In this phase 2 trial (NCT05582499), patients with stage II-III hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer were categorized into endocrine-based and targeted-based groups based on previously proposed similarity network fusion (SNF) subtyping by digital pathology classification and were then randomly assigned in a 1:1 ratio to receive precision or control treatment. The primary endpoint was pathological complete response (pCR). Among 251 randomized patients, 49 were classified into an endocrine-based group and 202 into a targeted-based group. Patients receiving precision treatment had a significantly higher pCR rate (11.1% [90% confidence interval (CI), 6.8-16.8] vs. 4.0% [90% CI, 1.6-8.2]; p = 0.033), with the benefit mainly derived from the targeted-based group (13.9% in precision vs. 4.0% in control; p = 0.026). Toxicity was manageable. Our findings highlight that guiding neoadjuvant precision treatment by SNF subtyping in patients with HR+/HER2- breast cancer showed potential clinical benefits, with improvement of pCR in the targeted-based group and better tolerance in the endocrine-based group.

ABSTRACT This phase II trial evaluated the efficacy and safety of combining niraparib with the PD‐1 inhibitor HX008 in patients with metastatic breast cancer who had germline DNA damage response (DDR) mutations. The study included 37 patients, divided into a primary cohort of HER2‐negative individuals with germline BRCA1/2 or PALB2 mutations (n = 29) and an exploratory cohort of patients who were either HER2‐negative with other DDR mutations, had brain metastases, or were HER2‐positive (n = 8). The main cohort achieved an objective response rate (ORR) of 76% and a disease control rate (DCR) of 97%, with a median progression‐free survival (PFS) of 7.3 months. The exploratory cohort had an ORR of 25% and a DCR of 75%, while patients with brain metastases showed a 40% ORR. Among treatment‐related adverse events of Grade 3 or higher, the most frequently observed were anemia (35.1%), thrombocytopenia (10.8%), and neutropenia (8.1%). No treatment‐related deaths were reported. Somatic XPO1 mutations correlated with better response. Somatic TP53 mutations significantly correlated with shorter PFS, while ASXL1 mutations correlated with longer PFS. This chemotherapy‐free regimen demonstrates promising efficacy and a tolerable safety profile in patients with metastatic breast cancer and germline DDR mutations, providing a novel therapeutic option for this patient population, even those with brain metastases.

Objectives: The molecular characterization of male breast cancer (MaBC) has long been understudied, primarily due to its rare occurrence. Clinical management of MaBC remains profoundly challenging, with current therapeutic strategies largely extrapolated from female breast cancer protocols. Methods: Through panel-based sequencing targeting BRCA1, BRCA2, and PALB2 variants, we delineated the genomic landscape of 96 MaBC cases. Subsequent whole-exome sequencing (WES) of 84 BRCA1/2- and PALB2-mutation-negative MaBC patients, compared against 4480 healthy controls, revealed compelling findings. Results: Pathogenic variants in BRCA1/2 and PALB2 were identified in 14.6% (14/96) of MaBC cases, with BRCA2 mutations predominating at 12.5% (n = 12). Notably, one patient harbored the BRCA1 c.4015G > T stop-gained mutation, while another exhibited the PALB2 c.481_482dupGA alteration. Our analysis further uncovered 170 pathogenic/likely pathogenic mutations, with RAD50, DMD, ARSA, and ABCC6 demonstrating recurrent mutations in MaBC. Conclusions: As the inaugural germline genomic investigation of MaBC in a Han Chinese population, this work reveals clinically actionable alterations with diagnostic and therapeutic implications. These discoveries not only advance our understanding of MaBC’s molecular architecture but also underscore the critical need for dedicated research into this malignancy.

Background: Advances in regional anesthesia techniques and the widespread use of ultrasound guidance have enabled safe and effective anesthesia for ambulatory breast cancer surgery, eliminating the general anesthesia-associated systemic effects. We therefore compared regional anesthesia with dexmedetomidine sedation to general anesthesia on the 15-item postoperative quality of recovery (QoR-15). Methods: Ninety-six patients scheduled for breast-conserving surgery and sentinel lymph node biopsy were randomly assigned to regional anesthesia with sedation or general anesthesia. In patients assigned to regional anesthesia, a 0.3% ropivacaine solution was used for pectoral and intercostal nerve blocks, followed by a dexmedetomidine infusion. In other patients, standardized general anesthesia was maintained with a laryngeal mask airway. The primary outcome was the QoR-15 score 6 h after surgery. Secondary outcomes included QoR-15 scores at 2 and 24 h; pain scores obtained using the numerical rating scale (NRS) at 2, 6, and 24 h; and the incidence of postoperative complications. Results: At postoperative hour 6, QoR-15 scores were significantly and meaningfully higher in patients given regional anesthesia [142 (136, 146)] than those assigned to general anesthesia [132 (127, 135), p < 0.01]. Regional anesthesia patients also had significantly higher QoR-15 scores at 2 and 24 h postoperatively. Two hours after surgery, regional anesthesia patients had lower pain scores at rest and during movement, needed less rescue analgesia [13 (27%) versus 27 (56%), p < 0.01], and had fewer experienced nausea and vomiting [1 (2%) versus 13 (27%), p < 0.01]. Moreover, patients assigned to regional anesthesia had fewer episodes of hypotension and smaller hemodynamic fluctuations during skin incision. In contrast, there were no significant differences in the incidences of postoperative hypotension and bradycardia in patients randomized to regional and general anesthesia. Conclusions: Recovery quality after breast-conserving surgery combined with sentinel lymph node biopsy was better with regional anesthesia combined with dexmedetomidine sedation than with general anesthesia. Regional anesthesia also improved pain control, intraoperative hemodynamic stability, and decreased nausea and vomiting.

Purpose The molecular characterization of male breast cancer (MaBC) has long been understudied, primarily due to its rare occurrence. Clinical management of MaBC remains profoundly challenging, with current therapeutic strategies largely extrapolated from female breast cancer protocols. Methods Through panel-based sequencing targeting BRCA1, BRCA2 and PALB2 variants, we delineated the genomic landscape of 96 MaBC cases. Subsequent whole exome sequencing (WES) of 84 BRCA1/2 and PALB2-mutation-negative MaBC patients, compared against 4,480 healthy controls, revealed compelling findings. Results Pathogenic variants in BRCA1/2 and PALB2 were identified in 14.6% (14/96) of MaBC cases, with BRCA2 mutations predominating at 12.5% (n = 12). Notably, one patient harbored the BRCA1 c.4015G > T stop_gained mutation, while another exhibited the PALB2 c.481_482dupGA alteration. Our analysis further uncovered 170 pathogenic/likely-pathogenic mutations and 388 rare variants of uncertain significance (VUS), with RAD50, DMD, ARSA, and ABCC6 demonstrating notable genetic pleiotropy. Conclusion As the inaugural germline genomic investigation of MaBC in a Han Chinese population, this work reveals clinically actionable alterations with diagnostic and therapeutic implications. These discoveries not only advance our understanding of MaBC's molecular architecture but also underscore the critical need for dedicated research into this malignancy.

The poly(ADP-ribose) polymerase inhibitor olaparib was recently approved in China for adjuvant treatment of certain patients with high-risk, human epidermal growth factor (HER2)-negative early breast cancer (eBC) and germline pathogenic/likely pathogenic mutations in BRCA1 and BRCA2 (gBRCAm). Further evidence on demographics, clinical characteristics, treatment patterns and outcomes is needed to inform local guideline updates and clinical decision-making for patients in China with gBRCAm and eBC who may be eligible for olaparib treatment. This retrospective study analysed deidentified electronic health records at the Fudan University Shanghai Cancer Center. Women ≥ 18 years of age diagnosed with eBC between 1 January 2012 and 31 December 2019 who had undergone definitive BC surgery were included. Patients with accessible gBRCA status were included alongside a similar-sized cohort of randomly selected, untested patients. Demographics, clinical characteristics, treatment patterns, pathological complete response (pCR) and invasive disease-free survival (IDFS) were described by tumour subtype and gBRCAm status. In total, 949 patients were included (gBRCA tested: n = 466; untested: n = 483). Among 89/466 (19.1

1084 Background: The combination of poly (ADP-ribose) polymerase inhibitors and immune-checkpoint inhibitors demonstrated synergistic antitumor activity in preclinical studies. Here we report the efficacy, safety, and biomarker analyses of the combination of niraparib and PD-1 inhibitor HX008 in metastatic breast cancer (MBC) patients with germline DDR gene mutations in a phase II trial (CHANGEABLE). Methods: Eligible patients had histologically confirmed MBC with at least one measurable disease and germline pathogenic/suspected pathogenic mutations in DDR genes. Patients were enrolled into two cohorts: the main cohort (HER2-negative MBC patients with gBRCA1/2, gPALB2, gCHEK2) and the exploration cohort (MBC patients with gDDR gene mutations and brain metastases). Simon's Two-Stage design was used for recruiting patients in the main cohort. Patients with HER2-negative MBC received niraparib 200 mg qd combined with HX008 200 mg q3w, while HER2-positive patients received additional anti-HER2 TKI pyrotinib 400mg qd if having brain metastases, until disease progression. The primary endpoint was ORR. NGS of tissue and ctDNA were performed for exploratory biomarker analyses. Results: As of January 12, 2024, 37 patients were enrolled. In the main cohort with gBRCA1/2 mutations (n = 28), ORR was 78.6% (22/28), with 3 patients having complete response. DCR was 96.4% (27/28). Median PFS was 7.3 months (95%CI 4.2 to 10.4). According to Simon's Two-Stage design, since two patients with gCHEK2 mutations in the first stage had only stable disease, the recruitment was terminated. One patient with gPALB2 mutation had stable disease and the remaining one is in the screening process. In the patients having brain metastases (exploration cohort), ORR was 40% (2/5) and DCR was 80% (4/5). The most common treatment-related adverse events of grade 3 or higher were anemia (13 [35.1%]), thrombocytopenia (4 [10.8%]), and neutropenia (3 [8.1%]). No treatment-related deaths were reported. In the biomarker analysis, NGS of 700 genes was performed on 24 patients with gBRCA1/2 mutations in the main cohort. No significant difference was found in ORR or PFS between gBRCA1 and gBRCA2 mutations. Somatic mutations in XPO1 (16 patients (73%), 15/18 PR+CR, 1/4 SD+PD) showed significant correlation with response. Somatic TP53 mutations are significantly correlated with shorter PFS, while ASXL1 mutations are significantly correlated with longer PFS. Four somatic mutations (AR_c.1418_1420del, AR_c.231_239dup, 2 DUSP22 mutations) showed a consistent trend of decreasing in PD samples, while NF1_c.3198-4dup showed a consistent trend of increasing in PD samples. Conclusions: The combination of niraparib and HX008 demonstrated promising clinical benefits with a tolerable safety profile in MBC patients with germline BRCA1/2 mutations, even in patients with brain metastases. Clinical trial information: NCT04508803 .

OBJECTIVE:To evaluate the efficacy and safety of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without carboplatin as adjuvant therapy for patients with high risk, early stage, triple negative breast cancer. DESIGN:Randomised, open label, phase 3 trial. SETTING:Fudan University Shanghai Cancer Center in China between March 2020 and March 2022. PARTICIPANTS:Female patients with operable high risk triple negative breast cancer (defined as either regional node positive or node negative with a Ki-67 labelling index of ≥50%) after definitive surgery. INTERVENTIONS:Patients were randomised in a 1:1 ratio into either the carboplatin arm (four cycles of two weekly epirubicin and cyclophosphamide followed by four cycles of weekly paclitaxel combined with carboplatin) or the control arm (four cycles of three weekly or two weekly epirubicin and cyclophosphamide followed by four cycles of weekly paclitaxel). MAIN OUTCOME MEASURES:The primary endpoint was disease-free survival in the intention-to-treat population. Secondary endpoints included recurrence-free survival, distant disease-free survival, overall survival, and safety. RESULTS:Of the 808 enrolled patients, 807 received study treatment. At a median follow-up of 44.7 months, estimated percentages of patients who would be disease-free at three years were 92.3% in the carboplatin arm and 85.8% in the control arm (hazard ratio 0.64, 95% confidence interval (CI) 0.43 to 0.95; P=0.03). However, the assessment of the proportional hazards assumption showed that it was violated (P=0.02). A piecewise hazard model showed that the hazard ratio changed over time: the hazard ratio was 0.31 (95% CI 0.13 to 0.73) for 0-12 months, 0.65 (0.39 to 1.09) for 12-36 months, and 1.98 (0.69 to 5.69) for >36 months. For secondary endpoints, the carboplatin arm was associated with improved outcomes in three year recurrence-free survival (93.8% v 88.3%; hazard ratio 0.59, 95% CI 0.37 to 0.93; P=0.02), three year distant disease-free survival (94.8% v 89.8%; hazard ratio 0.61, 0.37 to 0.98; P=0.04), and three year overall survival (98.0% v 94.0%; hazard ratio 0.41, 0.20 to 0.83; P=0.01). The incidence of grade 3-4 treatment related adverse events was 66.7% (269 of 403 patients) in the carboplatin arm and 55.0% (222 of 404 patients) in the control arm. No treatment related deaths occurred. CONCLUSIONS:The addition of carboplatin to adjuvant anthracycline/taxane based chemotherapy significantly improved survival outcomes in patients with high risk, early stage, triple negative breast cancer, driven by reduction of early recurrence risk without new safety concerns. TRIAL REGISTRATION:ClinicalTrials.gov NCT04296175.

1086 Background: Camrelizumab and nab-paclitaxel demonstrated promising anti-tumour activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC) in FUTURE trial. Anti-angiogenic agents have been reported to facilitate immune infiltration. Famitinib is a tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit. The FUTURE-C-PLUS trial (NCT04129996) which added famitinib to camrelizumab and nab-paclitaxel is a single-arm, phase 2 trial evaluating this novel triplet combinatorial strategy in patients with advanced immunomodulatory TNBC. Study design and the primary endpoint ORR has been reported previously (Zhi-ming Shao, et al. ASCO 2021, Abstract 1007). The final PFS data had been published in Clinical Cancer Research (Clin Cancer Res 2022;28:2807–17). Here, we reported the final overall survival of this trial. Methods: Briefly, this study enrolled women aged 18-70 years, with previously untreated, histologically confirmed, unresectable, locally advanced, recurrent or metastatic immunomodulatory TNBC. Immunomodulatory TNBC was defined as CD8 expression on at least 10% of cells using immunohistochemistry analysis. Eligible patients received the triple therapy. Results: Forty-eight patients were enrolled and treated between Oct 2019 and Oct 2020. The median follow-up was 33.1 months (range, 31.8–34.4). 39 (81.3%, 95% CI 70.2-92.3) patients had a confirmed objective response which has been reported in ASCO 2021. At this updating data cutoff (Feb 1, 2023), the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). While overall survival was 29.4 months (95% CI, 23.3-35.5). The disease control rate was 95.8% (46/48). The most common treatment-related grade 3 or 4 adverse events were neutropenia (16 [33.3%]), anemia (5 [10.4%]), febrile neutropenia (5 [10.4%]), and thrombocytopenia (4 [8.3%]). No new safety concerns were detected. No treatment-related deaths were reported. Conclusions: These data, combined with those from our previous reports, provide further evidence for the triplet combination of famitinib, camrelizumab and nab-paclitaxel as an active therapy in advanced Immunomodulatory TNBC. To our knowledge, this is the best overall survival reached in first-line treatment of advanced TNBC. A randomized controlled FUTURE-Super trial is ongoing to further validate these findings. Clinical trial information: NCT04129996 .

Background: BRCA1 and BRCA2 genes have been proven to be genetic susceptibility genes for breast cancer. Their mutations are closely related to hereditary breast cancer, and can also increase the risk of other cancers. Several studies have been conducted to examine the distribution and prevalence of BRCA1 and BRCA2 mutations as well as the penetrance of breast cancer in BRCA1/2 mutation carriers among different populations. However, most studies conducted among Chinese were hospital-based research, whichmay not reflect the real epidemiology in the population. In order to fill the gaps in community research, this study aims to screen genetic susceptibility genes of breast cancer patients in the Chinese community and establish a cohort of genetic high-risk populations. Methods: This is a multisite, prospective, cohort study which has been ongoing in 3 provinces of eastern China since 2019. Up to 5,000 breast cancer survivors will conduct BRCA1, BRCA2, PTEN, CHEK2, and PALB2 genetic susceptibility genes testing, provide clinical and genetic information and family history. Participants were followed up based on the results. Discussion: This is the first study of breast cancer and other common malignancies penetrance and genetic susceptibility gene mutation carrying possibility which is based on community breast cancer data. It is superior to data from hospitals and high-risk clinics. The establishment of a mutation prediction model suitable for the Chinese population still has high socio-economic value. Trial Registration: This study is registered at ClinicalTrials.gov. (Registration number NCT04265937).

目的 探讨双侧乳房重建手术的开展情况和影响因素.方法 对复旦大学附属肿瘤医院2000年1月至2019年12月间接受双侧乳房重建手术的病人资料进行回顾性分析,描述病人人口学、临床病理特征、双侧乳房重建手术规模、手术时机和方式,探讨双侧乳房重建手术方式选择过程中的影响因素.采用t检验、x2检验以及Fisher检验进行显著性检验;利用单因素及多因素回归分析,对上述影响因素进行统计学检验.结果 2913例病人接受乳腺癌全乳切除术后乳房重建,其中双侧乳房重建病人共118例,占重建总数的4.05％.双侧乳腺癌病人82例,对侧乳房预防性切除的单侧乳腺癌病人31例,15例病人为一侧或双侧延期乳房重建.双侧即刻重建者103例,占87.3％,10例病人行单侧乳房延期重建,5例行双乳延期重建.双侧植入物重建97例(82.2％),一侧植入物重建另一侧自体重建共9例(7.6％),其余12例(10.2％)为双侧自体重建.乳房切除动机(治疗性/预防性)、双侧乳房切除时机(同时性/异时性)以及辅助放疗与双侧乳房重建方式选择相关.多因素分析发现,异时性双乳切除病人与术后需要行辅助放疗的病人更倾向于选择一侧或双侧自体重建.同时行双乳切除接受即刻植入物重建时,扩张器-假体两步法占比更高,达76.5％.和单侧乳房重建比较,双侧乳房重建术后非计划再次手术和重建失败的比例差异无统计学意义.结论 当前国内双侧乳房重建的占比虽然较低,但是面临潜在的增长趋势.乳腺癌多学科团队应制订合理的手术适应证,结合病人意愿,选择恰当的手术时机和方式,从而使临床决策更为规范.

Supplementary Figure from Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial

Background Camrelizumab and nab-paclitaxel demonstrated promising anti-tumour activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC) in FUTURE trial. Anti-angiogenic agents have been reported to facilitate immune infiltration. Famitinib is a tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit. The FUTURE-C-PLUS trial (NCT04129996) which added famitinib to camrelizumab and nab-paclitaxel is a single-arm, phase 2 trial evaluating this novel triplet combinatorial strategy in patients with advanced immunomodulatory TNBC. Study design and the primary endpoint ORR has been reported previously (Zhi-ming Shao, et al. ASCO 2021, Abstract 1007). Here, we reported the updated results of this trial. Method Briefly, this study enrolled women aged 18-70 years, with previously untreated, histologically confirmed, unresectable, locally advanced, recurrent or metastatic immunomodulatory TNBC. Immunomodulatory TNBC was defined as CD8 expression on at least 10% of cells using immunohistochemistry analysis. Eligible patients received the triple therapy. Study design has been reported previously in ASCO 2021. Results Between Oct 2019 and Oct 2020, 48 patients were enrolled and treated. 39 (81.3%, 95% CI 70.2-92.3) patients had a confirmed objective response which has been reported in ASCO 2021. At this updating data cutoff (June 30, 2021), the median progression-free survival was 11.9 months (95% CI, 7.3-16.5) with the median follow-up was 14.0 months. While overall survival data were not mature yet, a promising overall survival rate was observed at 12 months (84•2%, 95% CI 73.4-95.0) and 18 months (73.6%, 95% CI 52.0-95.2). In the 39 responders, median duration of response was also not mature. The disease control rate was 95.8% (46/48). The most common treatment-related grade 3 or 4 adverse events were neutropenia (16 [33.3%]), anemia (5 [10.4%]), febrile neutropenia (5 [10.4%]), and thrombocytopenia (4 [8.3%]). No treatment-related deaths were reported. Conclusions These data, combined with those from our previous reports, provide further evidence for the triplet combination of famitinib, camrelizumab and nab-paclitaxel as an active therapy in advanced Immunomodulatory TNBC. To our knowledge, this is the best objective response rate reached in first-line treatment of advanced TNBC. A randomized controlled FUTURE-Super trial (NCT04395989) is keeping recruiting patients to further validate those findings. Citation Format: Li Chen, Yi-Zhou Jiang, Songyang Wu, Jiong Wu, Genhong Di, Guangyu Liu, Keda Yu, Lei Fan, Junjie Li, Yifeng Hou, Zhen Hu, Canming Chen, Xiaoyan Huang, Ayong Cao, Xin Hu, Shen Zhao, Xiaoyan Ma, Xiaoyu Zhu, Jianjun Zou, Wentao Yang, Zhonghua Wang, Zhi-ming Shao. Updated data from FUTURE-C-PLUS: Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for advanced, immunomodulatory triple-negative breast cancer, an open-label, single-arm, phase 2 trial [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 P2-14-04.

1007 Background: Camrelizumab (anti-PD-1 antibody) and nab-paclitaxel (nab-P) have demonstrated promising anti-tumour activity in patients with immunomodulatory (IM) subtype metastatic triple negative breast cancer (TNBC), with 52.6% of ORR observed in heavily pretreated patients in our previous umbrella trial (FUTURE). As antiangiogenic agents were known to enhance the response to immune checkpoint inhibitors, we assessed the efficacy and safety of novel triplet combination of famitinib (tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit), camrelizumab and nab-paclitaxel in patients with IM subtype advanced TNBC. Methods: In this prospective, single-arm, phase 2 study, eligible patients were 18-70 years and had treatment-naive IM subtype unresectable locally advanced or metastatic TNBC. IM subtype was defined as CD8+ by immunohistochemistry. Eligible patients received camrelizumab (200 mg iv, d1, 15, q4w) with nab-P (100 mg/m2 iv, d1, 8, 15, q4w) and famitinib (20 mg po qd, d1-28, q4w). Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. In the absence of intolerable toxicity, nab-P was to be administered for a minimum of 6 cycles. Primary endpoint was objective response rate according to RECIST v1.1. We explored the predictive biomarkers using targeted sequencing with a 484-gene panel. Results: From Oct 2019 to Oct 2020, 48 patients were enrolled. Confirmed objective responses were achieved in 39 (81.3%; 95% CI 70.2%-92.3%) of 48 patients in the intention-to-treat population and in 39 (84.8%; 95% CI 74.4%-95.2%) of 46 patients in the per-protocol population. Median time to response was 1.8 months (95% CI 1.8-2.0 months). With a median follow-up of 9.0 months, progression-free survival (PFS) and duration of response data were not mature. Thirty patients (62.5%) are still on the study treatment. The 9-month PFS rate was 60.2% (95% CI, 43.2% to 77.3%). Grade 3 or 4 adverse events were neutropenia (33.3%), anaemia (10.4%), febrile neutropenia (10.4%), thrombocytopenia (8.3%), hypertension (4.2%), hypothyroidism (4.2%), proteinuria (2.1%), septicemia (2.1%) and immune related myocarditis (2.1%). Adverse events that led to the discontinuation of any agent occurred in 6.3% of the patients. Two patients had treatment-related serious adverse events. No treatment-related deaths were reported. Biomarker analysis showed that somatic mutations of GSK3A may have the potential to predict immunotherapy response. Conclusions: Addition of famitinib to camrelizumab and nab-paclitaxel showed promising antitumour activity as first-line therapy with manageable toxicity profile for IM subtype advanced TNBC patients. Results from ongoing randomized controlled trial FUTURE-SUPER (NCT 04395989) are eagerly awaited. Clinical trial information: NCT04129996 .

BackgroundTo determine the histopathological and MRI features of BRCA1/2 mutation-associated familial breast cancers compared with those of BRCA1/2 mutation-negative and sporadic breast cancers and to further compare the imaging features of cancers from BRCA1 and BRCA2 mutation carriers according to lesion type on MRI.MethodsA retrospective review of medical records was conducted to determine tumour clinicopathologic features and MRI characteristics between June 2011 and July 2017, and 93 lesions with BRCA mutations, 93 lesions without BRCA mutations from familial breast cancers and 93 lesions from sporadic breast cancers were included. Histopathologic data, including immunohistochemistry findings and MRI data according to the BI-RADS lexicon, were reviewed. The association between MRI or histopathologic findings and BRCA mutations was analysed.ResultsBRCA-positive familial breast cancers had a higher number of IDCs with high nuclear grade and lymph node metastasis (all P<0.05), while the BRCA-negative group had a significantly lower Ki-67 index (P<0.001). BPE on MRI was found to be significantly lower for BRCA mutations of familial breast cancer (P=0.024). BRCA1 carriers tended to exhibit the triple-negative phenotype with a more benign shape and margin (P=0.006 and 0.019), whereas BRCA2 mutations were associated with the luminal phenotype and more malignant features.ConclusionsBRCA mutation carriers had a significantly higher number of IDCs with more aggressive cancer, and BRCA-negative cancers had low proliferation levels. Background features on MRI may help to identify BRCA status, while tumour characteristics can differentiate the BRCA1/2 mutation status, consistent with the differences in their clinicopathologic features.

Background Breast cancer is a one of the malignant carcinomas partially caused by genetic risk factors. Germline BRCA1 gene mutations are reportedly associated with breast cancers. Identification of BRCA1 mutations greatly improves the preventive strategies and management of breast cancer. The aim of our study was to investigate the frequency of the deleterious BRCA1 : p.Ile1845fs variant in breast carcinomas, as well as the correlation between p.Ile1845fs variant with clinicopathological parameters and clinical outcomes. Results A total of 23,481 clinically high-risk patients with breast cancer and 6489 healthy controls were recruited for p.Ile1845fs variant sequencing (either sanger or next generation sequencing). We identified 94 breast cancer patients (0.40%, 94/23481) as well as 11 healthy controls (0.17%, 11/6489) carried p.Ile1845fs variant. BRCA1 : p.Ile1845fs variant showed a higher frequency in patients with TNBC molecular typing (20.21%, 19/94) and family history (37.23%, 35/94) compared with non-carriers ( P = 3.62E-6 and 0.034, respectively). According to our data, we advanced the frequency of p.Ile1845fs variant and we confirmed that BRCA1 : p.Ile1845fs variant was associated with increased risk of breast cancer (OR = 2.36, 95%CI = 1.26–4.89, P = 0.004). Conclusions BRCA1 : p.Ile1845fs variant was a frequently pathogenic mutation in breast cancer in Han Chinese women and our data may be helpful for diagnosis and therapy of breast cancer.

Background: PTEN is a tumour suppressor gene that has been proven to be related to breast cancer incidence and tumour progression. The aim of this study was to investigate the frequency of PTEN mutations in breast carcinomas in China and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes. Material and methods: Trimmomatic, Burrows-Wheeler Aligner (BWA), ANNOVAR, SAMtools, and Sanger sequencing were used to analyse PTEN mutations and identify variants in Chinese breast cancer. The frequency of PTEN mutations and the relationships of PTEN mutations with clinicopathological parameters and clinical outcomes were evaluated in breast carcinomas in China. Results: The rate of PTEN germline mutation was 0.23% (n = 9) among 3955 unselected primary breast cancer patients. Of these 9 patients, 2 carried pathogenic mutations, and both were identified as having infiltrative carcinoma. One patient had a family history. The other 7 patients carried only PTEN germline variants that were not identified as pathogenic mutations. Conclusions: We studied the frequency of PTEN germline mutations in a sequential cohort of Chinese breast carcinoma patients. Based on these data, we hypothesize that the germline mutation of the PTEN gene is not closely related to the occurrence of breast cancer in the Chinese population. In the clinic, the PTEN germline mutation cannot be used as the basis for the detection of breast cancer.

Background The current randomized, controlled, multicenter clinical trial was conducted to investigate the efficacy of concurrent neoadjuvant chemotherapy (NCT) and estrogen deprivation in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods Eligible patients with AJCC stage IIB to stage IIIC, ER-positive, HER2-negative breast cancer were enrolled and randomly assigned to receive NCT with or without estrogen deprivation. The primary endpoint was the objective response rate (ORR). Results A total of 249 patients were assigned to either neoadjuvant chemoendocrine therapy (NCET) (125 patients) or the NCT group (124 patients). In the intention-to-treat analysis, the ORR was found to be significantly higher in the NCET group compared with the NCT group (84.8% vs 72.6%; odds ratio, 2.11 [95% CI, 1.13-3.95; P = .02). The efficacy of NCET was more prominent in tumors with a higher Ki-67 index (>20%), with an ORR of 91.2% reported in the NCET group versus 68.7% in the NCT group (P = .001). The pathologic complete response and pathological response rates did not differ significantly between the 2 groups. Although there was no significant difference with regard to progression-free survival (PFS) between the 2 groups (P = .188), patients with a higher baseline Ki-67 index appeared to derive a greater PFS benefit from NCET (2-year PFS rate of 91.5% in the NCET group vs 76.5% in the NCT group; P = .058). Adding endocrine agents to NCT did not result in significant differences in adverse events (grade 3 or 4; graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) between the 2 groups. Conclusions The addition of estrogen deprivation to NCT appears to improve the clinical response in patients with ER-positive, HER2-negative breast cancer, especially for those individuals with a higher Ki-67 index. Patients with a higher Ki-67 index might derive more PFS benefit from concurrent neoadjuvant treatment.

保乳整形的英文名称为“oncoplastic surgery”,最早于1993年由Audretsch等[1]提出.这种技术与传统保乳手术技术的差别在于能够把整形外科技术应用于部分乳房切除手术中,从而使病人既能避免全乳切除术,又能获得更好的乳房外形.这种技术最初流行于欧洲,最终在全球范围内得到接受. 大规模临床数据已经证实,保乳手术+放疗与全乳切除术具有相同的肿瘤安全性和存活率,同时可保留女性形体的完整性而使其获得更高的生活质量[2].但适合于接受传统保乳手术的乳腺癌病人非常有限,当肿瘤较大、肿瘤乳腺体积比例较高以及肿瘤位于特殊位置时,进行传统保乳手术往往会造成乳房变形,包括因腺体塌陷造成的乳房轮廓缺损以及因腺体和皮肤缺损导致的乳头移位和下皱襞变形,这些均严重影响乳房的外观,从而降低病人的满意度和生活质量.而保乳整形手术能够把整形外科技术应用至传统保乳手术中,使病人获得更好的乳房外形从而提高生活质量.