• We recommend clinical examination of the breasts and regional LNs as well as clinical assessment for distant metastases.

• Laboratory assessment should include CBC, renal and liver function tests, alkaline phosphatase and calcium levels, as well as pregnancy test for all women in the childbearing period.

• We recommend bilateral digital mammography and U/S Examination as standard imaging for evaluation of both breasts and LNs.

• We recommend Contrast enhanced MRI (or Contrast Mammography) is indicated if Mammography is non-conclusive and in special situations; Dense breast,  Invasive lobular carcinoma, Axillary lymph node metastasis of unknown primary and  In case of suspected multifocality/multicentricity with NACT and BCS planned.

• The disease stage should be assessed according to the AJCC TNM staging system, 8^th Edition. “Attached at Annexes “

• We recommend Imaging chest, abdomen, pelvis by CT scan and bone by bone scan   for higher-risk patients (locally advanced disease, signs, symptoms, or laboratory results suggesting metastases).

• FDG-PET-CT is recommended only when conventional methods are inconclusive of metastasis.

• We recommend U/S guided core biopsy for diagnosis of breast masses (at least 4 cores by a 14G needle placed in 10% formalin) + FNAB from axillary LNs

• We recommend Core biopsy to confirm the diagnosis and histo-pathological type, grade &to evaluate ER, PR, HER-2, KI-67.

• All patients of child-bearing age should be informed about the effect of CT on fertility and referred to a fertility team when needed

• DCIS should be preferentially treated with BCS and WBRT or, in cases of extensive or multicentric DCIS, mastectomy should be done.

•  Both tamoxifen and AIs may be used after local BCT for DCIS to prevent local recurrence and to decrease the risk of developing a second primary breast cancer.

• Following mastectomy for DCIS, tamoxifen or AIs might be considered to decrease the risk of contralateral breast cancer in patients with a high risk of new breast tumors.

• BCS with post-operative RT is strongly recommended as the preferred local treatment option for most patients with EBC.

• BCT should not be done in case of inflammatory BC, multicentric tumors, pregnancy, history of prior therapeutic radiation therapy (RT) that included a portion of the affected breast, diffuse malignant looking microcalcifications, and diffusely positive margins despite multiple attempts of re-excision.

• If mastectomy is indicated/preferred, breast reconstruction could be offered, except for primary inflammatory and other high-risk tumors where delays in systemic/radiation treatment would compromise care.

• SLNB is the standard axillary surgery in all cN0 patients.

• Following upfront BCS, further axillary surgery should not be done in cases with the following criteria:

- cN0,

- patients with micro metastatic spread or with limited SLN involvement (1-2  

   affected SLNs),

- subsequent whole breast radiotherapy,  

  eventually including the lower part of axilla, and

- adjuvant systemic treatment

•  ALND following positive SLNB with <3 involved SLNs is generally recommended only in case of expected high axillary disease burden or impact on further adjuvant systemic treatment decisions.

• Surgical planning following primary systemic therapy should consider the post-PST situation.

•  WBRT is recommended after BCS.

•  Hypo fractionated schedules are recommended: moderate (i.e. 15-16 fractions of < 3 Gy per fraction daily for all indications of post-operative radiotherapy)

•  Ultrahypo fractionated (i.e. 26 Gy in five daily fractions for whole-breast or chest wall, without reconstruction, irradiation).

• Post mastectomy radiotherapy (PMRT) is recommended for high-risk EBC, including involved resection margins, >4 involved ALNs, T3-T4 tumors and in the presence of combinations of other risk factors.

•  PMRT should be considered in patients with intermediate-risk features (e.g. lympho vascular invasion, age), including those with 1-3 positive ALNs (31).

• Several factors should be combined for decision of adjuvant systemic therapy as tumor size, lymph node status, lympho-vascular invasion, tumor grade, HR status, HER-2, Ki-67, age, ECOG performance status and comorbidities, and should be discussed in an MDT setting between different subspecialities.

• Tamoxifen 20 mg per day PO for 5 years should be the standard of care for low risk patients. If the patient becomes postmenopausal during or after the first 5 years of TAM, switching to AI is an option.

•  Addition of ovarian function suppression (OFS) to tamoxifen is recommended in patients younger than 40 years with adverse prognostic factors (T2 or more, positive LNs and high grade). The duration of OFS is 5 years.

• Adjuvant OFS plus an aromatase inhibitor (AI) for 5-10 years is recommended in high-risk patients or in case of contraindications for tamoxifen. The duration of OFS is 5 years.

• Tamoxifen 20 mg per day for 5 years should be considered only in very low risk patients. Extended adjuvant treatment with tamoxifen up to 10 years is recommended in intermediate and high risk patients with contraindications or intolerance to aromatase inhibitors.

•  Aromatase inhibitors should be  part of the adjuvant hormonal treatment of post-menopausal women using one of the following strategies: a) Upfront use for 5 years in high risk patients and those with contraindications to tamoxifen; b) Sequential treatment with 2-3 years of AI after 2 to 3 years of tamoxifen; and c) Extended adjuvant, with 2-5 years of AI after ending first 5 years of adjuvant endocrine therapy should be discussed with all patients with intermediate and high risk disease.

• Adjuvant chemotherapy is recommended in all patients with triple negative, Her-2 positive, high-risk luminal HER2-negative and node positive tumors irrespective of HR status.

• We recommend a Sequential regimen of 4 cycles of anthracyclines then 4 cycles of taxane.

• We recommend Adjuvant trastuzumab for all HER2 positive patients (IHC+++ or ISH positive for gene amplification) with invasive tumors >10mm

• We recommend, in low risk patients (node negative tumors less than 30mm in max dimension), adjuvant trastuzumab every 3 weeks for up to 6 months (9 cycles) in combination with taxane based chemotherapy, adjuvant radiotherapy or endocrine therapy.

• We recommend, in Intermediate risk patients (T2-3 or N1 disease) adjuvant trastuzumab every 3 weeks for one year (17 cycles) in combination with taxane based chemotherapy, adjuvant radiotherapy or endocrine therapy.

• In very high risk patients (T4 or N2-3), adjuvant trastuzumab +/- pertuzumab every 3 weeks is recommended for up to one year (17 cycles) in combination with taxane based chemotherapy, adjuvant radiotherapy or endocrine therapy.

• We recommend the TCH regimen, either combined by pertuzumab or not according to risk stratification, as a preferred systemic regimen in Her2 positive patients, especially for those with risk factors for cardiac toxicity.

• Neoadjuvant Systemic Therapy

• Neoadjuvant therapy should be indicated in all inoperable breast cancer (inflammatory BC, T4 or N2-3 disease) to allow operability irrespective of the biological subtype.

• Neoadjuvant therapy should also be indicated in operable patients to allow for breast conservation and in most patients with aggressive biological subtypes (as triple negative and HER2 positive tumors).

•  We recommend adding pertuzumab + trastuzumab to taxane based neoadjuvant chemotherapy in HER2 positive patients cT2 or more or Node positive.

• In post-menopausal patients with Luminal A like disease and significant co-morbidities, neoadjuvant endocrine therapy with at least 6 months of AIs should be considered.

• We largely recommend adding carboplatin to neoadjuvant taxane based chemotherapy in stage II and III triple negative patients in view of event free survival improvement in addition to higher pCR rate.

• We recommend, in patients with clinical stage cT1-3, N0 who attained pathological complete response (ypT0/is, N0) after neoadjuvant chemotherapy and anti-HER2 therapy, completion of one year trastuzumab every 3 weeks for a total of 1 year (17 cycles) of anti-HER2 including neoadjuvant doses.

• We recommend in patients with clinical stage cT4 or N1-3 who attained pathological complete response (ypT0, is N0) after neoadjuvant chemotherapy and anti-HER2 therapy, completion of one year of dual blockade with trastuzumab +/- pertuzumab every 3 weeks for a total of 1 year (17 cycles) of anti-HER2 including neo-adjuvant doses.

• We recommend, inpatients with TNBC who received neoadjuvant chemotherapy and who have a residual invasive disease at the time of surgery, offering adjuvant capecitabine for 6-8 cycles. 

• History and clinical examination is recommended 2-4 times per year for 2 years then every 6 months from 3^rd to 5^th year then annually thereafter.

• Annual bilateral (after BCT) or contralateral sono-mammography (after mastectomy) is recommended.