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Background: Although few patients with breast cancer experience tumor progression during neoadjuvant systemic therapy (NST), their extremely poor outcomes are similar to patients who fail to achieve pathological complete response (pCR). No reports have compared patients with pCR, non-pCR, and progression during NST to determine the survival outcomes.Methods: This retrospective chart review of patients with stage I–III breast cancer was conducted between January 2001 and December 2018. pCR was defined as no invasive cancer or in situ residuals in the breast and lymph nodes (ypT0 ypN0). Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan–Meier methods.Results: Of the 595 patients who received NST, 167 (29.2%) had pCR (pCR group), 404 (70.8%) responded to NST but did not have pCR (non-pCR group), and 24 (4.0%) experienced tumor progression during NST (PD group). The median DFS was 6.0 months, 154.0 months, and not reached in the PD, non-pCR, and pCR groups, respectively. The PD group had significantly shorter DFS than patients without tumor progression in the pCR and non-pCR groups [hazard ratios (HR) 13.0, 95% CI: 8.1–21.0, p < 0.01]. The median OS was 13.6 months (95% CI: 10.4–35.5) in the PD group and was not reached in the pCR and non-pCR (non-PD) groups. The OS was significantly poorer in the PD group than in the non-PD group (HR 15.8, 95% CI: 9.2–27.1, p < 0.01).Conclusion: The PD group had the poorest survival outcomes even after recurrence, thus warranting new treatment targets.

Background: Abemaciclib is a drug approved for ER-positive and HER2-negative metastatic or recurrent breast cancer and those treatable in an early setting. Some patients with ER-positive and HER2-negative breast cancer pretreated with abemaciclib and endocrine therapy may still benefit from abemaciclib rechallenge, especially in case of acquired resistance to endocrine therapy. However, there is no evidence for abemaciclib rechallenge. To address this, a single-arm phase 2 trial is planned to determine whether abemaciclib rechallenge has clinical benefits. Translational research to evaluate the gene alteration and immunohistochemistry will be conducted as an accompanying research to determine the predictive biomarkers of resistance or sensitivity to abemaciclib. Patients and Methods: The eligible patients are histologically confirmed with ER-positive and HER2-negative invasive breast cancer, locally advanced or metastatic, and previously received no more than two lines of endocrine therapy. The patients who previously received abemaciclib in combination with endocrine therapy led to a clinical benefit, including complete response, partial response, or stable disease, during abemaciclib-based treatment (≥6 months). The patients who previously received chemotherapy, immune checkpoint inhibitors (excluding perioperative systemic treatment), everolimus, olaparib, and palbociclib for advanced or metastatic diseases are excluded. The patients will be treated with abemaciclib 150 mg orally q12h on days 1 to 28 of a 28-day cycle. The other endocrine drug prescribed was not used in previous treatment. We will evaluate the gene mutations and/or amplification of ESR1, PIK3CA, CCNE1, FGFR1, RB1, TP53, NF1, MYC, AR, and MET at the time of inclusion and three months after day 1 and ctDNA and immunostaining levels of HER3, PTEN, CCNE1, FGFR1/2, and AR at the time of inclusion. The primary endpoint is progression-free survival (PFS), while the secondary endpoints are overall response rate, clinical benefit rate, chemotherapy-free interval, overall survival (OS), safety, and evaluation of the mechanism of sensitivity and resistance to abemaciclib. The expected median PFS for the study treatment arm is 5.0 months compared to the previous data of 3.0 months. The number of necessary cases is 59, with a significance level of 5% (two-sided) and power of 80% during the two-year recruitment period and one-year follow-up period. In the planned total of 65 cases, 10% is considered inappropriate. The planned duration of enrollment and follow-up is two years and one year, respectively. The planned total study duration is four years. Subgroup analysis will be performed on ESR1 and PIK3CA mutations, disease site (visceral/bone only/other), previous lines of therapy for advanced or metastatic disease (first and second), endocrine therapy for pretreatment (aromatase inhibitors/fuluvestrant), performance status (0/1), organs involved (1/2/≥3), age ( Citation Format: Meiko Nishimura, Takahiro Kogawa, Yuko Akaishi, Misato Ogata, Jun Masuda, Mitsuo Terada, Hitomi Sakai, Kazuki Nozawa, Sasagu Kurozumi, Takamichi Yokoe, Yukinori Ozaki Ozaki, Shu Yazaki, Mai Onishi, Tsutomu Iwasa, Takuma Onoe, Yuta Okumura, Sayaka Nakayama, Kanako Hagio, Yuko Takahashi, Hirokazu Tanino, Junji Tsurutani, Koji Matsumoto, Mototsugu Shimokawa, Toshimi Takano. Clinical evaluation of the efficacy and liquid molecular analysis of abemaciclib rechallenge upon progression to abemaciclib combination therapies for ER-positive HER2-negative metastatic breast cancer patients [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 OT2-19-02.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested that arthralgia was reduced in patients treated with ET plus CDK4/6i compared with that in those with ET-alone. We aimed to compare arthralgia rates in BC patients treated with/without CDK4/6i. We reviewed randomized controlled phase II/III trials investigating CDK4/6i with ET in hormone receptor-positive and epidermal growth factor 2-negative BC. Publications were retrieved from PubMed from January 2014 to April 2021. We compared arthralgia rates between patients who were administered ET plus CDK4/6i (CDK4/6i group) and those treated with ET-alone (control group). We reviewed 12 trials that reported data on adverse effects for arthralgia. These trials included 17,440 patients (9255 in the CDK4/6i group and 8185 in the control group). The arthralgia rate in the CDK4/6i group was significantly lower than that in the control group (27.6% vs. 34.8%, p .001), especially in early BC (28.8% vs. 37.3%, p .001). These suggested that the arthralgia rate in patients treated with ET plus CDK4/6i was lower than that in patients treated with ET-alone and that CDK4/6i may decrease the arthralgia rate in BC patients treated with ET, especially in early BC.

PurposeWomen diagnosed with early breast cancer are faced with a choice of surgical procedures. Although one of the essential factors in surgical shared decision making is the impact on the body image, the breast morphology after breast conserving surgery is particularly difficult to explain in a uniform manner due to large individual differences. MethodsPatients with breast cancer eligible for breast conserving surgery (BCS) were recruited between June 2020 and October 2021. We surveyed the patients’ satisfaction with our explanation method about breast morphology after BCS using 3D breast imaging in the form of a questionnaire.ResultsA total of 162 patients were enrolled and 137 (84.6%) answered the questionnaire. One hundred and sixteen patients (84.6%) answered that they were very satisfied or satisfied with our explanation method and 100 (73.0%) patients were very satisfied or satisfied with the 3D breast imaging. Some patients answered that visually understanding the breast morphology by 3D breast imaging helped them to prepare for BCS, or on the contrary, made them chose mastectomy with breast reconstruction because the postoperative deformation of BCS was found to be unacceptable. Only a few patients who actually underwent BCS felt that their postoperative morphology was more deformed than the preoperatively imagined one.ConclusionOur results suggest that our preoperative explanation method using 3D breast imaging was useful for shared decision making. We think that 3D breast imaging can help the patients to visualize the individual shape of their breast, and the tumor position and size.

Background Neoplastic seeding (NS) can occur after tissue biopsy, which is a clinical issue especially in mastectomy with immediate reconstruction. This is because postoperative radiation is not usually given and local recurrence of preserved skin flap may increase. The purpose of this study is to investigate the importance of preoperative evaluation of NS and the validity of biopsy scar excision. Patients and methods We retrospectively analysed 174 cases of mastectomy with immediate breast reconstruction. The primary endpoint is the frequency of clinical and pathological NS and the secondary endpoint is the problem of excision of needle biopsy site. Results Three cases (1.7%) had preoperative clinical findings of NS. Pathological examination revealed NS in all three cases. Biopsy scars could be excised in 115 cases among 171 cases without clinical NS. Pathological NS was found in 1 of 66 (1.5%) cases of which pathological examination was performed. Biopsy scars could not be excised in the remaining 56 cases: the biopsy scar could not be identified in 41 cases, and there was concern about a decrease in flap blood flow after excision in 15 cases. In 12 of these 15 cases, the scars were close to the skin incision; excision of these scars might have triggered skin necrosis between the incision and the biopsy scar excision site. No postoperative complications were observed. Conclusions It is important to preoperatively evaluate clinical NS, and biopsy scars should be excised in clinical NS cases. Even in cases without clinical NS, biopsy scar excision should be considered. It is also important to perform a biopsy in consideration of the incision design for reconstructive surgery., It is important to evaluate clinical neoplastic seeding (NS) due to biopsy. Biopsy scars should be excised in clinical NS cases. Excision should be considered even without clinical NS.

IntroductionThe antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has led to a change in the clinical management of breast cancer. Nausea and vomiting are the most common adverse events of T-DXd, which cannot be completely alleviated by standard prophylactic regimens. Olanzapine is particularly effective in preventing delayed nausea caused by chemotherapy. In this study, we will evaluate the efficacy of olanzapine in managing persistent nausea and vomiting during T-DXd treatment.Methods and analysisThe ERICA study is a multicentre, placebo-controlled, double-blind, randomised phase II study with the aim to evaluate the antiemetic effects of the prophylactic olanzapine (5 mg orally, on days 1–6) or placebo combined with a 1,5-hydroxytryptamine-3 (5-HT3)–receptor antagonist and dexamethasone in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer undergoing T-DXd treatment. For a period of 22 days from the day of T-DXd treatment, patients will document their experience in an electronic symptom diary daily during observational periods. The primary endpoint is the complete response rate, defined as no vomiting and no rescue medications during the ‘delayed phase’ of 24–120 hours post-T-DXd administration. In addition, we define 120–504 hour as the ‘persistent phase’ and 0–504 hours as the ‘overall phase’ for secondary endpoint analysis. We have estimated that a total sample size of at least 156 patients is needed to allow a power of 80% at a one-sided significance level of 20% in this study. The target sample size is set to 166 to account for possible case exclusions.Ethics and disseminationThe study protocol is approved by the West Japan Oncology Group protocol review committee and the SHOWA University Clinical Research Review Board. The study results will be presented at international conferences and published in a peer-reviewed journal.Trial registration numberjRCTs031210410.

Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

PurposeNivolumab is recommended for patients with advanced esophageal squamous cell carcinoma (aESCC) who are refractory or intolerant to fluoropyrimidine-based and platinum-based chemotherapy regardless of tumor proportion score (TPS). However, the predictive role of combined positive score (CPS) to predict nivolumab efficacy is unclear.MethodsWe retrospectively collected data from patients with aESCC, who were previously treated with fluoropyrimidines and platinum, and subsequently received nivolumab monotherapy between January 1, 2014 and September 15, 2020. Next, we examined the impact of CPS and TPS on clinical response to nivolumab. The inclusion criteria were refraction or intolerance to fluoropyrimidines and platinum, absence of comorbid malignancies, availability of tissue specimen for immunohistochemistry and programmed cell death-1 analysis results before initiating nivolumab.ResultsFifty patients were included (CPS, ≥ 10/1–10/< 1, n = 23/18/9; TPS, ≥ 10/1–10/< 1%, n = 17/8/25). The median progression-free survival were 4.1, 2.5, and 1.4 months in CPS ≥ 10, 1–10 (hazard ratio [HR] vs. CPS ≥ 10, 1.05; p = 0.90), and < 1 (HR vs. CPS ≥ 10, 3.75; p = 0.003) groups, respectively. Furthermore, among the patients with CPS ≥ 10/1–10/< 1, and TPS ≥ 10/1–10/< 1%, objective response rate were 32/25/0% and 36/0/19%. In addition, disease control rate were 63/50/11% (p = 0.04) and 65/40/38% (p = 0.30).ConclusionsThis study proposes that CPS can predict responses to nivolumab in patients with aESCC better than TPS, making it especially useful for predicting negative outcomes for those with CPS < 1.

Purpose: Breast cancer-related lymphedema (LE) significantly impairs the patients’ quality of life. Axillary lymph node dissection (ALND) is a strong risk factor for LE in breast cancer surgery. In addition, postoperative administration of docetaxel (DTX) has been reported to be a risk factor for LE in patients who undergo ALND. Herein, we performed a secondary analysis of the risk of objective LE after ALND using data from our previous study.Methods: Patients who visited the medical follow-up clinic between 12 November 2018 and 11 January 2019 and at least one year postoperatively were eligible for this study. Objective LE was defined as a difference of at least 2 cm between the affected and unaffected arms or when therapeutic intervention had already been performed for LE. The risk factors for objective LE according to taxane-containing regimen, radiation therapy, and body mass index and the effects of a taxane-containing regimen followed by supraclavicular irradiation on LE were examined.Results: Objective LE was observed in 52 patients (24%). Univariate and multivariate analyses showed that supraclavicular field irradiation was a statistically significant risk factor for objective LE. The sequential use of taxane-containing regimen and supraclavicular RT was more likely to be a risk factor for LE than ALND alone.Conclusion: The risk for LE was more likely to be higher with the sequential use of taxane-containing chemotherapy and supraclavicular field irradiation. Therefore, management of LE is important these cases.

Background Bevacizumab is an antiangiogenic agent, and that synergizes with chemotherapeutic drugs. When used in combination therapies, Bevacizumab is associated with adverse events such as hemorrhage, gastrointestinal perforation, delayed wound healing, and pneumothorax. However, the molecular mechanisms underlying these adverse events are not fully understood. Case summary A 45-year-old female with multiple lung metastases that were derived from primary breast cancer, was placed on Bevacizumab + paclitaxel therapy, since this combination has a potent antitumor effect. She reported dyspnea before cycle 3, day 1 and we therefore ran a chest X-ray, which detected a right pneumothorax. The coronal plane computed tomography revealed that one solid mass rapidly necrosed and was replaced by a cavity that passed through the bronchus in the right lower lobe. The cavity eventually ruptured the pleura and made the bronchopleural fistula that led to this pneumothorax. Thoracic cavity drainage using an intercostal catheter was performed. On the 7th day of drainage, the patient was discharged from our hospital on recovery. Recurrence of pneumothorax was not reported, and continuation of chemotherapy was made possible by changing the regimen. Conclusion Patients with lung metastases surrounding the bronchi and on the pleura should be monitored for pneumothorax by Bevacizumab-containing chemotherapies.

PurposeFluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab is the standard second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to fluoropyrimidines and oxaliplatin. However, the benefits of incorporating fluoropyrimidines into second-line chemotherapy for patients with mCRC who are refractory to fluoropyrimidines in first-line chemotherapy are unknown.MethodsWe retrospectively evaluated patients with mCRC who were administered irinotecan plus bevacizumab or FOLFIRI plus bevacizumab as second-line chemotherapy at a single institution from January 2010 to April 2020. We compared the efficacy and safety of irinotecan plus bevacizumab (IRI group) with those of FOLFIRI plus bevacizumab (FOLFIRI group).ResultsOf the 255 enrolled patients, 107 (IRI/FOLFIRI group, 31/76 patients) were eligible for analysis. After a median follow-up of 13.1 months (range, 1.2–48.4) and 14.3 months (range, 0.9–46.5) for the IRI and FOLFIRI groups, respectively, the median progression-free survival was 6.4 months and 5.8 months [adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.50–1.34, p=0.44] and the median overall survival was 16.6 months and 16.5 months (aHR, 1.01; 95% CI, 0.59–1.69; p=0.97) in the IRI and FOLFIRI groups, respectively. All grade nausea, vomiting, decreased appetite, stomatitis, hand-foot syndrome, neutropenia, thrombocytopenia, increased creatinine, Grade 3/4 neutropenia, and febrile neutropenia occurred more frequently in the FOLFIRI group than in the IRI group.ConclusionOmitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy may reduce adverse events without affecting antitumor activity in patients with mCRC who are refractory to fluoropyrimidines.

This study aimed to determine interstitial lung disease (ILD) incidences in patients receiving cancer drug therapies with or without bevacizumab treatment.Systematic searches of PubMed, Embase, and Cochrane Library were conducted in January 2021. The main inclusion criteria were randomized clinical trials that compared bevacizumab with standard treatment in patients with solid tumors. Cochrane Collaboration's Tool was used for assessing risk-of-bias.Thirteen records involving 7201 patients were included in the meta-analysis. There were 42 ILD events in bevacizumab groups and 72 in control groups. In bevacizumab groups, the odds ratio for ILD was 0.62 (95% CI 0.42-0.92; p = 0.02), which was a significantly lower incidence than the control. This tendency was shown in targeted therapy groups but not in the cytotoxic agent groups.Our data suggest that bevacizumab may reduce the incidence of ILD.

Background/aim Metastatic small bowel adenocarcinoma (SBA) is a rare disease with poor prognosis. This study aimed to explore the efficacy and safety of second-line chemotherapy for patients with SBA. Patients and methods We retrospectively reviewed the clinical characteristics of 27 metastatic patients with SBA after progression on first-line chemotherapy. The patients were divided into Cohort A, receiving second-line chemotherapy, and Cohort B, receiving best supportive care. Results Patients in Cohort B had higher age, worse performance status, and higher neutrophil-to-lymphocyte ratio compared with those in Cohort A. Cohort A showed significantly better overall survival (OS) compared with Cohort B (median OS, 15.6 vs. 3.4 months; p=0.002). Objective response rate, disease control rate, and median progression-free survival (PFS) for Cohort A were 7%, 74%, and 5.0 months, respectively. Patients who underwent irinotecan-based chemotherapy showed longer PFS and OS compared with those who underwent taxane-based chemotherapy. No significant adverse events were reported. Conclusion Second-line chemotherapy for metastatic SBA demonstrated clinical activity with acceptable toxicities.

We present a study of growth of quasicrystalline bismuth (Bi) thin films on the five-fold surface of the icosahedral Ag-In-Yb quasicrystal using scanning tunnelling microscopy (STM). The main building block of the Ag-In-Yb quasicrystal is a rhombic triacontahedral (RTH) cluster, which is formed by successive shells of atoms. The surface is formed at bulk planes which intersect the centres of the RTH clusters. We show that the deposited Bi atoms occupy vacant sites above the surface where the atoms of the RTH clusters would be and thus Bi grows with three-dimensional quasicrystalline order. Further deposition of Bi yields crystalline Bi islands aligned along high symmetry directions of the substrate.

OBJECTIVES Insufficient oral intake in advanced gastric cancer (AGC) limits the use of several drugs. We aimed to determine the oral intake status of patients with AGC during later-line chemotherapy. MATERIALS AND METHODS We retrospectively evaluated data of patients with AGC who experienced disease progression during first-line chemotherapy administered from January 2012 to December 2018 in a single institution. We defined "insufficient oral intake" as requiring daily intravenous fluids or hyperalimentation. Multivariate logistic regression was performed to identify oral intake-related factors. RESULTS Among 589 included patients, at disease progression during first-line, second-line, and third-line chemotherapy, 78.3% (461), 53.3% (314), and 30.4% (179) of patients, respectively, exhibited sufficient oral intake. Fourth-line chemotherapy was initiated for 22.2% (131) of patients, with 20.0% (118) exhibiting sufficient oral intake. During second-line and third-line chemotherapy, 11/67 (16%) and 2/39 (5%) patients, respectively, exhibited improvements in oral intake; 85/428 (19.9%) and 70/259 (27.0%), respectively, exhibited deteriorations in oral intake. Factors correlated to deterioration in oral intake during second-line chemotherapy were poor Eastern Cooperative Oncology Group Performance Status (odds ratio, 4.32; P

PurposeThe DESTINY-Breast04 clinical trial is currently investigating whether trastuzumab deruxtecan (T-DXd) is effective in HER2-low as well as HER2-positive breast cancer. This highlights the interest in treatment strategies for patients with HER2-low breast cancer. The current study was therefore designed to determine the frequency of HER2-low among all breast cancers, and to compare the prognosis of HER2-low patients with that of HER2-negative patients. MethodsWe retrospectively reviewed the biological data from 4,918 of 4,977 primary breast cancer patients who attended our institute. We quantified the overall frequency of breast cancer patients with a new HER2-low subtype that was defined by an immunohistochemistry score of IHC1+ or IHC2+/ISH-. We then compared the clinical characteristics and prognosis of HER2-low patients with that of patients who did not have HER2 amplification (HER2-0). ResultsLow HER2 expression was found in 3169 (64.4%) patients; 2860 (58.1%) were HR-positive and 309(6.3%) were HR-negative. Among HER2-0 patients, 681(13.9%) were HR-positive and 157(3.2%) were HR-negative. The HER2-0 group tended to have more poor prognostic factors than the HER2-low group, irrespective of HR status. There were no statistically significant differences between the prognosis of HER2-low and HER2-0 patients, regardless of HR status. However, patients in the HER2-low group tended to have better prognosis than those in the HER2-0 group.ConclusionHER2-low patients did not have a significantly different prognosis than HER2-0 patients, regardless of HR status. However, we should consider tailoring therapies for patients with HRE2-low early breast cancer according to their HR status.

The recently discovered antiferromagnetic 1/1 Au-Al-Tb approximant exhibits a whirling spin order oriented along the [111] direction. Here we report an investigation of the atomic structure of the (111) surface by scanning tunneling microscopy and density functional theory (DFT) calculations. Scanning tunneling microscopy reveals a Tb-terminated step-terrace morphology, with step heights appearing to minimize the number of broken bulk icosahedra. The atomic structure of the terraces is bias dependent, with Tb atoms imaged under positive bias and Au/Al atoms under negative bias. The surface is found to reconstruct, with the Au/Al atoms producing a linear row structure, an example of a surface reconstruction in a Tsai-type system. These observations are confirmed by DFT calculations.

The efficacy of adjuvant endocrine therapy for hormone receptor-positive breast cancer has been previously established. However, significant adverse events related to endocrine therapy cannot be ignored. T1 breast cancer is expected to have a good prognosis. Therefore, adjuvant endocrine therapy for T1a breast cancer patients is controversial. Thus, in this study, we examined the effect of endocrine therapy on the prognosis of T1N0 hormone receptor-positive, HER2-negative breast cancer patients in each tumor size group, and re-considered the application of endocrine therapy. We retrospectively obtained clinical and pathological data from medical records of 7635 patients who underwent surgery for breast cancer at Aichi Cancer Hospital between January 2000 and December 2017. The primary end point of our analysis was disease-free survival (DFS). The secondary end points were distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS). The log-rank test, cumulative survival generated curves with Kaplan–Meier methods and the hazard ratio (HR) calculated with a Cox regression model were used to assess the effects of endocrine therapy on prognosis. The 5-year DFS was worse in the non-endocrine therapy (non-ET) group (78%) than the endocrine therapy (ET) group (95%) in the T1c population (p

Chemotherapy is the mainstay treatment for advanced poorly differentiated gastrointestinal neuroendocrine carcinoma (GI-NEC), with platinum-containing regimens being the optimal first-line regimen. However, the role and efficacy of second-line chemotherapy for GI-NEC are unclear. This study aimed to evaluate the feasibility and efficacy of fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line therapy in patients with relapsed or recurrent GI-NEC after first-line platinum plus etoposide therapy. We retrospectively evaluated eight consecutive patients with unresectable GI-NEC treated between 2017 and 2020. The inclusion criteria were pre-treatment with platinum doublet therapy, performance status (PS) 0–2, having measurable lesions, and treatment with FOLFIRI as second-line therapy. The overall response rate, progression-free survival (PFS), overall survival (OS), safety, and relative dose intensity were evaluated. Five patients met the inclusion criteria. Overall, 37 cycles of FOLFIRI were administered. The relative dose intensities for irinotecan, continuous infusion of 5-FU, and a bolus injection of 5-FU were 76%, 72%, and 54%, respectively. Overall, 2 of the 5 patients achieved partial response (40%), and the duration of response (DOR) was 4.0 months. The PFS and OS rates were 5.8 (95% CI, 1.5-NA) and 11 (95% CI, 6.3-NA) months, respectively. Overall, 4 of the 5 patients (80%) proceeded with further chemotherapy. Grade ≥ 3 adverse events except hematological toxicity included febrile neutropenia (n = 2), anorexia (n = 2), and fatigue (n = 1). Treatment discontinuation due to treatment-related adverse events was not observed. FOLFIRI showed modest efficacy and feasibility for GI-NEC patients and has thus potential for patients who fail the first-line treatment.

Safely postponing the use of chemotherapy is important for quality of life maintenance in patients with hormone receptor-positive advanced breast cancer. In previous studies, a combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and fulvestrant prolonged the time to chemotherapy (TTC). In this study, we used real-world data to evaluate TTC in the context of CDK4/6i therapy.We performed a retrospective chart review of women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated at the Aichi Cancer Center Hospital. The patients were categorized into having received CDK4/6i therapy first (n = 41), second (n = 33), and none at all (n = 67). The change in TTC among the groups was examined.The median follow-up time was 13.8, 27.5, and 30.3 months in the CDK4/6i (first), CDK4/6i (second), and non-CDK4/6i groups, respectively. The median progression-free survival (PFS) with first-line therapy for metastasis was 30.0, 11.9, and 13.0 months, respectively (CDK4/6i [first] vs. non-CDK4/6i;Although PFS was significantly longer in the CDK4/6i (first) group than in the non-CDK4/6i group, TTC did not significantly differ among the three groups in real-world data. The non-CDK4/6i group showed a long TTC in patients with late recurrence and low risk at the primary lesion site, who benefited greatly from hormone monotherapy.

Background There are no established guidelines for the management of apocrine carcinomas of the breast; they are treated as a non-specific type of breast cancer. Case report We report on the case of a 40-year-old man who developed primary mediastinal apocrine carcinoma overexpressing human epidermal growth factor-2 (HER2). The patient initially underwent complete resection of a mediastinal mature teratoma with a focal apocrine carcinoma component. Two years after surgery, relapse was detected in multiple mediastinal lymph nodes. He received induction chemotherapy including docetaxel, trastuzumab, and pertuzumab; consolidative concurrent chemoradiation was added after six cycles. A complete response was confirmed using computed tomography following this multimodal therapy. After chemoradiation, adjuvant trastuzumab and pertuzumab were administered for 1 year and the patient has since had no evidence of progressive disease. Conclusion A multi-modal regimen that includes an anti-HER2 agent appears to be a promising treatment for patients with HER2-positive extramammary apocrine carcinoma.

Treatment options for patients with relapsed/refractory small cell lung cancer (R/R SCLC) are limited, and the efficacy of salvage therapies for heavily treated patients should be assessed. Here, we evaluated the efficacy of paclitaxel (PTX) in R/R SCLC patients. A single-institute retrospective chart review was conducted. The primary endpoint was overall survival (OS), whereas the secondary endpoints were progression-free survival (PFS), overall response rate, disease control rate (DCR), and safety. Thirty-one patients (median age, 69 [range, 56–80] years) were analyzed. The median follow-up period was 122 (range, 28–1121) days. The median OS and PFS were 4.4 and 2.2 months, respectively. Adverse events of grade 3 or higher, other than hematological toxicity, were febrile neutropenia and neuropathy. Multivariate analyses identified the following independent predictors of poor OS: performance status and lactate dehydrogenase at the upper limit of normal. PTX monotherapy showed moderate efficacy with acceptable toxicity in heavily treated patients with R/R SCLC patients.

e16045 Background: The ATTRACTION-3 trial showed that nivolumab (Nivo) significantly improved overall survival (OS) of patients (pts) with previously treated advanced esophageal squamous cell carcinoma (ESCC) regardless of tumor programmed cell death ligand-1 (PD-L1) expression assessed with tumor proportion score (TPS). On the other hand, pembrolizumab prolonged OS in advanced esophageal carcinoma pts with combined positive score (CPS) of ≥ 10 in the KEYNOTE-181 trial. Whether CPS can predict clinical outcome of Nivo in advanced ESCC pts remains unclear. Methods: We retrospectively evaluated advanced ESCC pts who received Nivo at a single institution between January 2014 and September 2020. The main eligibility criteria were as follows: refractory or intolerant to fluoropyrimidines and platinum, no prior anti-PD-1/PD-L1 antibody treatment, no comorbid malignancies, and available tissue specimens obtained before initiation of Nivo. PD-L1 immunostaining was performed using PD-L1 IHC 22C3 pharmDx assay, and the tumors were classified into three groups depending on CPS (≥ 10, 1–10, < 1). The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and OS were calculated using a multivariate Cox model that contained variables with p values < 0.05 in the univariate analysis. Results: Among 69 pts, 50 were eligible (CPS ≥ 10/CPS 1–10/CPS < 1, 23/18/9). Patient characteristics were as follows (CPS ≥ 10/CPS 1–10/CPS < 1): age, ≥ 65, 70/67/67%; male, 83/67/78%; PS ≥ 1, 61/72/44%; second-line treatment, 65/61/56%; disease status, recurrent, 61/33/78%; prior esophagectomy, 65/33/44%; prior radiotherapy, 57/56/56%; prior taxane, 52/28/44%; the number of metastatic sites, ≥ 2, 48/61/89%; lymph node metastasis, 78/83/89%, lung metastasis, 26/22/56%; liver metastasis, 17/17/44%. Among 42 pts (84%) with disease progression after Nivo treatment, 24 pts received salvage-line chemotherapy. The adjustment factor for PFS was liver metastasis, while that for OS was not detected. The median PFS was 4.1 months (mo) in CPS ≥ 10 and 2.5 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.06; 95% CI, 0.51–2.17; p = 0.864; aHR, 1.15; 95% CI, 0.54–2.36; p = 0.713), and 1.4 mo in CPS < 1 (HR vs. CPS ≥ 10, 3,78; 95% CI, 1.53–8.92; p = 0.005; aHR, 1.91; 95% CI, 0.67–5.39; p = 0.223). The median OS was 12.3 mo in CPS ≥ 10, 10.2 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.72; 95% CI, 0.75–4.00; p = 0.201), and 9.0 mo in CPS < 1 (HR vs. CPS ≥ 10, 2.31; 95% CI, 0.92–5.69; p = 0.075). Objective response rate (CPS ≥ 10/CPS 1–10/CPS < 1) in 40 pts who had measurable lesions were 32/25/0%, respectively. Conclusions: The pts with CPS of < 1 did not respond to Nivo. Our study suggests that CPS is useful for predicting response to Nivo in pts with advanced ESCC.[Table: see text]

234 Background: Nivolumab (Nivo) is a standard therapy after ramucirumab (RAM)-based second-line chemotherapy in patients (pts) with advanced gastric cancer (AGC). However, the relationship between angiogenesis-related factors and the efficacies of immune-checkpoint inhibitors after anti-angiogenic chemotherapy is unclear. Methods: We retrospectively evaluated pts with AGCs who received Nivo after RAM-based second-line chemotherapy at a single institution from Nov 2017 to Aug 2019. Clinical benefit of Nivo was defined as CR, PR, or >4 months of SD and non-CR/non-PD. In addition, preserved serum samples at time points of pre-RAM, pre-Nivo, and post-Nivo (within 12 weeks from the start of Nivo) were analyzed by using the designated panel, containing vascular endothelial growth factor-A/D (VEGF-A/D), placental growth factor (PlGF), soluble vascular endothelial growth factor receptor-1/2/3 (sVEGFR-1/2/3), Interleukin-6/8 (IL-6/8), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), angiopoietin-2, hepatocyte growth factor (HGF), interferon gamma (INF-γ), osteopontin (OPN), soluble neuropilin-1, and thrombospondin-2 (TSP-2). We investigated the association between angiogenesis-related factors and clinical outcomes with Nivo. Results: We evaluated 167 samples from 58 pts, including 10 pts (17.2%) exhibiting clinical benefit. Characteristics of pts were as follows: median age, 68; male, 74%; PS, 0/1-2, 17/83%; HER2 positive, 16%; prior gastrectomy, 40%; histology, intestinal/diffuse, 16/84%; disease status, metastatic/recurrent, 69/31%; lung metasstasis, 14%; liver metasstasis, 26%; peritoneum metastasis, 67%; lymph node metastasis, 31%. The median progression-free survival (PFS) and overall survival (OS) of Nivo were 1.7 and 6.2 months, respectively, with a median follow-up of 5.0 months. There were no correlations between pre-Nivo levels of angiogenesis-related factors and clinical benefit; however, the median post-Nivo/pre-Nivo VEGF-A ratio was significantly lower in pts with clinical benefit than in those without clinical benefit (0.44 versus 0.94, p = 0.008). By multivariate analysis using characteristics of pts and data from pre-Nivo samples, VEGF-A above the median level of 1400 pg/mL and sVCAM-1 below the median level of 1640000 pg/mL were independent prognostic factors for poor PFS (hazard ratio, 1.90, p = 0.033) and OS (hazard ratio, 2.02, p = 0.037), respectively. Conclusions: Our study suggests that rapid decline of serum VEGF-A level after Nivo and higher VEGF-A before Nivo were respectively associated with the clinical benefit of Nivo and poor survival in pts with AGC treated with Nivo after RAM-based second-line chemotherapy.

76 Background: FOLFIRI + bevacizumab (FOLFIRI + BEV) is a standard second-line chemotherapy (Cx) for metastatic colorectal cancer (mCRC) patients (pts) who are refractory or intolerant to fluoropyrimidines (FPs) and oxaliplatin (OX). However, the efficacy of continuing FPs as second-line Cx for pts who are refractory to FPs in first-line Cx remains unclear. Methods: We retrospectively evaluated mCRC pts who received irinotecan (IRI) + BEV or FOLFIRI + BEV as second-line Cx at a single institution from Jan 2010 to Apr 2020. The main eligibility criteria were ECOG performance status (PS) of 0-2, known KRAS status, a standard initial dose of fluorouracil (5-FU) (bolus 400 mg/m2, infusional 2400 mg/m2) in FOLFIRI + BEV and IRI (150 mg/m2), refractory to FPs, no prior use of IRI, and prior use of OX. We compared the efficacy and safety of IRI + BEV with those of FOLFIRI + BEV. The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and overall survival (OS) were calculated using a multivariate Cox model that contained variables with p < 0.05 in the univariate analysis to reduce the imbalance between both the treatments. Results: Among the 261 pts, 107 were eligible (IRI + BEV/FOLFIRI + BEV, 31/76 pts). Pt characteristics were as follows (IRI + BEV/FOLFIRI + BEV): median age, 67/62; ECOG PS, 1–2, 55/46%; KRAS mutant, 45/50%; BRAF V600E mutant, 6/11%; right-sided tumor, 19/43%; lactate dehydrogenase (LDH) ≥ 400 U/L, 13/12%; PFS of first-line Cx < 6 month (m), 39/30%; prior use of BEV, 84/63%. Relative dose intensity (RDI) (IRI + BEV/FOLFIRI + BEV) of IRI and BEV was similar in the groups; median RDI (range) of IRI, 80 (44–100) /83 (49–100) %; p = 0.560; median RDI of BEV, 86 (35–100) /83 (20–100) %; p = 0.681. Efficacies (IRI + BEV/FOLFIRI + BEV) after a median follow-up of 13.1/14.3 m were as follows: median PFS, 6.4/5.8 m (HR, 0.90; 95% CI, 0.57–1.38; p = 0.64; aHR, 0.82; 95% CI, 0.50-1.34; p = 0.44); median OS, 16.6/16.5 m (HR, 0.83; 95% CI, 0.51-1.32; p = 0.44; aHR, 1.01; 95% CI, 0.59-1.69; p = 0.97); objective response rate, 25.9/11.3%. Adjustment factors for PFS were prior colorectomy, number of metastatic sites, ECOG PS, liver metastasis, and the level of LDH, while those for OS were prior colorectomy, number of metastatic sites, liver metastasis, peritoneal metastasis, and the level of LDH. All subgroup analyses for PFS and OS according to the pt characteristics also showed no significant differences in the groups. All grade nausea (32/58%) and stomatitis (13/36%) and grade 3–4 neutropenia (23/58%) and febrile neutropenia (0/3%) were less common in the IRI + BEV than in the FOLFIRI + BEV group. Conclusions: Our study suggests that omitting 5-FU from FOLFIRI + BEV as second-line Cx for mCRC pts who are refractory to FPs may lower the occurrence of adverse events without impairing the treatment efficacy.