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Purpose Neoadjuvant endocrine therapy (NET) is a treatment option for estrogen receptor-positive (ER+) postmenopausal early breast cancer (EBC). This phase III trial evaluated the prognosis of EBC patients treated with/without chemotherapy (CT) following NET. Methods ER+/HER2−, T1c-2, and clinically node-negative EBC patients were enrolled in 2008–2013 and treated with endocrine therapy (ET) in weeks 24–28. All patients, excluding those with progressive disease (PD) during NET or ≥ 4 positive lymph nodes after surgery, were randomized to ET for 4.5–5 years with/without CT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included distant DFS (DDFS), overall survival (OS), and DFS/DDFS/OS according to clinical response to NET. Results Of 904 patients, 669 were randomized to CT+ET (n = 333) or ET alone (n = 336). The median follow-up was 7.8 years. DFS (CT+ET, 47 events; ET alone, 70 events) and DDFS did not reach the planned numbers of events. Eight-year DFS/DDFS rates were 86%/93% and 83%/92%, respectively. DFS was significantly better in CT+ET than ET alone in subgroups aged P = 0.016), T2 (P = 0.013), or Ki67 > 20% (P = 0.026). Progesterone receptor and histological grade were predictive markers for clinical responses to NET. Conclusion NET may be used as standard treatment for patients with ER+EBC. Although it is difficult to decide whether to administer adjuvant CT based solely on the effect of NET, the response to NET may help to inform this decision. Trial registration This study was registered at the UMIN Clinical Trials Registry under UMIN000001090 (registered 20 March 2008).

This study aimed to develop direct and response mapping algorithms from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 onto the 5-level version of EQ-5D index based on the gradient boosted tree (GBT), a promising modern machine learning method.We used the Quality of Life Mapping Algorithm for Cancer study data (903 observations from 903 patients) for training GBTs and testing their predictive performance. In the Quality of Life Mapping Algorithm for Cancer study, patients with advanced solid tumor were enrolled, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and 5-level version of EQ-5D were simultaneously evaluated. The Japanese value set was used for direct mapping, whereas the Japanese and US value sets were used for response mapping. We trained the GBTs in the training data set (80%) with cross-validation and tested the predictive performance measured by the root mean squared error (RMSE), mean absolute error (MAE), and mean error in the test data set (20%).The RMSE and MAE in the test data set were larger in the GBT approaches than in the previously developed regression-based approaches. The mean error in the test data set tended to be smaller in the GBT approaches than in the previously developed regression-based approaches.The predictive performances in the RMSE and MAE did not improve by the GBT approaches compared with regression approaches. The flexibility of the GBT approaches had the potential to reduce overprediction and underprediction in poor and good health, respectively. Further research is needed to establish the role of machine learning methods in mapping a nonpreference-based measure onto health utility.

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p

Background Eribulin is a chemotherapeutic drug that prolongs overall survival (OS) in patients with HER2-negative metastatic breast cancer (MBC), mainly in third-line or later chemotherapy (ChT) [1]. However, health-related quality of life (HRQOL) and efficacy in patients who receive eribulin as first- or second-line therapy is not well known. In contrast, S-1, an oral 5-fluorouracil derivative, shows similar OS to taxanes as first-line ChT and better HRQOL, based on a large phase III trial conducted in Japan [2]. Here, we compared the effect on HRQOL and efficacy of eribulin and S-1 in MBC patients in a first- or second-line ChT setting. Methods We planned an open-label, multicenter, randomized controlled phase III study at 50 hospitals in Japan. We enrolled patients with HER2-negative MBC who had no or one previous ChT for MBC regardless of prior administration of anthracyclines and taxanes. Patients were randomly assigned (1:1) to either eribulin (1.4 mg/m² administered on days 1 and 8 of a 21-day) or S-1 (40–60 mg twice daily for 14 consecutive days, followed by a 7-day break). Randomization was stratified by institution, age, treatment line, hormone receptor status, and time from surgery to recurrence. HRQOL assessment was conducted using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 questions (QLQ-C30) every six weeks until week 24, and then every nine weeks until week 42 after baseline assessment. The primary outcome measure was the global health status (GHS) score of EORTC QLQ-C30, with a prespecified non-inferiority margin of 10% for a difference in the proportion of patients experiencing deterioration at one year. Clinically meaningful deterioration was defined as a ≥ 10-point decrease from baseline GHS score or death. Secondary outcomes were OS, progression-free survival (PFS), and adverse events. We estimated that the study needed 330 patients to obtain 80% power for non-inferiority. This trial was registered with the University Hospital Medical Information Network, Japan (protocol ID 000021398). Results Between June 2016 and October 2019, 302 patients were enrolled, with 152 assigned to eribulin and 148 to S-1. The full analysis set for HRQOL assessment included 134 and 136 patients, while that for efficacy consisted of 141 and 144 patients, respectively. Overall compliance with the questionnaire was 85.6 %. Among the full analysis set for efficacy, 28 (19.9%) and 31 (21.5%) cases were triple negative, respectively. Eribulin and S-1 were administered as first-line ChT in 99 (70.2%) and 101 (70.1%) patients, respectively. Risk difference of GHS deterioration through one year for the eribulin versus S1 group was -0.66% (95% CI -12.47 to 11.16; P non-inferiority =0.077). Median time to first deterioration in GHS score was 5.64 months (95% CI 3.51–8.00) and 5.28 months (95% CI 3.28-7.80) (HR 1.07 [95% CI 0.79–1.45]; P =0.667); median OS was 35.0 months (95% CI 27.2-41.0) and 27.8 months (95% CI 24.6-33.5) (HR 0.69 [95% CI 0.50-0.95]; P=0.023); and median PFS was 6.07 months (95% CI 5.48-7.80) and 6.66 months (95% CI 5.48-7.77), respectively (HR 0.90 [95% CI 0.68-1.18]; P=0.427). No previously unrecognized adverse events were observed. Conclusions We found a marginal non-inferiority in HRQOL for eribulin, albeit that the difference was not statistically significant owing to the smaller than planned sample size. Time to first clinically meaningful deterioration was almost identical between the two arms, whereas OS was significantly extended with eribulin. These findings indicate that eribulin in first- or second-line ChT is acceptable as a standard regimen in this patient population. [1] Lancet 2011; 377: 914–23 [2] Lancet Oncol 2016; 17: 90–98 Citation Format: Yuichiro Kikawa, Kosuke Kashiwabara, Naruto Taira, Tsuguo Iwatani, Kojiro Shimozuma, Shoichiro Ohtani, Tetsuhiro Yoshinami, Junichiro Watanabe, Masahiro Kashiwaba, Ken-ichi Watanabe, Masahiro Kitada, Koichi Sakaguchi, Yuko Tanabe, Tomohiko Aihara, Hirofumi Mukai, Masato Takahashi. Eribulin versus S-1 as first- or second- line chemotherapy to assess Health-related Quality of Life and overall survival in HER2-negative metastatic breast cancer (RESQ study): a non-inferiority, randomized controlled trial [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 P1-03-01.

Combination therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and hormonal therapy as the first-line and second-line treatments has already been shown to be effective in patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in clinical trials. On the other hand, in clinical practice, CDK4/6 inhibitors are used not only as first-/second-line but also as later-line hormonal therapies, or for patients receiving prior chemotherapy in metastatic setting. However, the efficacy and safety of combination therapy in these patients remain unclear. In this study, we evaluate the clinical efficacy and safety of combination therapy with abemaciclib and hormonal therapy for chemotherapy-treated patients with HR+ HER2- MBC.This multi-institutional prospective cohort study will involve a total of 300 chemotherapy-treated patients with HR+ HER2- MBC. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, time to treatment failure, response rate, clinical benefit rate, and adverse events. The preplanned subpopulation analysis is the number of chemotherapy regimens for HR+ HER2- MBC (two or less vs. three or more), prior treatment history with CDK4/6 inhibitors other than abemaciclib (presence vs. absence) and menopausal status (pre vs. post). We also planned to determine PFS of the subpopulation treated with abemaciclib as maintenance therapy after chemotherapy.In this multi-institutional prospective cohort study, we evaluate the clinical efficacy and safety of combination therapy with abemaciclib and hormonal therapy for chemotherapy-treated patients with HR+ HER2- MBC. We also evaluate this combination therapy as maintenance therapy in patients who respond to early-line chemotherapy.

According to a recent report, a low Ki67 level after short-term preoperative hormone therapy (post-Ki67) might suggest a more favorable prognosis compared with a high post-Ki67 level in patients with hormone receptorpositive/human epidermal growth factor 2-negative (HR+/HER2-) breast cancer with high levels of Ki67. This study aimed to evaluate the pre-treatment genetic differences between these two patient groups. Forty-five luminal B-like patients were stratified into two groups, namely, a group with high (H→H) and one with low (H→L) Ki67 levels after short-term preoperative aromatase inhibitor (AI) treatment. We compared pre-treatment gene expression profiles between the two groups. In gene level analysis, there was no significant difference between the two groups by the class comparison test. In pathway analysis, five metabolism-related gene sets were significantly upregulated in the H→L group (p≤0.05). In the search for novel targets, five genes (PARP, BRCA2, FLT4, CDK6, and PDCD1LG2) showed significantly higher expression in the H→H group (p≤0.05). Several metabolism-related pathways were associated with sensitivity to AI. In the future, it will be necessary to seek out new therapeutic strategies for the poor prognostic group with high post-Ki67.

Combining palbociclib with letrozole or fulvestrant improved progression-free survival in hormone receptor (HR)-positive and human epidermal growth factor receptor-negative metastatic breast cancer. However, combining palbociclib to endocrine treatment increases toxicity and cost compared with the endocrine treatment alone. Moreover, palbociclib treatment may affect the outcome of the subsequent treatment because its benefit in terms of overall survival has not been observed yet. Therefore, it is crucial to examine whether palbociclib can improve clinical outcomes and quality of life (QoL) of patients in the real world.A prospective observational study with palbociclib is planned in 3 cohorts (A, B, and C) as per the line of endocrine treatment (i.e., first-line, second-line, or third-line or later-line treatment) for postmenopausal metastatic or unresectable breast cancer. The primary endpoint is progression-free survival in each treatment line, the most commonly used endpoint for global phase 3 studies. As per the results of these studies, the planned sample size is 700 cases: cohort A, 340 cases; cohort B, 200 cases; and cohort C, 130 cases. The secondary endpoints are overall survival, clinical benefit rate, time to chemotherapy, adverse events (AEs), patient-reported outcomes (PROs), and health-related QoL (HRQoL). These endpoints are evaluated again during the subsequent treatment. This study will examine whether the efficacy, safety, and QoL effects of palbociclib treatment in daily clinical practice are not inferior compared to those in clinical trials and whether palbociclib treatment affects the efficacy and safety of the subsequent treatment. Moreover, this study would provide information on the most effective time of adding palbociclib to endocrine treatment.The reproducibility of randomized clinical trials (RCTs) using real-world data must be confirmed to evaluate whether real-world treatment benefits are similar to those observed in RCTs. Although the efficacy of palbociclib has been confirmed in RCTs, Aes of this drug, including its toxicities and cost, are not comparable to those of mono-hormone therapies. Thus, PROs/HRQoL is an important element of this study because several patients with HR-positive metastatic breast cancer have diseases for which sequential hormone therapy is preferential.

Purpose To establish minimal important differences (MIDs) for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30) in patients with metastatic breast cancer. Methods The dataset was obtained from the SELECT BC-CONFIRM randomized clinical trial. Anchors obtained from patients (transition items) and clinicians (performance status) were used for anchor-based methods. Anchors obtained through 6 months after starting treatment were used for this analysis. Correlation coefficients of anchor and change in QLQ-C30 and effect size were used to qualify for estimating MIDs. Mean change method and generalized estimating equation were applied to estimate MIDs. Distribution-based methods were used for comparison. Results We analyzed a dataset of 154 metastatic breast cancer patients. MIDs were estimated in 8 of 15 scales of QLQ-C30. Estimated MIDs for within-group improvement varied from 7 to 15 and those for deterioration varied from − 7 to − 17. Estimated MIDs for between-group improvement varied from 5 to 11 and those for deterioration varied from − 5 to − 8 across QLQ-C30 scales. Patient-reported anchors were more susceptible to early changes in health status than clinician-reported anchors. Conclusion We provided the MIDs of the QLQ-C30 using both patient- and clinicians-reported anchors measured in a randomized trial of Japanese patients with metastatic breast cancer. We recommend patient-reported anchors for anchor-based estimation of MID. Our results can aid patients and clinicians, as well as researchers, in the interpretation of QLQ-C30.

Background: B7-H4 and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. However, the category of patients wherein these factors are highly expressed and how they are related to each other and programmed cell death ligand 1 (PD-L1) are not yet fully clear. Methods: Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of triple-negative breast cancer (TNBC). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression. The tumor immune microenvironment was evaluated based on stromal tumor-infiltrating lymphocytes (sTILs) (%), pattern classification of TILs, tumor stromal ratio, and tertiary lymphoid structure. Immunostaining for CD8 and FOXP3 was also performed. Results: B7-H4 expression was significantly high in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28-8) (p = 0.021). The H-scores of AR and B7-H4 were inversely correlated (ρ = -0.509, p < 0.001). AR expression was high in cases with IDO1 < 1% (p = 0.046), while B7H4 and IDO1 expression levels were inversely correlated in cases with AR Conclusions: In the population of TNBC, B7-H4 and PD-L1 expression were exclusively related to AR expression.B7-H4 and IDO1 expression was exclusive in the non-luminal androgen receptor subtype of TNBC. These trends in expression may help in the future selection of antiandrogenic agents and immune checkpoint inhibitors for patient treatment.

Purpose: Emojis are commonly used for daily communication and may be useful in assessing patient-reported outcomes (PROs) in breast cancer. The purpose of this study is to develop and validate an Emoji Sticker Scale (ESS) as a new PRO measurement. Methods: Eighteen original ESS items were developed from the PRO-CTCAE. In cohort one, the ESS validity and reliability were examined in patients with breast cancer, using a semi-structured five-question survey to investigate content validity. PROs with PRO-CTCAE and ESS were examined twice to determine criteria validity and test-retest reliability. In cohort two, the responsiveness of the scales were examined in patients treated with anthracycline, docetaxel, paclitaxel, and endocrine therapy. PROs with PRO-CTCAE and ESS were investigated two or three times, depending on the therapy. Results: Patients were enrolled from August 2019 to October 2020. In cohort one (n=70), most patients had no difficulties with the ESS, but 16 patients indicated that it was difficult to understand severities in the ESS. For criterion validity, Spearman rank correlation coefficients (rs) between PRO-CTCAE and ESS items were ≥0.41, except for “Decreased appetite.” For test-retest reliability, κ coefficients of the ESS were ≥0.41 for 16/18 items (88.9%). Response time was significantly shorter for the ESS than for PRO-CTCAE (ps≥0.41. Conclusion Parts of the original ESS developed from PRO-CTCAE require updating. However, this study provides a comprehensive confirmation of the validity, reliability, and responsiveness of the ESS.

Background: Trastuzumab Deruxtecan (T-DXd) is a novel antibody-drug conjugate that targets human epidermal growth factor receptor 2 (HER2) with a DNA topoisomerase I inhibitor payload and has demonstrated antitumor activity in clinical trials. Based on the results of a global Phase II clinical trial (DESTINY-Breast01, NCT03248492), T-DXd was conditionally approved for the treatment of patients with HER2+ unresectable or metastatic breast cancer who had received ≥2 prior anti-HER2 based therapies (US, EU, UK, etc) or after prior chemotherapy (Japan). With regards to the safety profile, the incidence of cumulative toxicities such as peripheral neuropathy and edema was lower with T-DXd as compared to what has been observed with taxanes. However, chemotherapy-induced nausea and vomiting (CINV), fatigue, and neutrophil count decrease were observed as treatment emergent adverse events (TEAE). Interstitial lung disease (ILD)/pneumonitis was especially observed in 15.2% of patients treated with T-DXd, leading to death in 2.7% of patients. These adverse events need appropriate monitoring and management in daily clinical practice. We hypothesized that electronic patient-reported outcomes (ePROs) monitoring would allow early detection of adverse events due to T-DXd and thus improve patient safety and quality of life (QoL). Study design: This is an open-label, multicenter, randomized controlled study comparing ePRO monitoring with routine follow-up of patients with HER2+ advanced or metastatic breast cancer who receive T-DXd in routine clinical practice. Patients randomized to the ePRO group are monitored through weekly PRO-CTCAE assessment as well as daily temperature and SpO2 measurement using the ePRO application on the patient's mobile device. Changes in symptoms are monitored by the attending physician using an electronic chart. In addition, an e-mail alert is sent to the site medical staff if any symptoms exceed a predetermined threshold. The primary endpoint of the study is the change from baseline in the EORTC QLQ-C30 (Global QoL) score at 24 weeks. Secondary endpoints include time to deterioration of Global QoL, EORTC FA12 score change, overall survival, progression-free survival, and adherence to the ePRO monitoring as assessed by the proportion of patients completing the questionnaires. Analysis of primary endpoint will be done using mixed effects models for repeated measures (MMRM) and sample size will be estimated based on the Wald test for differences between groups in mean parameters at 24 weeks. To detect 10-points score difference between the groups with a standard deviation of 24, with a two-sided alpha level of 10%, and a power of 87%, 55 patients would be required in each group. Enrollment started in March 2021. Clinical trial identification: jRCTs031200387 Citation Format: Takafumi Sangai, Yuichiro Kikawa, Mitsuchika Hosoda, Yohei Hamanaka, Yuko Tanabe, Tatsuya Yoshida, Kaori Tane, Daisuke Takabatake, Tetsuhiko Taira, Kazuhiro Araki, Takayuki Iwamoto, Mamoru Takada, Kazutaka Narui, Takeshi Yamaguchi, Akimitsu Yamada, Tomoko Miura, Yukari Uemura, Tomohiko Aihara, Hirofumi Mukai, Naruto Taira. Randomized study comparing electronic patient reported outcomes (ePROs) monitoring with routine follow up during trastuzumab deruxtecan treatment in patients with inoperable or metastatic breast cancer (PRO-DUCE study) [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 OT1-12-08.

Background: NET is one of option in postmenopausal PBC with ER+ and molecular signature is useful tool to determine with/without CT after surgery. We presented a relationship between molecular signature and response of NET in this study cohort (BCRT; 2018). Here we report the primary analysis of NEOS trial, a Phase III study that evaluated long-term prognosis with/without CT in ER+ PBC who received NET. Methods: Postmenopausal BC pts with ER +/HER2 negative, T1c-2, clinically node negative, under 76 years old were enrolled at primary registration. Pts were treated by letrozole (LET) in weeks 24-28 after primary enrollment. Pts experienced progression disease (PD) during neoadjuvant phase or with more than 4 positive lymph nodes in pathological findings after surgery were excluded at randomization and received any systemic therapy driven by investigators before or after surgery. Pts who met eligibility criteria were randomized 1:1 to LET for 4.5-5 years after CT or LET alone for 4.5-5 years without CT after surgery. Primary endpoint is disease-free survival (DFS) with/without adjuvant CT. Secondary endpoints include distant DFS (DDFS), overall survival (OS), DFS/DDFS/OS according clinical response of NET and QoL. Statistical analysis plan is as follow. The Hazard ratio (HR) will be compared with the threshold HRs obtained in a pre-study questionnaire survey to reach a conclusion about the choice between LET plus chemotherapy or LET alone. Based on these survey results, the HR thresholds used to choose between the two treatments were set at 0.9 and 0.6. After amendment, the selection probability was finally set as 80-85%. About 170 events were required for both arms. Results: Between May 2008 and June 2013, 904 patients were enrolled at primary registration from 100 institutions in Japan and 21 pts were withdrawn before neoadjuvant phase. 42pts were excluded by PD during NET. 172pts were not randomized because of non-eligible for second enrolled criteria after surgery and patient’s preference. 669pts were randomized (1:1) to adjuvant CT + ET (333pts) or ET alone (336pts). Patients’ characteristics (age, tumor size, progesterone receptor(PgR) status, nuclear grade (NG), clinical and pathological response of NET and a number of Ax LN metastasis) were well balance among two arms. Median follow up is 7.8 years. Primary endpoint (DFS) was not able to evaluated for necessity of chemotherapy because DFS events (CT+ET:46, ET alone:61) was lower compared with planned numbers (HR:0.74 (95%CI; 0.51, 1.09), P=0.13). DDFS was also not able to evaluated similar with DFS (HR:0.79 (95%CI; 0.46, 1.35) P=0.39). DFS/DDFS rate at 8Y were 85.6%/93.1% and 82.7%/91.7% in CT+ ET and ET alone, respectively. OS was not difference between two arms (HR 0.46 (95%CI; 0.20, 1.07) P=0.072). Both DDFS and locoregional events were lower in CT+ET than ET alone arm. A number of any secondary cancers was higher than DDFS events among both arms. DFS was statistically significant better in CT+ET arm than ET alone arm among any subgroups who < 60 years (HR:0.30, p=0.003, clinical T2 (HR:0.56, p=0.012) and ki67 >20% cases (HR:0.49, P=0.026) at baseline characteristics. No statistically significant difference of DFS between two arms according to response of NET (HR:0.76, P=0.35 in CR and PR group, HR:0.70, p=0.19 in SD group). PgR status, NG, a number of Ax LN metastasis were also not predictive factors about the difference of DFS between CT+ET and ET alone. Conclusion: The decision to use adjuvant chemotherapy could not be based solely on clinical response of NET. Adjuvant chemotherapy should be selected by any clinical factors and genomic tool regardless of response by NET for ER+ PBC. UMIN000001090 Citation Format: Hiroji Iwata, Tatsuya Toyama, Naruto Taira, Norikazu Masuda, Yutaka Yamamoto, Tomomi Fujisawa, Shoichiro Ohtani, Masahiro Kashiwaba, Takehiko Sakai, Yoshie Hasegawa, Rikiya Nakamura, Hiromitsu Akabane, Yukiko Shibahara, Hironobu Sasano, Takuhiro Yamaguchi. Primary analysis from NEOS trial: A randomized phase III study that assessed the long-term prognosis of estrogen receptor positive (ER+) primary breast cancer (PBC) pts who received neoadjuvant endocrine therapy (NET) with/without adjuvant chemotherapy (CT) [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 PD13-09.

Purpose This study aimed to determine whether continual electronic patient-reported outcome (ePRO) measurements at home can capture the fluctuations in health-related quality of life (HRQOL) scores between visits. Methods We performed a randomized controlled trial to compare the scores obtained by standard practice (paper-based measurements in the hospital) to scores by continuous measurement of ePRO at home. Metastatic cancer patients were randomly assigned to either the paper-based ( n = 50) or the ePRO group ( n = 52). EQ-5D-5L and EORTC QLQ C-30 scores were obtained on 3 different chemotherapy days in the paper-based group. Meanwhile, scores were obtained on the chemotherapy day and on days 3, 7, 10, and 14 in the ePRO group during 2 cycles. The first hypothesis of our study was that both scores at the same time points would be equivalent despite different measurement frequency, place, or mode of measurement. The second hypothesis was that PRO score–adjusted time would be different between the groups. For equivalence, the endpoint was the mean EQ-5D-5L index value on the chemotherapy day before the outpatient treatment. Only if equivalence was shown, quality-adjusted life-days (QALDs) were considered using all the data. Results The adjusted mean difference in the EQ-5D-5L index was determined to be −0.013 (95% confidence interval [CI]: −0.049 to 0.022); the 95% CI did not exceed the equivalence margin. Similarly, the mean difference in global health status (2.28 [95% CI: −2.55 to 7.11]) also showed equivalence. However, the QALD by EQ-5D-5L was significantly lower in the ePRO group by 1.36 per 30 d (95% CI: −2.22 to −0.51; P = 0.0021). Conclusions Continual measurements of the HRQOL at home by ePRO may yield more detailed profiles of the HRQOL.

Background It is unclear what interventions can sustain long-term higherphysical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. Methods This was an open-label randomized controlled trial for patients with stage 0-III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents(METs)/week at 1 year after registration. Results From 01/03/2016 to 15/03/2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = 0.492) and between the education and control groups (62% and 53%, P = 0.126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = 0.0083), BMI (P = 0.0034), and body fat percentage (P = 0.0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = 0.0038) compared to control group. Conclusions Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival. Trial registration UMIN000020595 at UMIN Clinical Trial Registry Date of first registration: 01/03/2016

PURPOSE This systematic review aimed to investigate the efficacy of telemedicine (TM) using videoconferencing systems in outpatient care for patients with cancer. METHODS We searched six electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, ICTRP, and ClinicalTrials.gov) through June 2021 to identify randomized controlled trials that evaluated the use of TM using videoconferencing systems compared with usual face-to-face care in outpatient care for patients with cancer. We assessed the certainty of evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS From the 2,400 articles screened, six randomized controlled trials were eligible for this study. Two studies evaluated the use of TM in cancer follow-up and four investigated psychotherapy for cancer. TM using videoconferencing systems may result in no differences in primary outcomes such as patient satisfaction (standardized mean difference, 0.11; 95% CI, –0.18 to 0.40) and outpatient attendance complete proportion (risk difference, 0.02%; 95% CI, –0.04 to 0.09), and secondary outcomes such as medical professional satisfaction, time devoted to outpatient care, and depression score. The certainty of evidence for these outcomes was low. Although the average money spent on outpatient visit was a primary outcome, the level of evidence was uncertain. CONCLUSION Our results suggest that TM using videoconferencing systems in outpatient care for patients with cancer may be as effective as usual face-to-face care. Use of TM more frequently may be considered for patients with cancer who are expected to obtain benefit from TM using videoconference systems.

PURPOSE We report findings on quality of life (QoL) in the RESPECT trial, which compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). PATIENTS AND METHODS Patients age 70-80 years with human epidermal growth factor receptor 2-positive surgically treated breast cancer were randomly assigned to receive trastuzumab (T) or trastuzumab plus chemotherapy (T + C). QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Philadelphia Geriatric Center Morale Scale, Hospital Anxiety and Depression Scale, Patient Neurotoxicity Questionnaire, and Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline and after 2, 12, and 36 months. Comparisons were based on individual changes from baseline and were performed by Fisher’s test or mixed-model repeated-measures. RESULTS Among 275 patients in the parent study, 231 (84%) (average age: 74 years) were included in the analysis. At 2, 12, and 36 months, 198, 177, and 178 patients completed surveys, and the mean FACT-G scores at each survey point were 78.9, 80.4, 82.7, and 79.1 in group T and 79.5, 74.5, 78.4, and 78.5 in group T + C. Compared with group T + C, the proportion of patients showing QoL deterioration (≥ 5 points decrease from baseline in FACT-G) was significantly lower at 2 months (31% v 48%; P = .016) and 12 months (19% v 38%; P = .009). In group T, the Hospital Anxiety and Depression Scale score ( P = .003) and the proportion of severe sensory peripheral neuropathy ( P = .001) were significantly lower at 2 months, and Philadelphia Geriatric Center Morale Scale and Tokyo Metropolitan Institute of Gerontology Index of Competence scores were significantly higher ( P = .024, .042) at 12 months. At 36 months, there were no significant differences in any QoL items. CONCLUSION Detrimental effects of adjuvant chemotherapy on global QoL, morale, and activity capacity lasted for at least 12 months but were not observed at 36 months.

Background As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). Patients and methods Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians’ discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. Results Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. Conclusions FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC., Highlights • This study compared febrile neutropenia (FN) incidences of 3 breast cancer regimens. • FN incidences were >20% in the 3 regimens (FEC, E(A)C; TC); TC showed the highest. • The relative dose intensities in visiting and non-visiting groups were at high level. • Age and pretreatment absolute neutrophil count were found as significant FN factors.

Objective This study examined the pharmacokinetics, safety and anti-tumor activity of docetaxel at a dose of 100 mg/m2 in Japanese patients with advanced or recurrent breast cancer. Methods Japanese patients with advanced or recurrent breast cancer received docetaxel at a dose of 100 mg/m2 intravenously every three weeks. The pharmacokinetics were assessed during the first cycle. The patients were allowed to receive supportive care drugs based on the indications and dosages in Japan. Results Six eligible patients aged 39-65 years old and 27 treatment cycles were analyzed. All patients experienced one or more adverse events (AEs). The common AEs were neutropenia, thrombocytopenia, alopecia, rash, diarrhea, neuropathy (sensory), fatigue, nausea, fever, hypoalbuminemia, alanine transaminase (ALT) increased, constipation, and taste alteration. Grade 3 or 4 AEs included neutropenia, leukopenia, anemia, lymphopenia, decreased appetite, γ-glutamyl transpeptidase (GTP) increased, aspartate transaminase (AST) increased, ALT increased, hypertension and cellulitis which were all reversible. There were no cases of febrile neutropenia, serious AEs or deaths. The median number of cycles was six. Dose reductions were not observed and most cycles were administered at their intended doses. No complete response and three partial responses were observed in four assessable patients with evaluable lesions. The maximum concentration and area under the blood concentration-time curve were 3,417.5 ng/mL and 4.35 μg・hr/mL (mean), respectively. Conclusion Docetaxel at a dose of 100 mg/m2 was tolerable with acceptable safety profiles and effective for Japanese patients with advanced or recurrent breast cancer with appropriate supportive therapies, and pharmacokinetic (PK) profiles which corresponded approximately with the findings of previous clinical studies.

To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m2 vs. MD: 220 mg/m2 vs. LD 180 mg/m2). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM). A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC., Highlights • Nab-Paclitaxel at 260 mg/m2 is used to treat metastatic breast cancer (MBC). • Nab-Paclitaxel frequently causes severe neuropathy or myalgia. • A reduced nab-paclitaxel dose of 180 mg/m2 q3w was effective and had less toxicities. • Therapeutic indices of reduced doses were increased compared to the standard dose.

BackgroundPrevious study results have suggested that local treatment of isolated lung metastases, may be beneficial and increase overall survival (OS) in highly selected patients. However, these were all retrospective studies. We designed this prospective cohort study to investigate the therapeutic and diagnostic clinical situation of oligometastatic breast cancer in the lung, as well as the prognosis outcomes of patients with this disease.MethodsWe enrolled patients with less than 3 lung nodules which suspected as oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were choice by each physician. The primary outcome was OS of patients with oligometastasis of breast cancer detected in the lung and secondary outcomes were the efficacy and safety of surgery for lung oligometastases. The study was in accordance with the relevant national/institutional guidelinesResultsBetween May 2015 and May 2019, 14 patients were enrolled at 5 centers. Resection of lung nodules (metastasectomy) was performed 11 (78.6%) of 14 patients and one was diagnosed with primary lung cancer. Metastasectomy were all performed employing video-assisted thoracic surgery (VATS) and achieved complete resection without perioperative complication. Systemic therapies such as chemotherapy, as well as endocrine and molecular target therapies were administered to all patients except one who declined all treatments offered. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%. Progression events occurred in 6 patients: 3 (30%) with and 3 (100%) without metastasectomy. Whereas 2 of 10 patients with metastasectomy survived 5 years without progression, progression events occurred all patients without metastasectomy within 1 year.ConclusionLung metastasectomy was worthwhile as a diagnostic evaluation and possibly provide long-term benefit in some patients. Phase 3 trials might be required to provide definitive evidence and to provide criteria for selecting patients. Trial registrationThis study was approved by the Institutional Review Board (IRB No. 960) of the Okayama University Hospital, Okayama, Japan, and was registered in the clinical trials database UMIN (UMIN000016999) on 31 March 2015. Written informed consent was obtained from all enrolled patients.

Introduction Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy. Patients and Methods We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III. Results Among hormone receptor–positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node–positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II. Conclusion In hormone receptor–positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.

OBJECTIVE: Nab-paclitaxel (nab-PTX) has superior efficacy compared to conventional paclitaxel in metastatic breast cancer (MBC), but chemotherapy-induced peripheral neuropathy (CIPN) is more frequent with nab-PTX. In a single arm phase 2 trial (CA002-0LD), low dose nab-PTX (175 mg/m2) every 3 weeks (q3w) resulted in a good objective response rate (39.5%) without CIPN of grade 3 or higher. Therefore, we conducted a randomized controlled study to evaluate the optimal dose of nab-PTX by comparing a low dose (LD) and a medium dose (MD) to the standard dose (SD). Here, we evaluate the patients-reported outcomes (PROs) and health-related quality of life (HRQoL) in the ABROAD study. PATIENTS AND METHODS: Three different doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2) were administered in patients with HER2-negative metastatic breast cancer. The primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates with the three doses were estimated by logistic regression. The optimal dose was selected by 2-step selection. First, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was dropped. Then, a dose with an estimated incidence of grade 3/4 neurotoxicity >10% was also dropped. PROs and HRQoL were assessed as secondary endpoints at baseline, and during the 2nd, 4th and 6th courses of protocol treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Patient Neurotoxicity Questionnaire (PNQ), Cancer Fatigue Scale (CFS) and EuroQol 5 Dimension (EQ-5D). The primary outcome for PROs and HRQoL was the FACT-Taxane trial outcome index (TOI), and inter-group comparison was performed using a mixed effect model for repeated measures (MMRM). This trial was registered with the University Hospital Medical Information Network (UMIN), Japan (protocol ID C000012429). RESULTS: A total of 141 patients were randomly assigned to SD (n=47), MD (n=46) or LD (n=48) nab-PTX. PFS analysis showed that LD nab-PTX at 180 mg/m2/3 weeks was the optimal dose with good clinical efficacy and tolerability for patients with MBC (reported by Hara at ASCO2019). Longitudinal analysis (MMRM) showed that the difference from the baseline FACT-Taxane TOI score at MD and LD were significantly better than that at SD (MD vs. SD p CONCLUSION: Our results show that low dose nab-PTX at 180 mg/m2/3 weeks could be an optimal dose for PFS and from the perspectives of PROs and HRQoL. Citation Format: Hiroaki Kato, Fumikata Hara, Masahiro Kitada, Masato Takahashi, Yuichiro Kikawa Yuichiro Kikawa, Eiko Sakata, Yoichi Naito, Yoshie Hasegawa, Tsuyoshi Saito, Tsutomu Iwasa, Junji Tsurutani, Naruto Taira, Tsutomu Takashima, Kosuke Kashiwabara, Tomohiko Aihara Tomohiko Aihara, Hirofumi Mukai. Patient-reported outcomes in a randomized, optimal dose finding, phase II study of triweekly nab-paclitaxel in patients with metastatic breast cancer (the ABROAD study) [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 P2-15-04.

Background In hormone receptor (HR)-positive / human epidermal growth factor receptor 2 (HER2)-negative breast cancers, high Ki-67 predicts poor prognosis. Recently, it has been reported that among breast cancers with high Ki-67, low Ki-67 after short-term preoperative hormone therapy (post Ki-67) might predict favorable prognosis compared to high post Ki-67 (SABCS 2017). However, the differences in gene expression profiling of breast cancers between high and low post Ki-67 among high Ki-67 before treatment are unclear. Therefore, this study aimed to clarify genetic differences in two groups and to explore novel therapeutic targets for the poor prognostic group after the treatment. Methods Seventy-seven patients with primary HR-positive / HER2-negative breast cancer who received an aromatase inhibitor for 2 weeks [NCBI Gene Expression Omnibus repository GSE80077:19 cases, GSE20181:58 cases] were enrolled in this study. Forty-five patients with high pre Ki-67 among them were stratified into two groups, high (H→H) and low (H→L) post Ki-67 after short-term preoperative hormone therapy. We compared gene expression profiling in two groups about the followings. 1) 3 genes (ESR1, PGR and ERBB2) related to classical clinical treatment strategy of breast cancer, immune- and inflammatory-related genes 2) 178 pathways (gene set analysis) 3) 41 genes that are targeted by FDA-approved drugs or have been investigated with clinical trials as molecular target agents for various malignant tumors including breast cancer Results 1) TNF that is inflammatory-related gene were significantly overexpressed in H→L group (P=0.021). However, 3 genes related to clinical treatment of breast cancer and immune-related genes expression had no significant difference between two groups. 2) 5 gene sets (Tryptophan metabolism, Propanoate metabolism, beta-Alanine metabolism, SNARE interactions in vesicular transport and Nucleotide excision repair) were significantly upregulated in H→L group. (P ≤ 0.005) 3) 5 targeted genes (PARP, BRCA2, FLT4, CDK6 and PDCD1LG2) were significantly overexpressed in H→H group (P ≤ 0.05). Conclusions There were different gene expression and biological processes in two groups stratified by post-Ki67. In the future, it is necessary to seek new therapeutic strategies for poor prognostic group with high post-Ki67 in considerations of these differences. Citation Format: Yukiko Kajiwara, Takayuki Iwamoto, Yusuke Otani, Miwa Fujihara, Yoko Suzuki, Minami Hatono, Takahiro Tsukioki, Kengo Kawada, Mariko Kochi, Hirokuni Ikeda, Tadahiko Shien, Naruto Taira, Hiroyoshi Doihara. Gene expression profiling of breast cancers between high and low Ki-67 after short-term preoperative hormone therapy among hormone receptor-positive / human epidermal growth factor receptor 2-negative breast cancers with high Ki-67 [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 P5-13-04.

Background: Currently, treatment for older breast cancer patients is largely based on data derived from trials enrolling younger patients; thus, the standard of care for older breast cancer patients remains controversial. Aim: To investigate the clinicopathological characteristics, treatments, and prognosis in older stage II and III breast cancer patients using data from the Japanese Breast Cancer Registry (JBCR). Methods: We reviewed data from the JBCR, a nationwide registry of newly diagnosed and operated primary breast cancer patients in Japan. To clarify those characteristics, we compared clinicopathological characteristics, treatments, and prognosis among three groups: older group, patients aged ≥75 years; young-old group, patients aged 65–74 years; post-menopause group, patients aged 55–64 years. Results: In total, we reviewed 56,093 cases of stage II/III breast cancer diagnosed between 2004 and 2011 (older: n=12,727; young-old: n=17,860; post-menopause: n=25,506). The estrogen receptor (ER) positivity rate was higher (older vs. young-old vs. post-menopause: 73.3% vs. 72.0% vs. 68.0%) and HER2 positivity rate was lower in the older group than in the other two groups (12.9% vs. 16.8% vs. 23.6%) (p The following table shows the rate of administration of adjuvant systemic therapy according to the ER and HER2 status. Age (years)≥7565–7455–64p-valueER+Chemotherapy10.042.562.9 Nearly half of the older patients (48.3%) who received chemotherapy received either cyclophosphamide-methotrexate-fluorouracil or oral fluorouracil. As for hormone therapy, tamoxifen was used more frequently in the older group than in the young-old and post-menopause groups (16.5% vs. 8.6% vs. 7.2%). The following table shows the results of the 5-year overall survival (OS) and breast cancer-specific survival (BCSS) analyses: Conclusions: Chemotherapy was less common in older patients, especially patients with HER2+ or triple negative breast cancer, resulting in worse BCSS. As older patients tend to have several comorbidities, comprehensive geriatric assessment might be helpful in determining systemic therapies for older patients. Age (years)≥7565–7455–64p-valueER+OS/BCSS (%)84.1/94.592.5/96.093.2/94.9 Citation Format: Akimitsu Yamada, Masataka Sawaki, Hiraku Kumamaru, Hiroaki Miyata, Kanako Nakayama, Chikako Shimizu, Mika Miyashita, Naoko Honma, Itaru Endo, Naruto Taira, Shigehira Saji. Systemic therapy for and prognosis of older stage II and III breast cancer patients: Evaluation of data from the Japanese breast cancer registry [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 P2-14-06.

Background: Patient reported outcomes (PROs) have been increasingly important in breast cancer treatment. The questionnaires to evaluate PROs require high response compliance, simplicity, and friendliness. Recently, the communication with Emojis has become friendliness because of the development of social networking services and electronic devices. Therefore, we developed the Emoji scale, a novel indicator to evaluate PROs. Furthermore, two-step validation pilot studies were planned to examine the reliability of the Emoji scale for breast cancer patients at a single center. Pilot 1(Step 1) Aims: To evaluate the content validity (the primary endpoint), concurrent validity and test retest reliability of the Emoji scales (secondary endpoints). Eligibility criteria: (1) Patients with stage 0-III breast cancer. (2) Patients who have been over 1 year since the end of the initial treatment such as surgery, chemotherapy, and radiation therapy or (3) hormone receptor positive patients who have been over 1 year from the start of the endocrine therapy. (4) Patients aged >20 years who understand Japanese. Methods: The participants will complete the PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE) and Emoji scale questionnaires regarding 18 cancer related symptoms twice. First, both questionnaires will be completed in a consulting room while the staff will track the time required for completion of each questionnaire. Thereafter, the patients will be asked if there are any difficult or confused items. Second, both questionnaires will be completed again at home 7 days later. The number of planned participants is 100. Statistical analyses: Content validity will be evaluated by categorizing the comments from participants, and the nature of problems will be determined. The correlation coefficient between the PRO-CTCAE and Emoji scale scores will evaluate the concurrent validity. For the test-retest reliability, the kappa statistic between each scale at different time will be used. We will compare the time required for completion with using the t-test. Pilot 2(Step2) Aims: To evaluate the responsiveness (the primary endpoint), the effect size, the concurrent validity and comparison of the average score between participants with high and low Performance Status. (the secondary endpoints). Eligibility criteria: (1) Patients with stage 0-IV breast cancer who are scheduled to start chemotherapy or endocrine therapy. (2) Patients aged >20 years who understand Japanese. Methods: The participants will complete both the PRO-CTCAE and Emoji scales before they start a new breast cancer treatment (T1). Those will comprise chemotherapy (Cohort A: anthracycline based regimens, Cohort B: docetaxel based regimens, Cohort C: paclitaxel based regimens, Cohort E: eribulin based regimens, and Cohort F: capecitabine/S1 based regimens) or endocrine therapy (Cohort D: tamoxifen/aromatase inhibitor). After several weeks, the participants will complete the same questionnaires again (T2). This time interval will depend on the therapy, and some participants will be complete once again the questionnaires (T3) a few weeks after T2. The number of planned participants is 30 in each cohort. Statistical analyses: Responsiveness will be evaluated by the correlation coefficient between the change from the baseline to second or third score of each scale. The effect size of the Emoji scale will be determined by the difference between the average score of the second or third and that of the baseline divided by the standard deviation of the baseline score. The correlation coefficient for each scale at each time will evaluate the concurrent validity at each time. A comparison of the average scores between PS will be performed using the t-test. Citation Format: Yoko Suzuki, Naruto Taira, Yukiko Kajiwara, Mariko Kochi, Takayuki Iwamoto, Hirokuni Ikeda, Tadahiko Shien, Hiroyoshi Doihara, Yuichiro Kikawa, Yukari Uemura. Validation study of the Emoji scale in evaluating patient reported outcomes for breast cancer patients [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 OT3-19-01.

Background: The randomized controlled trial (RCT) is accepted as the standard clinical trial to decide a standard therapy, but it remains unclear whether or not elderly patients benefit as much as other patients from participation in an RCT. In the RESPECT study (NCT01104935), the relative value of trastuzumab (H) monotherapy as an adjuvant treatment was compared in an RCT with the standard combination treatment with chemotherapy (H+CT) in patients over 70 years old with HER2-positive invasive breast cancer (BC) who received curative surgery. This cohort study was aimed at comparing prognoses between RCT participants (RCT group) and non-participants (Cohort group). Methods: Patients were divided into RCT participants, and those who did not agree to participate in the RCT despite meeting the eligibility criteria and receiving the explanation given by the investigator. In the RCT group patients were randomized to H or H+CT; in the Cohort group treatment was selected for each patient based on the discretion of the treating physician and the patient's wishes without intervention. Treatment categories were divided into three groups: (1) trastuzumab monotherapy group (cH group), (2) trastuzumab plus chemotherapy group (cH+CT group), and (3) those who received either no therapy at all, or any other anticancer therapies without H (cOther group). The primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), relapse-free survival, safety, health-related quality of life (HRQOL) and comprehensive geriatric assessment. Results: A total of 275 patients in the RCT group and 123 patients in the Cohort group, in total 398 patients, were enrolled in this study between October 2009 and October 2014. The median age was 74.0 years in the RCT group, 74.5 years in the Cohort group and the median follow-up time was 4.1 years and 3.2 years, respectively. Patients were classified as Stage I: 41.8%, 42.5%; IIA: 41.5 %, 40.8%; IIB: 13.5%, 13.3%; and IIIA: 1.5%. 3.3%, respectively (P = 0.51), there were no significant differences between the two groups. Treatment categories in the Cohort group were: (1) cH group; 43% (n = 52), (2) cH+CT group; 30% (n = 36), cOther group; 27% (n = 32). The planned analysis showed that DFS at 3 years was 91.4% in the RCT group vs 89.3% in the Cohort group (adjusted hazard ratio (HR) = 1.30; 95%CI, 0.72-2.35, P = 0.38). In patients in the cH+CT, cH and cOther group, DFS at 3 years was 92.3%, 89.2% and 82.5%, respectively. DFS in patients in the cH+CT and the cH group was significantly better than that of the cOther group (adjusted HR = 3.79; 95%CI = 1.35-10.64, P = 0.01). DFS in the cH group showed a better tendency compared with cOther (adjusted HR = 2.59; 95%CI, 0.87-7.73, P = 0.08). The incidence of grade 3/4 non-hematological adverse events in the RCT group was relatively higher compared with the Cohort group (18.5% vs 10.8 %, P = 0.05). Conclusion: The prognosis did not vary between the RCT and Cohort groups. H-containing regimens are often chosen for elderly patients with HER2-positive breast cancer. The prognosis of patients who received any H-containing regimen, even H monotherapy, was better than those who were not treated with H. Citation Format: Shinichi Baba, Masataka Sawaki, Yukari Uemura, Tsuyoshi Saito, Kokoro Kobayashi, Hiroaki Kawashima, Michiko Tsuneizumi, Noriko Sagawa, Hiroko Bando, Masato Takahashi, Miki Yamaguchi, Tsutomu Takashima, Takahiro Nakayama, Masahiro Kashiwaba, Toshiro Mizuno, Yutaka Yamamoto, Naruto Taira, Hiroji Iwata, Tatsuya Toyama, Koichiro Tsugawa, Yasuo Ohashi, Hirofumi Mukai. A cohort study to evaluate the efficacy and safety of postoperative adjuvant therapy in HER2-positive elderly breast cancer patients (RESPECT-cohort study) [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 P3-14-02.

Background: The standard chemotherapy treatment strategy for patients with advanced/metastatic breast cancer (ABC) is the continuation of the same drug until tumor progression. However, despite continued antitumor effects, continuation of a drug often becomes difficult because of cumulative adverse events, such as peripheral neuropathy. Methods: This multicenter, randomized, Phase II study in patients with estrogen receptorpositive (ER+) human epidermal growth factor receptor 2-negative (HER2−) ABC aimed to compare 2 treatment strategies following induction therapy with 4-6 cycles of the combined use of weekly paclitaxel (wPTX) and bevacizumab (BV). Patients in Arm A continued with wPTX+BV, whereas patients in Arm B were switched from wPTX to maintenance endocrine therapy (endocrine+BV) until disease progression, followed by wPTX+BV re-induction. The primary endpoint was time to failure of strategy (TFS), defined as the time from randomization to a qualifying event (addition of a new agent not in the primary regimen, progressive disease during or after planned therapy, or death). Secondary endpoints were overall survival (OS), progression-free survival, safety, and quality of life (QoL). Sequential plasma and serum biomarkers were analyzed for predicting/monitoring the response. Result: Of 160 patients enrolled to receive induction therapy with wPTX+BV, 125 patients responded to treatment (complete response [CR], partial response [PR], or stable disease) and were randomized to either of the 2 treatment arms. Median follow-up was 21.3 months. Aromatase inhibitor (AI), fulvestrant, or AI with a luteinizing hormonereleasing hormone (LH-RH) analogue was used as maintenance endocrine therapy. The primary endpoint of TFS was 8.87 months (95% CI: 5.68-13.80) in the wPTX+BV continued group (Arm A) and 16.82 months (95% CI: 12.88-18.99) in the maintenance endocrine+BV group (Arm B) (hazard ratio [HR], 0.51; p Conclusion: This is the first study showing the benefit of maintenance endocrine therapy in patients with ER+ HER2− advanced breast cancer who responded to a fixed dose of chemotherapy. (UMIN: UMIN000012179; ClinicalTrials.gov: NCT01989780) Funding: Chugai Pharmaceutical CO., LTD. Citation Format: Shigehira Saji, Masahiro Kitada, Toshimi Takano, Masahiro Takada, Tohru Ohtake, Tatsuya Toyama, Yuichiro Kikawa, Yoshie Hasegawa, Tomomi Fujisawa, Masahiro Kashiwaba, Takanori Ishida, Rikiya Nakamura, Yutaka Yamamoto, Uhi Toh, Hiroji Iwata, Norikazu Masuda, Naruto Taira, Satoshi Morita, Shinji Ohno, Masakazu Toi. A randomized, multicenter, phase II study evaluating the efficacy of interventional maintenance endocrine therapy with bevacizumab following fixed cycles of bevacizumab plus paclitaxel in advanced/metastatic ER-positive HER2-negative breast cancer: JBCRG-M04 BOOSTER trial [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 P2-15-01.

Further research is needed to compare the impact of interactive Telemedicine using videoconferencing systems with usual face-to-face care in the outpatient with cancer. The aim of this study is to review systematically the efficacy of interactive telemedicine using videoconferencing systems in this setting, including feasibility, satisfaction and cost.

Background The HORSE-BC study previously demonstrated that second-line endocrine therapy (ET) for patients with acquired endocrine-resistant metastatic breast cancer (MBC) still provided a clinically meaningful benefit. Herein, we investigated the health-related quality of life (HR-QOL) in the HORSE-BC study. Methods Patients with acquired endocrine-resistant MBC who were scheduled for second-line ET were recruited. The HR-QOL was assessed at baseline, and 1 and 3 months after second-line ET initiation. To investigate the minimally important difference (MID) in the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), we evaluated the means and standard deviations for the distribution-based method, and differences in the change in HR-QOL for the anchor-based method. We also investigated the association between FACT-ES total scores and clinical benefit. Results Overall, 56 patients were enrolled. Of these, 47 were analyzed. When defined as 1/3 standard deviation estimates based on the distribution method, the calculated MID was 5.9. The MIDs of the FACT-ES total scores based on the anchor method were 7.7 for decline and 4.1 for improvement. The MID decline proportions were 6.1% and 14.7% lower in patients who experienced clinical benefits than in those who did not at 1 and 3 months, respectively. The ratios of MID improvement in patients who experienced clinical benefits were 18.3% and 3.2% higher, respectively; the mean change in the FACT-ES total score from baseline improved in patients who experienced clinical benefits. Conclusions Maintaining the HR-QOL as determined by FACT-ES may be associated with clinical benefits in patients with acquired endocrine-resistant MBC treated with ET.

Anticancer treatment regimens typically cause unpleasant side-effects. We aimed to investigate the benefit of switch maintenance endocrine therapy plus bevacizumab after fixed cycles of first-line induction chemotherapy with weekly paclitaxel plus bevacizumab in patients with oestrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer.BOOSTER was a prospective, open-label, multicentre, randomised, controlled, phase 2 study done in 53 hospitals in Japan. Eligible patients were women aged 20-75 years, with an Eastern Cooperative Oncology Group performance status of 0-1, who had not received chemotherapy for ER-positive, HER2-negative advanced or metastatic breast cancer. All patients received four to six cycles (in which 4 weeks of treatment constitute one cycle) of weekly paclitaxel plus bevacizumab induction therapy (weekly paclitaxel 90 mg/mBetween Jan 1, 2014, and Dec 31, 2015, we enrolled 160 patients who began weekly paclitaxel plus bevacizumab induction therapy. 125 (78%) patients (responders) were randomly assigned to endocrine therapy plus bevacizumab (n=62; n=61 in the full analysis set) or weekly paclitaxel plus bevacizumab (n=63; n=63 in the full analysis set). Among 61 patients in the switch maintenance endocrine therapy plus bevacizumab group, 32 (52%) were reinitiated on weekly paclitaxel plus bevacizumab. At a median follow-up of 21·3 months (IQR 13·0-28·2), TFS was significantly longer in the endocrine therapy plus bevacizumab group than in the weekly paclitaxel plus bevacizumab group (median 16·8 months [95% CI 12·9-19·0] vs 8·9 months [5·7-13·8]; hazard ratio 0·51 [0·34-0·75]; p=0·0006). The most common grade 3-4 non-haematological adverse events after randomisation were proteinuria (in ten [16%] of 61 patients in the endocrine therapy plus bevacizumab group vs eight [13%] of 63 patients in the weekly paclitaxel plus bevacizumab group), hypertension (six [10%] vs six [10%]), and peripheral neuropathy (one [2%] vs six [10%]). One treatment-related death was reported in the weekly paclitaxel plus bevacizumab group (duodenal ulcer perforation).Switch to maintenance endocrine therapy plus bevacizumab with the possibility of weekly paclitaxel reinduction if needed is an efficacious alternative, with a better safety profile, to continuing weekly paclitaxel plus bevacizumab in patients with ER-positive, HER2-negative advanced or metastatic breast cancer who have responded to induction therapy.Chugai Pharmaceutical.For the Japanese translation of the abstract see Supplementary Materials section.