1% SD:66.1%, pathological response were G5:3% G4+G3:47.4% G2+G1:49.6%, Ki67 change were &amp;lt;1%: 22.8% decrease but &amp;gt;1%:45.1% no decrease: 32.1%. The correlation and consistency among the response evaluated differently were poor [table 1]. The per-treatment ER/PR/Her-2/Ki67 showed low degree of correlation with responses [table 2]. Pre-treatment ER≥90% and PR≥90% and Her-2 coudln't predict better response. The correlation and consistency among response evaluated in different system Conclusion: The correlation and consistency among the results of response to neoadjuvant endocrine therapy evaluated by different system were poor. ER/PgR/Her-2/Ki67 showed low degree of correlation to responses. It's difficult to predict response to Arimidex neoadjuvant endocrine therapy by using ER/PgR/Her-2/Ki67 expression. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-11.

The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER- positive breast cancer

The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER- positive breast cancer

The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER- positive breast cancer

519 Background: Neoadjuvant chemotherapy (NACT) or hormonal therapy (HT) is being used increasingly to downstage locally advanced and large operable breast cancer. Following this treatment, inoperable breast cancer often becomes fully resectable, and tumors requiring mastectomy may be successfully removed by breast-conserving surgery (BCS). Patient selection is important to optimize neoadjuvant therapy (NAT), especially in elderly postmenopausal women with co-morbid conditions. Methods: Between March 1998 and March 2003, 121 postmenopausal (PM) women with ER(+) and/or PgR(+) breast cancer (BC) T2N1–2, T3N0–1, T4N0M0 assigned NAT with either CT Dox 60 mg/m2 + Pac 200 mg/m2, every 3 weeks, 4 cycles, n=62 patients (pts), or HT with aromatase inhibitors, anastrazole 1 mg, n = 30 pts, 3 months). The primary endpoint was to compare overall objective response (OR) determined by clinical (palpation) and mammogr. Secondary endpoint was the number of pts who qualified for BCS + radiotherapy (50 Gy for 25 fractions). Results: Table 1. OR rate (clinical and mammogr.) was statistically similar ( p > 0.05 ) in the CT and anastrazole groups. Tendency to more BCS took place in the anastrozol arm that in the CT arm ( 37.9 % vs 20.6 % p=0.054). Local recurrence rate were similar for pts receiving CT or HT (3,2 % and 3,4%, at 34 months median follow up ). In CT arm the most frequent grade III/IV toxicity was alopecia ( 79.3 5 ), neutropenia ( 43.1 %), cardiotoxicity (6.8 %), diarrhea (1.7%). HT was well tolerated. The most commonly adverse events were hot flushes (23.3%), vaginal discharge (6.6%), musculosskeletal disorders (1.7%). Conclusions: NAHT with aromatase inhibitors (anastrazole) is a reasonable alternative to CT for PM women with ER and/or PgR - positive cancer in clinical situation where the low toxicity of the regimen is considered an advantage, for example, for women over 70. No significant financial relationships to disclose.