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Background: Neoadjuvant chemotherapy (NAC) has evolved significantly and has been widely accepted for downstaging disease in early-stage and locally advanced breast cancer patients. Since the optimal surgical intervention of the breast for patients receiving NAC remains controversial, we aim to investigate the survival outcome of patients treated with different surgical management. Methods: Patients with invasive breast cancer that underwent NAC in Fudan University Shanghai Cancer Center from January 2010 to June 2019 were involved in this study. Based on surgical intervention of the breast following NAC, patients were divided into mastectomy and breast conservation groups. To be specific, the mastectomy group involved patients who received mastectomy alone or mastectomy plus immediate breast reconstruction (M+IBR), while the breast conservation group evolved patients who underwent conventional breast-conserving surgery (CBCS) and oncoplastic surgery (OPS). Surgical interventions were performed by breast surgeons. Propensity scores matching was utilized for group matching. Results: A total of 2080 patients were enrolled in this study. Among them, 1819 (87.5%) patients were categorized as mastectomy group, and 261 (12.5%) patients were classed as breast conservation group. In the mastectomy group, mastectomy alone and M+IBR accounted for 82.5% (1715/2080) and 5% (104/2080) patients respectively. As for breast conservation, 170 (8.2%) and 91 (4.4%) patients were treated with CBCS and OPS after NAC. Over 9-years of research, the proportion of breast conservation steadily increased in patients after NAC. Notably, the percentage of patients undergoing OPS increased from 0.43 % to 7.60 % throughout the 9 years. Moreover, increasing rate of M+IBR was also observed in the study cohort, whereas fewer patients opted for mastectomy alone as surgical intervention after NAC. Compared with mastectomy group, patients underwent BCS showed younger age (P < 0.001), as well as higher proportion of normal BMI (P = 0.022), pre-menopausal status (P < 0.001), and triple-negative breast cancer (P < 0.008). Additionally, patients with tumors of advanced clinical T stage (P < 0.001) and TNM stage (P = 0.002) were more often to be treated with mastectomy (Table 1). After propensity score matching, 460 patients were matched successfully (Table 2). Compared with the mastectomy group, significant benefits in overall survival (Hazard ratio 0.51, [95% confidence interval: 0.27-0.96]; p=0.044) and disease-free survival (Hazard ratio 0.62, [95% confidence interval: 0.39-0.99]; p Conclusions: Tumor biology can significantly impact the surgical decision in patients administrated with NAC. Breast conservation was a safe alternative for mastectomy in the NAC setting without compromising survival outcomes. Table 1. Clinicopathologic characteristics of patients in mastectomy and breast conservation groups. Table 2. Balanced statistics of patients receiving mastectomy and breast conservation after propensity score matching. Table 3. Survival analysis between matched cohort of patients receiving mastectomy (n=230), breast-conserving therapy (n=230). Citation Format: Yuting Sang, Jiajian Chen, Benlong Yang, Shuang Hao, Xiaoyan Huang, Guangyu Liu, Zhimin Shao, Jiong Wu. Surgical options of the breast and clinical outcomes in breast cancer patients after neoadjuvant chemotherapy: a single-center retrospective study. [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 P2-14-02.

Background: Despite the use of targeted therapy has revolutionized the treatment in the neoadjuvant setting for early, locally advanced, HER2-positive breast cancer, these approaches still have limited efficacy, which calls for persistent exploration for optimized treatment strategy. KN026 is a bispecific monoclonal antibody that targets the distinct extra-cellular domains II (Pertuzumab binding site) and IV (Trastuzumab binding site) of HER2. KN026 has better anti-tumor activity than either Trastuzumab or Pertuzumab used alone, and also aimed to demonstrate similar or better anti-tumor response than Trastuzumab in combination with Pertuzumab. Here we report the preliminary results of KN026 and docetaxel as neoadjuvant treatment in patients with HER2-positive early or locally advanced breast cancer (LABC). Methods: Treatment naive patients with HER2-positive early (T1c or 2, N1, M0; T2 or 3, N0, M0) or locally advanced breast cancer (T1c or 2 or 3, N2, M0; T3N1M0; T1c or 2 or 3, N3a or 3b, M0) were enrolled to receive 4 cycles of KN026 (30mg/kg, ivgtt d1, q3w) and docetaxel (75 mg/m2 ivgtt d1, q3w) neoadjuvant treatment. The primary endpoint was total pCR rate (tpCR; defined as absence of any residual invasive cancer in the breast and lymph nodes) [ypT0/is, ypN0]). Secondary endpoints were pCR in the breast (bpCR, defined as absence of any residual invasive cancer in the breast [ypT0/is]), ORR (objective response rate), safety, PK (pharmacokinetics) and immunogenicity. The study is still ongoing, and the planned enrollment number is 30. This study is registered in ClinicalTrials.gov, number NCT04881929. The data cutoff date was April 15, 2022. Results: Between August 8, 2021, and April 15, 2022, a total of 15 patients were enrolled from 5 sites. 7 (46.7%) patients were stage II, and 8 (53.3%) patients were stage III; 12 (80%) patients with lymph node metastases, and 3 (20%) patients without lymph node metastases; 7 (46.7%) patients were hormone receptor positive, and 8 (53.3%) patients were hormone receptor negative. As of April 15, 2022, 4 patients are still under neoadjuvant therapy, 1 patient withdrew from the study earlier due to AE during neoadjuvant treatment period, and 10 patients completed the surgery. Of the 10 patients who completed surgery, tpCR rate were 50% (5/10, 95% CI: 18.7%-81.3%), bpCR rate were 50% (5/10, 95% CI:18.7%-81.3%), and ORR were 100% (10/10, 95% CI: 69.2%-100%). The incidence of TRAE and Grade ≥3 TRAEs were 100% (15/15) and 53.3% (8/15) respectively. The most common TRAE were alopecia (14/15, 93.3%), white blood cell decreased (10/15, 66.7%), anemia (10/15, 66.7%), diarrhea (9/15, 60.0%), neutrophil count decreased (9/15, 60.0%), alanine aminotransferase increased (8/15, 53.3%) and hypoalbuminemia (8/15, 53.3%). The Grade ≥3 TRAE include neutrophil count decreased (8/15, 53.3%), white blood cell decreased (5/15, 33.3%), alanine aminotransferase increased (1/15, 6.7%), and lymphocyte count decreased (1/15, 6.7%). No Grade 5 TRAEs occurred. 3 TRAEs (Alanine aminotransferase increased, blood bilirubin increased and neutrophil count decreased) leading to KN026 interruption, and no TRAE leading to KN026 discontinuation. 1 SAE (hepatitis E-not TRAE; outcome: recovered) occurred in 1 patient, without other SAE or death throughout the study. Conclusions: KN026 and docetaxel as neoadjuvant treatment has shown promising clinical benefit for patients with HER2-positive early or locally advanced breast cancer with an acceptable and manageable safety profile. Further validation in a large-scale randomized controlled trial is warranted. Citation Format: Jiong Wu, Benlong Yang, Linxiaoxi Ma, Mingliang Zhang, Kun Wang, Yiding Chen, Zhimin Fan, Jing Zhang, Summer Xia. KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer: A single arm, multicenter, phase 2 study [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 OT2-16-04.

Background: Asian women have relatively small breast sizes compared to European American women, so the latissimus dorsi flap (LDF) is the most commonly used autologous flap for breast reconstruction in Chinese patients with breast tumor. To explore the current status of LDF with or without implants (IMP) breast reconstruction in China, we conducted this study. Methods: This study was a single-center retrospective study that included breast tumor patients who underwent LDF breast reconstruction in Fudan University Shanghai Cancer Center (FUSCC) from 2000 to 2019. The basic clinicopathological information, the timing and type of reconstruction, postoperative hospitalization time and serious complications requiring surgical intervention were analyzed. Continuous variables were expressed as mean values or median values, while categorical variables were expressed as frequencies. Data were analyzed by using Chi-square and Kruskal-Wallis tests. All P values reported were two-sided and were calculated at a significance level of 0.05. Results: A total of 2868 patients who underwent breast reconstruction for breast tumor were analyzed in this study, 785 (27.4%) patients used LDF for breast reconstruction, and 397 (13.8%) patients underwent autologous breast reconstruction utilizing abdominal flap. The number of breast reconstruction patients and the diversity of reconstruction procedures were increasing year by year. Breast reconstructions utilizing LDF have decreased as a percentage of breast reconstructions, but have increased in number in the past few years. Among patients with LDF breast reconstruction, the majority (97.3%) underwent immediate reconstruction, 11 patients underwent delay reconstruction, and 10 patients underwent immediate-delay reconstruction. 448 patients underwent expanded LDF breast reconstruction, and 337 (42.9%) patients underwent LDF combined with IMP breast reconstruction. 13 patients underwent restoration of reconstructed breast with LDF, 12 of which were changed to LDF±IMP reconstruction due to unsatisfactory outcome of expander reconstruction or failed implant reconstruction, and one patient was changed to LDF reconstruction from failed abdominal flap reconstruction. In terms of pathological type, 629 (80.1%) patients had invasive carcinoma, 129 (16.4%) had carcinoma in situ, 18 (2.3%) patients had phyllodes tumor and 9 (1.1%) patients had other malignancies. The median reconstruction age of the patients was 37 years old, the mean BMI was 21.76kg/cm2, and the mean postoperative length of stay was 11.13 days. There were no significant differences in postoperative hospitalization time, reconstruction age, BMI, pT, ER, PR, HER2, Ki67, and radiotherapy between patients with expanded LDF and LDF combined with IMP breast reconstruction. Patients with neoadjuvant therapy (P=0.045), phyllodes tumors or other malignant tumors (P=0.023), and those with more metastatic lymph nodes (P=0.031) were tent to expanded latissimus dorsi flap reconstruction. Serious complications requiring surgical intervention occurred in 13 patients (1.65%), including 7 patients who underwent surgical debridement or scar repair due to wound infection and poor healing, and 3 patients who removed the implant due to implant infection. The reconstructed latissimus dorsi flaps necrosis occurred in 3 patients, and the reconstructed breasts were removed in these patients. There was no significant difference in the incidence of serious complications requiring surgical intervention between patients with expanded LDF and those with LDF combined with implant reconstruction, P=0.79. Conclusions: LDF±IMP breast reconstruction is a mature breast reconstruction procedure in our center with high safety. Whether combined with implant reconstruction did not affect the postoperative hospitalization time and the incidence of serious complications. Citation Format: Shuyue Zheng, Jiajian Chen, Shuang Hao, Benlong Yang, Xiaoyan Huang, Guangyu Liu, Jiong Wu. Current status of latissimus dorsi flaps with or without implants for breast reconstruction in patients with breast tumor: A single-center retrospective study [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 P2-15-07.

Background: A dose relationship may exist for both antitumor activity and toxicity of docetaxel in breast cancer (BC) patients, while 86% grade 4 neutropenia and 12% febrile neutropenia (FN) were reported when pretreated advanced breast cancer (ABC) patients received 100 mg/m2 docetaxel monotherapy without hematopoietic support. PHEDRA was a randomized, double-blind, multicenter, phase 3 study comparing the efficacy and safety of adding pyrotinib to trastuzumab and docetaxel as neoadjuvant treatment in women with HER2+ early or locally ABC (ClinicalTrials.gov: NCT03588091). We conducted this exploratory analysis to evaluate the effectiveness of mecapegfilgrastim, a long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF), as primary prophylaxis for neoadjuvant chemotherapy-induced neutropenia in BC patients. Methods: Patients with HER2-positive early or locally ABC were randomly assigned (1:1) to pyrotinib arm receiving 4 neoadjuvant cycles of docetaxel (100 mg/m2 iv d1 q3w), trastuzumab (8 mg/kg iv, cycle 1 d1, then 6 mg/kg d1 q3w), and pyrotinib (400 mg po qd, d1-21, q3w) or placebo arm with placebo, trastuzumab and docetaxel. Per protocol, patients were required to receive a single, 6-mg fixed dose of mecapegfilgrastim on Day 2 of each cycle. Other G-CSF was permitted if mecapegfilgrastim was unavailable at the local center or patients occurred mecapegfilgrastim intolerance. The incidence of neutropenia, FN, time to first neutropenia onset, duration per neutropenia event and cumulative neutropenia duration during neoadjuvant treatment period; and the incidences of grade 3/4 neutropenia, FN and decreased WBC count in Cycle 1 to 4 (C1-4) were presented. The data cutoff date was April 30, 2021. Results: Between July 23, 2018 and January 8, 2021, 355 patients were randomized (pyrotinib arm, n=178; placebo arm, n=177). Among them, 291 (82.0%) patients received a single, 6-mg fixed dose of mecapegfilgrastim in Cycle 1 and 270 (76.1%) patients received mecapegfilgrastim in each of the 4 cycles. Grade 3/4 neutropenia was reported in 33 (18.5%) patients in the pyrotinib arm and 36 (20.3%) patients in the placebo arm. Five (2.8%) patients in the pyrotinib arm and 2 (1.1%) patients in the placebo arm developed FN (5 FN occurred in C1; 2 FN occurred in C2). Median duration of grade 3/4 neutropenia was 3 days in the pyrotinib group and 3 days in the placebo group. Median cumulative duration of grade 3/4 neutropenia was 4 days and 3 days in the pyrotinib group and the placebo group, respectively. Grade 3/4 neutropenia mainly occurred during the first cycle of treatment for both pyrotinib (13.5%) and placebo arm (15.8%), reduced in the second cycle (5.9% vs 4.0%) and thereafter (C3: 1.8% vs 3.4%; C4: 2.4% vs 1.7%). Similar trends were observed for grade 3/4 WBC count decreased in Cycle 1 to 4. No grade 4 infection occurred. Overview of neutropenia, FN and WBC count decreased was summarized in Table 1. Consistent findings were observed in 291 mecapegfilgrastim treated patients. Conclusion: The exploratory analysis demonstrated 6-mg fixed dose of mecapegfilgrastim was effective when administrated as primary prophylaxis for neoadjuvant chemotherapy-induced neutropenia, which could be considered as a new treatment option for its advantage of once-per-cycle dosing and convenient dose management. Table 1.Overview of neutropenia, febrile neutropenia and WBC count decrease during neoadjuvant treatment period.Docetaxel+Trastuzumab+Pyrotinib(N=178)Docetaxel+Trastuzumab+Placebo (N=177)All randomized patients(N=355)Neutropenia, n (%)Any grade57 (32.0)54 (30.5)111 (31.3)Grade 16 (3.4)5 (2.8)11 (3.1)Grade 218 (10.1)13 (7.3)31 (8.7)Grade 315 (8.4)20 (11.3)35 (9.9)Grade 418 (10.1)16 (9.0)34 (9.6)Median time to first onset (IQR), days7 (6-63)6 (6-49)7 (6-53)Median duration per grade 3 or higher neutropenia, days (range)3 (1-16)3 (2-12)3 (1-16)Median cumulative duration of grade 3 or higher neutropenia, days (range)4 (2-16)3 (2-14)3 (2-16)FN, n (%)5 (2.8)2 (1.1)7 (2.0)Grade 3 or higher neutropenia, n (%) *Cycle 124 (13.5)28 (15.8)52 (14.6)Cycle 210 (5.9)7 (4.0)17 (4.9)Cycle 33 (1.8)6 (3.4)9 (2.6)Cycle 44 (2.4)3 (1.7)7 (2.1)Grade 3 or higher FN, n (%) *Cycle 12 (1.1)2 (1.1)4 (1.1)Cycle 22 (1.2)02 (0.6)Cycle 3000Cycle 4000Grade 3 or higher WBC count decreased, n (%) *Cycle 120 (11.2)20 (11.3)40 (11.3)Cycle 28 (4.7)2 (1.1)10 (2.9)Cycle 32 (1.2)1 (0.6)3 (0.9)Cycle 44 (2.4)2 (1.1)6 (1.8)Note: IQR, interquartile range; FN, febrile neutropenia; WBC, white blood cell.*The denominator indicates number of patients with mecapegfilgrastim for prophylaxis use in this cycle. Citation Format: Min He, Benlong Yang, Jiong Wu, Zhenzhen Liu, Hongjian Yang, Jinhai Tang, Kun Wang, Yunjiang Liu, Haibo Wang, Peifen Fu, Shuqun Zhang, Qiang Liu, Zefei Jiang, Shusen Wang, Jian Huang, Chuan Wang, Shu Wang, Yongsheng Wang, Linlin Zhen, Xiaoyu Zhu, Shulin Liu, Ping Yan, Jianjun Zou. Mecapegfilgrastim for primary prophylaxis of neutropenia in 355 HER2+ breast cancer patients treated with neoadjuvant docetaxel in combination with trastuzumab and/or pyrotinib: Exploratory analysis from randomized, double-blind, phase 3 PHEDRA 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 P5-18-10.

Background: Neoadjuvant therapy is an important part of treatments for patients with locally advanced operable breast cancer. Addition of HER2 targeted therapy to neoadjuvant therapy greatly improves the pathological complete response (pCR) and prognosis in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. As the essential markers for targeted therapy decision, HER2 status was reported that might be loss in patients undergo neoadjuvant therapy. Therefore, we evaluated the ratio of HER2 loss and its prognostic impact in HER2-positive breast cancer patients treated with neoadjuvant therapy in a large cohort.Methods: A total of 706 patients with HER2-positive breast cancer without distant metastasis who were diagnosed at the Department of Breast Surgery of Fudan University Cancer Hospital from September 2013 to January 2020 and received neoadjuvant treatment were enrolled in the study. After the neoadjuvant treatment, all patients underwent breast surgery. Patients who did not achieve complete pathological remission (non-PCR) would assess the discordance rate of HER2 status between pre- and post-treatment specimens. The expression of HER2 was assessed by immunohistochemistry or combined with fluorescence in situ hybridization (FISH).Results: 35.5.% (n=251) of HER2-positive breast cancer patients who received neoadjuvant therapy achieved pCR. They have prolonged overall survival than who did not achieve pCR (non-pCR) (hazard ratio [HR], 0.26; P = 0.0068). 83.5% (380/455) of the residual tumor lesions were re-tested by immunohistochemistry in non-PCR group. Among them, patients with loss of HER2 positivity accounted for 18.15% (n=69). The rate of HER2 loss was evaluated separately according to baseline status. In IHC 3+ group, 90.7% (258/289) patients remained as HER2 positive after treatment; In IHC 2+ group, 89.3% (47/78) were still HER2 positive while in IHC result 1+ group, 41.7% (5/12) were identified as HER2 positive. The loss of HER2 expression was significantly related to the baseline low HER2 expression (P Clinicopathological characteristics of HER2-positive breast cancer patients.Characteristics No. (%)No. of patients706Age at diagnosis, Median (range, years)59 (23-75)cT stageT04 (0.6)T193 (13.2)T2452 (64.0)T3109 (15.4)T448 (6.8)cN stageN081 (11.5)N1/N2506 (71.7)N3119 (16.8)ER statusPositive636 (90.1)Negative70 (9.9)PR statusPositive615 (87.1)Negative91 (12.9)HER2 statusIHC 3+, FISH-positive481 (68.12)IHC 3+, N/A98 (13.9)IHC 2+, FISH-positive113 (16.0)IHC 1+, FISH-positive14 (1.98) HER2 status before and after neoadjuvant therapy in patients with HER2-positive breast cancer.Primary tumorn (%)Residual tumorn (%)HER2 statusHER2 statusPositive379 (100)Positive304 (80.2)Negative75 (19.8)HER2 status identified by IHCHER2 status identified by IHCHER2 3+289 (76.3)HER2 3+249 (86.2)HER2 2+31 (10.7)HER2 1+6 (2.1)HER2 03 (1.0)HER2 2+HER2 3+14 (17.9)HER2 2+53 (67.9)HER2 1+9 (11.5)HER2 02 (2.6)HER2 1+HER2 3+2 (16.7)HER2 2+3 (25.0)HER2 1+5 (41.7)HER2 02 (16.7) Citation Format: Yuting Sang, Jiong Wu, Benlong Yang. Loss of HER2 expression in HER2-positive breast cancer patients after neoadjuvant therapy [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 P2-13-20.

Background: Diarrhea is a common side effect of many anti-cancer treatments, including chemotherapeutic agents, tyrosine kinase inhibitors, and pelvic radiotherapy. PHEDRA was a randomized, double-blind, multicenter, phase 3 study comparing the efficacy and safety of adding pyrotinib (an irreversible pan-ErbB inhibitor) to trastuzumab and docetaxel (pyrotinib arm) vs placebo, trastuzumab, and docetaxel (placebo arm) as neoadjuvant treatment in women with HER2+ early or locally advanced breast cancer (ClinicalTrials.gov: NCT03588091). We conducted this exploratory analysis to evaluate the effectiveness of proactive diarrhea management (PDM) according to the recommendation from independent data monitoring committee. Methods: Between July 23, 2018 and January 8, 2021, 355 patients were enrolled and randomized, of whom 212 and 143 patients were randomized before and after the implementation of PDM strategy. The diarrhea management strategy was strengthened with the early identification and proactive management of diarrhea, including use of loperamide as first choice of antidiarrheal agents and strict application of loperamide recommended dose (4 mg initially and an additional 2 mg following each diarrhea stool, not exceeding 16 mg/day). Primary prophylaxis with loperamide was not allowed. The incidence, severity, onset, and duration of diarrhea were summarized. The data cutoff date was April 30, 2021. Results: Of all 178 patients with pyrotinib arm, there were 43 (40.6%) and 56 (77.8%) patients applied loperamide as the first choice of antidiarrheal agents before and after the PDM implementation, respectively. The incidence of grade 3 diarrhea has decreased from 50.0% before the PDM implementation to 36.1% after the PDM implementation (Table 1). During neoadjuvant treatment period, grade 3 diarrhea mainly occurred during the first cycle of treatment for both treatment arms (C1: 20.8%), showing a sharp decreased trend during the following cycles (C2: 8.7%; C3: 5.4%; C4: 4.5%). Furthermore, among patients with pyrotinib arm, the incidences of grade 3 diarrhea in the first, second cycle and thereafter were lower in patients enrolled after the implementation of PDM than those enrolled before the PDM implementation (C1: 29.2%. vs 44.3%; C2: 10.1% vs 21.8%; C3: 7.2% vs 14.1%; C4: 4.5% vs 11.1%). Among patients with pyrotinib, compared with those enrolled before the PDM implementation, the median duration per diarrhea episode (4 days [IQR, 2-9] vs 2 days [1-5]), median duration per grade 3 diarrhea episode (2 days [IQR, 2-3] vs 2 days [1-2]), and median cumulative duration of grade 3 diarrhea (6 days [IQR, 3-9] vs 2 [2-5] days) were shortened in those enrolled after the PDM implementation. During neoadjuvant treatment period, 31 (17.4%) patients experienced diarrhea leading to pyrotinib dose reduction, and only 1 (0.6%) patient discontinued study treatment due to diarrhea in the pyrotinib arm. Conclusion: Pyrotinib tolerability was improved with PDM, which reduced the incidence and duration of grade 3 diarrhea. Grade 3 diarrhoea occurred mainly during the first cycle of treatment and reduced in the second cycle and thereafter. Diarrhea in the pyrotinib group was characterized by early onset and short duration and was generally manageable. Table 1.Characteristics of treatment-emergent diarrheaBEFORE the implementation of PDMAFTER the implementation of PDMPyrotinib+Trastuzumab+Docetaxel(N=106)Placebo+Trastuzumab+Docetaxel(N=106)Pyrotinib+Trastuzumab+Docetaxel(N=72)Placebo+Trastuzumab+Docetaxel(N=71)Diarrhea incidence, n (%)All grade106 (100.0)57 (53.8)72 (100.0)36 (50.7)Grade 112 (11.3)32 (30.2)7 (9.7)28 (39.4)Grade 241 (38.7)18 (17.0)39 (54.2)6 (8.5)Grade 353 (50.0)7 (6.6)26 (36.1)2 (2.8)Cycle 147 (44.3)4 (3.8)21 (29.2)2 (2.8)Cycle 222 (21.8)2 (1.9)7 (10.1)0Cycle 314 (14.1)05 (7.2)0Cycle 411 (11.1)2 (1.9)3 (4.5)0Grade 4 or 50000Median time to the first onset, days (IQR)All grade4 (2 to 5)7 (4 to 28)3 (2 to 4)6 (5 to 12)Grade 39 (5 to 11)16 (7 to 24)9 (6 to 12)11 (6 to 16)Median duration per diarrhea episode, days (IQR)All grade4 (2 to 9)2 (2 to 4)2 (1 to 5)2 (1 to 3)Grade 32 (2 to 3)2 (2 to 2)2 (1 to 2)1 (1 to 1)Median cumulative duration, days (IQR)Grade 36 (3 to 9)2 (2 to 3)2 (2 to 5)1 (1 to 1)Median time since the first onset to recovery, days (IQR)All grade7 (3 to 12)2 (2 to 4)3 (1 to 10)2 (1 to 4)Note: PDM, proactive diarrhea management; IQR, interquartile range. Citation Format: Benlong Yang, Jiong Wu, Zhenzhen Liu, Hongjian Yang, Jinhai Tang, Kun Wang, Yunjiang Liu, Haibo Wang, Peifen Fu, Shuqun Zhang, Qiang Liu, Zefei Jiang, Shusen Wang, Jian Huang, Chuan Wang, Shu Wang, Yongsheng Wang, Linlin Zhen, Fei Wu, Shulin Liu, Xiang Lin, Jianjun Zou. Proactive diarrhea management improved tolerability of pyrotinib in combination with trastuzumab and docetaxel in patients with HER2+ early or locally advanced breast cancer: Exploratory analysis from randomized, double-blind, phase 3 PHEDRA 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 P5-18-06.

Background Mitoxantrone hydrochloride injection for lymph tracing (MHI) is a novel lymphatic tracer for sentinel lymph node (SLN) in patients with early breast cancer but exhibited remarkable liver, kidney, and hematologic toxicities in previous studies. Here, the pharmacokinetics and pharmacodynamics profiles of MHI were evaluated to surmise safety and tolerability. Methods Phase 1 open-label, single center, and dose escalation study was performed. Ten patients with invasive breast cancer received 0.5, 1.0, or 2.0 mL of MHI into the breast tissues surrounding the tumor for lymphatic mapping. All of these patients were injected with 2 mCi nuclide-labeled sulfur colloid as a self-control 24 to 48 hours before surgery. Safety was assessed by the incidence of adverse events graded by the National Cancer Institute Common Terminology Criteria, version 4.0.3 (CTCAE4.0.3). Blood samples for pharmacokinetic analyses were collected before and after administration at 15, 30, 60, 120, and 240 min of the injection of MHI. Results Up to the cutoff date of the study (Aug 8, 2018), no dose-limiting toxic effects or obvious allergic reactions were observed. Only one case of an adverse event was certainly related to MHI, where it caused blue discoloration of the local skin over the injection site after the operation, but this stain gradually went away. The peak level of MHI was achieved after 15-30 min post injection and completely eliminated from the plasma after 60 min. There were no significant differences in the number of lymph nodes detected by MHI and radioactive colloid. Only one patient with lymph node macrometastases had no SLN detected by either the radioactive colloid or the MHI. Conclusions At a dose of up to 2.0 mL, MHI was well tolerated and safe for conducting SLN biopsies in patients with breast cancer. Although there was a case with blue discoloration of the local skin over the injection site after the operation, and remained for a short period of time, but the overall safety was acceptable. Here, we approached a novel SLN tracing slant; however, more investigations of MHI should be performed for further evaluations. (Chinadrugtrials.org.cn number: CXHL1301201, Date of registration: October 12, 2015.).

BACKGROUND The objective of this study was to determine an axillary pathologic complete response (pCR) and its influencing factors in patients with hormone receptor (HR)-positive breast cancer and cytologically proven axillary lymph node metastases. A prediction nomogram was established to provide information for the de-escalation of axillary management in these patients after neoadjuvant chemotherapy. METHODS The authors retrospectively enrolled all patients with HR-positive breast cancer in the neoadjuvant chemotherapy data set of Fudan University Shanghai Cancer Center. All data were prospectively collected. From 2007 to 2016, 533 consecutive patients were included. Multivariate logistic regression analysis was performed, after which a nomogram was constructed and validated. RESULTS An axillary pCR was achieved in 168 patients (31.5%), the which was much higher than the proportion of those who achieved a breast pCR (103 patients; 19.3%). Patients who had human epidermal growth factor receptor 2-positive disease (P = .004), a better primary tumor response (P = .001), earlier clinical stage (P = .045), and lower estrogen receptor expression (P

Tumor-infiltrating PD-1hi dysfunctional CD8+ T cells have been identified in several tumors but largely unexplored in breast cancer (BC). Here we aimed to extensively explore PD-1hiCD8+ T cells in BC, focusing on the triple-negative BC (TNBC) subtype. Flow cytometry was used to study the phenotypes and functions of CD8+ T-cell subsets in peripheral blood and surgical specimens from treatment-naive BC patients. RNA-seq expression data generated to dissect the molecular features of tumoral PD-1neg, PD-1lo and PD-1hi CD8+ T cells. Further, the associations between tumoral PD-1hi CD8+ T cells and the clinicopathological features of 503 BC patients were explored. Finally, multiplexed immunohistochemistry (mIHC) was performed to evaluate in situ PD-1hiCD8+ T cells on the tissue microarrays (TMAs, n=328) for prognostic assessment and stratification of TNBC patients. PD-1hiCD8+ T cells found readily detectable in tumor tissues but rarely in peripheral blood. These cells shared the phenotypic and molecular features with exhausted and tissue-resident memory T cells (TRM) with a skewed TCR repertoire involvement. Interestingly, PD-1hiCD8+ T cells are in the state of exhaustion characterized by higher T-BET and reduced EOMES expression. PD-1hiCD8+ T cells found preferentially enriched within solid tumors, but predominant stromal infiltration of PD-1hiCD8+ T subset was associated with improved survival in TNBC patients. Taken together, tumoral PD-1hiCD8+ T-cell subpopulation in BC is partially exhausted, and their abundance signifies ‘hot’ immune status with favorable outcomes. Reinvigorating this population may provide further therapeutic opportunities in TNBC patients.

The current National Practice Questionnaire of implant-based breast reconstruction (IBBR) (NPQi) was to assess the clinical practice of mesh-assisted IBBR in China.A questionnaire was mailed to 110 hospitals in China, which have more than 200 breast cancer operations performed in 2017. The survey mainly included questions on the type and timing of IBBR, questions about the use of TiLOOP® Bra and acellular dermal matrix (ADM) and the complications of IBBR.IBBR was routinely carried out in 86.36% (95/110) hospitals. IBBR was the most frequently-used (65.7%, 4,296/6,534) BR after mastectomy with a median of 24 cases (IQR 7.5-65) in each hospital. TiLOOP® Bra and ADM were available in 49.5% and 33.7% hospitals, respectively. Hospitals with ADM offered were more likely to located in economically developed regions (65.6%), when compared with hospitals without any mesh offered (14/35, 40.0%, P = 0.036) and with only TiLOOP® Bra offered (16/28, 57.1%, P = 0.032). The surgery volume was largely variated from hospitals without any mesh offered (median 380 cases, IQR 304-550), with only TiLOOP® Bra offered (median 790 cases, IQR 439-1096, P = 0.001) and with ADM offered (median 797 cases, IQR 497-1528, P 0.001). Higher proportion of one-stage mesh-augmented direct-to-implant BR and lower proportion of autologous BR were observed in hospitals with mesh offered. The reported major complications were similar between hospitals with or without mesh offered.The NPQi has provided a valuable insight into the current practice of IBBR and mesh used in China. The introduction of mesh-assisted techniques has revolutionized the clinical practice.

Objective Patients preoperatively diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) exhibit a significant risk for upstaging on final pathology, which leads to major concerns of whether axillary staging is required at the primary operation. The present study aimed to identify clinicopathological factors associated with upstaging in patients preoperatively diagnosed with DCIS by CNB.Methods The present study enrolled 604 patients (cN0M0) with a preoperative diagnosis of pure DCIS by CNB, who underwent axillary staging between August 2006 and December 2015, at Fudan University Shanghai Cancer Center (Shanghai, China). Predictive factors of upstaging were analyzed retrospectively.Results Of the 604 patients, 20.03% (n = 121) and 31.95% (n = 193) were upstaged to DCIS with microinvasion (DCISM) and invasive breast cancer (IBC) on final pathology, respectively. Larger tumor size on ultrasonography (> 2 cm) was independently associated with upstaging [odds ratio (OR) 1.558, P = 0.014]. Additionally, patients in lower breast imaging reporting and data system (BI-RADS) categories were less likely to be upstaged (4B vs. 5: OR 0.435, P = 0.002; 4C vs. 5: OR 0.502, P = 0.001). Overall, axillary metastasis occurred in 6.79% (n = 41) of patients. Among patients with axillary metastasis, 1.38% (4/290), 3.31% (4/121) and 17.10% (33/193) were in the DCIS, DCISM, and IBC groups, respectively.Conclusions For patients initially diagnosed with DCIS by CNB, larger tumor size on ultrasonography (> 2 cm) and higher BI-RADS category were independent predictive factors of upstaging on final pathology. Thus, axillary staging in patients with smaller tumor sizes and lower BI-RADS category may be omitted, with little downstream risk for upstaging.

BACKGROUND: In early breast cancer, a non-invasive method with higher sensitivity and negative predictive value (NPV) is needed to identify and recognize more indolent axillary lymph nodes (ALNs). This study aimed to assess whether a novel high-resolution dedicated ALN positron emission tomography (LymphPET) system could improve sensitivity in detecting early breast cancer (clinical N0–N1 stage). METHODS: A total of 103 patients with clinical stage T1–2N0–1M0 breast cancer were evaluated by (18)F-fluorodeoxyglucose ((18)F-FDG) LymphPET. The maximum single-voxel PET uptake value of ALNs (maxLUV) and the tumor-to-background ratio (TBR) for fat (TBR1) and muscle (TBR2) tissue were calculated. Then, 78 patients with cN0 stage breast cancer received sentinel lymph node biopsy alone or combined with axillary lymph node dissection (ALND), and 25 patients with cN1 stage breast cancer underwent fine-needle aspiration. RESULTS: A total of 99 invasive breast carcinoma cases were included in this study. The diagnostic sensitivity of LymphPET was 88%, specificity was 79%, false-negative rate was 12%, the false-positive rate was 21%, positive predictive value was 75%, NPV was 90%, and accuracy was 83%. The maxLUV was superior to TBR1 and TBR2 in detecting ALNs, with 0.27 being the most optimal cutoff value. CONCLUSIONS: The (18)F-FDG LymphPET system can be used to identify and recognize more indolent ALNs of breast cancer due to greater sensitivity and a much higher NPV.

Background: The aim of this study was to assess if a novel high-resolution dedicated axillary lymph node Positron Emission Tomography (LymphPET) system could improve sensitivity analysing Lymph Node involvement in early breast carcinoma with clinical N0-N1 stage. Methods: A total of 103 patients with clinical stage of T1-2N0-1M0 breast cancer were evaluated with LymphPET. The maximum single-voxel PET uptake value of Axillary Lymph Node (maxLUV) and the tumor-to-background ratio (TBR) for fat (TBR1) and muscle (TBR2) tissue were calculated. Then, seventy-eight patients with cN0 stage received sentinel lymph node biopsy (SLNB) alone or in combination with ALN dissection (ALND) and 25 patients with cN1 stage underwent fine-needle aspiration (FNA). Results: Ninety-nine invasive breast carcinoma entered this study. The diagnostic sensitivity of LymphPET was 87.80%, specificity was 79.31%, false-negative rate was 12.20%, false-positive rate was 20.69%, positive predictive value was 75.00%, negative predictive value was 90.20%, and accuracy was 82.83%. The maxLUV was superior to TBR1 and TBR2 in the detection of ALN, with 0.27 being the most optimal cutoff value. Conclusion: The 18F-FDG LymphPET could be used to identify and recognize more indolent ALNs of the breast cancer because of more sensitivity and much higher negative predictive value.

Objective Breast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics, management and outcomes of young breast cancer patients over time. Methods Females under 40 years of age diagnosed with breast cancer during the periods 1999−2017 and 1999−2015 were identified in the Fudan University Shanghai Cancer Center (FUSCC) and the population-based Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up. Results The proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ (DCIS) (from 8.8% to 16.9%; P

Aim:Mitoxantrone is an antineoplastic antibiotic used in the treatment of acute leukemia, lymphoma, prostate and breast cancer. Mitoxantrone Hydrochloride Injection for tracing has a high degree of lymph node tropism by changing the dosage form, which penetrates into lymphatic capillaries through the interstitial space and enriches regional lymph nodes through the gland to stain the lymph nodes blue to achieve lymph node tracing effect. This study is aim to evaluate the efficacy and safety of Mitoxantrone Hydrochloride injection(MHI) for tracing sentinel lymph nodes in patients with early-stage breast cancer.Materials & methods: This study was a phase 3, multicenter, self-controlled, non-inferiority trial designed to assess the efficacy and safety of sentinel lymph node tracing with the investigational drug in patients with early-stage breast cancer. All subjects received MHI combined with Technetium-99m(99mTc-Sc), prior to SLNB. The sentinel node identification rate was compared between MHI and 99mTc-Sc to evaluate non-inferiority and concordance. Results: Data were collected from 381 patients in 6 centers all across China. The SLN detection rate was 96.9% (369/381) when using MHI and 97.4% (371/381) when using the standard technique(Table 1). There was no significant difference in the success rate of SLN detection between the two groups(P > 0.05). Since the lower limit of 95% confidence interval was greater than or equal to -5%, the success rate of SLN detection of MHI was non-inferior to that of 99mTc-Sc. In the combination group, 380 cases (99.5%) were successfully detected with SLN. 202 nodes (13.1%) were detected by the MHI but not by the 99mTc-Sc, and 222 nodes (14.4%) were detected by the 99mTc-Sc but not by the MHI(Table 2). All adverse events recovered within one month after intervention.Conclusion: This prospective, multicenter study has shown the Mitoxantrone Hydrochloride injection for tracing to be non-inferior to the standard technique (99mTc-Sc) for breast SLNB. The Mitoxantrone Hydrochloride injection for tracing can be used alone or combined with radioactive material.Key words:Mitoxantrone Hydrochloride injection(MHI), Tracing, Technetium-99m(99mTc-Sc), sentinel lymph node (SLN), Early-Stage Breast Cancer. Attachments: Table 1.SLN detection rate - comparing the Mitoxantrone Hydrochloride Injection and 99mTc-Sc for TracingSLN detection rates [n (%)]Mitoxantrone Hydrochloride Injection for TracingTotalAt least one node detectedNo nodes detected99mTc-ScPositive361 (94.8%)10 (2.6%)371 (97.4%)Negative8 (2.1%)2 (0.5%)10 (2.6%)Total369 (96.9%)12 (3.1%)381(100%) Table 2.Detected nodes-comparing the Mitoxantrone Hydrochloride Injection and 99mTc-Sc for TracingPer node detection rates [n (%)]Mitoxantrone Hydrochloride Injection for TracingTotalPositiveNegative99mTc-ScPositive869 (56.3%)222 (14.4%)1091 (70.7%)Negative202 (13.1%)251 (16.3%)453 (29.3%)Total1071 (69.4%)473 (30.6%)1544 (100%) Citation Format: Benlong Yang, Dechuang Jiao, Jiajian Chen, Chunjian Wang, Lidan Jin, Wenhe Zhao, Xueqiang Gao, Haibo Wang, Jun Li, Haidong Zhao, Di Wu, Zhiming Fan, Shujun Wang, Zhenzhen Liu, Yongsheng Wang, Jiong Wu. A phase 3, multicenter, self-controlled, non-inferiority trial comparing mitoxantrone hydrochloride injection for tracing versus technetium-99m in the detection of axillary sentinel nodes in patients with early-stage breast cancer [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 P1-01-10.

BACKGROUND: There are limited nationwide data regarding breast cancer surgery in China. The Chinese Anti‐Cancer Association's Committee of Breast Cancer Society and the Chinese Society of Breast Surgeons conducted a nationwide survey to examine the use of and barriers associated with surgical options among patients with breast cancer. METHODS: Surveys were sent via e‐mail to the directors of 110 centers that performed at least 200 breast cancer operations in 2017. The electronic questionnaire contained 183 questions and covered six aspects, including demographic information about the hospitals and surgeons, surgical practice, and application of breast reconstruction. RESULTS: The selected hospitals were from 31 provinces or municipalities. The overall proportion of breast‐conserving surgery (BCS) was 22%. Local gross domestic product was significantly related to the rate of BCS (p = .046). Sentinel lymph node biopsy was performed routinely in 76% of hospitals. Only 14.5% (16/110) of hospitals used the dual‐tracer method, including radioisotopes. For patients with cN0 disease receiving BCS with one or two positive sentinel lymph nodes, 20% (22/110) of hospitals accepted omitting axillary lymph node dissection (ALND). For patients who underwent mastectomy, only 4% (4/110) of hospitals accepted omitting ALND. There was an obvious polarization trend in the proportion of oncoplastic breast‐conserving surgery (OPS); 35/110 (32%) performed OPS in fewer than 10% of cases, whereas 36/110 (33%) performed OPS in more than 50% of cases. OPS was more likely to be performed in academic hospitals. Volume displacement was more commonly used than volume replacement (p < .001). Breast reconstruction was routinely performed in 96/110 (87%) of hospitals, 62% of which involved cooperation with the plastic surgery department. Factors influencing breast reconstruction after mastectomy included the establishment of a plastic surgery department, regional economy, and cooperation between the plastic and general surgery departments. Overall, the proportion of breast reconstruction procedures after mastectomy was 10.7%, with 70% being implant‐based reconstruction, 17% autologous tissue reconstruction, and 13% a combination. Overall, 22% of the hospitals predominantly performed immediate breast reconstruction. For delayed reconstruction, two‐stage implant‐based breast reconstruction was the first choice for 46% of centers, whereas 20% of centers chose autologous reconstruction. Among the 96 centers that performed autologous‐based reconstruction, 96% performed latissimus dorsi flap reconstruction, 65% performed transverse rectus abdominis musculocutaneous flap reconstruction, and 45% used deep inferior epigastric artery perforator flaps. CONCLUSION: The results are of great value for promoting the implementation of a consensus on diagnostic and treatment standards, development of guidelines for breast cancer, and training of breast specialists. IMPLICATIONS FOR PRACTICE: This study aimed to establish comprehensive baseline data on the status of current breast cancer treatment in China by presenting the statistics on clinical treatments and surgeries, the distribution of clinical stages, and the demographic characteristics of patients. This report is based on a survey conducted by the Chinese Anti‐Cancer Association's Committee of Breast Cancer Society and the Chinese Society of Breast Surgeons, which examined the use of breast cancer surgical options in hospitals all over the country and the factors hindering the adoption of procedures and techniques. This study makes a significant contribution to the literature because there are limited nationwide data regarding breast cancer surgery in China.

Objective The aim of the current study is to determine the clinical value of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction using internal mammary as recipient vessels and to investigate the risk factors of internal mammary lymph nodes metastasis. Methods The clinical data of all free abdominal flap breast reconstructions using internal mammary as recipient vessels performed from November 2006 to April 2016 in Department of Breast Surgery, Fudan University Shanghai Cancer Center were included into the study. The incidence of internal mammary lymph node biopsy and the rate of metastasis were described. The differences between groups were compared using χ2 test. Univariate and multivariate Logistic regression analysis was conducted to evaluate risk factors of internal mammary lymph node metastasis. Results A total of 125 patients met the inclusion criteria, 89 (71.2%) of whom adopted unilateral immediate breast reconstructions. 64.8% of them were diagnosed with primary invasive breast cancer, while 27.2% were carcinoma in situ. According to AJCC TNM staging system, the percentages of patients with stage 0, I, II, III were 27.2%, 26.4%, 27.2% and 8.0%. 62 (49.6%) patients had internal mammary lymph nodes harvested. 6.4% (4/62) of those who adopted internal mammary lymph nodes biopsies were diagnosed with internal mammary lymph nodes metastasis, all in immediate breast reconstructions. 72 (57.6%) patients cut off costicartilage (the second or third costicartilage) during the exposure of internal mammary vessels. The excision of costicartilage is not associated with the harvest rate of internal mammary lymph node (P>0.05). All of the 4 patients upstaged their TMN stage of tumor after internal mammary lymph node metastasis and adopted adjuvant chemotherapy and radiotherapy. Up to May 2016, no recurrence or distant metastasis was reported. In Logistic regression analysis, larger invasive tumor size and axillary lymph node metastasis were found to have correlations with internal mammary lymph node metastasis (larger invasive tumor size: P=0.029; axillary lymph node metastasis: P=0.004), while tumor location or immunohistochemical subtype had no correlations. In addition, axillary lymph node metastasis was proved to be a independent risk factor of internal mammary lymph node metastasis (P=0.036) while tumor size was not. Conclusions Internal mammary lymph nodes found incidentally during internal mammary recipient vessel exposure for free flap breast reconstruction could provide surgeons with important information for further treatment. This approach for internal mammary lymph node biopsy revealed an appreciable success rate and should be promoted in clinical practice. The size of invasive tumor and the axillary lymph node metastasis were associated with internal mammary lymph node metastasis.Objective The aim of the current study is to determine the clinical value of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction using internal mammary as recipient vessels and to investigate the risk factors of internal mammary lymph nodes metastasis. Methods The clinical data of all free abdominal flap breast reconstructions using internal mammary as recipient vessels performed from November 2006 to April 2016 in Department of Breast Surgery, Fudan University Shanghai Cancer Center were included into the study. The incidence of internal mammary lymph node biopsy and the rate of metastasis were described. The differences between groups were compared using χ2 test. Univariate and multivariate Logistic regression analysis was conducted to evaluate risk factors of internal mammary lymph node metastasis. Results A total of 125 patients met the inclusion criteria, 89 (71.2%) of whom adopted unilateral immediate breast reconstructions. 64.8% of them were diagnosed with primary invasive breast cancer, while 27.2% were carcinoma in situ. According to AJCC TNM staging system, the percentages of patients with stage 0, I, II, III were 27.2%, 26.4%, 27.2% and 8.0%. 62 (49.6%) patients had internal mammary lymph nodes harvested. 6.4% (4/62) of those who adopted internal mammary lymph nodes biopsies were diagnosed with internal mammary lymph nodes metastasis, all in immediate breast reconstructions. 72 (57.6%) patients cut off costicartilage (the second or third costicartilage) during the exposure of internal mammary vessels. The excision of costicartilage is not associated with the harvest rate of internal mammary lymph node (P>0.05). All of the 4 patients upstaged their TMN stage of tumor after internal mammary lymph node metastasis and adopted adjuvant chemotherapy and radiotherapy. Up to May 2016, no recurrence or distant metastasis was reported. In Logistic regression analysis, larger invasive tumor size and axillary lymph node metastasis were found to have correlations with internal mammary lymph node metastasis (larger invasive tumor size: P=0.029; axillary lymph node metastasis: P=0.004), while tumor location or immunohistochemical subtype had no correlations. In addition, axillary lymph node metastasis was proved to be a independent risk factor of internal mammary lymph node metastasis (P=0.036) while tumor size was not. Conclusions Internal mammary lymph nodes found incidentally during internal mammary recipient vessel exposure for free flap breast reconstruction could provide surgeons with important information for further treatment. This approach for internal mammary lymph node biopsy revealed an appreciable success rate and should be promoted in clinical practice. The size of invasive tumor and the axillary lymph node metastasis were associated with internal mammary lymph node metastasis. Citation Format: Quan C, Huang N, Yang B, Zhang Y, Huang X, Chen J, Wu J. A single-center report of 125 cases of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-06.

Tumor-infiltrating lymphocytes (TIL) and immunity gene signatures have been reported to be significantly prognostic in breast cancer but have not yet been applied for calculation of risk of recurrence in clinical assays. A compact set of 17 immunity genes was derived herein from an Affymetrix-derived gene expression dataset including 1951 patients (AFFY1951). The 17 immunity genes demonstrated significant prognostic stratification of estrogen receptor (ER)-negative breast cancer patients with high proliferation gene expression. Further analysis of blood and breast cancer single-cell RNA-seq datasets revealed that the 17 immunity genes were derived from TIL that were inactive in the blood and became active in tumor tissue. Expression of the 17 immunity genes was significantly (p, Genomic testing: Tumor-infiltrating immune cells express detectable gene signature The elevated expression of 17 immunity-related genes is associated with better outcomes among women with aggressive forms of estrogen receptor–negative breast cancer. Zhiyuan Hu from the University of North Carolina at Chapel Hill, USA, and colleagues identified the 17-gene set by analyzing a larger expression dataset from close to 2,000 patients. Single-cell sequencing revealed that the genes were turned on in a group of cancer-fighting immune cells known as tumor-infiltrating lymphocytes, but were inactive in circulating blood cells. The researchers incorporated the immunity-related genes into a larger panel of genes involved in proliferation, invasion and other relevant biological processes. The resulting 72-gene test was an accurate predictor of the risk for developing distant metastases. The findings suggest that immunity-related genes should be incorporated into current multi-gene prognostic assays for women with breast cancer.

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast‐conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006–2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non‐evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006–2010 to 53.8% in 2011–2015 (P

Summary Background Fat necrosis is one of the most common complications following free flap breast reconstruction. Although a minor complication, fat necrosis can compromise esthetic results and confuse with cancer recurrence. Perfusion-related factors and post-operative radiotherapy are the known risks. However, the influence of adjuvant chemotherapy on fat necrosis prevalence remains unknown. Methods Our initial experience of 88 consecutive breast reconstructions with free abdominal flaps was reviewed. The prevalence of fat necrosis was recorded and the risk factors were analyzed using univariate and multivariate logistic regression models. Results The overall prevalence of fat necrosis was 36.4% in this series. In a multivariate logistic regression model, adjuvant chemotherapy significantly increased the risk of fat necrosis. The relative risk was 4.762 (95% confidence interval (CI), 1.767–12.831; p = 0.002). There was no evidence of a specific chemotherapeutic agent causing fat necrosis. The first cycle of adjuvant chemotherapy was frequently delivered earlier in patients with fat necrosis than those without fat necrosis, although this tendency was not statistically significant. Conclusions Our initial experience with free flap breast reconstruction seems to suggest that chemotherapy may increase the risk of fat necrosis following immediate breast reconstruction. Patients should be fully informed, and the initiation of post-operative chemotherapy may be adjusted accordingly.

The one-step nucleic acid amplification (OSNA) assay is an innovative method for the diagnosis of sentinel lymph node (SLN) metastases in breast cancer patients. The aim of the present study was to clinically validate the OSNA assay and compare its results with postoperative serial sectioning in a Chinese breast cancer population. A prospective study of 370 consecutive SLNs from 115 patients was conducted at our institution. A total of 311 SLNs underwent OSNA assay analysis. All SLNs were sectioned in approximately 2-mm pieces. OSNA assay and postoperative serial sectioning were performed on alternate divided node samples. The postoperative serial sectioning histology diagnosis was used as the standard. The overall rate of agreement between OSNA assay and the postoperative serial sectioning was 95.2 % [95 % confidence interval (CI) 91.6–96.9 %], with a sensitivity of 83.3 % (95 % CI 66.5–93.0 %), a specificity of 96.7 % (95 % CI 93.7–98.4 %), a positive predictive value of 76.9 % (95 % CI 60.3–88.3 %), and a negative predictive value of 97.8 % (95 % CI 95.0–99.1 %) based on the number of SLNs sampled before the discordant cases analyses. Eleven out of 15 discordant cases can be explained by tissue allocation bias. Our study shows that the OSNA assay is more standardized, objective, and reproducible and can utilize more lymphoid tissue than the traditional pathological examination methods. OSNA can also distinguish between micrometastasis and macrometastasis, thereby enabling us to further study the significance of micrometastasis. Since there is a lack of standardization and reproducibility of pathological examination and diagnostic criteria of the SLNs, we recommend that the OSNA assay can be used in daily clinical diagnostic work.

Objectives The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. Materials and methods Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. Results Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8–919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5–23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P

Purpose Clinical data suggest that the estrogen receptor (ER) contributes to chemotherapeutic responsiveness. However, ER status alone is not consistently predictive. In this study, we used a microarray approach to find novel ER-related genes that predicted chemotherapy responses, with the hope of providing a robust multi-variable prediction method. Methods One hundred and ten patients with stages II and III breast cancer were included. They received four preoperative cycles of a weekly PCb (paclitaxel plus carboplatin) regimen. A total of 55 training cases were used for marker discovery and for identification of any ER-related genes that may have been associated with a chemotherapeutic response (“training cases”). The other 55 patients were available as an independent validation set (“validation cases”) to test, using immunohistochemistry (IHC). Results In the training set, 20 significantly differentially expressed genes were identified. Among these 20 genes, TFF1, ESR1, GATA3 and TFF3 were found to be ER-related. Among 55 independent validation cases, univariate analysis indicated that clinical variables and ER-related genes were all significantly associated with pCR. It was shown that the pCR rate was as high as 80% when these five factors were all negative. In contrast, these five factors were all positive in seven of nine chemo-resistant patients. Conclusion In conjunction with levels of ER-related genes, expression of ER protein may provide important predictive outcomes for responses to neoadjuvant chemotherapy and may allow for the identification of a subgroup of patients who could significantly benefit from chemotherapy (or who may be resistant to it).

This abstract was not presented at the conference. Citation Format: Yang B, Wu J. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-01-01.

Background Patients diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) have a great chance of upgrading invasive cancer on the final pathology. Positive axillary lymph nodes can be found in these patients. The present study sought to identify clinicopathological factors associated with upgrading and axillary lymph nodes metastasis in patients preoperatively diagnosed with DCIS by CNB. Materials and Methods This study identified 604 patients (cT1-3N0M0) with preoperative diagnosis of pure DCIS by CNB who had undergone axillary evaluation from August 2006 to December 2015 at Fudan University Shanghai Cancer Center (FUSCC). Predictors of upgrading and axillary lymph nodes metastasis were analyzed, respectively. Results Of all 604 patients, 513 (84.93%) and 91 (15.07%) patients had undergone sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Overall, 121 (20.03%) and 193 (31.95%) patients were upgraded to DCIS with microinvasion (DCISM) and IDC on final pathology, respectively. Positive axillary lymph nodes were identified in 41 (6.79%) patients, of which 35 (5.80%) patients had 1-2 positive axillary lymph nodes, 6 (0.99%) patients had 3 or more positive axillary lymph nodes. Among patients with axillary lymph nodes metastasis, 4 (9.76%), 4 (9.76%) and 33 (80.48%) patients were in DCIS, DCISM and IDC group, respectively. Predictors of upgrading included tumor size on ultrasonography (P=0.001), Ki-67 (P=0.046) and molecular subtype (P=0.007) in univariate analysis. In multivariate analysis, patients with larger tumor size on ultrasonography (>2cm) (OR 1.767, P=0.001) were more likely to be upgraded on final pathology. Also, ER+ HER2+ patients were more likely to be upgraded than ER+ HER2- patients (OR 1.659, P=0.047). Factors associated with axillary lymph nodes metastasis included nipple discharge (P2cm) reached statistical significance in multivariate analysis (OR 5.959, P Conclusion The data of upgrading and axillary lymph nodes metastasis in patients with an initial diagnosis of DCIS by CNB was comparable in this cohort with published data. Despite of a 51.98% upgrading rate, the rate of axillary lymph nodes metastasis in these patients is low, which supports the omission of axillary evaluation in selected patients. Citation Format: Si J, Yang B, Guo R, Huang N, Quan C, Chen J, Wu J. Can axillary evaluation be omitted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-06.

Background The goal of this study was to evaluate patient satisfaction with four common types of breast reconstruction performed at our institution: latissimus dorsi myocutaneous (LDM) flap reconstruction with or without implants, pedicled transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction, and free deep inferior epigastric perforator (DIEP) flap reconstruction. Methods A custom survey consisting of questions that assessed general and aesthetic satisfaction was sent to patients who had undergone breast reconstruction in the last 5 years. The clinical data and details of the surgery were also collected from the patients who returned the surveys. We compared satisfaction rates across the four breast reconstruction types and analyzed the effects of various factors on overall general and aesthetic satisfaction rates using a binary logistic regression model. Result A total of 207 (72%) patients completed the questionnaires. Overall, significant differences in general and aesthetic satisfaction among the four procedures were not observed. A multivariate analysis revealed that the factor “complications” (p = 0.001) played a significant role in general satisfaction and that the factors “> 2 years since reconstruction” (p = 0.043) and “age > 35 years” (p = 0.05) played significant roles in overall aesthetic satisfaction. Conclusion The present study demonstrated that the type of breast reconstruction might not influence satisfaction in Chinese patients.

To explore the current trends of breast reconstruction (BR) for breast cancer patients in China.A questionnaire was designed for this study, and it included questions on surgeon demographics, number of mastectomy and BR, type and timing of BR, reconstructive choices in the setting of preoperative or postoperative radiotherapy or chemotherapy, etc. All data were collected until December 2012. Questionnaires were sent to 52 members of the Committee of Breast Cancer Society by e-mail or mail.By July 2013, 41 questionnaires had been returned. Among all, 5 were excluded for not performing BR. These 36 hospitals covered 22 provinces and municipalities in China. A total of 538 surgeons working in the general surgery or oncological surgery department, but only 123 (22.9%) were qualified to perform BR. In 2012, except for 4 missing data, 24, 763 mastectomies were performed in 32 hospitals; among them, 1120 (4.5%) received BR. According to these 36 respondents, 32 (88.9%) performed prosthetic (1, 843 cases in all) while 4 (11.1%) performed prosthetic BR with acellular dermal matrix (17 cases in all) from the time of their first BR operation to the end of 2012. During the same period, 965 latissimus dorsi myocutaneous flaps with implant were performed in 23 (63.9%) hospitals while 738 latissimus dorsi myocutaneous flaps without implant were performed in 32 (88.9%) hospitals. At the same time, 366 pedicled transverse rectus abdominis myocutaneous flap BRs were performed in 28 (77.8%) hospitals, while 155 abdominal free flap BRs were carried out in 9 (25.0%) hospitals. The overall complication rate was 18.2%. Postoperative radiotherapy had some effect on influencing the esthetic outcomes of BR, so the autologous BR was recommended, but the timing remained controversial. Regarding chemotherapy, most respondents concluded that it had no effect or only a mild effect. The overall cosmetic outcomes of the reconstructed breasts satisfied the majority of physicians and patients.With more attention paid to the quality of life after mastectomy, more and more BRs are needed, but the ratio is still low in China. To improve this situation, more efforts are needed, including the improvement of the intrahospital framework of multi-disciplinary service, the training for doctors and the educational program for patients, etc.

Purpose: In previous study, we had shown that miR-621 could sensitize breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. In this study, we aimed to define miR-621 prognosis value in breast cancer patients, and to explore the potential molecular mechanisms. Experimental Design: 70 patients with stages II and III breast cancer were included as validation set. The correlation between miR-621 expression level and prognosis in breast cancer patients was confirmed. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of miRNA-dependent prognosis. Results: We validated that lower than higher miR-621 expression level was markedly associated with poor metastasis-free survival in breast cancer patients(P=0.03). In breast cancer cell lines, ectopic overexpression of miR-621 inhibited proliferation, migration, invasion, and metastasis both in vitro and in vivo. The potential miR-621-target genes were determined by TargetScan and miRNA CLIP-seq database. Among those, PAK7 was verified as one of the direct targets of miR-621 in breast cancer cells, whose expression level positively associated with recurrence and metastasis in breast cancer patients. The molecular mechanisms by which miR-621/PAK7 axis regulates recurrence and metastasis may involve regulation of epithelial-mesenchymal transition (EMT) in breast cancer cells. Conclusions: Our study revealed a strong correlation between miR-621 expression and metastasis in breast cancers. High level of miR-621 was negatively associated with poor metastasis-free survival. The increased metastasis-free survival may be mediated by down-regulation of PAK7 gene, which leads to reduced EMT in breast cancer cells. Therefore, miR-621 may represent a therapeutic target for early metastasis breast cancer. Citation Format: Xue J, Chi Y, Chen J, Yang B, Wu J. miR-621 suppresses the metastatic cascade in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-03-08.