Germline mutations in cancer-predisposition genes are critical for clinical risk assessment and therapeutic decisions in breast cancer, yet large-scale genomic studies and population-specific tools remain limited for Asian populations. In this prospective clinic-based cohort study, 2700 unselected Chinese breast cancer patients underwent germline sequencing for single nucleotide variations, insertion/deletions, and large genomic rearrangements using a clinically validated 32-gene panel. Multiplex ligation-dependent probe amplification was used for confirmation of copy number variations. A multivariate logistic regression model (PEEKABOO) was developed to predict mutation probability. Therapeutic impact was assessed in 632 patients receiving neoadjuvant therapy. The overall prevalence of deleterious germline variants was 11.4

ABSTRACTBackgroundSentinel lymph node biopsy (SLNB) using radioisotope tracer plus blue dye is the gold standard after neoadjuvant chemotherapy (NAC) in initially cN1 breast cancer patients, but clinical use still has limitations. This study aims to examine diagnostic performance of dual indocyanine green (ICG) and methylene blue tracing for SLNB in patients who have completed NAC for breast cancer with initially cN1 disease.MethodsAdult women (20–80 years of age) scheduled to undergo NAC for biopsy‐proven cT0‐3N1M0 primary invasive breast cancer were consecutively enrolled in this prospective, multicenter, cohort study. Upon the completion of NAC, SLNB was conducted using ICG and methylene blue, followed by axillary lymph node dissection. The primary outcome was the detection rate (DR); secondary outcomes included the false‐negative rate (FNR) and adverse events associated with the use of tracers.ResultsA total of 156 patients were enrolled; all underwent SLNB after NAC. The median number of lymph nodes retrieved during SLNB was 3 (range: 0–11). The DR was 97.4% (152/156; 95% CI, 93.6%–99.0%). The FNR was 6.7% (4/60; 95% CI, 2.6%–15.9%). Negative predictive value was 95.7% (88/92; 95% CI, 89.4%–98.3%). In the subgroup analysis stratified by ycN status, FNR was 4.0% (1/25; 95% CI, 0.7%–19.5%) and 8.6% (3/35; 95% CI, 3.0%–22.4%) in the ycN0 and ycN+ subgroups, respectively. No allergic reaction was reported.ConclusionsSLNB with ICG plus methylene blue achieved a high DR and a very low FNR in breast cancer patients with initially cN1 disease.Trial RegistrationClinicalTrials.gov (https://www.clinicaltrials.gov/), NCT02869815

Background: HER2-positive breast cancer exhibits unique characteristics that can significantly influence patients’ response to neoadjuvant therapy. There is a critical need for a platform that facilitates in vitro drug screening and tailors personalized treatment regimens for such patients. Previously, we introduced an in vitro model named ‘patient-derived tumor-like cell clusters' (PTCs), a cell cluster including tumor cells, mesenchymal cells, and lymphocytes, which accurately replicates the structural, functional, and micro-environmental features of the original tumors. Our retrospective research has shown that PTCs could serve as a reliable preclinical model for drug screening, and thereby, to guide neoadjuvant therapy strategies for patients with breast cancer. This prospective, phase II, open-label study (ClinicalTrials.gov No. NCT04750122) aims to prospectively investigate efficacy of personalized neoadjuvant therapy guided by drug sensitivity profiles of PTCs in HER2-positive breast cancer and to reveal biomarkers associated with resistance to anti-HER2 targeted therapies. Methods: Tissues were obtained by core needle biopsy of candidate patients and cultured to generate PTCs, which were subsequently subjected to drug sensitivity testing and bulk RNA sequencing. Patients with HER2-positive breast cancer were assigned to neoadjuvant therapy according to their individual drug sensitivity profiles. The treatment regimens included THP (taxanes, trastuzumab, and pertuzumab), TCbHP (taxanes, carboplatin, trastuzumab, and pertuzumab), or treatment of physician’s choice (TPC). After completing neoadjuvant therapy, surgery was performed to evaluate the pCR rates of PTC-guided treatment (PGT) and TPC. For the PTCs subjected to RNA-seq, drug sensitivity testing was conducted using H, P, trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-Dxd), respectively. The gene expression data was then analyzed to identify potential biomarkers by differentially-expressed-gene analysis and to establish a predictive model for therapeutic efficacy by logistic regression analysis. Results: From April 2021 to July 2023, a total of 729 samples were collected by core needle biopsy from candidate patients, among whom 592 patients were diagnosed as invasive breast cancer. The success rate of generating PTCs through invasive breast cancer was 83.4%. Overall, 24 patients with HER2+ breast cancer that successfully constructed PTCs and drug sensitivity tests were enrolled in this study. Nineteen patients (79.2%) had T2-3 tumors and nineteen (79.2%) had node-positive disease. The in vitro drug sensitivity profiles suggested that 6 patients (25%) were sensitive to THP, 14 (58.3%) were sensitive to TCbHP, and 4 (16.7%) were resistant to both. Following neoadjuvant treatment, the patients that received THP treatment achieved a pCR rate of 83.3%, while the patients that were sensitive to TCbHP rather than THP achieved a pCR rate of 78.6%. Compared to only 1 out of the 4 patients with resistant PTCs achieved pCR, 16 of the 20 patients receiving PGT achieved pCR (80.0% vs 25.0%, p=0.027). In subgroup analyses of the PGT counterparts, the pCR rates were 62.5% for HR+/HER2+ patients and 91.7% for HR-/HER2+ patients. Besides, 14 PTC samples carried on bulk RNA sequencing. As a result, 5 co-upregulated genes (PLBD1, BMP3, HLA-DRB5, IGLV2-14, TIAF1) and 5 co-downregulated genes (EPN3, KCNK15, ACSF2, AC025048.2, PIP4K2B) were identified in the resistant group compared with the sensitive group. The multidrug resistance signature was utilized to establish a predictive model, of which the area under curves were 100.0% for predicting response to H, P, T-DM1, and T-Dxd. Conclusion: The in vitro drug screening PTC platform could serve as a promising approach for tailoring personalized neoadjuvant treatment strategies for HER2-positive breast cancer. The identification of multidrug resistance signature emerges as a practical and effective biomarker for forecasting the response to anti-HER2 targeted therapies. Citation Format: Yaqian Xu, Chaobin Wang, Xiangui Zhang, Shenyi Yin, Houpu Yang, Fei Xie, Yuan Peng, Yang Yang, Wei Du, Jianzhong Xi, Shu Wang. Personalized Neoadjuvant Therapy Guided by Drug Screening of Patient-Derived Tumor-Like Cell Clusters in HER2-Positive Breast Cancer: A Prospective Phase II Study and Exploratory Analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-11-16.

Background:Circulating tumor DNA (ctDNA) is a potential biomarker not only capable of monitoring the treatment response during neoadjuvant therapy (NAT) or rescue therapy, but also identifying minimal residual disease (MRD) and detecting early relapses after primary treatment. However, it remains uncertain whether the detection of ctDNA at diagnosis, before any treatment, can predict the prognosis for patients with early breast cancer. The objective of our study was to evaluate the predictive value of baseline ctDNA for prognosis in patients with early breast cancer.Methods:A total of 90 patients with early breast cancer and 24 healthy women were recruited between August 2016 and October 2016. Peripheral blood samples were collected from patients at diagnosis, before any treatment. Blood samples were processed and subjected to targeted deep sequencing with a next-generation sequencing (NGS) panel of 1,021 cancer-related genes. The recurrence-free survival (RFS) and invasive disease-free survival (iDFS) were reported.Results:The 90 patients with breast cancer included 6 patients with ductal carcinoma in situ (DCIS) and 84 patients with invasive breast cancer. Within the cohort of patients with invasive breast cancer, ctDNA were detected in 57 patients, with a ctDNA detection rate of 67.9%. Meanwhile, no ctDNA was detected in DCIS patients. Among 84 patients with invasive breast cancer, patients with high-level ctDNA had a significantly lower RFS compared to patients with low-level ctDNA (log-rank P=0.0036).Conclusions:Our study suggested that ctDNA at diagnosis, before any treatment, could potentially serve as a biomarker to predict the prognosis for patients with early breast cancer. However, further follow-up and more studies with large sample sizes are required to confirm these findings.

Purpose It is still unclear which patients diagnosed with DCIS through biopsy can benefit from lymph node surgery. We aimed to developed and validated a nomogram to predict the risk of upstaging to invasion, and explore the factors related to lymph node metastasis in biopsy diagnosis of DCIS patients. Methods A retrospective study was conducted on 526 cases diagnosed with DCIS before surgery in the period of January 2016 to December 2022. Nomograms for predicting the probability of invasion disease were constructed according to multivariate logistic regression analysis. This nomogram was validated using a second data set of 133 patients between January to December 2023. Univariate and multivariate analysis were used to evaluate the risk factors for lymph node metastasis. Results Underestimating invasive carcinoma occurred in 42.0% of patients, of whom 37 had positive lymph node. Core needle biopsy, mass on mammography, moderate nuclear grade of DCIS and increased Ki-67 expression were associated with upstaging. Nomogram developed depending on these factors showed acceptable performance on predicting upstaging (AUC 0.724). This nomogram was validated in a second dataset with an AUC of 0.641. calcification on mammography, mass on MRI performance and large radiological size were independent risk factors of lymph node metastasis. Conclusion Underestimating invasive carcinoma with DCIS detected prior to surgery is common, but with a low probability of lymph node metastasis. This nomogram and factors associated with positive lymph node may provide help in selecting suitable patients for axillary lymph node excision.

Background The ring-shaped cohesin complex is an important factor for the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we use super-resolution imaging to reveal the unique role of cohesin subunit RAD21 in cohesin loading and chromatin structure regulation. Results We directly visualize that up-regulation of RAD21 leads to excessive chromatin loop extrusion into a vermicelli-like morphology with RAD21 clustered into foci and excessively loaded cohesin bow-tying a TAD to form a beads-on-a-string-type pattern. In contrast, up-regulation of the other four cohesin subunits results in even distributions. Mechanistically, we identify that the essential role of RAD21 is attributed to the RAD21-loader interaction, which facilitates the cohesin loading process rather than increasing the abundance of cohesin complex upon up-regulation of RAD21. Furthermore, Hi-C and genomic analysis reveal how RAD21 up-regulation affects genome-wide higher-order chromatin structure. Accumulated contacts are shown at TAD corners while inter-TAD interactions increase after vermicelli formation. Importantly, we find that in breast cancer cells, the expression of RAD21 is aberrantly high with poor patient survival and RAD21 forms beads in the nucleus. Up-regulated RAD21 in HeLa cells leads to compartment switching and up-regulation of cancer-related genes. Conclusions Our results provide key insights into the molecular mechanism by which RAD21 facilitates the cohesin loading process and provide an explanation to how cohesin and loader work cooperatively to promote chromatin extrusion, which has important implications in construction of three-dimensional genome organization.

Adenoid cystic carcinoma (ACC) is an extremely rare type of breast cancer. The role of adjuvant treatments for ACC remains controversial. Patients with a histology-confirmed diagnosis of ACC of the breast were identified based on the SEER (Surveillance, Epidemiology and End Results) database. Propensity score matching (PSM) was performed to balance the baseline characteristics. The Kaplan–Meier method and Cox regression models were performed to determine the impact of the adjuvant chemotherapy (CT) and radiotherapy (RT) associated with breast cancer-specific survival (BCSS) and overall survival (OS). A total of 1036 patients with ACC of the breast were included. After a median follow-up of 11.3 years, the 10-year OS and BCSS rate was 76.2% and 92.6%, respectively. After PSM, adjuvant CT converted into neither OS (Log-rank p = 1.000) nor BCSS (Log-rank p = 0.900) benefits in patients with ACC of the breast. Adjuvant RT also did not improve OS (Log-rank p = 0.060) and BCSS (Log-rank p = 0.400). According to the univariate stratified analysis, adjuvant RT was favorable for OS in patients who underwent breast-conserving surgery (HR 0.66, 95% CI 0.45, 0.99, p = 0.042). From the multivariate analysis, histology grade and nodal status were independent prognostic factors for both OS and BCSS. In conclusion, ACC of the breast presented a favorable prognosis. Adjuvant treatment, especially adjuvant CT, might not be essential for patients with this disease.

Purpose The combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer. Patients and methods This randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75 mg/m 2 d1 plus capecitabine 1000 mg/m 2 twice d1–14, q3w) or TE (docetaxel 75 mg/m 2 d1 plus epirubicin 75 mg/m 2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety. Results Between September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0–27.3%; P = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2–46.1%; P = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent iDFS and OS rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile. Conclusion The anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients. Trial Registration ACTRN12613000206729 on 21/02/2013, retrospectively registered.

With the understanding of the biological characteristics of breast cancer and the improvement of systemic treatment, the treatment concept of breast cancer has changed, and the treatment strategy of axillary lymph nodes has also been constantly changing. With the change of these concepts, a large number of relevant clinical trials have been gradually carried out. The NSABP B04 study took the lead in exploring the transformation of axillary treatment strategies in the classic breast cancer treatment. Although this study did not change the clinical practice of axillary treatment at the time, it provided a preliminary data basis for a subsequent series of clinical studies on axillary preservation. In these changes, sentinel lymph node biopsy, as a milestone in the surgical treatment of breast cancer, has become the standard staging procedure for axillary negative patients. Since then, a series of related clinical studies have also been carried out, among which the results of studies on patients with low-load axillary metastasis have confirmed the feasibility of axillary preservation in some patients, which has influenced and changed clinical practice. In addition, the results of the study make it possible for some patients to preserve the axilla after neoadjuvant therapy reduce postoperative upper extremity edema effectively. Whether axillary surgery can be completely eliminated, and whether axillary dissection can be waived for patients with positive axilla after neoadjuvant therapy under the premise of equal survival benefit have also received extensive attention.

腋窝分期不仅可以判断乳腺癌病人的预后,而且可以指导后续治疗.腋窝淋巴结清扫术(axillary lymph node dissection,ALND)是传统的腋窝分期术式,但是,ALND后并发症的出现会严重影响病人的生活质量.前哨淋巴结活检术(sentinel lymph node biopsy, SLNB)已经成为腋窝临床阴性病人的主流分期术式,减少了腋窝手术后的并发症.随着系统治疗及新辅助治疗的不断进步,相关研究对于部分低负荷腋窝淋巴结转移的病人以及新辅助治疗后淋巴结转阴的病人进行了保留腋窝的探索.

Background Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients. Methods Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People’s Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed. Results One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26–82] years vs 54 [25–90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred. Conclusion Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China. Trial registration ClinicalTrials.gov. Registration number NCT03606616 . Retrospectively registered on 31 July 2018.

Purpose: The dilemma of undertreatment and overtreatment of elderly breast cancer patients is common. This study aimed to investigate clinicopathological features, treatment modalities, and survival in women diagnosed with breast cancer at age 70 years or over, and to assist clinicians in developing individualized treatment plans by balancing the risks of breast cancer-specific death (BCSD) and other cause-specific death (OCSD). Methods: This retrospective study included 420 women who were diagnosed with pathologically confirmed invasive breast cancer at age 70 years or older from January 2008 to December 2015 at Peking University People's Hospital (PKUPH). We collected baseline health status, tumor characteristics, treatment choices, and outcomes and created nomograms for clinicians to estimate individualized BCSD and OCSD risk directly. Results: During a median follow-up of 71.5 months (range 2 to 144 months) in patients with stage I–III tumors, breast cancer specific survival (BCSS) was 92.4% (376/407) and overall survival (OS) was 78.1% (318/407). There were 89 deaths, and 65.2% (58/89) were non-breast cancer related. Upon multivariate analysis by Cox regression model, tumor size, positive lymph nodes, Ki-67, and surgery were independent predictors of BCSS, and comorbidities, positive lymph nodes, Ki-67, surgery, and endocrine therapy were independent predictors of OS. Propensity score weighted (PSW) was applied to analyze therapeutic efficacy, and there was BCSS and OS benefit with surgery (both p < 0.001), BCSS benefit with chemotherapy (p = 0.029), BCSS and OS benefit with endocrine therapy (p = 0.006 and 0.004), and neither BCSS nor OS benefit with radiotherapy (RT) (p = 0.348 and 0.289). Competing-risk nomograms were developed to estimate cumulative mortality probabilities for BCSD and OCSD for individual patients according to clinicopathologic characteristics and treatments. The calibration curves displayed exceptionally, with C-indexes 0.714 for BCSD and 0.717 for OCSD. Conclusions: Older patients had greater risk of dying from non-breast cancer causes. Surgery, chemotherapy, and endocrine therapy were associated with improved survival. Competing risk nomograms allowed individual assessment of BCSD and OCSD, based on clinicopathological characteristics and treatment options, and can be used as a tool to help in choosing appropriate treatment strategies. This study was approved by the Peking University People's Hospital Research Ethics Board on September 4, 2018.

The survival of patients with breast cancer has been greatly improved by comprehensive treatment including surgery, radiotherapy, and systemic treatment, among which surgical treatment remains the mainstay. Breast surgeons must not only master surgical skills but also develop the ability to treat disease comprehensively. To improve the ability of breast surgeons in China to diagnose breast cancer early, perform reasonable surgical treatment, and provide comprehensive treatment orientation, the Chinese Society of Breast Surgery (CSBrS) has reported the key issues in the diagnosis and treatment of invasive breast cancer through opinion collection and expert discussion. The group evaluated the relevant evidence using the grading of recommendations assessment, development, and evaluation system and developed the clinical practice guideline for diagnosis and treatment in patients with invasive breast cancer: CSBrS practice guidelines 2021 with the aim of providing guidance for the clinical practice of breast surgeons in China. Level of Evidence and Recommendation Strength Level of evidence standard[1] Recommendation strength standard[1] Recommendation strength review committee There were 71 voting committee members for these guidelines: 58 from breast surgery departments (81.7%), five from medical oncology departments (7.0%), three from medical imaging departments (4.2%), two from a pathology department (2.8%), one from a radiotherapy department (1.4%), and two epidemiologists (2.8%). Target Audience Clinicians specializing in breast diseases in China. Recommendations Recommendation 1: Breast cancer screening. - Breast cancer screening Level of evidence Recommendation strength 1.1 Women with average risk 1.1.1 Begin at 40 years[2] I A 1.1.2 Annual screening mammography[3–5] I A 1.1.3 Annual ultrasound[6–9] I A 1.2 Women with increased risk 1.2.1 Begin before 40 years[2] I A 1.2.2 Annual screening mammography[3–5] I A 1.2.3 Annual ultrasound[6–9] I A 1.2.4 Annual breast MRI[2,10,11] I A MRI: Magnetic resonance imaging. Recommendation 2: Breast cancer diagnosis. - Breast cancer diagnosis Level of evidence Recommendation strength 2.1 Imaging diagnosis 2.1.1 Diagnostic mammography[12] I A 2.1.2 Ultrasound[12] I A 2.1.3 Breast MRI[13–16] I A 2.2 Pathology diagnosis 2.2.1 Image-guided lesion biopsy a. Core needle biopsy[12,17] I A b. Vacuum-assisted breast biopsy[12,17] I A c. Wire-guided biopsy[17] I A 2.2.2 Image-guided lymph node biopsy a. Fine needle biopsy[12,17] I A b. Core needle biopsy[12,17] I A MRI: Magnetic resonance imaging. Recommendation 3: Breast cancer surgery treatment. - Breast cancer surgery treatment Level of evidence Recommendation strength 3.1 Breast surgery 3.1.1 Lumpectomy[18,19] I A 3.1.2 Total mastectomy[12] I A 3.1.3 Modified radical mastectomy[20] I A 3.1.4 Skin-sparing mastectomy[21] II A 3.1.5 Nipple-sparing mastectomy[22] II A 3.2 Surgical axillary staging 3.2.1 Sentinel lymph node biopsy[23] I A 3.2.2 Axillary lymph node dissection[12] I A 3.3 Oncoplastic and reconstructive surgery 3.3.1 Oncoplastic techniques for breast conservation[12,17] II A 3.3.2 Breast reconstruction following mastectomy 3.3.2.1 Timing of reconstruction a. Immediate reconstruction[12,17] II A b. Delayed reconstruction[12,17] II A c. Delayed-immediate reconstruction[12,17] II A 3.3.2.2 Type of reconstruction a. Implant reconstruction[12,17] II A b. Autologous tissue reconstruction[12,17] II A c. Autologous tissue combined with implant reconstruction[12,17] II A Recommendation 4: Breast cancer radiation therapy. - Breast cancer radiation therapy Level of evidence Recommendation strength 4.1 Whole breast radiation therapy after lumpectomy[24] I A 4.2 Radiation to chest wall and regional lymph nodes after mastectomy and ≥N2[25] I A 4.3 Radiation to chest wall and regional lymph nodes after mastectomy and N1[26] I A 4.4 Radiation to chest wall after mastectomy and ≥T3[27] II A Recommendation 5: Breast cancer systemic therapy. - Breast cancer systemic therapy Level of evidence Recommendation strength 5.1 Adjuvant systemic therapy 5.1.1 Adjuvant endocrine therapy for HR-positive patients[12,28] I A 5.1.2 Adjuvant HER2-targeted therapy for HER2-positive patients[12,28] I A 5.1.3 Adjuvant chemotherapy for high-risk recurrence patients[12,28] I A 5.2 Neoadjuvant systemic therapy 5.2.1 Indications for neoadjuvant therapy a. Inoperable breast cancer (T4 or ≥N2)[12,28] I A b. Large primary tumor patient who desires breast conservation[12,28] I A c. Evaluation of drug sensitivity in vivo[12,28] I A 5.2.2 Strategy for neoadjuvant therapy a. Clarify clinical stage, pathological diagnosis, histological grade and molecular characteristics before treatment[12,28] I A b. Demarcate the tumor bed before treatment[12,28] I A c. Tumor response should be routinely assessed during treatment[12,28] I A d. Pathological evaluation for primary tumor and lymph node after treatment[12,28] I A HR: Hormone receptor; HER2: Human epidermal growth factor receptor 2. Recommendation 6: Breast cancer follow-up. - Breast cancer follow-up Level of evidence Recommendation strength 6.1 Interval for follow-up 6.1.1 1–4 times per year within 5 years of surgery[12] II A 6.1.2 Annually after 5 years of surgery[12] II A 6.2 Content of follow-up 6.2.1 Loco-regional recurrence a. Ultrasound[12] II A b. Mammography[12,29] I A 6.2.2 Distant metastasis a. Screening of distant metastases is not recommended for asymptomatic patients[30,31] I A b. Tumor markers III C c. CT of chest III C d. CT/ ultrasound/MRI of abdomen III C e. Bone scan III C f. FDG PET/CT III C 6.2.3 Complication of surgery Lymphedema[12] II A 6.2.4 Complication of medication a. Endometrial evaluation during treatment of tamoxifen[12] II A b. Assessment of bone mineral density during treatment of aromatase inhibitor[12] II A 6.2.5 Guidance of a healthy lifestyle[12] II A CT: Computed tomography; FDG PET: 18F-deoxyglucose positron emission tomography; MRI: Magnetic resonance imaging. Recommendation 7: Recurrent/metastatic breast cancer treatment. - Recurrent/metastatic breast cancer treatment Level of evidence Recommendation strength 7.1 Biopsy and Determination of tumor ER/PR and HER2 status on metastatic site[12,28] II A 7.2 Surgical resection ± radiation therapy if possible for local/regional recurrence[12,17] II A 7.3 Systemic therapy according ER/PR and HER2 status on metastatic site[12,28] I A ER/PR: Estrogen receptor/progesterone receptor; HER2: human epidermal growth factor receptor 2. Discussion Mammography remains the most important screening technique because it is the only technique to demonstrate a mortality reduction.[2–4] The experts discussed the efficiency of breast ultrasound screening and reached a consensus [Supplementary File 1, https://links.lww.com/CM9/A539]. Although current evidence does not support the use of breast MRI to screen women at average risk of breast cancer, the benefits of screening MRI for early detection of breast cancer in women at high risk have been demonstrated in multiple studies.[9] The panel does not recommend contrast-enhanced breast MRI for screening in women at general risk, but consent MRI screening for women with high-risk.[2,10] The experts discussed the use of contrast-enhanced breast MRI in diagnosis of breast cancer and reached a consensus [Supplementary File 2, https://links.lww.com/CM9/A540]. The experts discussed the surgical treatment for breast, the axillary staging, and the reconstruction of breast, and reached a consensus [Supplementary File 3, https://links.lww.com/CM9/A541]. The experts discussed the neoadjuvant therapy and reached a consensus [Supplementary File 4, https://links.lww.com/CM9/A542]. The results of a meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) showed that whole-breast irradiation can reduce both the risk of recurrence and the risk of breast cancer death.[24] Results from the Danish Breast Cancer Cooperative Group82 b and c study and the EBCTCG meta-analysis showed that for patients who underwent mastectomy and had positive lymph nodes, radiotherapy not only reduced the risk of regional recurrence but also achieved a survival benefit, including for patients with one to three positive lymph nodes.[25,26] Therefore, the panel recommends post-operative radiotherapy for patients with positive lymph nodes. A meta-analysis showed that regular mammography is helpful for early detection of local recurrence and reduction of breast cancer mortality.[29] For patients with local/regional recurrence, the panel recommended that R0 surgical resection should be performed if possible and that radiotherapy should be decided according to the previous radiotherapy. If the tumor is not technically resectable, the clinician should consider systemic therapy to achieve best response, then resect the tumor if possible.[11,16] List of Compiling Committee Members (In Alphabetical Order by Surname) Zhong-Wei Cao, De-Dian Chen, Yuan-Jia Cheng, Xue-Ning Duan, Zhi-Min Fan, Pei-Fen Fu, Bao-Liangguo, Jian Huang, Jun Jiang, Hong-Chuan Jiang, Feng Jin, Hua Kang, Rui Ling, Jin-Ping Liu, Ke Liu, Li-Yuan Liu, Miao Liu, Qian Liu, Yin-Hua Liu, Yun-Jiang Liu, Zhen-Zhen Liu, Da-Hua Mao, Jiang-Hua Ou, Yuan Peng, Xiang Qu, Guo-Sheng Ren, Ai-Lin Song, Er-Wei Song, Li-Li Tang, Xing-Song Tian, Chao-Bin Wang, Chuan Wang, Fei Wang, Jiang-Dong Wang, Shu Wang, Shui Wang, Xiang Wang, Jiong Wu, Fei Xie, Ling Xin, Zhi-Gang Yu, Jiang-Guo Zhang, Jin Zhang, Jing-Hua Zhang, Wei Zhu, Ang Zheng, Qiang Zou. Conflicts of interest The expert committee for these guidelines declares no conflict of interest. These guidelines are a reference for breast disease specialists in clinical practice. However, the guidelines are not to be used as the basis for medical evaluation, and do not play an arbitrating role in the handling of any medical disputes. The guidelines are not a reference for patients or non-breast specialists. The Chinese Society of Breast Surgery assumes no responsibility for results involving the inappropriate application of these guidelines, and reserves the right to interpret and revise the guidelines.

This study aimed to assess the efficacy of the combination of indocyanine green (ICG) and methylene blue (MB) dye in early breast cancer patients undergoing sentinel lymph node biopsy (SLNB). Between January 2011 and December 2015, 1061 early breast cancer patients underwent SLNB were included. SLNB was performed for enrolled patients by injection of both ICG and MB. Detection rate, positivity, and number of sentinel lymph nodes (SLNs) by ICG and MB were analysed. Axillary recurrence and arm lymphedema at 5.6-year follow-up were reported. The combination of ICG and MB resulted in a very high detection rate of 99.6%, the median number of sentinel lymph nodes was 3. A total of 374 histologically confirmed positive SLNs were detected in 237 patients, 96.6% of the positive patients and 94.1% of the positive nodes could be identified by the combination of ICG and MB. After a median follow-up of 5.6 (2–9.3) years, 0.64% of patients with negative SLNs had ipsilateral axillary recurrence, and the incidence of arm lymphedema was 2.1%. Although the missing isotope control weakens the interpretation of the findings, the dual tracing modality of ICG and MB, without involvement of radioactive isotopes, was an effective method for SLNB in patients with early breast cancer. ACTRN12612000109808. Registered on 23 January 2012.

Objective: To examine treatment outcomes of breast phyllodes tumors and the prognosis factors of local recurrence. Methods: This retrospective cohort study included 276 patients who underwent surgical resection at Breast Center, Peking University People's Hospital from January 2011 to December 2019. Tumor subtype and histopathological features were determined from pathology reports, and the deadline of follow-up was September 30th, 2020. All 276 patients underwent open surgery, including 17 patients of mastectomy, and 259 patients of lumpectomy. The enrolled patients were all female, with age of (41.5±11.3) years (rang: 11 to 76 years), and tumor diameter of 35(28) mm (M(QR)). The Kaplan-Meier method and Log-rank test were used for survival analysis. The multivariate analysis was implemented using the Cox proportional hazard model. Results: According the pathologic test, there were 191 patients of benign phyllodes tumor, 67 patients of borderline tumor and 18 patients of malignant tumor. There were 249 patients with a follow-up of more than 6 months, and 14.1% (35/249) had local recurrence. The time-to-recurrence was (28.6±22.2) months (range: 2 to 96 months), (29.1±18.1) months (range: 2 to 80 months), (32.1±30.1) months (range: 5 to 96 months) and (12.0±6.9) months (range: 8 to 20 months) for benign, borderline and malignant phyllodes tumors. Tumor diameter (≥100 mm vs.<50 mm, HR=3.968, 95%CI: 1.550 to 10.158, P=0.004) and malignant heterologous element (yes vs. no, HR=26.933, 95%CI: 3.105 to 233.600, P=0.003) were prognosis factors of local recurrence. One death from malignant phyllodes occurred after distant metastasis. The 3-year disease-free survival rates of benign, borderline and malignant phyllodes tumor were 88.2%, 81.7% and 81.4% (P=0.300). Conclusion: Phyllodes tumors have a considerable local recurrence rate, which may be associated with tumor diameter and malignant heterologous element.

人类表皮生长因子受体-2(HER-2)阳性乳腺癌包括激素受体阳性及激素受体阴性乳腺癌,激素受体阳性、HER-2阳性乳腺癌两条信号通路共同作用促进肿瘤细胞增殖,且两条信号通路之间存在交互作用,这部分病人新辅助化疗联合靶向治疗的病理完全缓解(pCR)率低于激素受体阴性病人.针对这部分病人新辅助治疗的强化及优化可以从以下三个方向进行探索:标准双靶治疗基础上联合传统内分泌治疗或强化的内分泌治疗、抗HER-2治疗的进一步强化联合或不联合内分泌治疗、内分泌联合靶向的降阶优化治疗.已有小样本研究就上述三种治疗策略进行了相应的探索,结果并不十分一致.因此,对于激素受体阳性、HER-2阳性的早期乳腺癌,化疗联合靶向治疗仍然是新辅助治疗的标准方案,同时也期待更多大样本的研究及长期随访结果提供更多的循证医学证据,使病人得到更加精准的治疗.

Background Although traditional intraoperative assessments (ie, frozen sections) may lower reoperation rates in patients with breast cancer, time/tissue limitations and accuracy concerns have discouraged their routine clinical use. Full-field optical coherence tomography (FFOCT) and dynamic cell imaging (DCI) are novel optical imaging techniques offering rapid histologic approximations that are unfettered by requisite handling steps. This study was conducted to determine the feasibility and diagnostic utility of FFOCT and DCI in examining breast and lymph node specimens during breast cancer surgery. Methods FFOCT and DCI were applied to normal and cancerous breast tissue, benign breast lesions, and resected axillary lymph nodes. The tissues were then subjected to conventional processing and staining (hematoxylin-eosin) for purposes of comparison. Results A total of 314 specimens, including 173 breast biopsies (malignant, 132; benign/normal, 41) and 141 resected lymph nodes (tumor-positive, 48; tumor-negative, 93), were obtained from 158 patients during breast surgery for prospective imaging evaluations. In breast cancer diagnosis, the minimum sensitivities (FFOCT, 85.6%; DCI, 88.6%) and specificities of optical imaging (FFOCT, 85.4%; DCI, 95.1%) were high, although they diverged somewhat in nodal assessments (FFOCT sensitivity, 66.7%; FFOCT specificity, 79.6%; DCI sensitivity, 83.3%; DCI specificity, 98.9%). Conclusions These timely and tissue-sparing optical imaging techniques proved highly accurate in diagnosing breast cancer and nodal metastasis. They compare favorably with routine histologic sections and demonstrate their promise in this setting.

Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumorlike cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical application in precision oncology. PTC tests of 59 patients with gastric, colorectal, or breast cancers revealed an overall accuracy of 93% in predicting their clinical outcomes. We implemented PTC to guide chemotherapy selection for a patient with mucinous rectal adenocarcinoma who experienced recurrence with metastases after conventional therapy. After three cycles of a nonconventional therapy identified by the PTC, the patient showed a positive response. These findings need to be validated in larger clinical trials, but they suggest that the PTC model could be prospectively implemented in clinical decision-making for therapy selection.

Ultrasound diagnosis of axillary lymph nodes has the advantages of ease, convenience and low cost; however, most previous studies evaluated lymph node metastasis of the entire axilla rather than the association between the ultrasound features of a single lymph node and its pathology. This prospective study was performed to explore the ultrasound features of lymph nodes observed in bionic medium in vitro and to develop a lymph node-specific model for prediction of metastasis based on analysis of the association between the ultrasound features and pathology of each lymph node. From November 1, 2017 to December 19, 2017, 373 nodes (54 patients) were enrolled into the modeling group; from December 20, 2017 to January 12, 2018, 139 lymph nodes (22 patients) were enrolled into the validation group. Lymph nodes from sentinel lymph node biopsy or axillary lymph node dissection were enrolled. Individual lymph nodes were placed in bionic medium and observed separately using ultrasound. Traditional ultrasound features of metastatic nodes (long axis, short axis, cortical thickness and hilum loss) were recorded, and the longitudinal-to-transverse axis ratio (L/T) and cortical proportion were calculated. Pathologic results specific to each lymph node were recorded. On the basis of two-level binary logistic regression, independent predictors of lymph node metastasis in the modeling group were lymph node long axis (p = 0.004), short axis (p < 0.001), L/T (p = 0.006), cortical thickness (p = 0.001) and hilum loss (p < 0.001). When analysis was done at the node level, the areas under the curve of the modeling and validation groups were 0.97 and 0.75, respectively. When validation was done at the patient level, the areas under the curve of the modeling and validation groups were 0.96 and 0.93, respectively. The model for prediction of metastasis based on the ultrasound features and pathology of each lymph node is of good predictive value for lymph node metastasis.