Clinical practice guidelines for diagnosis and treatment of invasive breast cancer: Chinese Society of Breast Surgery (CSBrS) practice guidelines 2021

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.