[引文]  Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159-182. 

doi:10.1016/j.annonc.2023.11.016

European Society for Medical Oncology (ESMO)，欧洲肿瘤内科学会

Breast cancer screening

Hereditary breast cancer

Histomorphological assessment, biomarkers and molecular pathology

Recommendations

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  The complete medical and family history must be evaluated, including menopausal status (if in doubt, serum estradiol and follicle-stimulating hormone levels should be measured) [V, A].

  
  

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  [18F]2-fluoro-2-deoxy-D-glucose (FDG)–positron emission tomography (PET)–CT scanning may be used instead of CT and bone scintigraphy particularly for high-risk patients and when conventional methods are inconclusive [II, B].

  
  

General treatment principles

Figure 2

Patient communication and shared decision making

Locoregional treatment

Advances in management of axillary LNs    See Figure 3 for a treatment algorithm on the management of axillary LN (ALN) involvement with primary surgery or primary systemic/neoadjuvant therapy.

Figure 3

Regional LN status remains one of the strongest prognosticators of long-term outcome in EBC. Sentinel LN biopsy (SLNB) is the standard staging approach for clinically negative ALNs at diagnosis or after neoadjuvant ChT. SLNB is associated with less shoulder stiffness, pain and arm swelling morbidity than complete ALN dissection (ALND). With appropriate training, high identification rates (≥97%), low false-negative rates and favourable ALN recurrence rates following SLNB are achievable.11 Notably, isolated ALN recurrence occurs in <1% of negative SLNBs despite a false-negative rate of 5%-10%.12

Micrometastases (0.2-2.0 mm) (N1mic) or isolated tumour cells (N0itc+) in treatment-naïve ALNs are prognostically equivalent to N0 disease, with local and systemic treatment options selected based on other tumour- and patient-based parameters. Based on the IBCSG 23-01 trial, further ALN treatment is not required if a sentinel LN (SLN) has micrometastases unless neoadjuvant therapy was given.13 Routine IHC or PCR for the evaluation of SLNs in patients unexposed to neoadjuvant ChT is therefore not recommended.14

Micrometastases after neoadjuvant ChT indicate a non-pathological complete response (pCR) which is associated with worse prognosis than micrometastases in treatment-naïve LNs.15

For cases with macrometastatic spread to the SLN, the ACOSOG Z0011 trial reported similar outcomes without ALND for patients with clinical T1-T2 cN0 invasive breast cancer who had 1-2 SLNs containing metastases but no gross extracapsular extension (treated with BCS, tangential post-operative RT including part of the axilla and adjuvant systemic therapy).12 For patients who do not meet these criteria, and for patients with more than two positive SLNs, ALND remains the standard of care. Another option for patients with cN0 disease and SLN metastases is axillary RT, as demonstrated by the AMAROS and OTOASOR studies.16,17 Nodal involvement-based indications for systemic therapy options (e.g. abemaciclib, olaparib) need to be considered by a multidisciplinary team (MDT) when choosing between ALND and RT in case of positive SLNs. The question of whether patients who have undergone mastectomy with or without an indication for PMRT (low-risk tumours, T <5 cm) can forego ALND after positive SLNB remains unresolved.18 The benefit of ALND in patients with micrometastatic and macrometastatic SLNs after neoadjuvant ChT is currently being investigated. Thus, until outcomes are reported from randomised trials, ALND is recommended for ypN1mi as well as any macrometastatic disease (ypN+) regardless of other features. There are currently no available data on isolated tumour cells in ALND after neoadjuvant ChT.

Occult breast cancer presents as regional LN metastases without an identifiable primary lesion within the breast. It constitutes <0.5% of all new breast cancer cases. Routine diagnosis requires breast MRI and systemic staging, preferably by FDG–PET–CT. ALND with whole-breast RT (WBRT) and regional RT is the preferred treatment. Systemic therapy, including neoadjuvant therapy, should be according to recommendations by subtype and stage.19

(Neo)adjuvant systemic treatment

HR-positive, HER2-negative EBC    Figures 4 and 5 provide treatment algorithms and Supplementary Table S5, available at https://doi.org/10.1016/j.annonc.2023.11.016 , provides an overview of adjuvant therapy for patients with HR-positive, HER2-negative EBC.

Figure 4

Figure 5

HR-positive, HER2-negative tumours are the most common type of EBC, accounting for >70% of all cases worldwide. Risk factors for recurrence of HR-positive cancers are well established (see the ‘Screening, diagnosis, pathology and molecular biology’ section of this guideline).

Treatment is individualised based on tumour stage and biology [subtype (Supplementary Material Section 4, available at https://doi.org/10.1016/j.annonc.2023.11.016 , provides details on subtype classification)], menopausal status and the several classes of therapeutic interventions available, including ET, ChT and targeted therapy. Although the relative benefit of ChT and ET might be the same in different subgroups, the absolute benefit depends on the individual risk of recurrence. The absolute benefit should be considered in conjunction with the side-effects of each treatment in an informed decision-making process with the patient.

Anatomic risk variables (tumour size, nodal status) do not influence treatment sensitivity or the relative benefit from adjuvant therapy; however, by guiding therapy selection, they can have a major impact on absolute risk reduction. Higher-risk HR-positive tumours generally warrant aromatase inhibitor (AI)-based therapy, consideration of ChT, targeted treatments, extended adjuvant ET and, for premenopausal women, ovarian function suppression (OFS) and ChT.

For most HR-positive, HER2-negative, screening-detected breast cancer, surgery is the initial treatment modality. For women with larger tumours or clinical nodal involvement, neoadjuvant systemic therapy may be preferred. Neoadjuvant ChT can be effective for surgical downstaging of HR-positive, HER2-negative cancers; however, pCR is uncommon although it occurs more frequently in young patients and/or patients with high-grade tumours.39 For selection of appropriate neoadjuvant treatments, similar considerations as for adjuvant therapy apply.

Adjuvant ChT reduces the relative recurrence risk and improves survival in women by 25%-30% irrespective of the subtype.40, 41, 42, 43, 44 Defining cohorts most appropriate for ChT increasingly depends on classifying tumours based on genomic signatures as well as other biological factors (i.e. ER, PgR, HER2 and Ki-67) that refine prognosis beyond pathology alone. The combination of low grade and/or low Ki-67 level with strong ER/PgR expression and endocrine response to a short course of preoperative ET may serve as surrogates for a sufficiently favourable biology.45,46 Among postmenopausal women with node-negative disease or with 1-3 positive nodes and low-risk genomic signature scores/low-risk biology, adjuvant ChT did not further reduce recurrence rates compared with ET alone.47, 48, 49 Among premenopausal women with node-negative disease or 1-3 positive nodes and low-risk genomic signature scores, adjuvant ChT did reduce recurrence rates compared with ET alone.47,49 Some of this benefit may be due to ChT-induced amenorrhoea, though it is unclear precisely how much of the difference is accounted for by direct cytotoxicity against micrometastatic cancer versus secondary endocrine effects of ChT. Endocrine response assessment using Ki-67 response (Ki-67 ≤10%) after a 4-week preoperative ET regimen may be used to estimate benefit from adjuvant ChT in patients with 0-3 involved LNs.45,46 For women with HR-positive, HER2-negative breast cancer warranting ChT, anthracycline, taxane and alkylator-based ChT regimens are standard but non-anthracycline-based regimens may be appropriate for stage I and II cancers with limited nodal involvement.

Adjuvant ET is almost universal for patients with HR-positive invasive breast cancer of any stage and HER2 status and reduces the risk of locoregional recurrence, distant metastatic recurrence and contralateral breast cancer, while improving overall survival (OS).50,51

Among premenopausal women with higher-risk HR-positive cancers, OFS paired with an AI or tamoxifen reduces the likelihood of recurrence and improves OS versus tamoxifen alone. OFS with an AI reduces recurrences compared with OFS with tamoxifen.51 In postmenopausal women, AIs, used either upfront or sequentially after 2-3 years of tamoxifen, offer lower risk of recurrence compared with tamoxifen alone, especially in higher-stage cancers.51 Standard treatment duration is 5 years but extended durations to 7 or 10 years further lower recurrence risk and increase survival, particularly in higher-stage cancers.52,53

The use of adjuvant bisphosphonate therapy in postmenopausal women with EBC, as well as premenopausal women receiving OFS, can lower the risk of tumour recurrence and mitigate the side-effects of osteopenia/osteoporosis seen with AIs. A meta-analysis published by The Early Breast Cancer Trialists’ Collaborative Group indicates a benefit irrespective of the HR status and bisphosphonate type or regimen. Large randomised trials of adjuvant denosumab have had mixed results in terms of impact on breast cancer outcomes and it is therefore not recommended.54,55

Targeted therapy with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in addition to ET has been widely studied in EBC. The addition of abemaciclib for 2 years reduced the absolute risk of recurrence at 4 years by 6.4% (hazard ratio 0.664, 95% CI 0.578-0.762, P < 0.0001) in a cohort of women with HR-positive, HER2-negative breast cancer with either ≥4 involved LNs, 1-3 positive nodes with either T3 (>5 cm) tumours or grade 3 histology or Ki-67 expression ≥20%.56 The NATALEE trial evaluated the addition of ribociclib 400 mg/day (days 1-21 of every 28-day cycle) for 3 years to adjuvant ET in women with American Joint Committee on Cancer (eighth edition) stage II (either N0 with grade 2-3 and/or Ki-67 ≥20% or N1) or stage III HR-positive, HER2-negative breast cancer. It reached its primary endpoint with a 3.3% improvement in 3-year invasive disease-free survival (iDFS) (hazard ratio 0.748, 95% CI 0.618-0.906, P = 0.0014).57 Pending approval by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA), this could potentially be another option for intermediate- and high-risk disease.

In patients with gBRCA1/2m and high-risk HER2-negative tumours, adjuvant olaparib for 1 year improves DFS (hazard ratio 0.63, 95% CI 0.5-0.78) and OS (hazard ratio 0.68, 95% CI 0.47-0.97, P = 0.009) irrespective of HR status. At 4 years, the absolute differences in iDFS and distant DFS were 7.3% (95% CI 3.0% to 11.5%) and 7.4% (95% CI 3.6% to 11.3%), respectively. Patients with HR-positive tumours had to have ≥4 involved LNs at diagnosis or a clinical and pathological stage plus ER and nuclear grade (CPS + EG) score ≥3 to be eligible for inclusion in the trial.58

Though supportive interventions can reduce many therapy-related side-effects, considering the modest reductions in recurrence or improvement in OS with many common treatments for ER-positive breast cancer, especially in lower-risk tumours, patient preferences are an important part of the equation governing adjuvant treatment recommendations.

HER2-positive EBC  The addition of trastuzumab to ChT improves OS by approximately one-third. The relative magnitude of the survival benefit for patients with HR-positive EBC is the same as for those with HR-negative EBC after 10 years of follow-up; however, the latter have earlier recurrences.59 Figure 6 provides a treatment algorithm for patients with HER2-positive EBC.

1. Figure 6
   

Neoadjuvant and post-neoadjuvant systemic treatment based on pCR  In patients with clinical stage II-III disease, the preferred option is initial preoperative systemic therapy followed by local therapy, with the aim of evaluating treatment efficacy by pathological response assessment, guiding risk stratification, reducing the extent of surgical need and determining the adjuvant treatment plan. Patients with a pCR after neoadjuvant treatment demonstrate a substantially lower risk of disease recurrence.39 However, patients with a high initial tumour burden are still at elevated risk of relapse even with a pCR.60,61 The presence of residual invasive tumour in the breast or nodes indicates poorer outcomes.39 Anthracycline–taxane-based combinations with HER2-targeted agents have been a backbone of (neo)adjuvant ChT in patients with HER2-positive disease62 but are associated with a very low, but potentially serious risk of cardiac toxicity and secondary acute myeloid leukaemia (one additional treatment-induced leukaemia per 400-500 patients).63,64 Anthracycline-free regimens comprising carboplatin with taxanes have been tested in phase II (PREDIX HER2, TRAIN2, TRYPHAENA) and III (BCIRG-006) clinical trials, reporting similar outcomes to anthracycline-containing regimens and improved cardiac safety.65, 66, 67, 68 Neoadjuvant ChT combined with dual HER2 blockade [trastuzumab–pertuzumab (HP)] results in higher pCR rates compared with trastuzumab alone, translating into improved outcomes, particularly among patients with LN-positive cancers.69 In low-to-intermediate-risk HER2-positive, HR-negative disease, 12 weeks of paclitaxel in combination with HP without post-operative anthracyclines showed a pCR rate of >90% and an iDFS at 5 years of ∼98% in highly selected patients in a single-arm phase II study.70 This regimen is currently being evaluated in other optimisation trials.71

Patients with pCR after standard neoadjuvant systemic therapy should continue anti-HER2 therapy for a total duration of 1 year.70 The phase III KATHERINE trial reported improved outcomes in patients who had residual invasive cancer and received adjuvant trastuzumab emtansine (T-DM1) instead of trastuzumab; the proportion of patients free of invasive disease at 3 years was 88.3% versus 77.0%, respectively.72 T-DM1 significantly decreased the risk of recurrence of invasive breast cancer or death (hazard ratio 0.50, 95% CI 0.39-0.64, P < 0.001). T-DM1 was effective irrespective of the HER2 status in the non-pCR specimen.73 Adjuvant RT and ET may safely be given concurrently with T-DM1 but data are limited for patients having extensive nodal irradiation including internal mammary nodes.74 For patients with a pCR who were clinically node negative at initial diagnosis, the addition of pertuzumab to trastuzumab should not be considered on a routine basis in the post-neoadjuvant treatment setting. There is potential benefit in patients who are suspected to have been node positive at baseline (∼30% of patients11).75

Adjuvant therapy for HER2-positive breast cancer  Patients with HER2-positive breast cancer treated with initial surgery should receive adjuvant treatment with HER2-directed therapy plus ChT and ET if HR positive. ESCAT scores apply only in the case of HER2 gene amplification by FISH/chromogenic in situ hybridisation.

De-intensification of adjuvant treatment can be considered for pathological stage pT1 pN0 disease, using a regimen of weekly paclitaxel for up to 12 doses along with 12 months of trastuzumab. This de-intensified regimen provided low recurrence rates in a prospective single-arm phase II trial, reporting 10-year iDFS, breast cancer-specific survival and OS rates of 91.3%, 98.8% and 94.3%, respectively.76

The APHINITY trial compared adjuvant HP with trastuzumab–placebo, both in combination with anthracycline-based (78%) or non-anthracycline-based ChT. The initial report demonstrated that HP significantly improved 3-year iDFS (hazard ratio 0.81, 95% CI 0.66-1.00, P = 0.045).77 With longer follow-up, the N+ subgroup maintained a clear iDFS benefit favouring HP, with an 8-year iDFS of 86% versus 81% (hazard ratio 0.72, 95% CI 0.60-0.87) without significantly improving OS; no benefit was seen in the node-negative subgroup.75 The HR-positive cohort derived at least the same benefit as the HR-negative group.75

Duration of adjuvant treatment with HER2-targeted therapy    The length of trastuzumab administration in the adjuvant setting has been established based on the results of pivotal trials, which have arbitrarily chosen a duration of 12 months.59 The HERA trial reported no additional benefit from 2 years of treatment.78 Clinical studies have investigated the non-inferiority of a shorter duration of trastuzumab of 6 months versus 12 months. The PERSEPHONE trial claimed non-inferiority for 6 months versus 12 months of trastuzumab treatment,79 while others could not rule out non-inferiority.80 While these results are considered inconclusive, the benefit of 12 months versus 6 months of trastuzumab may need to be balanced against the baseline risk of recurrence in resource-constrained settings with limited ability to provide 12 months of treatment.81 It remains unknown whether patients who achieve a complete response to neoadjuvant ChT plus HER2-targeted therapy need to complete 12 months of trastuzumab.

Tyrosine kinase inhibitors as adjuvant therapy  Adjuvant tyrosine kinase inhibitors have been evaluated in clinical trials in HER2-positive EBC. None of the trials evaluating lapatinib in EBC significantly improved outcomes. The phase III ExteNET trial evaluated 1 year of extended therapy with neratinib after completion of 1 year of adjuvant trastuzumab. This trial showed that neratinib significantly improved iDFS overall (hazard ratio 0.73, 95% CI 0.57-0.92, P = 0.0083) but largely in the subgroup of HR-positive tumours (hazard ratio 0.60, 95% CI 0.43-0.83, P = 0.063).82,83 The study was conducted before the advent of pertuzumab- or T-DM1-based therapies, which are now standard. Neratinib is associated with high rates of moderate to severe diarrhoea; however, implementation of a dose escalation schedule and optimisation of prophylactic interventions can result in lower grade 3 diarrhoea rates, better therapeutic adherence and lower discontinuation rates.84

TNBC    Figure 7 provides a treatment algorithm for patients with early TNBC.

Figure 7

Neoadjuvant ChT is the standard for T1c/N0 or greater TNBC. The majority of patients with pT1a pN0 disease do not benefit from adjuvant ChT while data on the efficacy of adjuvant ChT in pT1b pN0 are unclear. Patients with low-grade TNBC of specific histologies (e.g. adenoid cystic, secretory, medullary) seem to derive little or no benefit from adjuvant ChT, particularly in those with low-risk clinical features, although confidence in these results is limited by small numbers and the retrospective nature of the data.85,86

The agents in the ChT regimens do not differ between neoadjuvant and adjuvant treatment other than the use of pembrolizumab in the neoadjuvant setting for high-risk patients. However, neoadjuvant treatment allows pathological response-guided adjuvant treatment that can improve survival, and is therefore the preferred strategy. Evidence-based regimens without immune checkpoint inhibitors (ICIs) are sequential: anthracycline-based therapy followed by a taxane or taxane–carboplatin or vice versa. The benefit from carboplatin is independent of gBRCA1/2m status.87,88 The standard anthracycline-based regimens are doxorubicin–cyclophosphamide (AC) or epirubicin–cyclophosphamide (EC) given for four cycles over 8 or 12 weeks followed by a taxane given for four cycles over 8 or 12 weeks. Dose-dense therapies, including dose-dense AC or EC and weekly paclitaxel, are preferred.41 Six cycles of a non-anthracycline, taxane-based regimen, such as docetaxel–cyclophosphamide or a taxane plus carboplatin, may be used as an alternative in patients for whom anthracyclines are contraindicated. Adding carboplatin to the taxane improves pCR rates and event-free survival (EFS) but its impact on OS is less certain. Patients with gBRCA1/2m respond very well to standard anthracycline–taxane-based ChT irrespective of platinum use. Single-agent poly (ADP-ribose) polymerase (PARP) inhibitors induce high (>40%) pCR rates, but are not considered standard of care as neoadjuvant therapy and may be best reserved for adjuvant therapy for patients with residual disease after PST. pCR remains a prognostic factor regardless of gBRCA1/2m status.87, 88, 89

In patients with stage II-III TNBC, a four-drug ChT regimen of taxane–carboplatin followed by AC or EC, all combined with pembrolizumab, improved pCR rate and EFS at 3 years (hazard ratio 0.63, 95% CI 0.48-0.82, P < 0.001). Pembrolizumab was continued after surgery for nine 3-week cycles. The benefit from pembrolizumab was independent of PD-L1 status.90 In a phase III trial using a nab-paclitaxel–anthracycline backbone, neoadjuvant atezolizumab also improved pCR rate regardless of PD-L1 status.91 A randomised phase II study using nab-paclitaxel and EC as ChT backbone with or without durvalumab (only given in the neoadjuvant setting) resulted in a numerical non-significant improvement in pCR rate but significantly improved EFS and OS.92

Residual disease after neoadjuvant therapy    In the CREATE-X trial, adjuvant capecitabine improved DFS (hazard ratio 0.70, 95% CI 0.53-0.92, P = 0.01) and OS (hazard ratio 0.59, 95% CI 0.39-0.90, P = 0.01); this benefit was only significant in patients with TNBC tumours.93 Two recent reviews found that adjuvant capecitabine improved OS, by a relative reduction of 12%-30% in patients with TNBC but little evidence of impact in those with HR-positive disease.94,95 Low-dose capecitabine also improves outcomes after standard non-platinum-containing adjuvant ChT.96

It is unknown whether post-neoadjuvant capecitabine adds benefit in patients receiving post-neoadjuvant continuation of their ICI or olaparib (indicated as adjuvant therapy for patients with gBRCA1/2m tumours and non-pCR or ≥pT2 or ≥pN1 if treated with initial surgery). No efficacy results are available for either of these combinations in the adjuvant setting. The understanding of safety of olaparib–capecitabine is also insufficient to support use of this combination.

Special situations    Refer to the Supplementary Material Section 8, available at https://doi.org/10.1016/j.annonc.2023.11.016 , for further details on elderly patients, male breast cancer and other special populations.

Adjuvant therapy for DCIS

Recommendations

HR-positive, HER2-negative EBC

HER2-positive EBC

TNBC

General follow-up considerations

Reproductive and sexual health considerations

Psychosocial considerations

Recommendations

SCREENING, DIAGNOSIS,PATHOLOGY ANDMOLECULARBIOLOGY

Section1.Breastcancerscreening

Breast cancer screening programmes have been initiated for women at average riskof developing breast cancer in order to optimise outcomes through early detection.Screening in women with a strong family history or known germline BRCA1/2mutations (gBRCA1/2m) and other high-risk pathogenic variants (PVs) should followthe ESMO Clinical Practice Guideline (CPG) for risk reduction and screening ofcancerinhereditary breast-ovarian cancer syndromes (HBOC).1

The European Commission Initiative on Breast Cancer (ECIBC) recommendspopulation-based mammography screening every 2 years for average-risk women50-69 years of age, with conditional recommendations for women in younger andolder age groups.2 The greatest mortality reduction has been shown in the age group50-69 years, while evidence for the effectiveness of mammography screening inwomen 45-49 or >70 years is increasing.3-6Either tomosynthesis or digitalmammographyare recommended for screening.7,8

The magnitude of the effect of mammography screening on breast cancer mortalityreduction is uncertain.9In a UK-based review of randomised controlledmammography trials, a 20% relative reduction in breast cancer mortality wasestimated in women 50-70 years of age.8,10Recent studies have demonstrated thatscreening from 40 years of age reduces the risk of death from breast cancer by up to50%.3,4,6,11,12

There is no consensus regarding recommendations for ultrasound (US) or magneticresonance imaging (MRI) as supplementary screening methods in women with highbreast density without a strong family history.13-15Furthermore, these methods arenotrecommendedby the ECIBC.2

Section2.Diagnosisand imaging

Diagnosis is based on clinical examination in combination with imaging, whichshould include bilateral diagnostic mammography and US of both breasts andregionallymphnodes(LNs).16Two-dimensionaldigitalmammographyshouldbeused in the symptomatic setting. Where available and appropriate, digital breasttomosynthesis (with or without synthetic mammography) and contrast-enhancedmammography canbeconsideredas alternatives.17

MRI is recommended in case of uncertainties following standard imaging and inspecial clinicalsituations suchas:

• FamilialbreastcancerassociatedwithgBRCA1/2mandotherhigh-riskPVs

• Lobular cancers (including detection of extensive multifocality, contralateralbreastcanceror toplanconservative surgery)

• Suspicionofmultifocalityand/ormulticentricity

• Discrepancybetweenconventionalimagingandclinicalexamination

• 
  

• Whenthefindingsofconventionalimagingareinconclusive(e.g.apositiveaxillarylymphnode with anoccultprimarytumour)

• Presenceofbreastimplants

Section3.Hereditarybreastcancer

Genetic counselling, testing and patient management for carriers of gBRCA1/2m andother high-risk PVs should follow the ESMO CPG for risk reduction and screening ofcancerinHBOC.1

Germline PVs in BRCA1/2 account for 5%-10% of all breast cancers and areassociatedwithanelevatedlifetimeriskofdevelopingbreastandovariancancers,aswellasothermalignancies.18Theuse ofmultigenepaneltests isincreasing.

These tests yield an 8%-9% detection rate of PVs in genes associated withincreased breast cancer risk, about half of which are a gBRCA1/2m.19 Other relevanthigh- and moderate-penetrance germline PVs are found in TP53, PALB2, ATM andCHEK2,althoughmanagementrecommendationsvaryaccordingtothemutationandthegenepenetranceis generally lowerthan forBRCA1/2.1

Identification of germline mutations informs disease management and follow-up;patients with gBRCA1/2m and other PVs may opt for different locoregional breastcancer management and contralateral surgical prophylaxis, and warrant moreintensive risk-reducing measures for other malignancies such as ovarian cancer.1High-risk patients with gBRCA1/2m may be candidates for adjuvant therapy with apoly(ADP-ribose)polymerase(PARP) inhibitor.

Germline testing for PVs in BRCA1/2 should be offered for patients who meet therespective national criteria and for those who are candidates for adjuvant olaparibtherapy.20,21

Section4.Histomorphologicalassessment,biomarkersandmolecularpathology

The aim of pretreatment pathological evaluation of breast cancer is to provide acomplete histomorphological, immunohistochemical and, if necessary, molecularassessment of breast cancer at the time of diagnosis (Supplementary Table S1).Evaluation should include histology from the primary tumour and histology/cytologyof the axillary nodes (if node involvement is suspected). For pre-therapeuticcharacterisation, a core needle biopsy (2-4 cores) should be carried out on thetumour and suspicious LNs (if this will change the treatment plan). The tissue shouldbeformalin-fixedparaffin-embedded(FFPE)withstandardisedfixationtime.

Pathological diagnosis should be made according to the World Health Organization(WHO)classificationoftumours22andtheeightheditionoftheUnionforInternationalCancer Control (UICC) tumour–node–metastasis (TNM) staging system(SupplementaryTables S2-S4).23

Histological grade, tumour-infiltrating lymphocytes (TILs)24and the presence ofductal carcinoma in situ (DCIS) and lymphovascular invasion are typical elements ofthe basic tumour characterisation. The most important immunohistochemistry (IHC)biomarkers are estrogen receptor (ER), progesterone receptor (PgR), humanepidermal growth factor receptor 2 (HER2) and a proliferation marker such as Ki-67;reporting is based on the American Society of Clinical Oncology/College of AmericanPathologistsguidelinesforassessmentofhormonereceptor(HR)status(i.e.ERand

PgR)25and HER2 status.26For Ki-67 and TILs, the International Ki-67 in BreastCancer Working Group27and International TILs Working Group 201428guidelinesshould be used. TIL scoring provides prognostic and predictive information but TILthresholds for medical decision making have not been established and should not beusedalone fortreatment decisions.

Ki-67 expression levels are most informative for prognosis of luminal breast cancerwhen the level is ≤5% (low proliferation, low risk) or ≥30% (high proliferation, highrisk) because technical reliability of distinguishing values between 5% and 30% islimited. A decrease of Ki-67 (≤10%) after short term (4-6 weeks) preoperativeendocrine therapy (ET) in postmenopausal patients with HR-positive, HER2-negativebreast cancerisprognosticandmay indicateendocrineresponsiveness.29,30

Although HER2-low status is currently only relevant in the metastatic setting, itshould be reported in early breast cancer (EBC) as a basis for possible futuretherapeutic decisions; it may also have implications for the design of external qualityassurance programmes. HER2 low is defined as IHC 1+ or 2+ and in situhybridisation(ISH)negativeinmetastaticdisease.31ForreportingofHER2 results,itisimportanttostatethe IHCscoreas 0,1+,2+or 3+.

HER2-negative tumours with 1%-9% ER and/or PgR expression (ER low/PgR low)behave similarly to and have similar clinical outcomes to triple-negative breastcancers (TNBCs). Many HR 1%-9% IHC-positive cancers show molecular featuresof HR-negative cancer and are therefore unlikely to benefit from ET. However, anuncertain proportion of these patients with HR-low cancers may have a sufficientlevel of HR expression to benefit from ET. In the absence of randomised clinical trialevidence to demonstrate benefit from adjuvant ET, treatment recommendationsshould be individualised based on patient preferences, with careful consideration ofthe risk versus benefit from long-term ET. Tumours with low HR expressionconstitute a biologically mixed entity and are considered HR low, not HR negative.32Therefore, patients with HR 1%-9% IHC-positive cancers should be included in trialsdesignedforHR-negative cancerstogeneratemore evidence.

In contrast to metastatic TNBC, programmed death-ligand 1 (PD-L1) expression isnotcurrentlyrelevantfortherapeuticdecisionsinEBC.33TNBCshouldbeinformed

by IHC and is defined as ER <1%, PgR <1% and HER2 score 0, 1 or 2+ withnegativeFISH or chromogenic ISH.

Participation in external quality assurance programmes is strongly recommended. Ifassessment of biomarkers is not possible in a preoperative biopsy, or if results arenot consistent with pathological features, repeat assessment in the surgical sampleisrecommended.

For prognostication and treatment decision making, tumours can be grouped intosurrogate intrinsic subtypes,34 defined by routine histology and IHC data, as luminalA like, luminal B like, HER2 positive and triple negative. Luminal A-like tumours aretypically low grade, strongly ER positive/PgR positive and HER2 negative and havelow proliferation. Luminal B-like tumours are HR positive but may have variabledegrees of ER/PgR expression, are higher grade and have higher proliferation thanLuminal A-like tumours. Gene expression assays (e.g. EndoPredict, MammaPrint,Oncotype DX, Prosigna and others) have been introduced in many countries forprognostic assessment of HR-positive, HER2-negative breast cancer. The assaysdiffer in terms of genes as well as technology, but all can identify a low- tointermediate-riskgroupthatmightnotbenefitfromadjuvantchemotherapy(ChT).

Gene expression tests should only be used in a clinically intermediate-risk situation(based on IHC biomarkers and clinical parameters). It is recommended to use onlyoneassayfor any individual patient.

Prognosis in patients who received neoadjuvant ChT and did not obtain apathologicalcompleteresponse(pCR)canbeestimatedbythepretreatmentclinicalstage and post-treatment pathological stage plus ER status and tumour grade35,whichalsohasbeen validated for luminal tumours.36

Tumour mutation testing is important for treatment decisions in metastatic breastcancer,37however, clinical utility has not yet been demonstrated in EBC and it is notmandatory. Mutations should be reported using the ESMO Scale for ClinicalActionability of molecular Targets (ESCAT) reporting system (Supplementary TableS8).38

Regarding histological assessment of lesions, a core needle biopsy is preferred tofine-needleaspiration(FNA)becauseinvasiveness—aprerequisiteforstarting

neoadjuvant therapy—cannot be demonstrated in FNA samples. Microcalcifications,mainly only visible on mammogram, should be biopsied with a vacuum-assisteddevice.8If systemic neoadjuvant therapy is likely/expected, marking the primarytumour with a clip is recommended. If suspicious locoregional LNs are detected, atleastoneineachregionshould bebiopsied andpreferablyalsomarked.

When there is an intermediate risk after standard IHC and clinical assessment, agene expression test should be carried out in HR-positive, HER2-negative tumoursto identify low-risk tumours that would not benefit from treatment with ChT. Ki-67analysis after short preoperative ET may add information about tumour endocrineresponsiveness; Ki-67 ≤10% post-ET is considered to indicate endocrineresponsiveness and low risk. If preoperative ET is used in HR-positive, HER2-negative disease, gene expression analysis must be carried out in the diagnosticpretreatment biopsy, not in the surgical specimen. PD-L1 testing in EBC is notrequiredfor clinical decision making.

STAGINGANDRISKASSESSMENT

Section5.Stagingand riskassessment

Disease stage and final pathological and clinical assessment of surgical specimensshould be made according to the WHO classification of tumours22and the eighthedition of the UICC TNM staging system.23Minimum blood work-up (a full bloodcount, liver and renal function tests, alkaline phosphatase and calcium levels) isrecommended before surgery and systemic (neo)adjuvant therapy. Chest, abdomenand bone imaging is recommended for higher-risk patients (high tumour burden,aggressive biology or clinical signs, symptoms or laboratory values suggesting thepresence of metastases). [18F]2-fluoro-2-deoxy-D-glucose (FDG)–positron emissiontomography (PET)–CT scanning may be useful for high-risk patients and whenconventionalmethodsare inconclusive.

Validatedgeneexpressionprofilesmaycomplementpathologyassessmentandhelpwith adjuvantChTdecisionmakinginclinically intermediate-risksituations.

Assessment of distant metastases (bone, liver and lung) is recommended only inpatientswithstageIIb andhigherdisease(especiallywithextendedLNinvolvement), patients with a high risk of recurrence at first diagnosis and/or insymptomatic patients.37,39Brain imaging should not be routinely carried out inasymptomatic patients. The minimum imaging work-up for staging includescomputed tomography (CT) of the chest and abdomen and bone scintigraphy. FDG–PET–CTmay be usedinsteadofCT and bone scintigraphy.37

MANAGEMENT OFLOCALANDLOCOREGIONALDISEASE

Section6. Generaltreatmentprinciples

Where available, treatment should be carried out in specialised breast units/centresand provided by a multidisciplinary team specialised in breast cancer, consisting ofat least medical oncologists, breast surgeons, gynaecologists, radiation oncologists,breast radiologists, breast pathologists and breast nurses (or similarly trained andspecialised health care practitioners).40,41Such centres are defined as specialisedinstitutions or departments that care for a high volume of breast cancer patients, e.g.a minimum of 150 new EBC cases per year. The breast unit/centre should have in-house plastic/reconstructive surgeons, psychologists, physiotherapists, fertilityspecialists and geneticists or be able to refer patients to such specialists in othercentres.Participation in clinicaltrials is recommended.

Treatment of EBC involves a combination of local modalities [surgery, radiotherapy(RT)], systemic treatments (ChT, ET, molecularly targeted therapies,immunotherapy)andsupportivemeasures,deliveredindiversesequences.Theuseof predictive biomarkers (i.e. ER, PgR, HER2, Ki-67 and approved gene expressionsignatures)iswell establishedinaidingtreatmentrecommendations.

Particular attention must be paid to the treatment of EBC in special populations, e.g.very young or elderly patients. However, age is a continuous variable and cut-offs instudies are always arbitrarily chosen. For clinical decision making, biological age ismoreimportantthanchronologicalage.42

In younger premenopausal patients, fertility issues should be discussed andguidanceonfertility-preservationtechniquesshouldbeprovidedbeforetheinitiationof any systemic treatment.43-47 For details about fertility preservation, please refer tothe ESMO CPG for fertility preservation and post-treatment pregnancies in post-pubertalcancer patients.48

Section7.Patientcommunicationandshareddecisionmaking

Following a diagnosis of breast cancer, patients find themselves in a new andunfamiliar landscape. Intensity of stress and specific pressures vary from patient topatient and should be addressed individually with management tailored to theindividual’sneeds. Patientsshouldbeactivelyinvolvedinallmanagementdecisions.

As part of optimising breast cancer outcomes and survivorship, all patients shouldhave equitable access to the full range of reproductive care options that may benecessary at different points in their breast cancer journey, including pregnancycounselling,contraceptionand fertility preservation.

Information on diagnosis and treatment choice should be given repeatedly (bothverbally and in writing) in a comprehensive and easily understandable manner, usingpatient-centred websites or similar sources of information. Most patients willremember the information provided to them in a fragmented way. Patients needspace, both physically and timewise, to process and comprehend information abouttheirdiagnosisso theycancopepsychologicallywiththetreatmentplan.

Section8.Specialsituations

Elderly patients. Due to the limited data from randomised studies, strongrecommendations cannot be made regarding the use of (neo)adjuvant systemictherapies inthis population.Full dosesof drugsshouldbe usedwhenever feasible.In patients suitable for standard ChT, single-agent capecitabine or docetaxel havebeen demonstrated to be inferior to the standard multidrug regimen [doxorubicin–cyclophosphamide [AC] or cyclophosphamide–methotrexate–fluorouracil (CMF)].49,50Sequential, single-agent therapy (e.g. doxorubicin followed by paclitaxel and thencyclophosphamide) is as effective as combination ChT (e.g. AC followed bypaclitaxel) and is associated with lower acute toxicity, making this approach anoptionforanypatient,especiallyolderpatients.51,52Ageriatricmultidimensional

assessment should be carried out prior to treatment decisions; the G8 tool can beusedasascreeningtoolto selectpatientsneedinga fullgeriatricassessment.53

Male breast cancer. Most breast cancer cases in male patients are luminal-likeductal invasive carcinoma and occur in older men. Tamoxifen is the standardadjuvant ET; aromatase inhibitors (AIs) must be combined with gonadotropinhormone-releasing hormone (GnRH) analogues.54 ChT and anti-HER2 therapy andregimens using other targeted novel agents as indicated [e.g. immunotherapy,cyclin-dependent kinase 4/6 (CDK4/6) or PARP inhibitors] should follow the samerecommendations as for female patients with breast cancer.55-57Population-basedstudies have indicated that ~20% of male patients with breast cancer will have aninherited risk factor; therefore, genetic counselling and testing should beconsidered.58

Other special situations. Sarcomas (primary, secondary and angiosarcomas) aregenerally managed with surgery alone; adjuvant irradiation or ChT in some settingsmay be considered.59Lymphoma isolated to the breast, including breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL), is often treated with surgeryalone,withgoodoutcomesaftercompleteresection.60ForBIA-ALCLwithincompleteresections or advanced disease, systemic therapies have been used. Other types oflymphomasofthebreast shouldfollowlymphoma-specificguidelines.61

Supplementary Table S1. Summary of biomarkers used in standardised histopathological, immunohistochemical andmolecularpathologyassessmentinEBC

EBC, early breast cancer; ER, estrogen receptor; ET, endocrine therapy; gBRCA1/2, germline BRCA1/2, GoR, grade ofrecommendation; H&E, haematoxylin–eosin; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC,immunohistochemistry; ISH, in situ hybridisation; MBC, metastatic breast cancer; NGS, next-generation sequencing; PgR,progesteronereceptor; TIL,tumour-infiltratinglymphocyte;TNBC, triple-negativebreastcancer.

Supplementary Table S2. Clinical classification of breast tumours according tothe UICC TNMeighthedition

ExcisionalbiopsyofaLNorbiopsyofa sentinelnode,intheabsenceofassignmentof a pT, is classified as a clinical N, e.g. cN1. Pathological classification (pN) is usedfor excision or sentinel LN biopsy only in conjunction with a pathological Tassignment.

ALN, axillary lymph node; DCIS, ductal carcinoma in situ; FNA, fine-needleaspiration; LCIS, lobular carcinoma in situ; LN, lymph node; Tis, carcinoma in situ;TNM,tumour–node–metastasis; UICC,UnionforInternationalCancerControl.

aMicroinvasion is the extension of cancer cells beyond the basement membrane intothe adjacent tissues with no focus >0.1 cm in greatest dimension. When there aremultiplefociofmicroinvasion,thesize ofonlythelargestfocusis used toclassify themicroinvasion. Do not use the sum of all individual foci. The presence of multiple fociofmicroinvasionshouldbenoted,asitiswithmultiplelargerinvasivecarcinomas.

bInvasionofthedermisalonedoes notqualifyas T4.Chest wallincludes ribs,intercostalmusclesandserratusanteriormusclebutnotpectoralmuscle.

cInflammatory carcinoma of the breast is characterised by diffuse, brawny indurationof the skin with an erysipeloid edge, usually with no underlying mass. If the skinbiopsy is negative and there is no localised measurable primary cancer, the Tcategory is pTX when pathologically staging a clinical inflammatory carcinoma (T4d).Dimplingoftheskin,nippleretractionorotherskinchanges,exceptthoseinT4bandT4d,mayoccur inT1,T2 orT3 withoutaffectingthe classification.

dClinically detected is defined as detected by clinical examination or by imagingstudies (excluding lymphoscintigraphy) and having characteristics highly suspiciousfor malignancy or a presumed pathological macrometastasis based on FNA biopsywith cytological examination. Confirmation of clinically detected metastatic diseasebyFNA withoutexcisionbiopsyis designatedwith a(f)suffix,e.g. cN3a(f).

ReproducedfromBrierleyetal.withpermission.23

Supplementary Table S3. Pathological classification of breast tumoursaccordingto the UICCpTNMeighthedition

ALN, axillary lymph node; FNA, fine-needle aspiration; H&E, haematoxylin–eosin;IHC, immunohistochemistry; ITC, isolated tumour cell; LN, lymph node; p,pathological; SLNB, sentinel lymph node biopsy; SN, sentinel node; TNM, tumour–node–metastasis; UICC,Union forInternational CancerControl.

aWhen classifying pT the tumour size is a measurement of the invasive component.Ifthereisalargeinsitu component(e.g.4 cm)andasmallinvasivecomponent(e.g.0.5 cm),the tumour iscoded pT1a.

bITCs are single tumour cells or small clusters of cells ≤0.2 mm in greatest extentthat can be detected by routine H&E stains or IHC. An additional criterion has beenproposedtoincludeaclusterof<200cellsinasinglehistologicalcrosssection.

Nodes containing only ITCs are excluded from the total positive node count forpurposesofNclassificationandshouldbeincludedinthetotalnumberofnodesevaluated.

cClinically detected is defined as detected by imaging studies (excludinglymphoscintigraphy) or by clinical examination and having characteristics highlysuspiciousformalignancyorapresumedpathologicalmacrometastasisbasedonFNA biopsy with cytological examination. Not clinically detected is defined as notdetected by imaging studies (excluding lymphoscintigraphy) or not detected byclinicalexamination.

ReproducedfromBrierleyetal.withpermission.23

Supplementary Table S4. Staging of breast tumours according to the UICCTNMeighthedition

mi, micrometastases; Tis, carcinoma in situ; TNM, tumour–node–metastasis; UICC,Unionfor InternationalCancer Control.

aT1includesT1mi.

ReproducedfromBrierleyetal.withpermission.23

SupplementaryTableS5.OverviewofadjuvanttherapyforHR-positive,HER2-negativeEBC

AI, aromatase inhibitor; ChT, chemotherapy; EBC, early breast cancer; ER, estrogen receptor; ET, endocrine therapy; gBRCA1/2,germlineBRCA1/2;HER2,humanepidermalgrowthfactorreceptor2;HR,hormonereceptor; LN,lymphnode;m,mutation;N,

node; OFS, ovarian function suppression; OS, overall survival; PgR, progesterone receptor; RS, recurrence score; T, tumour; TN,tumour–node.

aRisk stratification factors for ET include tumour size, extent of nodal involvement, tumour grade, degree of ER/PgR expression,high Ki-67 or other proliferation measures and adverse genomic signature results. For lower-risk cancers, either tamoxifen or an AIfor 5 years is standard. With increased risk, AI becomes preferred to tamoxifen, longer durations become appropriate and OFS isprogressivelyadded for younger women, especially those<35 yearsofage.

bFor node-negative tumours, non-anthracycline regimens may suffice as adjuvant ChT; anthracycline-, taxane- and alkylator-basedregimensarepreferredfor higher-stage cancers warranting ChT.

cAsadjuvanttherapyforpurposesofpreventingdistantmetastaticrecurrence.

dBenefits of ChT reflect tumour biology and menopausal status. Premenopausal women with lower-risk tumours who are notadvised/recommendedtoreceiveOFSmay benefitmore from ChT.

eThe role of ChT is largely determined by tumour pathobiology including high-risk genomic signature scores (preferred) or highgradeand/or highKi-67 (>30%).

fLimited follow-up from a single study suggests that adjuvant abemaciclib may reduce recurrence in high-risk node-positive cancerscharacterised by stage, grade and/or Ki-67 (>20%). In cases that are potential candidates for both abemaciclib and olaparib,olaparibispreferredduetostatistically significantOS benefit.

gAdjuvant olaparib is indicated in BRCA1 or BRCA2-associated cancers with high-risk features that would typically warrant ChT,such as multiple positive LNs and/or residual disease after neoadjuvant ChT. In patients who are potential candidates for bothabemaciclibandolaparib, olaparibis preferreddue tostatistically significantOSbenefit.

hUseofAIinpremenopausalwomendemandsOFS.

i‘Lowrisk’implieslow-riskgenomicscore(preferred;e.g.Endopredict'Low';MammaPrint‘Low’or'UltraLow';OncotypeDXRS

≤15; Prosigna RS ≤60; luminal A on formal signature testing) and/or lower-risk features on traditional pathological analysis includinglower-grade histology, robust ER and PgR expression and lower measures of proliferation. ‘High risk’ implies high-risk genomicscore (Endopredict 'High'; MammaPrint ‘High’; Oncotype DX ≥26; Prosigna >60; luminal B) and/or higher-risk features on traditionalpathologicalanalysis includinghigher-gradehistology,lower ERandPgRexpressionandhighermeasuresofproliferation.

jThereisno evidenceofbenefitfor OFS beyondfiveyears’durationoftherapy.

Table adapted with permission from St Gallen International Consensus Guidelines 2023.34 © 2023 European Society for MedicalOncology.Published by Elsevier Ltd. Allrights reserved.

SupplementaryTableS6.Notable potentiallong-termside-effectsrelatedtoadjuvantbreastcancertreatmenta

aOccurrences are rare and patients generally recover; quality of life in general recovers by end of therapy to that of beforetreatmentstart.

SupplementaryTableS7.BiomarkersandmoleculartargetsforprecisionmedicinesandcorrespondingESCATscores

AC,doxorubicin–cyclophosphamide;AI,aromataseinhibitor;ChT,chemotherapy;CISH,chromogenicinsituhybridisation;EC,epirubicin–cyclophosphamide;ER,estrogenreceptor;ESCAT,ESMOScaleforClinicalActionabilityofmolecularTargets;ET,endocrine therapy; gBRCA1/2, germline BRCA1/2; HER2, human epidermal growth factor receptor 2; HP, trastuzumab–pertuzumab; HR, hormone receptor; IHC, immunohistochemistry; m, mutation; OFS, ovarian function suppression; N, node;NA, not applicable; NGS, next-generation sequencing; pCR, pathological complete response; PgR, progesterone receptor; T-DM1,trastuzumab–emtansine;TNBC,triple-negativebreastcancer.

aESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the guideline authorsand assisted as needed by the ESMO Translational Research and Precision Medicine Working Group. ESCAT defines therelevance of a genomic alteration to a matched targeted therapy and does not apply to prognostic use or to guide local or systemiccytotoxicagents.

bI-A, alteration–drug match is associated with improved outcome with evidence from randomised clinical trials showing thealteration–drugmatchina specifictumourtyperesultsina clinicallymeaningfulimprovementofa survivalendpoint.38

cESCATapplicableifHER2 geneamplificationby FISH/CISH.

SupplementaryTableS8.ESMO-MCBStable fortherapies/indicationsinEBC

ChT, chemotherapy; CI, confidence interval; DFS, disease-free survival; EBC, early breast cancer; EFS, event-free survival; EMA,European Medicines Agency; ESMO-MCBS, ESMO-Magnitude of Clinical Benefit Scale; ET, endocrine therapy; FDA, Food andDrug Administration; gBRCA1/2, germline BRCA1/2; HER2, human epidermal growth factor receptor 2; HR, hormone receptor;iDFS, invasive disease-free survival; ITT, intent to treat; LN, lymph node; NEB, no evaluable benefit; NS, not significant; OS, overallsurvival;pCR,pathologicalcompleteresponse;QoL,qualityof life;RT,radiotherapy;T-DM1,trastuzumab–emtansine;TNBC,

triple-negativebreastcancer.

aESMO-MCBS v1.183 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have beencalculated and validated by the ESMO-MCBS Working Group and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).

bEMA approval was based on data from Cohort 1 of the monarchE study; however, analysis of Cohort 1 was not a prespecifiedendpointandthe dataarethereforenoteligiblefor ESMO-MCBSscoring.Scoring isbasedon theITT analysis.

c98.5%CI.

dEMA approval is restricted to patients with hormone receptor-positive HER2-positive breast cancer who completed adjuvanttrastuzumab-based therapy <1 year. This is based on an unplanned post hoc subgroup analysis and is not eligible for ESMO-MCBSgrading. MatureOS wasnot statistically significant.

Supplementary Table S9. Levels of evidence and grades of recommendation(adapted from the Infectious Diseases Society of America-United States PublicHealthService Grading Systema)

Levelsofevidence

Gradesofrecommendation

aBypermissionofOxfordUniversityPressonbehalfoftheInfectiousDiseasesSocietyof America.84

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编辑：Amy  博士生

上海理工大学

上海理工大学乳腺肿瘤智能诊断与治疗研究中心

中国整形美容协会/精准与数字医学分会青年理事

审校：韩宝三 博士

上海交通大学医学院附属新华医院乳腺外科 主任，学科带头人，医学博士，博士后，主任医师

上海交通大学医学院 硕士研究生、博士研究生导师、博士后导师

上海理工大学 医疗与食品学院 硕士研究生、博士研究生导师、博士后导师

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出品

  本专业资讯由全国百余家医院和以下组织联合荣誉出品：

1 中国妇女发展基金会/与美丽同行·女性健康关爱计划

2 北京金兰纪念乳腺医学研究院

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4 中国乳房重建外科联盟

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7 乳腺外科学大讲堂

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9 最后一公里·精准乳腺整复万名医师培训计划

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12 中国整形美容协会/精准与数字医学分会/乳房整形专业委员会

13 中国医促会/肿瘤整形与康复专业委员会/乳腺肿瘤整形外科学组

14 中国医促会/肿瘤整形与康复专业委员会/肿瘤健康科普学组

15 中国康复医学会健康管理专业委员会/乳腺健康管理学组

16 上海交通大学医学院附属新华医院乳腺外科

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