Erratum to “Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study”

The role of hormone therapy as a neoadjuvant to radical prostate radiotherapy.

Background: Early biologic response to endocrine therapy, such as changes in Ki67 labeling index (LI), has been suggested to predict long-term outcomes in hormone sensitive breast cancer. The addition of a CDK4/6 inhibitor to endocrine therapy has been shown to augment biological response in breast cancer. Pre-operative Endocrine Prognostic Index (PEPI) scores, generated based on post-treatment Ki67 LI, have been shown to predict patient outcomes. EndoPredict® is a multigene assay that predicts the risk of distant recurrence in patients with operable estrogen receptor (ER)-positive HER2-negative breast cancer. This study was conducted to evaluate the efficacy of the neoadjuvant endocrine therapy plus palbociclib versus neoadjuvant endocrine therapy plus placebo. Patients and Methods: This is a phase III randomized, double-blind study of neoadjuvant hormonal therapy plus palbociclib versus neoadjuvant hormonal therapy plus placebo in untreated pre/peri- and post-menopausal women with operable, hormone receptor-positive (ER and/or progesterone receptor), HER2-negative breast cancer. The other major inclusion criteria included tumor size ≥ 15mm, T1c-3N0-1, Ki67 LI ≥14% by central assessment, and no previous history of radiotherapy or systemic therapy for breast cancer. Patients were randomly assigned 1:1 to receive 16 weeks of hormonal therapy plus palbociclib or hormonal therapy plus placebo. Hormonal therapy consisted of letrozole for post-menopausal patients and tamoxifen plus LH-RH agonist for pre/peri-menopausal patients. The co-primary endpoints included PEPI score and EPclin Risk Score, a score combining EndoPredict® molecular score with clinical factors. These scores were sequentially analyzed on a modified intent-to-treat basis according to the gatekeeping procedure: if statistical significance was detected on the PEPI score, the statistical significance of EPclin Risk Score would be assessed. The sample size was 100 patients in each arm, which was calculated with < 5% type I error rate (two sided) and 80% power. Results: Between 16 July 2019 – 7 July 2021, 141 eligible patients were randomized from 25 participating institutes in Japan, Korea, Taiwan, Hong Kong and Australia. One hundred twenty-six patients completed the treatment duration and surgical samples were collected to evaluate endpoints. All randomized patients were evaluable for safety assessment. Randomization was well-balanced in terms of age, menopausal status and cancer stage. The proportion of patients who had a low, moderate, or high PEPI score was 15.2%, 50.0% and 34.8% in the hormonal therapy plus palbociclib arm and 13.3%, 55.0% and 31.7% in the hormonal therapy plus placebo arm, respectively. There was no statistically significant difference in PEPI score between two arms (one-sided p-value=0.563). The proportion of patients who had a high risk EPclin Risk Score seemed lower in the palbociclib arm than in the placebo arm (62.1% vs 68.3%) although hypothesis testing was not performed on EPclin Risk Score because statistical significance was not detected on the PEPI score. No new safety signals were found in the study. Permanent discontinuation from the study in association with adverse events was reported for 7 (9.7%) patients in the hormonal therapy plus palbociclib arm and for 0 patients in the hormonal therapy plus placebo arm. Conclusions: The addition of palbociclib to neoadjuvant hormonal therapy did not improve efficacy measured by PEPI score. In palbociclib arm, the rate of patients who had a high risk EPclin Risk Score after treatment was lower than in placebo arm. Translational researches are ongoing to analyze molecular changes by treatments. The role of chemotherapy after neoadjuvant therapy is under investigation. Clinical trial identification: NCT03969121 Funding: Pfizer Inc. Citation Format: Takayuki Ueno, Louis W.C. Chow, Wonshik Han, Chiun Sheng Huang, G Bruce Mann, Satoshi Morita, Hironori Haga, Elham Fakhrejahani, Takayuki Kobayashi, Kenichi Inoue, Mariko Tokiwa, Hirofumi Suwa, Tomoyuki Aruga, Sachiko Minamiguchi, Yosuke Yamada, Yuko Tanabe, Masahiro Takada, Toshinari Yamashita, Hiroji Iwata, Chi-Feng Chung, Sachiko Takahara, Eriko Tokunaga, Shigeru Imoto, Eun Sook Lee, Yasuaki Sagara, Jee Hyun Kim, Richard H DeBoer, Hyun-Ah Kim, Hung Wen Lai, Ming-Feng Hou, Michelle White, Yoshiko Umeyama. Neoadjuvant hormonal therapy plus palbociclib versus hormonal therapy plus placebo in women with operable, hormone sensitive and HER2-negative primary 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 P5-09-01.

Neoadjuvant therapy in breast cancer has evolved from a modality able to facilitate surgery into a sophisticated treatment approach, where patterns of response influence the extent of surgery (i.e. breast and axilla) and inform treatment decisions in the adjuvant setting. This is particularly true for patients diagnosed with HER2-positive or triple-negative breast cancer (TNBC). In the subset of estrogen receptor-positive (ER+) disease, the neoadjuvant treatment model has proven to be a successful clinical research tool. Studies investigating pharmacodynamic markers (i.e., Ki67) demonstrated the differences in the relative effectiveness of tamoxifen versus aromatase inhibitor and, more recently, neoadjuvant studies with endocrine therapy plus CDK4/6 inhibitors demonstrated the efficacy of CDK4/6 inhibitors in potentiating the effects of endocrine therapy through a profound suppression of Ki67. However, in clinical practice neoadjuvant endocrine therapy remains underutilized. Routinely, ER+ candidates for neoadjuvant therapy are treated with chemotherapy with minimal attention to disease biology. By contrast, disease biology plays a major role in the adjuvant setting, and the “old notion” of disease burden predicting chemotherapy benefit is fading away. The disconnect between the choices of systemic therapy in the neoadjuvant versus adjuvant setting in ER+ breast cancer has multiple roots: 1) Physicians and patients may expect higher response rates to neoadjuvant chemotherapy; 2) genomic biomarkers to guide chemotherapy treatment decisions were developed using material from surgical specimens; 3) there are limited data with neoadjuvant endocrine therapy in premenopausal women; and 4) the objectives with neoadjuvant endocrine therapy are not always clear. While additional clinical studies are warranted, the available clinical data suggest neoadjuvant endocrine therapy is an appropriate treatment approach for patients with ER+ disease. When selecting patients by ER+ status only, response rates to neoadjuvant endocrine therapy are similar or higher than chemotherapy. Clinical studies have successfully used diagnostic biopsies for genomic profiling, and if anything, the quality of FFPE material should be superior due to pre-analytical variables (e.g., reduced ischemic time). Additionally, neoadjuvant endocrine therapy for ER+ breast cancer and favorable disease biology fulfills the promise of a tailored treatment approach and avoids unnecessary use of cytotoxic therapy. When selecting neoadjuvant endocrine therapy for patients, it is important to understand some key points regarding this treatment approach. The maximum treatment response is not expected before four to six months of therapy, and the interpretation of pathologic response should not be confounded by data from HER2+ and TNBC. Residual disease after neoadjuvant endocrine therapy is not a predictor of survival outcomes. And, lastly, if the patient was not deemed as an ideal candidate for neoadjuvant chemotherapy at baseline, the extent of residual disease should not be used a predictor of chemotherapy benefit. There are, however, caveats and extensive disease at the time of surgery (e.g., four or more positive nodes) might justify a course of adjuvant chemotherapy. In summary, neoadjuvant endocrine therapy should not be a treatment of exception for elderly patients when trying to avoid the toxicities of chemotherapy. Neoadjuvant endocrine therapy is an effective treatment modality with proven clinical utility for postmenopausal patients with ER+ breast cancer. Citation Format: O Metzger. Neoadjuvant therapy for hormone receptor-positive breast cancer: challenges and advances [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 ES5-1.

This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single neoadjuvant chemotherapy or endocrine therapy, specifically in the context of hormone receptor-positive (HR+) breast cancer treatment. We conducted a thorough literature search across several databases, including China National Knowledge Infrastructure, Wanfang, Weipu, Chinese Journal Full-text Database, PubMed, Web of Science, Cochrane Library, and EMBASE, adhering to the guidelines outlined in the PRISMA statement. Our specific focus was on identifying randomized controlled trials that directly compared the combined approach of neoadjuvant chemotherapy and endocrine therapy with single chemotherapy or endocrine therapy in the context of treating HR+ breast cancer. Subsequently, we utilized statistical packages implemented in R software to perform comparative analyses of key clinical indicators, encompassing the complete response, objective response rate (ORR), disease control rate, pathological complete response (pCR), and adverse reactions. A total of 11 randomized controlled trials, involving 1359 patients, all of whom met our inclusion criteria and were thus included in our comprehensive analysis. Within this cohort, 688 patients (50.63%) administered neoadjuvant chemotherapy combined with endocrine therapy (NCET), 642 patients (47.24%) received neoadjuvant chemotherapy (NCT) alone, while 29 patients (2.13%) underwent neoadjuvant endocrine therapy (NET) alone. The results of our meta-analysis revealed that NCET exhibited a statistically significant enhancement in both ORR and pCR (P < .05). Nonetheless, when compared to NCT or NET, NCET did not yield a significant impact on complete response, disease control rate, and safety (P > .05). In addition, NCET demonstrated a significant improvement in ORR among patients with HR+, HER2-negative breast cancer (P < .05). However, it was also linked to a heightened incidence of serious adverse reactions within this particular patient subgroup (P < .05). The combination of Neoadjuvant chemotherapy and endocrine therapy stands out as a significant contributor to enhancing the ORR and pCR for HR+ breast cancer patients. For breast cancer patients with HER2- status, NCET demonstrates a remarkable improvement in ORR but is also associated with the emergence of adverse reactions.

Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study

581 Background: While neoadjuvant chemotherapy (NACT) has been established as the standard of care for medically fit patients, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for the treatment of women with estrogen-receptor (ER) positive, HER-2 negative breast cancer. Rates of pCR are known to be low in this population, but there is inconsistent data regarding downstaging and long-term outcomes in a non-trial setting with NET vs NACT. Methods: A prospective institutional databaseof breast cancer patients treated with neoadjuvant therapy at the British Columbia Cancer Agency from 2012-2016 was analyzed to identify all medically fit patients with ER positive, HER2 negative breast cancer. Patients were then divided into two groups: those who received NET or NACT. Baseline characteristics were compared between groups. A matched analysis (age, stage and grade) was then performed to compare rates of downstaging, pCR and scores from a validated neoadjuvant therapy outcomes calculator (CPS+EG). Results: A total of 154 patients met eligibility criteria for this study. One hundred and six patients (69%) received NACT and 48 (31%) received NET. Women offered NACT were significantly younger (51 vs 64y, p &lt; 0.001) than those offered endocrine therapy and presented with a higher clinical stage (LR 27.93, p = 0.002). According to multiple linear regression for downstaging, clinical stage followed by NACT were the most important predictors of downstaging. When matched for age, stage and grade, downstaging was significantly higher with NACT (31/48, 65%) as compared to NET (12/48, 25%), p &lt; 0.001. Of these, 12.5% achieved pCR with NACT as compared to 2.1% with NET, LR 4.243, p = 0.039. No significant differences in CPS+EG scores were identified when comparing NACT to NET. Conclusions: Significantly higher rates of downstaging were achieved with NACT as compared to NET when patients were matched for age, stage and grade. Rates of pCR remain low for ER-positive breast cancer patients. Although not validated with the use of NET, CPS+EG scores predicting long-term outcomes were not significantly different with NET compared to NACT.

Taking a Second Look at Neoadjuvant Endocrine Therapy for the Treatment of Early Stage Estrogen Receptor Positive Breast Cancer During the COVID-19 Outbreak.

e11605 Background: Hormone therapy is recommended for treating patients with luminal A type early breast cancer by the International Conference in St. Gallen, 2011. However, precisely which neoadjuvant therapeutic strategies are optimal for such patients still remains controversial. We retrospectively evaluated the treatment responses to neoadjuvant chemotherapy (NAC) or neoadjuvant endocrine therapy (NAE) in patients with ER (+)/HER2 (-) breast cancer. Methods: Four hundred and sixty-one patients with primary breast cancer underwent surgery between November 2007 and October 2012. Of 243 patients with hormone receptor (+)/HER2 (-) breast cancer, 63 with ER (+)/HER2 (-) breast cancer were preoperatively treated with either NAC (n=47, median age: 49 years) or NAE (n=16, median age: 63 years). Four cycles (c) of FEC 100 (epirubicin 100 mg/m2 + 5-fluorouracil and cyclophosphamide 500 mg/m2) followed by 4 cycles of Docetaxel (75 mg/m2) every 3 weeks were administered for the NAC treatment regimen, while Letrozole was administered for 6 months for the menopausal patients in the NAE treatment protocol. Results: NAC did not alter the ER status, while the ER status was decreased by NAE (from 83% to 62%). NAE altered the ER status (positive rate; from 83 % to 62 %), but NAC did not. The PR status was decreased by both NAC and NAE (from 51% to 30% and from 63% to 9%, respectively). ER (P=0.0327) and PR (P=0.0019) were statistically decreased after NAE compared to that observed after NAC. The response rates determined by RECIST {PD/SD/PR/CR (%)} in the NAC- and NAE-treated patients were 2/34/58/6 and 0/50/50/0, respectively. The rate of tumor shrinkage was 41% (3.9 to 2.3 cm) after NAC and 39% (2.3 to 1.4 cm) after NAE. The pathological complete response rate was 9% after NAC and 6% after NAE. The recurrence rate in the stage I/II patients was 5% (2/38) after NAC and 0% (0/16) after NAE for short-term outcomes. Conclusions: The hormone status significantly changed after NAE compared to that observed after NAC. Both of the NAC and NAE treatment protocols caused a decrease in the tumor size. As a result, both of these therapeutic modalities were found to improve the rate of breast-conserving surgery.

CDK4/6 inhibitors as neoadjuvant treatment in breast cancer—what can we learn?

Background: In early ER+ breast cancer, neo-adjuvant (NA) endocrine therapy (ET) may identify a subset of patients with endocrine sensitive disease with excellent outcomes without chemotherapy. In patients receiving a NA aromatase inhibitor, on- therapy, short term (day 14) Ki-67 of &amp;lt;10% and post NA pre-operative endocrine prognostic index (PEPI) 0 at surgery are associated with low relapse rates without chemotherapy. Ribociclib, a novel CDK4/6 inhibitor is active in ER+ metastatic breast cancer. We hypothesize that ribociclib+letrozole as NA ET for stage II-III breast cancer will increase the number of women with a PEPI 0 at surgery. Trial Design: Randomized, placebo-controlled, multi-center, phase II, investigator initiated trial of NA letrozole +/- ribociclib in postmenopausal women with ER+, HER2-, breast cancer. Subjects will be randomized 1:1:1 to letrozole 2.5 mg daily + placebo, letrozole 2.5mg daily + ribociclib 600mg daily on D1-21 of a 28 day cycle (intermittent dosing), or letrozole 2.5mg daily + ribociclib 400mg daily (continuous dosing). Treatment will be continued for 6 months followed by surgery. Research core biopsies and blood will be collected at baseline, at day 14, and at surgery. A Ki67 &amp;gt;10% at day 14 will result in discontinuation of the subject from the protocol as this may be an early indicator of resistance to endocrine therapy. An MRI will be done after 2 months of therapy to assess response/progression. Primary endpoint is a PEPI score of 0 at surgery. Key Eligibility Criteria: Postmenopausal (natural or surgical) women with stage II/III ER+, HER2- breast cancer. Must have a palpable breast mass of at least 2 cm. Multicentric/contralateral invasive disease not allowed. Ipsilateral/contralateral DCIS is allowed. Inflammatory breast cancer is excluded. Specific Aims: Primary objective: To determine if ribociclib+letrozole as a 24 week NA ET increases rate of PEPI score of 0 at surgery compared to letrozole. Secondary objectives: To determine if ribociclib+letrozole as a 24 week NA ET increases the proportion of tumors with complete cell cycle arrest compared to letrozole; to determine if ribociclib in combination with letrozole for 24 weeks results in improved 5 year RFS compared to letrozole; to examine differences in response rates between the two ribociclib containing arms vs letrozole. Statistical Methods: The two ribocilib containing arms (n=80) will be combined for analysis against placebo + letrozole (n=40). Assuming that addition of ribociclib will increase the rate of PEPI 0 by 20%, and setting Type I error rate at 10% and Type II error rates at 20% in the final analysis, a sample size of 80 women in the treatment arms (40 in each arm) and 40 women in the control arm are needed to show significance. Patient accrual and target accrual: Participating sites include The Univ of Kansas Med Ctr, City of Hope National Med Ctr, Massachusetts General Hospital, University of Miami Sylvester Comprehensive Cancer Ctr, University of Arkansas for Medical Sciences, and University of Wisconsin. The trial has accrued 16 patients with a target accrual of 120 patients. Accrual should be complete in 2/2017. Contact information: Qamar Khan, MD (qkhan@kumc.edu). Citation Format: Khan QJ, Prochaska LH, Mohammad J, Yuan Y, O'Dea A, Bardia A, Wisinski K, Hard M, Baccaray S, Makhoul I, Wagner J, Laura S, Ma C, Sharma P. Femara plus ribociclib or placebo as neo-adjuvant endocrine therapy for women with ER+, HER2-negative early breast cancer - The Feline trial [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 OT3-02-06.

Background With current imaging technologies, assessing response to neoadjuvant chemotherapy (NAC) or neoadjuvant endocrine therapy (NET) remains a challenge for patients with invasive lobular carcinoma (ILC). Therefore, we evaluated imaging features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and after neoadjuvant therapy in a cohort of patients with ILC, including the longest tumor diameter (LD), functional tumor volume (FTV), and peak signal enhancement ratio (SER). FTV is the sum of all image voxels enhancing above a set threshold within a defined region, and has been validated as a predictor of recurrence-free survival (RFS) for breast cancer. SER is a measure of contrast wash-in and wash-out and reflects neovascularity of tumors. We determined whether baseline and post-treatment imaging features differed by type of neoadjuvant therapy and if they were associated with RFS in neoadjuvantly treated ILC regardless of treatment type. Methods With institutional review board approval, a retrospective analysis of pre- and post-treatment breast DCE-MRI was performed on a cohort of ILC patients receiving neoadjuvant therapy between 1998 and 2017. We compared pre-treatment, post-treatment, and percent reduction (α) in LD, FTV, and peak SER by neoadjuvant treatment type (i.e. NAC or NET) using the Wilcoxon rank-sum test. Univariate t-tests, Chi-squared tests, analysis of variance, and Spearmen’s correlation were used to evaluate associations of clinicopathologic features and treatment type. Univariate and multivariate associations with RFS in the entire neoadjuvantly treated cohort adjusting for treatment type were evaluated using the log-rank test and Cox proportional hazards models. Results A cohort of 76 patients with pre- and post-treatment MRI were included in this study, of whom 42 (55.3%) received NAC and 34 (44.7%) received NET. The NAC group was significantly younger (55 vs. 60 years, p=0.013), less likely to have stage 1 disease (26.2% vs. 73.5%, p&amp;lt;0.001), and showed a trend of having more human epidermal growth factor 2 receptor-positive (HER2) tumors. The mean follow up time was 4.9 years with no difference between treatment groups. Patients in the NAC group had significantly larger pre-treatment LD and FTV but no difference was found in pre-treatment peak SER between groups. Post-treatment LD, FTV, and peak SER did not differ between treatment groups (Table 1). Those receiving NAC had significantly greater reduction in FTV compared to those receiving NET; αLD and α peak SER did not differ. In a multivariate Cox proportional hazards model including all patients in the cohort, higher pre-treatment peak SER was significantly associated with worse RFS regardless of neoadjuvant treatment type when adjusting for age, stage, receptor subtype, and tumor grade (hazard ratio 1.3, p=0.005, 95% CI 1.1-1.6). Neither LD nor FTV were associated with RFS on multivariate analysis. ConclusionPre-treatment peak SER measured by MRI may provide prognostic information beyond standard clinicopathologic variables in patients with ILC receiving either neoadjuvant chemotherapy or endocrine therapy. Further evaluation in a larger ILC cohort is needed to validate our initial findings. Table 1. Comparison of MR imaging features of ILC patients receiving neoadjuvant chemotherapy and neoadjuvant endocrine therapy.Overall(n=76)NAC(n=42)NET(n=34)P-valuePre-treatment (median, IQR)LD (cm)2.7, 1.6-5.44.6, 2.5-71.8, 1.4-3.20.0006FTV (cc)5.8, 2.2-16.48.7, 4.1-24.23.0, 0.9-80.0004SER0.9, 0.8-1.00.9, 0.9-1.00.9, 0.8-1.10.8335Post-treatment (median, IQR)LD (cm)1.1, 0-1.91.0, 0-1.81.3, 0-1.90.6071FTV (cc)0.5, 0.1-1.80.3, 0.1-1.80.7, 0.3-1.80.2196SER0.9, 0.8-1.00.8, 0.8-1.00.9, 0.8-1.10.2321Percent reduction (%)LD44.6, 15.1-10079.6, 33.8-10033.8, 10.1-1000.0958FTV93, 72.5-97.495.8, 90.7-99.172.6, 43.1-94.5&amp;lt;0.0001SER8.5, -11.1-19.710.7, -6.0-21.81.9, -15.1-17.90.3041 Citation Format: Geraldine Tran, Ella Jones, Wen Li, Kelly Fahrner-Scott, David Newitt, Bonnie Joe, Laura Esserman, Nola Hylton, Rita Mukhtar. DCE-MRI derived imaging features for characterizing invasive lobular breast cancer and predicting recurrence-free survival after neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-08.

Background Survival of breast cancer has improved and treatments related changes and long term effect regarding weight gain and metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivor especially young women. We sought to compare changes in body mass index (BMI), metabolic profiles and neutrophil lymphocyte ratio (NLR) in patients who underwent 6 months of neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) before/ after NST and 3 years after treatment. Methods Prospective, randomized, phase III trial (NEST) which compared 24 weeks of response of NCT with Adriamycin and cyclophosphamide(AC) followed by docetaxel (T) and NET with goserelin and tamoxifen. Among them, 123 patients from NEST trial in Asan Medical Center were retrospectively reviewed to evaluate metabolic changes such as BMI, blood pressure (BP), total cholesterol (TC), fasting glucose, and NLR.BP was classified according to 2017 AHA guideline such as normal, elevated, HTN stage I and HTN stage II. NLR was calculated from the differential leukocyte count by dividing neutrophil percentage by lymphocyte percentage in routine blood cell counts. Results The mean age of patients was 42 years old. BMI were significantly increased during NCT (22.6 to 23.7, p&amp;lt;0.05), and recovered after 3 year follow up. BMI change were not observed before and after NET and 3 year follow up (23.2, 22.0 and 23.2 respectively p&amp;gt;0.05, all) In the NCT group, the normal group of BP increased from 35 (58%) patients to 40(67%) patients and the elevated group decreased from 12 patients (20%) to 2 patients (3.3%). HTN stage I group was increased from 8 (13%) to 12 (20%) and HTN stage II group increased from 5 (8%) to 6 (10%) after NCT (p=0.001). There were no significant changes of BP during NET. The mean value of initial total cholesterol before NCT was 184.6mg/dL, 215.98 mg/dL after NCT (p&amp;lt;0.05, before vs after), 179 mg/dL after 3 years of treatment (p&amp;lt;0.05, after vs 3 yrs.). In the NET group, the mean initial cholesterol before NET was 185mg/dL, 176.3 mg/dL (p=0.04, before vs after) after NET, and 179.4 mg/dL after 3 yrs. follow up (p=0.23, before vs after 3years). In the NCT group, the mean fasting glucose were significantly increased while NCT (95.75mg/dL to 111.61mg/dL, p&amp;lt;0.05), and recovered after 3 year follow up (95.78 mg/dL, p&amp;lt;0.05). In the NET group, the mean fasting glucose changes were not observed before and after NET and 3 year follow up (97.78mg/dL, 99.04mg/dL and 99.06mg/dL respectively p&amp;gt;0.05, all). NLR was increased from 2.02 to 4.43 after NCT (p&amp;lt;0.05) and decreased from 2.13 to 1.57(p&amp;lt;0.05) after NET. Conclusion NCT causes worsening of metabolic profiles such as BMI, blood pressure, TG, and fasting glucose, which is recovered over 3 years. In the NET group, there were no significant changes in BMI, BP and fasting glucose but total cholesterol was significantly decreased after NET treatment. NLR was increased after NCT but decreased after NET. Citation Format: Ho-Hyun Ryu, Ji-Seon Kim, Il-Yong Chung, Jong-Won Lee, Beom-Seok Ko, Byung-Ho Son, Sei-Hyun Ahn, Hee-Jeong Kim. Comparison of metabolic changes after neoadjuvant endocrine and chemotherapy in ER positive, HER2 negative premenopausal women with breast cancer [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 P3-02-08.

Neoadjuvant therapy in breast cancer can downstage axillary lymph nodes and reduce extent of axillary surgery. As such, accurate determination of nodal status after neoadjuvant therapy and before surgery impacts surgical management. There are scarce data on the diagnostic accuracy of breast magnetic resonance imaging (MRI) for nodal evaluation after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), a diffusely growing tumor type. We retrospectively analyzed patients with stage 1–3 ILC who underwent pre-operative breast MRI after either neoadjuvant chemotherapy or endocrine therapy at our institution between 2006 and 2019. Two breast radiologists reviewed MRIs and evaluated axillary nodes for suspicious features. All patients underwent either sentinel node biopsy or axillary dissection. We evaluated sensitivity, specificity, negative and positive predictive values, and overall accuracy of the post-treatment breast MRI in predicting pathologic nodal status. Of 79 patients, 58.2% received neoadjuvant chemotherapy and 41.8% neoadjuvant endocrine therapy. The sensitivity and negative predictive value of MRI were significantly higher in the neoadjuvant endocrine therapy cohort than in the neoadjuvant chemotherapy cohort (66.7 vs. 37.9%, p = 0.012 and 70.6 vs. 40%, p = 0.007, respectively), while overall accuracy was similar. Upstaging from clinically node negative to pathologically node positive occurred in 28.0 and 41.7%, respectively. In clinically node positive patients, those with an abnormal post-treatment MRI had a significantly higher proportion of patients with ≥4 positive nodes on pathology compared to those with a normal MRI (61.1 versus 16.7%, p = 0.034). Overall, accuracy of breast MRI for predicting nodal status after neoadjuvant therapy in ILC was low in both chemotherapy and endocrine therapy cohorts. However, post-treatment breast MRI may help identify patients with a high burden of nodal disease (≥4 positive nodes), which could impact pre-operative systemic therapy decisions. Further studies are needed to assess other imaging modalities to evaluate for nodal disease following neoadjuvant therapy and to improve clinical staging in patients with ILC.

Background:Adjuvant endocrine therapy remains the standard of care for patients (pts) with early stage, HR+ BC who can safely omit chemotherapy based on RS results; however, the role of NET remains unclear. There are limited data regarding the optimal duration of treatment with NET and the ideal patient (pt) population for NET in terms of age and RS result. This question rose to critical importance amidst the COVID-19 pandemic, during which NET was utilized more broadly in attempts to delay surgery or chemotherapy while preserving optimal pt outcomes. This study re-examines the use of NET among a cohort of pts with HR+ BC randomized to NET or neoadjuvant chemotherapy (NCT) based on RS (performed on initial core biopsy specimens).Methods:Data were pooled from two independent studies performed at Emory’s Winship Cancer Institute and Massey Cancer Center at Virginia Commonwealth University (VCU) from 2010-2012. These studies evaluated rates of clinical and pathologic complete response (pCR) among pts with early stage, HR+ BC assigned to treatment groups based on RS results. Pts with RS 0-10 received NET (Group (Grp) A), RS 11-24/25 (Emory 11-24 vs VCU 11-25) were randomized to NET (Grp B) or NCT (Grp C), and those with RS 25/26-100 received NCT (Grp D). Associations between RS result, neoadjuvant therapy and pCR in the breast, lymph nodes (LN) and breast plus LN were evaluated using Fisher’s exact test. Results:109 pts were included in this analysis. The Emory cohort was younger (median age 56 years (yrs) vs 63 yrs in VCU cohort) and more diverse (37.5% African American (AA) vs 18.6% AA in VCU cohort). The pts were predominantly post-menopausal (69.6% Emory vs 83.1% VCU). Nodal status among the Emory cohort was evenly divided with 50% N0 and 50% N+, while the majority of VCU pts were N0 (76.3% N0 vs 22.0% N+). Pts were grouped based on RS result: RS &amp;lt;11 (18% Emory vs 20.3% VCU), RS 11-24/25 (36% Emory vs 55.9% VCU) and RS 24/25 or higher (46% Emory vs 23.7% VCU). Pts with low RS result were older (median 64 yrs vs 59 yrs among RS &amp;gt; 24/25) with higher percentage of low-grade tumors (47.6% grade 1 vs 5.4% grade 1 among RS &amp;gt;24/25). With regard to pCR, there were no significant differences among pts with low or intermediate RS results, as no pts in these groups achieved pCR in the breast or breast + LN (Table). Pts with RS result 25/26-100 (Grp D) were the only pts shown to achieve pCR in breast + LN (18.9%, p= 0.0043 across groups). Notably, while pts on the Emory study received longer courses of NET (median 10 months vs 5.5 months), there were no significant differences in pCR across RS result subgroups noted between the two institutions. Conclusion:Our results demonstrate that the use of Oncotype DX Breast Recurrence Score® or other genomic assays in the neoadjuvant setting may help guide treatment decisions when considering the use of NET versus NCT. Pt age and length of endocrine therapy as well as pt preferences should be considered when determining neoadjuvant treatment plans. There are currently ongoing studies evaluating the use of NET with CDK4/6 inhibitors that will offer further insight into optimal neoadjuvant treatment strategies in HR+ BC. Subsequent phase III evaluation of the role of genomic assays in the neoadjuvant setting is feasible and may help determine whether NET + CDK 4/6 inhibitors could replace NCT for pts with higher RS values. Table: pCR according to treatment groups (All Eligible Patients)VariableGroup A (N=21)Group B (N=23)Group C (N=22)Group D (N=37)P value (a)pCR Breast0 (0.0%)0 (0.0%)0 (0.0%)8 (21.6%)0.0016pCR Nodes0 (0.0%)1 (4.3%)3 (13.6%)2 (5.6%)0.2977pCR Breast + Nodes0 (0.0%)0 (0.0%)0 (0.0%)7 (18.9%)0.0043(a) Fisher's exact test was used for categorical variables with cell counts &amp;lt;5.Note: Group A= Recurrence Score &amp;lt;11,Group B= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NET,Group C= Recurrence Score 11-24 (Emory study) or 11-25 (VCUstudy) receiving NCT,and Group D= Recurrence Score &amp;gt;24 (Emory study) or &amp;gt;25 (VCUstudy).Note: 1 patient did not receive SLNB(sentinel lymph node biopsy) or ALND (axillary lymph node dissection) and is excluded from the denominator for pCR Nodes. Citation Format: Caitlin Taylor, Aimee Foreman, Christy Russell, Dipankar Bandyopdhyay, Xiaoyan Deng, Lisa Floyd, Amelia Zelnak, Ruth O'Regan, Harry Bear, Jane Meisel. Using Oncotype DX Breast Recurrence Score® (RS) assay to define the role of neoadjuvant endocrine therapy (NET) in early-stage hormone receptor positive (HR+) breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-02.

Background: Small prospective studies show comparable response rates (RR) and breast conservation rates (BCR) among neoadjuvant endocrine therapy (NET) and neoadjuvant chemotherapy (NCT) in post-menopausal hormone receptor (HR) positive breast cancer patients. Recently we reported statistically significant differences in utilization, trends, RR, BCR and overall survival (OS) outcomes in HR positive post-menopausal women from NCDB (2004-2014) at ASCO 2017 meeting. The absolute difference in OS calculated at 5 yrs for NCT vs NET was 10.9%. However, we were not able to exclude human epidermal growth factor receptor (HER-2) positive group due to the unavailability of information. Therefore, our results might have been skewed. Thus, here we report RR, BCR and OS outcomes in post-menopausal women with HR positive, HER-2 negative breast cancer using NCDB from 2010-2014 during which HER-2 status was recorded. Methods: We extracted data on HR positive, HER-2 negative breast cancer patients aged ≥ 50 without metastasisfrom the NCDB registry (2010-2014). RR and BCR between NET and NCT was assessed using univariate and multivariate analysis. OS was calculated using Kaplan Meier analysis with hazard ratio (HR) from cox regression model. We excluded patients who did not receive adjuvant endocrine therapy after NCT and patients who received adjuvant chemotherapy after NET as this could affect OS. Results: Out of 25,609 breast cancer patients reported in NCDB from 2010-2014, 19,988 women met our inclusion criteria. 5759 received NET and 14,229 received NCT. On multivariate analysis NET use was higher in academic centers [Odds ratio (OR) 1.327, 95% CI 1.222-1.440], patients with age&amp;gt;70 (OR 6.213, 95% CI 5.615-6.875)]. NET use was lower in black race (OR 0.774, 95% CI 0.679- 0.882), tumors with higher grade (OR 0.160, 95% CI 0.141-0.181), higher T stage (OR 0.352, 95% CI 0.314-0.395), higher N stage (OR 0.209, 95% CI 0.177-0.246) and private insurance (OR 0.65, 95% CI 0.525- 0.806), (all p&amp;lt;0.0001). RR was significantly higher for patients receiving NCT (88.7%) compared to NET (77.1%), with an adjusted OR (aOR) of 2.058, however the mastectomy rate was higher in NCT (68.9%) compared to NET group (48.9%) with aOR of 1.755. OS was calculated in 15,268 women. OS rate was 98.0% vs 98.9% at 1 yr for NET vs NCT and 73.6% vs 76.9% at 5 yrs for NET and NCT respectively with adjusted hazard ratio (HR) of 1.216; 95% CI (1.072-1.380). Conclusions : Our analysis demonstrates higher response rate with NCT over NET even in HER-2 negative HR positive breast cancer. However, more patients underwent mastectomy in the NCT group despite high RR. Statistically significant improvement in OS was also seen with the use of NCT however the magnitude was less pronounced compared to our previous cohort which included HER-2 positive as well as negative patients. Limitations that should be considered in this registry based study are: differences in surgical technique, patient's choice, duration and choices of adjuvant therapy. Citation Format: Basnet A, Wang D, Sivapiragasam A. Neoadjuvant chemotherapy vs neoadjuvant endocrine therapy in ER/PR positive HER-2 negative post-menopausal women with breast cancer, is one superior than other? A NCDB analysis [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 P6-15-08.