Background Radiation therapy (RT) after breast conserving surgery (BCS) is the current standard of care for patients with early stage breast cancer. However, individual absolute recurrence risks and hence benefits of RT vary substantially. A study showed significant association between local recurrence (LR) risk and PAM50-defined intrinsic subtypes and Risk of Recurrence scores (ROR).1 The objective of EXPERT, a co-lead study of Breast Cancer Trials-Australia & New Zealand (BCT-ANZ), and Breast International Group (BIG), is to optimize local therapy for early breast cancer through precise individualized quantification of LR risk to identify patients for whom RT after BCS may be safely omitted. Trial design This is a randomized, non-inferiority, phase III study of women who plan to receive adjuvant endocrine therapy for Prosigna (PAM50)-defined luminal A breast cancer with ROR ≤60 resected by BCS. Women are randomized to receive adjuvant whole breast RT and endocrine therapy or endocrine therapy alone and followed-up for 10 years after randomization. Major eligibility criteria Females aged ≥50 years; histologically confirmed invasive breast carcinoma ≤2 cm, grade 1 or 2, ER and PgR ≥10%, HER2-negative and node-negative; treated by BCS with negative margins for invasive carcinoma and associated DCIS; Prosigna (PAM50)-defined Luminal A subtype and ROR ≤60; and plan to receive adjuvant endocrine therapy. Specific aims Primary: To determine if omission of RT is not inferior to RT in terms of LR-free interval after BCS. Secondary: To evaluate the impact of omission of RT on regional, local-regional and distant recurrence-free interval; disease-free survival (DFS); invasive DFS; overall survival; salvage RT or mastectomy rate; toxicity; endocrine therapy adherence; patient reported outcomes; and health economic outcomes. Statistical methods An estimated 5-year LR rate in the target population is expected to be 1% with RT. A rate of 4% is considered non-inferior as a worthwhile trade-off against RT toxicity. Using O'Brien-Fleming boundary for rejecting non-inferiority, 29 LR events are required for final analysis expected 8 years after the first patient is randomized. Two interim analyses will be conducted after 10 and 21 events. If the stratified log-rank test statistic exceeds the upper boundary at interim or final analysis, the hypothesis of non-inferiority will be rejected and it will be concluded that no RT is inferior to RT. Accrual: Target (1170), actual: 82 (June 2018) The study was activated in Australia in August 2017, with global activation planned for Q4 2018. Recruitment is expected to be completed in 4.5 years. Contact information Professor Boon Chua, UNSW Sydney and Prince of Wales Hospital, NSW, Australia; email boon.chua@health.nsw.gov.au; T +61 2 49255239. Registration: NCT02889874 References Fitzal F, Filipits M, Fesl C, et al. Predicting local recurrence using PAM50 in postmenopausal endocrine responsive breast cancer patients. JCO 2014;32(15 suppl):1008. Citation Format: Chua BH, Gray K, Krishnasamy M, Regan M, Zdenkowski N, Loi S, Mann B, Forbes JF, Wilcken N, Spillane A, Martin A, Badger H, Jafari S, Fong A, Mavin C, Corachan S, Arahmani A, Martinez J-L, Francis P. Examining personalized radiation therapy (EXPERT): A randomised phase III trial of adjuvant radiotherapy vs observation in patients with molecularly characterized luminal A breast cancer [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 OT2-04-03.

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Objectives: To determine if the starting time of chemotherapy influences on illness-free survival and general survival in a cohort of Mexican patients with breast cancer. MethOds: A prospective study over 5 years was performed on 88 women with breast cancer from the National Medical Centre "La Raza" of the Mexican Institute of Social Security (IMSS) with the following characteristics: stages I-III and positive criteria for adjuvant chemotherapy. The time range for the chemotherapy administration was 0 to 2, 3 and > 4 months. The analysis was performed regarding chemotherapy administration time interval using a Kaplan-Meier estimator. The Cox model was adjusted to see the relationships between the global survival and the oestrogen and progesterone hormone receptor variables and HER2/NEU as well as their basal characteristics. Results: For both IFS and GS there was a significantly statistical difference on the survival distributions related to starting time of chemotherapy which had a higher probability from a range of 0 to 2 months (median GS 59 months median IFS 49 months; p-value< 0.001). Regarding general survival, the hormonal receptors for oestrogen, progesterone and HER2/NEU do not influence on the Cox model (p-value= 0.137, 0.823, 0.524 respectively); for the Cox model with basal characteristics, age, pathological state and time interval between surgery and chemotherapy influenced significantly on GS (p-value< 0.05) cOnclusiOns: The probability of survival for IFS and GS improve when chemotherapy is administered within the first 2 months after surgery. Also, there was a greater risk for GS when time interval between surgery and chemotherapy was prolonged. This delay for the starting time of chemotherapy will impact without a doubt in the health systems´ economy, generating more expenses for attention.

Background: Triple negative breast cancer (TNBC) is a subtype with a high risk of relapse in the early disease setting. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. A growing body of evidence indicates that TNBC is more immunogenic than other subtypes of breast cancer and promising clinical activity has been reported with atezolizumab (an anti–PD-L1 antibody) in Phase 1/1b metastatic TNBC trials. Furthermore, the anti-tumor activity of PD-1/PD-L1 targeting drugs is hypothesized to be enhanced when co-administered with chemotherapy. ALEXANDRA/IMpassion030 will evaluate the efficacy and safety of atezolizumab in combination with standard adjuvant chemotherapy in early TNBC. Methods: ALEXANDRA/IMpassion030 is a global, prospective, randomised, open-label Phase 3 trial investigating the efficacy, safety and pharmacokinetic (PK) profile of adjuvant atezolizumab plus standard chemotherapy versus chemotherapy alone in early TNBC. In total, 2300 patients diagnosed with non-metastatic operable stage II or III TNBC confirmed by central pathology review will be randomised. TumorPD-L1evaluationwill be performed centrally. Patients will be stratified by type of surgery, nodal status, and PD-L1 status. The adjuvant treatment will consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. Primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumour tissue and blood samples will be collected for biomarker research. The first site was activated in May 4th, and approximately 430 sites are expected to be open globally in 30 countries. This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials. Clinicaltrials.gov NCT03498716. Citation Format: Ignatiadis M, McArthur H, Bailey A, Martinez J-L, De Azambuja E, Metzger O, Lai C, Ponde N, Goulioti T, Daly F, Bouhlel A, Balta V, Van Dooren V, Viale G, Maetens M, Dufrane C, Nguyen Duc A, Winer E, Gelber R, Piccart M. ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early triple negative breast cancer [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 OT3-05-02.