Chumsri, Saranya

AbstractPurpose:Patients with HER2+ breast cancer benefit from trastuzumab-containing regimens with improved survival. Adaptive immunity, including cytotoxic T-cell and antibody immunity, is critical to clinical efficacy of trastuzumab. Because Th cells are central to the activation of these antitumor effectors, we reason that HER2 patients treated with trastuzumab may benefit by administering vaccines that are designed to stimulate Th-cell immunity.Patients and Methods:We developed a degenerate HER2 epitope–based vaccine consisting of four HLA class II–restricted epitopes mixed with GM-CSF that should immunize most (≥84%) patients. The vaccine was tested in a phase I trial. Eligible women had resectable HER2+ breast cancer and had completed standard treatment prior to enrollment and were disease free. Patients were vaccinated monthly for six doses and monitored for safety and immunogenicity.Results:Twenty-two subjects were enrolled and 20 completed all six vaccines. The vaccine was well tolerated. All patients were alive at analysis with a median follow-up of 2.3 years and only two experienced disease recurrence. The percent of patients that responded with augmented T-cell immunity was high for each peptide ranging from 68% to 88%, which led to 90% of the patients generating T cells that recognized naturally processed HER2 antigen. The vaccine also augmented HER2-specific antibody. Immunity was sustained in patients with little sign of diminishing at 2 years following the vaccination.Conclusions:Degenerate HLA-DR–based HER2 vaccines induce sustainable HER2-specific T cells and antibodies. Future studies, could evaluate whether vaccination during adjuvant treatment with trastuzumab-containing regimens improves patient outcomes.

PURPOSE Recent trials have shown potential benefit of extended adjuvant endocrine therapy and relatively high risk of recurrence (RoR) after 5 years in hormone receptor-positive (HR+) human epidermal growth factor receptor 2–negative (HER2−) breast cancer. Although risk of late relapse in HR+ HER2− breast cancer is fairly well defined, the risk in HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab-based chemotherapy remains largely unknown. METHODS We included 3,177 patients with HER2+ breast cancer treated with adjuvant chemotherapy alone or with trastuzumab from the North Central Cancer Treatment Group N9831 (ClinicalTrials.gov identifier: NCT00005970 ) and National Surgical Adjuvant Breast and Bowel Project B-31 (ClinicalTrials.gov identifier: NCT00004067 ) trials. RESULTS Overall, HR+ breast cancer was significantly associated with improved recurrence-free survival (RFS) during the first 5 years (hazard ratio, 0.65; 95% CI, 0.56 to 0.77; P < .001). Among patients treated with trastuzumab, cumulative hazard for RFS was lower in patients with HR+ HER2+ breast cancer during the first 5 years (10.96% v 17.48%; hazard ratio, 0.60; 95% CI, 0.45 to 0.79; P < .001). However, there was no significant difference in RFS based on HR status during years 5 to 10 (hazard ratio, 1.32; 95% CI, 0.93 to 1.88; P = .12). A comparable degree of trastuzumab benefit was observed in HR+ and HR− breast cancers ( P for interaction = .87). Furthermore, we observed low RoR in years 5 to 10 among patients with HR+ HER2+ breast cancer: 3.23% in patients without lymph node involvement (N0) and 6.39% in patients with involvement of one to three lymph nodes (N1). CONCLUSION The benefit of adjuvant trastuzumab persists for a long time. A distinct pattern of recurrence was observed between HR+ and HR− HER2+ disease but with similar degree of benefit from adjuvant trastuzumab. RoR in years 5 to 10 in HR+ HER2+ breast cancer is low, particularly in patients with N0 or N1 disease.

Abstract Background: Immune checkpoint inhibitors (ICPIs) have led to dramatic improvement in outcome of several cancers. Program death ligand1 (PD-L1) staining and tumor mutational burden (TMB) have emerged as independent predictive biomarkers of ICPIs in lung cancer. Here we examine the landscape of TMB and PD-L1 expression in breast cancer and present a case of patient with high TMB and PD-L1 negative breast cancer with exceptional response to ICPIs. Methods: Hybrid-capture based comprehensive genomic profiling of 395 cancer related genes using the FoundationOne assay was performed on 14,867 breast carcinomas sequenced in the course of routine clinical care. Ventana (SP-263) PD-L1 status (n=1425) and hormone receptor status was available for a subset of patients. Subgroup analyses were performed based on histological type [invasive lobular carcinoma (ILC, n=740)], molecular subtypes [ER-positive (ER+; n= 1371), HER2-amplified (HER2+; n=1522), and TNBC (n=917)], patient age (≤45, 46-60, ≥61), and local vs. metastatic disease (n=5241 and 6710). Results: Consistent with previous reports, the rates of positive PD-L1 staining are highest in TNBC (14%) and lowest in HER2+, ILC, and ER+ disease (6.0%, 5.1%, 2.3%). Interestingly, the rate of PD-L1 positivity, defined as ≥1% tumor staining, was significantly lower in metastatic disease vs. local disease (6.3% vs. 11.1%; p = 0.005). The frequency of high TMB, defined as &gt;10 mutations/mb, was greatest in ILC and HER2+ disease (13.6% and 9.9%) and lowest in TNBC and ER+ disease (7.0% and 6.9%). Rates of high TMB were associated with increased patient age (3.7%, 9.3%, and 12.8% frequency in patients ≤45, 46-60, and ≥61) and were significantly higher in metastatic vs. local disease (11.1% vs 5.3%; p&lt;2E-23). PD-L1 positive and TMB high populations were not significantly co-occurrent (OR = 1.02, p = 0.87). Similar percentages of PD-L1 positivity were observed in both TMB low (9.3%) and TMB high (9.5%). However, among patients with very high TMB (&gt;20 mut/mb), there was a significant association between TMB and PD-L1 positivity (OR = 2.6, p = 0.023). Nevertheless, even with high cutoff, 79% of the TMB high samples were PD-L1 negative. We also report on a stage IIIb (T4, N2, M0) ER+ HER2- breast cancer patient with high TMB (40muts/mb) and negative PD-L1 IHC who previously progressed on aromatase inhibitor with CDK4/6 inhibitor and chemotherapy but achieved durable complete response of &gt; 1 year with nivolumab in combination with capecitabine. Conclusions: Predictive biomarkers for ICPIs are critical to identify a subset of breast cancer patients who may respond to immunotherapy. TMB high and PD-L1 positivity do not significantly co-occur and the majority of TMB high cases were PD-L1 negative. Nevertheless, this group of patients may still benefit with ICPIs. Further studies are needed to evaluate this subset of patients. Citation Format: Ethan Sokol, Lee Albacker, Aixa Soyano, Ricardo Parrondo, Brenda Ernst, Emmanuel Gabriel, Garrett Frampton, Jeffrey Ross, Siraj Ali, Jon Chung, Saranya Chumsri. Incidence of high tumor mutation burden (TMB) and PD-L1 positivity in breast cancers and potential response to immune checkpoint inhibitors (ICPIs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4894.

Abstract Treatment of estrogen receptor positive (ER+) breast cancer have included single-agent endocrine therapy, such as with aromatase inhibitors (AIs) and, more recently, AIs in combination with the cyclin-dependent kinase 4/6 inhibitor palbociclib. While combination therapy is effective, drug resistance is a well-known phenomenon and breast cancer cells can acquire resistance to aromatase inhibitor and palbociclib individually. In anticipation of patient who may become resistant to combination therapy with aromatase inhibitor (letrozole) and palbociclib, this current study has 1) developed MCF7Ca cells resistant to both letrozole and palbociclib (MCF7Calet+palb); 2) characterized them in comparison to drug naïve (MCF7Ca) and letrozole alone-resistant (LTLTCa) cells; and 3) explored potential treatments. Characterization of MCF7Calet+palb cells by phase contrast microscopy, mammosphere assays, and invasion assays, indicate that they have more basal/mesenchymal morphology, produce more mammospheres (an indicator of cancer stem cells; 150±10 vs. 80±10 in MCF7Ca and 123± 8 in LTLTCa cells), and are more invasive (1200±50 cells vs. 791±15 in MCF7Ca cells). The more aggressive phenotype of MC7Calet+palb correlated with changes in protein expression. Compared to the other cell lines, MCF7Calet+palb expressed significantly lower fold expression levels of cell cycle cyclin D1 (0.2±0.1), phosphorylated CDK9 (0.5±0.1), and phosphoRb and total Rb (0.4±0.2), but higher levels of phosphoCDK1 and CDK2 (1.4±0.1 and 3.1±0.6). Regarding growth pathway proteins, MCF7Calet+palb comparably had increased HER2 and phosphorylated Akt (6.2±1.3 and 3.3±1.2, resp.) as LTLTCa vs. MCF7Ca cells, but had even more reduced levels of ERα (0.04 vs. 0.1±0.4 in LTLTCa and 1±0.01 in MCF7Ca). Cancer stem cell marker breast cancer resistance protein (BCRP) was increased further in MCF7Calet+palb cells (2.11-fold). Based on these results, the effect of dinaciclib, a broader range CDK inhibitor, was studied. In MTT assays, dinaciclib was shown to be effective in inhibiting cell viability in all three cell types. Dinaclicib’s IC50s were 1.4 nM (MC7Ca) 9.5 nM (LTLTCa) and 12.4 nM in MCF7Calet+palb cells, while palbociclib IC50s were 1.5 μM, 11.2 μM, and 118 μM, respectively. Dinaciclib also significantly reduced mammosphere formation 0.01-fold and cell invasion/migration by 0.3-fold vs. untreated. Lastly, preliminary exome sequencing data suggested highly mutated FGFRL1, ARL11, and FCGBP genes, among others, when MCF7Calet+palb cells were compared to MCF7Ca cells. Overall, these results suggest that acquired resistance to combination therapy with letrozole and palbociclib induces genetic, molecular, and phenotypic changes in breast cancer cells, and that dinaciclib may be an effective treatment to either treat and/or prevent this resistance. Citation Format: Armina Kazi, Emily Shukdinas, Saranya Chumsri, Gauri J. Sabnis. Characterization of breast cancer cells resistant to letrozole and palbociclib combination therapy and the potential of dinaciclib to treat such resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1014.

3142 Background: Recent studies have demonstrated a benefit of adjuvant capecitabine, particularly in triple negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy. However, biomarkers to predict which patients are more likely to benefit from capecitabine are needed. Methods: The nanoString Breast Cancer 360 (BC360) and PanCancer Immunoncology (IO360) panels were used to quantify mRNA expression in TNBC samples in the FinXX trial. FinXX is a phase III trial which randomized high risk patients to receive either 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (Arm A: T+CEF) vs. 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (Arm B: TX+CEX). Gene signature scores were analyzed using prespecified algorithms developed by nanoString. Digital Spatial Profiling was carried out using GeoMX platform. Results: A total of 111 TNBC patients in FinXX trial were included (57 in Arm A and 54 in Arm B) with 10.2 years median follow up. There were 7 cancer- and immune-related gene signatures identified by BC360 and IO360 panels that were significantly associated with improved recurrent free survival favoring an addition of capecitabine. These include cytotoxic cell signature (HR 0.37, 95%CI 0.15-0.92, p 0.03), endothelial signature (HR 0.18, 95%CI 0.04-0.83, p 0.03), mast cell signature (HR 0.43, 95%CI 0.21-0.88, p 0.02), PDL2 gene (HR 0.29, 95%CI 0.09-0.99, p 0.05), immunoproteasome (HR 0.34, 95%CI 0.13-0.89, p 0.02), exhausted CD8 (HR 0.29, 95%CI 0.09-0.97, p 0.04), and PD1 (HR 0.44, 95%CI 0.20-1.02, p 0.05). Conclusions: Analysis of RNA abundance signatures strongly suggests that there are important immune features that are associated with benefit from capecitabine in TNBC. However, analysis of RNA extracted from whole tumor sections lacks spatial discrimination. We anticipate that a more detailed, spatially-defined analysis of protein abundance, using the novel NanoString GeoMX platform, will provide more insights and define specific immune features associated with improved outcome. Additional results of GeoMX will be reported at the meeting. Clinical trial information: NCT00114816.

e14048 Background: Cancer associated macrophage like cells (CAMLs), a circulating stromal cell subtype, has been shown as an independent prognostic indicator of survival in late stage metastatic breast cancer when cells enlarge to ≥50µm. However, no study has evaluated the clinical relationship between changes in CAML size and their ability to predict treatment response. While CAMLs are prognostic for progression, we hypothesized that monitoring changes in CAMLs after initiation of therapy may be predictive for responsiveness of new treatment regimens. Methods: A prospective 12 months blind multi-institutional pilot study was undertaken to evaluate CAMLs before, and after, induction of a new line of investigational therapy based on CT scans. Patients with progressive metastatic breast cancer (n = 29) who had failed at least 2 prior therapies were recruited. A baseline (BL) blood sample was taken prior to induction of a new therapy and a 2nd sample (T1) taken after initiation (~30 days). Blood was filtered by CellSieve filtration.The quantities and sizes of CAMLs were analyzed based on PFS hazard ratios (HRs) by censored univariate analysis. Results: CAMLs were found in 97% of BL samples and 93% of T1 samples. At first CT scan, after the assigned dose of investigational treatment, 17 of 29 patients had clinical progression with 14/17 (82%) patients having an increased CAML size and 3/17 (18%) having a decreased CAML size. The remaining 12 of 29 patients saw clinically stable, or regression, of disease with 10/12 (83%) having decreased CAML size and 2/12 (17%) having increased CAML size. Overall CAML size change after therapy induction was 83% accurate at predicting response or progression based on CT scans. Further, patients with increasing CAML size at T1 had a 4 month mPFS vs 10 month mPFS for decreasing CAMLs, with a lower 12 month PFS HR = 3.7 (95%CI = 1.5-10.1, p = 0.020). Conclusions: Our data suggests that in metastatic breast cancer, monitoring CAMLs changes over the first 30 days of treatment accurately predicts responsiveness of disease to new treatments. Further, we suggests using blood sampling may increase the clinical value of blood based diagnostics by rapidly predicting the benefit of subsequent therapies.

Abstract Background We investigated the clinical outcomes and behavior of HER2+ EBC according to centrally tested HR status in pts treated with modern chemotherapy (CT) and trastuzumab (T)-based regimens. Patients and methods ALTTO is an international phase 3 trial in HER2+ EBC pts randomized to 4 adjuvant anti-HER2 treatment arms: T alone, lapatinib (L) alone, their sequence (T-&gt;L) or their combination (T+L). Pts in the L alone arm were excluded from the present analysis. HER2 and HR status were centrally tested for all patients. HER2 status was defined based on the 2007 ASCO/CAP guidelines. HR-positive (HR+) was defined as ≥1% tumor cells with expression of estrogen (ER) and/or progesterone receptors.We investigated the prognosis of pts with HR+ or negative (HR-) HER2+ EBC, the risk of developing early (years 0-5) and late (years 6-8) recurrences, the factors impacting this risk, and the patterns of relapse according to HR status. Univariate and multivariate Cox proportional hazard models were used to compare hazard rates within the HR subgroups; a conditional landmark analysis was conducted to investigate late recurrences. For the hazard ratios for HR status, an interaction between log(time) and HR status was included as proportional hazard assumption was not satisfied. Results This analysis included 6,271 HER2+ pts of whom 3,601 (57%) had HR+ and 2,670(43%) HR- EBC. Median follow-up was 6.93 years (range 6.81-6.96). 5-year disease-free survival (DFS) was 86% (85-87) in HR+ and 83% (82-85) in HR- pts; 8-year DFS was 80% (78-81) in HR+ and 79% (77-81) in HR- pts. The mean annual hazards of recurrence in years 0-5 were 3% in HR+ and 4% in HR- pts, while in years 6-8 they were 3% in HR+ and 2% in HR- pts. The hazard ratios for HR status (ref=HR-) were 0.60 (0.51-0.72) overall, 0.74 (0.65-0.85) for years 0-5 and 1.61 (1.17-2.24) for years 6-8. In HR+ pts, risk factors for recurrence overall were age ≥65 (p=0.01), tumor size pT3-4 (p&lt;0.001), nodal status pN1-3 (p&lt;0.001), tumor grade 2 or 3 (p&lt;0.001), anthracycline-only CT (p&lt;0.001), no use of aromatase inhibitors (p&lt;0.001), and ER&lt;10% (p=0.01). Main risk factors for recurrence in both years 0-5 and years 6-8 were pN2-3 (p=0.04 for both) and high (≥5) HER2 FISH ratio (p=0.02 for both). In HR- pts, risk factors for recurrence overall were BMI (obesity or underweight; p=0.01), pT3-4 (p&lt;0.001), pN1-3 (p&lt;0.001) and anthracycline-only CT (p&lt;0.001). No significant risk factors for recurrence in years 0-5 were identified. Main risk factor for recurrence in years 6-8 was BMI (obesity; p=0.002). HR+ pts had lower incidence of visceral disease (58.8% vs. 69.6%; p=0.005) and lung metastasis (18.5% vs. 27.8%; p=0.006); bone was the most common site of first recurrence (30%). Conclusions This large analysis of centrally tested HR+ and HR- HER2+ EBC provides strong evidence on the existence of two different diseases within the HER2+ population based on HR expression. These up-to-date estimates of pts outcomes after modern CT and T-based regimens may be used as “historical control” for the design of future de-escalation or escalation trials separately in HR+ and HR- HER2+ EBC pts. Citation Format: Lambertini M, Campbell C, Gelber RD, Viale G, McCullough A, Tonghua L, Hilbers F, Korde LA, Werner O, Chumsri S, Jackisch C, Wolff AC, Vaz-Luis I, Ferreira AR, Prat A, Moreno Aspitia A, Piccart M, Loi S, de Azambuja E. Dissecting the effect of hormone receptor (HR) status expression in patients (pts) with HER2-positive (HER2+) early breast cancer (EBC): Exploratory analysis from the ALTTO (BIG 2-06) trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-14.

Abstract Background: Recent studies have demonstrated a benefit of adjuvant capecitabine in early stage breast cancer, particularly in patients with residual disease after neoadjuvant chemotherapy. Subset analyses suggest that patients with triple negative breast cancer (TNBC) may be more likely to benefit with capecitabine in this setting. However, more precise biomarkers to predict which patients are most likely to benefit from capecitabine are needed. Methods: The NanoString Breast Cancer 360TM (BC360) panel was used to quantify mRNA expression in FFPE tissue samples from patients with TNBC in the FinXX trial. Gene signature scores were analyzed using prespecified algorithms developed by NanoString. 30 additional custom genes related to capecitabine metabolism and function were added. Patients in FinXX trial were randomized to receive either 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF) or 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Cox proportional hazard ratio (HR) was used to determine the association of each gene signature with recurrence free survival (RFS). Results: A total of 111 samples from patients with TNBC in the FinXX trial were available for gene expression analysis. 57 patients were treated with T+CEF and 54 patients were treated with TX+CEX. The median age was 52 years and median follow up was 10.2 years. Consistent with the previous analysis of the FinXX trial, patients with TNBC had nonsignificant but favorable RFS with capecitabine (HR 0.60, 95% CI 0.27-1.3, p 0.2). Among 39 individual genes and metagene signatures generated with the BC360 panel, there were 4 gene signatures significantly associated with improved RFS favoring an addition of capecitabine with TX+CEX compared to T+CEF. These were the cytotoxic cell signature (HR 0.37, 95%CI 0.15-0.92, p 0.03), endothelial signature (HR 0.18, 95%CI 0.04-0.83, p 0.03), mast cell signature (HR 0.43, 95%CI 0.21-0.88, p 0.02), and PDL2 gene (HR 0.29, 95%CI 0.09-0.99, p 0.05). PAM50 intrinsic subtype was not predictive of capecitabine benefit within this TNBC subset. Moreover, we identified additional individual 12 genes that were significantly associated with capecitabine benefit (p-FDR&lt;0.05). Among these genes, high expression of CES1, which encodes an enzyme that activates capecitabine, was significantly associated with improved RFS when treated with capecitabine (HR 0.71, 95%CI 0.32-1.61 with p-interaction=0.04). Conclusion: Our analyses demonstrated potential predictive individual genes and metagene signatures that may be used to identify TNBC patients who are more likely to benefit from adjuvant capecitabine. Interestingly, several gene signatures related to immune response and genes related to capecitabine activation were associated with improved outcome in TNBC patients treated with capecitabine in the FinXX trial. While these findings are compatible with basic science reports, future studies are needed to validate the significance of these gene signatures as predictive biomarkers for capecitabine benefit. Citation Format: Chumsri S, Asleh K, Brauer HA, Mashadi-Hossein A, Lauttia LS, Lindman H, Nielsen TO, Joensuu H, Thompson EA. Predictive gene signatures of adjuvant capecitabine benefit in triple negative breast cancer in the FinXX trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-05.

Abstract Background: Combining cyclin dependent 4/6 kinase inhibitors (CDK4/6i) with endocrine therapy (ET) has resulted in clinically significant improvements in progression-free survival (PFS) in persons with hormone-receptor (HR)-positive metastatic breast cancer (MBC). However, nearly all patients will progress on CDK4/6i and ET and the mechanisms associated with primary and secondary resistance are mostly unknown. The identification of biomarkers associated with response to CDK4/6i is therefore a major research priority. PROMISE is a multicenter prospective cohort study designed to perform a comprehensive “omic” assessment of blood, tumor, urine and the fecal microbiome to identify alterations in molecular or cellular features associated with primary endocrine resistance (e.g. disease progression ≤ 12 months on treatment) and acquired resistance to CDK4/6i. Additionally, patient derived xenografts (PDX) and organoids are generated to test new drug strategies designed to reverse resistance to CDK4/6i and ET. Methods: Eligible participants include women for whom palbociclib is recommended in combination with either letrozole (first-line) or fulvestrant (second-line) therapy for HR-positive MBC. As of July 2018, 14 patients have been enrolled; the target accrual is 250 patients, who will be followed over the course of 36 months and followed for at least 12 months after the close of enrollment. Blood and tumor biopsies are obtained at baseline, at the end of cycle 2, and at progression. Whole exome sequencing (germline and tumor) and RNAseq (whole transcriptome) are performed on tumor samples in a CAP/CLIA lab (TEMPUS) and results will be provided back to all patients for later use. Additionally, PDX and organoids are generated from tumor biopsies at baseline and during progression. Blood, stool, and urine samples are collected for additional correlative studies. The primary objective of this trial is to identify novel genomic variants and pathways associated with early progression (≤ 12 months) among women with advanced HR-positive breast cancer treated with palbociclib and ET. Secondary objectives include identification of the biomolecular features within the gut (stool) microbiome and exploration of the metabolomics and proteomics of ER-positive MBC. Results from the interrogation of these biospecimens will be critical to gain insights into treatment resistance. Funding is provided by Mayo Clinic Center for Individualized Medicine, TEMPUS, and an ASCO Career Development Award (COS). ClinicalTrials.gov Identifier: NCT03281902. Citation Format: O'Sullivan CC, Suman VJ, Kalari KR, Moyer A, Sung J, Moreno-Aspitia A, Northfelt DW, Liu MC, Haddad TC, Chumsri S, Couch FJ, Weinshilboum RM, Wang L, Goetz MP. Genetic analysis in blood, urine, stool and tumor samples from patients with advanced or metastatic estrogen receptor positive and HER2 negative breast cancer receiving palbociclib and endocrine therapy (PROMISE) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-02-08.