Table 3.

SEOM clinical practice guidelines for early breast cancer (2022): summary of recommendations

Recommendation	Category, grade
Diagnosis and initial workup
Bilateral mammography and ultrasound of breast and regional lymph nodes in patients with suspected breast cancer	I, A
Core needle biopsy (preferably under ultrasound or stereotactic guidance) in patients with suspected breast cancer	I, A
Fine needle aspiration or core biopsy of suspicious lymph nodes	II, A
Immunohistochemical evaluation of estrogen and progesterone receptors together with HER2 expression (following ASCO-CAP guidelines) should be performed in the breast biopsy	I, A
Bilateral breast MRI, with histologic confirmation of additional findings, as part of initial staging in cases of positive axillary nodes; occult primary breast cancer; Paget’s disease of the nipple; lobular carcinoma; multifocal, multicentric lesions, and breast cancer implants	I, B
Bilateral breast MRI is recommended before and after neoadjuvant treatment to define the extent of disease and monitor response to treatment	III, A
Laboratory testing as part of initial staging of patients with confirmed breast cancer	III, C
Additional staging with chest and abdomen CT and bone scan in patients with stage III disease and/or with clinical or laboratory findings suggestive of metastases	III, B
Staging PET/CT can be of use when traditional imaging test are equivocal	III, A
Evaluation of cardiac function in patients requiring anthracyclines and/or trastuzumab	I, A
Surgery
Consideration of BCS as first surgical option in stages I-II. Mastectomy is indicated in cases of tumor multicentricity, small breast size for tumor volume, inability to achieve negative surgical margins after multiple resections, and contraindications to radiotherapy	I, A
No indication of additional excision in patients with no ink on invasive tumor or DCIS after BCS	I, A
Patients with BC and germline BRCA1/2 mutations can be considered for BCS with similar local control rates. Bilateral mastectomy should be offered as part of an appropriate counseling process in BRCA1/2 mutation carriers	I, A
Sentinel lymph node (SLN) biopsy is standard in patients with clinically negative axillary nodes	I, A
Axillary lymph node dissection should be omitted in patients with stage I–II disease and < 3 positive axillary nodes after SLN biopsy and lumpectomy followed by adjuvant systemic therapy and radiotherapy	I, A
Axillary lymph node dissection may be omitted in patients with stage I–II disease and < 3 three positive axillary nodes after SLN biopsy and mastectomy, provided that adjuvant systemic therapy and regional nodal irradiation including the axilla is indicated	III, B
In patients with cN0 tumors, SLNB is the standard axillary staging procedure after NST	I, A
In patients with cN1 receiving NST, ALND might be avoided in patients with downstaging of axilla to clinically negative if three or more sentinel nodes are identified and all of them are negative, or when the involved node(s) marked at diagnoses is/are removed as well as the sentinel node and all are free of tumor cells	II, B
In patients receiving NST, ALND should be performed in women with any residual disease on sentinel node biopsy	I, A
In patients with cN2-3 tumors receiving NST, ALND should be performed regardless of response to NST	I, A
Adjuvant radiotherapy
Adjuvant radiation therapy (RT) is the standard treatment after BCS	I, A
Hypofractionated schemes are preferred for external beam whole radiation therapy after BCS	I, A
Breast irradiation may be safely omitted after BCS in elderl low-risk ER-positive tumors assuming a higher rate of local recurrence	I, A
Regional nodal irradiation should be administered in patients with ≥ 4 involved nodes after BCS or mastectomy	I, A
Regional nodal irradiation is recommended in patients with 1–3 involved nodes after BCS or mastectomy in cases with adverse prognostic factors (triple negative, HER2, luminal B cancers)	I, B
Regional nodal irradiation is recommended in patients with residual nodal disease after NST and BCS or mastectomy	I, B
Postmastectomy radiation therapy to the chest wall and regional node irradiation should be administered in patients with ≥ 4 involved nodes	I, A
Decision-making for systemic adjuvant treatment in HR-positive HER2-negative breast cancer
In breast cancer with HR-positive and HER2 negative, genomic platforms are not recommended in clinically low-risk patients (pT1a-b N0, low grade, ER high) and/or in patients who are not eligible for CT	I, D
In breast cancer with HR-positive and HER2 negative genomic platforms are not recommended in: 1–3 involved nodes coexisting with other high-risk factors and/or premenopausal patients, or with > 3 positive nodes for whom adjuvant CT is indicated	I, D
Oncotype Dx is recommended in premenopausal patients with node negative tumors to predict benefit from adjuvant CT	I, A
Oncotype DX and MammaPrint may be used to guide adjuvant treatment in postmenopausal or > 50 year old patients with node negative disease or 1–3 positive nodes	I, A
EndoPredict may be used to guide adjuvant treatment in postmenopausal or > 50 year old patients with node negative disease or 1–3 positive nodes	II, B
Prosigna may be used in postmenopausal patients with node negative tumors	II, B
Dynamic changes of Ki67 after 2 weeks of preoperative ET in postmenopausal women may be considered as a surrogate prognostic factor	II, B
Adjuvant and neoadjuvant systemic treatment of luminal breast cancer
Adjuvant therapy should be started before 12 weeks after surgery	I, A
Adjuvant ET should be offered to any patient with HR positive disease (ER or PgR, if either or both are positive defined as ER and/or PR > 1/10%), regardless of other prognostic factors	I, A
Recommendations for endocrine therapy in premenopausal patients
Adjuvant ET with tamoxifen for five years is recommended as a standard treatment for low-risk premenopausal women with HR positive breast cancer	I, A
Extended adjuvant ET with tamoxifen for up to 10 years should be considered in high-risk patients who remain premenopausal during the entire adjuvant period	I, B
Ovarian function suppression plus ET (preferentially with an AI) should be considered in high-risk premenopausal patients who recover ovarian function in the first 12–18 months after CT	I, A
In patients treated with ovarian function suppression, regular monitoring of estrogen levels should be performed during the first year, especially in younger patients in whom OFS is achieved with LHRH analogues	I, A
In premenopausal patients becoming postmenopausal during the first 2–5 years of tamoxifen, a switch to aromatase inhibitor should be considered after evaluating the risk of late recurrence	II, A
Recommendations for endocrine therapy in postmenopausal patients
For postmenopausal women, both non-steroidal and steroidal AI are superior to tamoxifen	I, A
Adjuvant ET for postmenopausal patients may consist of any of the following alternatives, after considering risk factors and individual preferences: Upfront AI AI after 2–3 years of tamoxifen AI after 5 years of tamoxifen (letrozole and anastrozole) as extended adjuvant therapy, especially in intermediate- to high-risk (node positive) patients	I, A
Extended adjuvant therapy (optimal duration: 7.5–8 years) should be discussed with nearly all patients, except those with a very low risk of relapse	I, A
Extended adjuvant therapy with AI for more than 8 years offers minimal benefit	I, C
In high-risk postmenopausal patients who decline or do not tolerate AI, 10 years of tamoxifen should be considered	I, A
General recommendations for adjuvant treatment
Adjuvant bisphosphonates are recommended in women with low-estrogen status and/or treatment-related bone loss	I, A
Adjuvant abemaciclib for 2 years in combination with adjuvant ET should be considered in high-risk patients (defined as tumors with ≥ 4 positive nodes or 1–3 nodes and either tumor size > 5 cm, histologic grade 3, or Ki-67 > 20%)	I, A
Adjuvant olaparib for 1 year in combination with adjuvant ET should be considered in patients with germline pathogenic BRCA mutations, treated with adjuvant or NAC and with high-risk tumors (defined as tumors with ≥ 4 positive nodes in the adjuvant setting or as a CPS + EG score of ≥ 3 without pCR in the neoadjuvant setting)	I, A
Recommendations for adjuvant chemotherapy
Adjuvant CT for HR + HER2-negative breast cancer is recommended for tumors defined as high-risk tumors defined by either clinical or genomic characteristics: T2-4 and/or axillary node involvement N2-3, extensive LVI, high Ki67, low ER expression, younger age or premenopausal status, and intermediate- to high-risk genomic score	I, A
Sequential anthracycline/taxane-based regimen is the standard for most patients	I, A
CT should be administered for 12–24 weeks (4–8 cycles)	I, A
AC or EC are the standard anthracycline-based regimens, which should not include 5-FU	I, A
The use of dose-dense schedules (with granulocyte colony-stimulating factor support) should be considered in high-risk tumors	I, A
In selected lower-risk patients, 4 cycles of anthracycline- or taxane-based CT or CMF may be used	II, B
Non-anthracycline regimens may be used in patients at risk for cardiac complications	I, A
Recommendations for male patients with breast cancer
In male patients with HR + HER2-negative breast cancer, tamoxifen is the standard treatment	III, A
In male patients with HR + HER2-negative breast cancer and a strong contraindication for tamoxifen, a combination of an AI plus a luteinizing hormone-releasing hormone agonist may be considered	III, B
CT indications and regimens should follow the same recommendations as those for breast cancer in female patients	III, A
Recommendations for neoadjuvant therapy
CT drugs and drug regimens used in the preoperative setting should be selected according to rules identical to those in the postoperative setting	I, A
A sequential regimen of anthracyclines and taxanes is recommended in those patients in whom NAC is indicated for HR-positive and HER2 negative breast cancer	I, B
NET alone may be offered to those postmenopausal patients with strongly HR-positive tumors (RE > 60% or RE 40–60% and PR > 10%)	I, A
NET in postmenopausal patients should include an aromatase inhibitor during at least 6–8 months or until maximum response	II, B
NET with AI plus ovarian suppression might be considered in highly selected premenopausal patients with luminal A tumors with no indication for CT and who are not candidates for optimal surgery	II, C
Neoadjuvant and adjuvant systemic treatment of HER2 breast cancer
Patients with HER2-positive tumors > 2 cm tumor size and/or node-positive disease should be treated with NST including dual HER2 blockade with trastuzumab and pertuzumab and CT with sequential taxanes/anthracyclines or taxane/carboplatin combinations	I, A
Selection of neoadjuvant regimens without anthracyclines may be used if seeking to avoid cardiotoxicity	II, B
HER2Dx may be used to provide estimates of the likelihood of achieving pCR and of the risk of recurrence	II, B
Addition of standard 12-month adjuvant trastuzumab to CT is recommended for HER2 positive breast cancer both in node-positive and in node-negative tumors with a tumor size > 1 cm	I, A
Addition of adjuvant trastuzumab to CT may be considered in cases of node-negative HER2 positive breast cancer with tumor size of 0.5–1.0 cm	II, B
For adjuvant CT of HER2 positive breast cancer, 4 cycles of AC or EC followed by 3 months of paclitaxel (P) or docetaxel (D) or both in combination with trastuzumab (AC/EC P/D + H) or docetaxel, carboplatin and trastuzumab (TCH) are the preferred regimens	I, A
In node-negative, stage I, HER2-positive tumors single-agent weekly paclitaxel and trastuzumab for 12 weeks followed by single-agent trastuzumab (to complete one year) should be considered	II, B
Adjuvant dual HER2 blockade with trastuzumab and pertuzumab for 18 cycles may be considered in patients with node-positive, HER2-positive breast cancer. In clinically node-positive patients that have received neoadjuvant treatment, up to 18 cycles of pertuzumab may be continued after surgery	II, B
Extended adjuvant treatment with neratinib after one year of trastuzumab may be considered in patients with node positive and HR-positive HER2-positive breast cancer	I, B
In patients with pCR after standard NST, adjuvant therapy with trastuzumab should be administered until one full year of total anti-HER2 therapy has been completed	I, A
Adjuvant T-DM1 for 14 cycles, instead of trastuzumab, should be considered in patients with HER2-positive breast cancer and residual disease after standard NST	I, A
In patients with HER2-positive and HR + breast cancer, adjuvant ET should be administered following the same principles as in HER2-negative HR + disease	I, A
Adjuvant and neoadjuvant systemic treatment for triple negative breast cancer
When upfront surgery followed by adjuvant CT is the preferred option for triple negative breast cancer, the regimen should include an anthracycline and a taxane, although a taxane-cyclophosphamide combination or taxane monotherapy might be an alternative in patients at high risk for cardiac toxicity	I, B
Adjuvant CT may be considered for 0.6–1 cm tumors after discussing potential risks and benefits with the patient	III, B
NAC for triple negative breast cancer should include anthracyclines and taxanes, preferably with dose-dense sequential regimens	I, A
Carboplatin improves the pCR rate and event-free survival and may be considered as part of NAC for triple negative breast cancer patients	I, B
Addition of neoadjuvant pembrolizumab to NAC should be considered in the neoadjuvant setting for triple negative breast cancer irrespective of PD-L1 expression. Adjuvant pembrolizumab might be administered as adjuvant treatment	I, B
Adjuvant capecitabine for 6–8 cycles should be considered in high-risk, triple negative breast cancer with residual invasive disease at surgery following standard NAC	I, B
Adjuvant olaparib for 1 year should be considered in individuals with germline BRCA1/2 mutations and high-risk triple negative breast cancer with residual invasive disease at surgery following standard NAC	I, B
Follow-up of early breast cancer
Healthy lifestyles, especially an active lifestyle, are recommended to prevent tumor recurrence and to improve quality of life	II, B
For early breast cancer, regular follow-up visits are recommended every 3–6 months during the first 2 years, every 6 months from years 3–5, and annually thereafter	III, A
Annual ipsilateral (after BCS) and/or a contralateral mammography is recommended for follow-up of early breast cancer	II, A
MRI of the breast may be considered for follow-up of young patients with dense breast tissue or with genetic or familial predisposition	II, B
Ultrasound or contrast-enhanced mammography may be considered as an additional study under the indication of a radiologist in doubtful cases or when there is a contraindication to MRI	III, B
There is no demonstrated survival benefit of including tumor markers or imaging tests (other than breast imaging) in the follow-up of asymptomatic patients	I, D