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IMPORTANCE: The extent of changes in estradiol levels in male patients with hormone receptor–positive breast cancer receiving standard endocrine therapies is unknown. The sexual function and quality of life related to those changes have not been adequately evaluated. OBJECTIVE: To assess the changes in estradiol levels in male patients with breast cancer after 3 months of therapy. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 2 randomized clinical trial assessed 56 male patients with hormone receptor–positive breast cancer. Patients were recruited from 24 breast units across Germany between October 2012 and May 2017. The last patient completed 6 months of treatment in December 2017. The analysis data set was locked on August 24, 2018, and analysis was completed on December 19, 2018. INTERVENTIONS: Patients were randomized to 1 of 3 arms: tamoxifen alone or tamoxifen plus gonadotropin-releasing hormone analogue (GnRHa) or aromatase inhibitor (AI) plus GnRHa for 6 months. MAIN OUTCOMES AND MEASURES: The primary end point was the change in estradiol levels from baseline to 3 months. Secondary end points were changes of estradiol levels after 6 months, changes of additional hormonal parameters, adverse effects, sexual function, and quality of life after 3 and 6 months. RESULTS: In this phase 2 randomized clinical trial, a total of 52 of 56 male patients with a median (range) age of 61.5 (37-83) years started treatment. A total of 3 patients discontinued study treatment prematurely, 1 in each arm. A total of 50 patients were evaluable for the primary end point. After 3 months the patients’ median estradiol levels increased by 67% (a change of +17.0 ng/L) with tamoxifen, decreased by 85% (−23.0 ng/L) with tamoxifen plus GnRHa, and decreased by 72% (−18.5 ng/L) with AI plus GnRHa (P

Background Over 90% of male breast cancer (BC) patients (pts) have hormone receptor (HR) positive disease. Until today tamoxifen is considered to be the standard of care in male BC pts. Due to the low incidence of male BC, there is a lack of data regarding efficacy and safety. Therapeutic strategies are extrapolated from the standard of care of female BC. However, no prospectively randomized study in male BC pts has been conducted so far. The Male-GBG54 study is the first prospective, randomized, multicenter trial evaluating the efficacy and safety of different endocrine treatment options in male BC patients. Patients and Methods In the phase II Male-GBG54 trial (NCT01638247), pts were randomized to receive either tamoxifen 20 mg/day per os (p.o.) or tamoxifen 20mg/day p.o. + GnRHa subcutaneous (s.c.) q3m or exemestane 25 mg/day p.o. + GnRHa s.c. for 6 months as (neo)adjuvant or metastatic therapy. Further treatment was conducted as per local guidelines. Primary objective was the suppression of oestradiol in the three treatment arms after 3 months of therapy. Secondary objectives comprised oestradiol suppression after six months, compliance and safety of the three therapies, the level of different steroidal hormones (testosterone, dihydrotestosterone, SHBG, FSH, LH) and osteocalcin in the three arms. Quality of Life was assessed using the Aging Male Symptom Score, International Index of Erectile function and International Prostate Symptom Score. Tissue and blood was collected for translational research. Male BC pts with a Karnofsky Index ≥60%, normal blood lipids, and no history or evidence of prostate cancer were eligible. 14 pts per group were needed for the F-test to have 80% power to detect a difference in mean oestradiol decrease between the three therapeutic groups at the 5% significance level. The final sample size was calculated as 48 patients, as a non-parametric test (Kruskal-Wallis) was chosen in case the oestradiol levels are not normally distributed within the study population. Results Between October 2012 and May 2017, 55 pts were randomized within 24 centers in Germany. 52 pts were included in the adjuvant and 2 pts in the metastatic setting of whom 48 pts were fully evaluable and comprised the analysis set. The median age was 62 years (range 37-83 years). The baseline characteristics were well balanced between the 3 treatment groups. Karnofsky Index ranged from 60%-100%, 36.4% had received prior chemotherapy and 12.7% had HER2-positive BC. The majority had a pT2 (52%), pN0 (58.0%) BC. 3 serious adverse events were reported, none was related to the study treatment. Conclusion This is the first prospective randomized trial worldwide evaluating the impact of three different endocrine treatments in male breast cancer. The therapy was well tolerated without safety signals. At the meeting, final results of the primary and secondary endpoints will be present. Citation Format: Reinisch M, Seiler S, Hauzenberger T, Schmatloch S, Strittmatter HJ, Zahm DM, Thode C, Jackisch C, Furlanetto J, Strik D, Stickeler E, Marmé F, Janni W, Schmidt M, Kamischke A, Rudlowski C, Nekljudova V, von Minckwitz G, Loibl S. Male-GBG54: A prospective, randomised multi-centre phase II study evaluating endocrine treatment with either tamoxifen +/- gonadotropin releasing hormone analogue (GnRHa) or an aromatase inhibitor + GnRHa in male breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-10.

(1) PURPOSE The aim of the prospective trial was to determine if cell survival in a breast cancer spheroid model following cytostatic treatment in vitro predicts treatment response in breast cancer patients receiving equivalent neoadjuvant therapy. (2) PATIENTS AND METHODS Three-dimensional spheroids were directly generated from fresh tumor biopsy samples of 78 patients eligible for neoadjuvant therapy. Cell survival in vitro, as well baseline clinical and pathological characteristics were correlated with the outcome following treatment of each patient to determine the factor(s) most highly associated with pathological complete response (pCR i.e.ypT0/ypN0) at surgery. (3) RESULTS Cell survival after treatment in the breast cancer spheroid model proved to be a sensitive and specific predictor for pCR in individual breast cancer patients. A mean cell survival of 21.8% was found in the breast cancer spheroid model for 22 patients with pCR versus 63.8% in 56 patients without pCR (P = .001). A receiver operator characteristic analysis determined an area under the ROC curve of 0.86 (95% CI: 0.77 to 0.96) for cell survival compared to classic factors i.e. negative hormone receptor and positive Her2/neu status, and age ≤ 50 years at primary diagnosis (AUC = 0.80, 95% CI: 0.70 to 0.90). A cutoff of 35% cell survival was proposed, which grouped patients according to likelihood for pCR. Out of the 32 patients with values below this threshold, 21 patients (65.6%) and one patient (2.2%) with a cell survival greater than 35% achieved pCR respectively; (sensitivity 95.5% (95% CI: 0.86 to 1.00); specificity 80.4% (95% CI: 0.70 to 0.91)).The specificity was improved to 81% (95% CI: 58 to 95%) if the patient was treated per-protocol. A positive correlation was also found between cell survival in vitro and residual tumor size (P = .021), indicating the possibility of the model to predict degree of response. (4) CONCLUSION The breast cancer spheroid model is a valuable predictor for treatment outcome in patients undergoing neoadjuvant chemotherapy for primary breast cancer. Preclinical selection of the most efficient drugs is a prerequisite to improve pCR. Citation Format: Kathrin ML Halfter, Nina Ditsch, Hans-Christian Kolberg, Holger Fischer, Tanja Hauzenberger, Franz Edler von Koch, Ingo Bauerfeind, Gunter von Minckwitz, Ilona Funke, Alexander Crispin, Barbara Mayer. Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – The SpheroNEO study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-13.

TPS1141 Background: Anthracyclines (A) followed by taxanes (T) are standard of care for neoadjuvant therapy in breast cancer (BC). A reverse sequence of T followed by A was suggested to achieve higher pCR rates. Previous studies have shown that dual anti-HER2 blockade is superior to trastuzumab (H) alone and thus can increase the pCR rate by 20%. Nab-paclitaxel (nP) is a solvent-free formulation of P encapsulated in albumin and might also improve the pCR rate with eventually lower toxicity. Methods: The GeparSepto study (NCT01583426) will randomize 1200 patients to either nP (150 mg/m²) q1w or P (80mg/m²) q1w for 12 weeks followed by 4 cycles conventionally dosed EC (E 90mg/m², C 600 mg/m²) q3w for 4 cycles. Primary objective is to compare the pCR rate (ypT0+ ypN0). Patients with untreated, histologically confirmed cT2- cT4d BC can be included. HER2+ patients receive H (loading dose 8mg/kg; 6 mg/kg) plus pertuzumab (loading dose 840 mg; 420 mg) q3w concomitantly. Biomaterial including FFPE from core biopsy, serum, plasma and full blood is collected. HER2, ER, PgR, Ki67 and SPARC status will be centrally assessed prior to randomization for stratification. P was assumed to achieve a pCR rate of 33% which will be increased to 41% when using nP, corresponding to an odds ratio of 1.41. To investigate resistance to anti-HER2 treatment, patients with HER2+ BC are randomized prior to start of chemotherapy to receive either 6 weeks H, pertuzumab or the combination as biological window with biomaterial collection prior to start of therapy and after week 6 prior to start of chemotherapy. Results: After been approved by ethics committees and authorities recruitment started in 7/2012 in 56 sites. 293 patients were recruited (53 HER2+; 240 HER2-) by 1st Feb 2013. A first safety interim analysis is planned after 60 patients have finished therapy. Conclusions: GeparSepto investigates the efficacy of neoadjuvant nP compared to solvent-based P given weekly with a dual blockade of the HER2 receptor in HER2-pos BC. Interim safety results for nP will be presented. The window-substudy is funded within the EU-FP7 project RESPONSIFY No 278659. Clinical trial information: NCT01583426.