Annals of Oncology 24: 2206–2223, 2013 R3 조영학 Personalizing the treatment of women with early breast cancer : highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 Annals of Oncology 24: 2206–2223, 2013 R3 조영학

Introduction Since the 2011 St Gallen Consensus have seen substantial progress in treatment of early invasive breast cancer genomic atlas of the disease : use of aromatase inhibitors Further data became available reducing the necessity for axillary dissection optimal duration of adjuvant trastuzumab in HER2-positive disease duration of adjuvant tamoxifen

St Gallen 2013: news and progress Axillary dissection can safely be omitted micrometastatic disease in sentinel nodes undergoing breast-conserving surgery and whole breast radiation therapy with up to two macroscopically positive sentinel nodes Safety and efficacy of shorter courses of whole breast radiation therapy (40 Gy in 15 or 42.5 Gy in 16 fractions) Over previous standard of 50 Gy in 25 fractions ATLAS trial reported superiority for 10 years compared with 5 years of adjuvant tamoxifen Particular benefit of letrozole premenopausal at diagnosis but became postmenopausal by the time of letrozole administration Optimal duration of trastuzumab therapy in HER2-positive : 1 year

Breast cancer subtypes

Breast cancer subtypes Many different multi-gene assays provide prognostic information Decisions about inclusion of chemotherapy in the treatment of patients with ER-positive, HER2-negative 21-gene RS (recurrence score) : prognostic information 70-gene signature : Only high RS values (>31) For many societies, the cost of these multi-gene assays remains prohibitive Differing implications for the utility or futility of adjuvant cytotoxic therapy Luminal A-like : more endocrine sensitive, indolent, better prognosis Luminal B-like : less endocrine sensitive, more aggressive, worse prognosis

Panel deliberations (1) Surgery of the primary Breast conserving therapy Absolute contraindications Margins involved with invasive carcinoma or DCIS after repeated resection unless postoperative radiation could be delivered relative contraindications very young age (<35 years) extensive or diffuse microcalcifications Multicentric disease tumour location near the nipple mutations of the BRCA1 or BRCA2 genes Nipple-sparing surgery margin close to the nipple was not involved MRI should not be routinely used in the assessment of newly diagnosed breast cancer 패널 토의

Panel deliberations (2) Surgery of the axilla safely omitted one or two positive sentinel nodes following BCS when whole breast radiation therapy is planned required if no radiotherapy was planned three or more involved sentinel nodes nodes were clinically involved before surgery and confirmed by biopsy

Panel deliberations (3) Radiation therapy short course radiotherapy (40 Gy in 15 or 42.5 Gy in 16 fractions) not requiring radiotherapy following BCS elderly and those with substantial comorbidity Post-mastectomy radiotherapy four or more positive nodes presence of adverse tumour pathology positive deep margins tumours greater than 5cm regardless of the nodal status

Panel deliberations (4) Pathology useful surrogate definition of Luminal A-like as distinct from Luminal B-like disease using a combination of ER, PgR and Ki-67(prognostic marker in early breast cancer) High Ki-67 status : ≥20% intrinsic subtypes : whether or not chemotherapy was used, but not the choice of the cytotoxic regimen multi-gene assay in node-negative, ER-positive and HER2-negative cases unnecessary low-risk : tumour size of ≤1 cm in the setting of negative lymph nodes higher risk : tumour size >5 cm, inflammatory breast cancer, four or more involved nodes, very low ER positivity (e.g. 5%)

Panel deliberations (5) Adjuvant endocrine therapy in premenopausal women tamoxifen alone was the default adjuvant endocrine therapy Adjuvant endocrine therapy in postmenopausal women some postmenopausal women could be treated with tamoxifen alone treatment should start with the aromatase inhibitor at high risk initial aromatase inhibitor therapy could be replaced by tamoxifen after 2 years Extension of aromatase inhibitor therapy beyond the first five years node-positive initial treatment was tamoxifen initial therapy was <5 years of an aromatase inhibitor

Panel deliberations (6) Adjuvant cytotoxic chemotherapy Indication histological grade 3, high Ki-67, low hormone receptor status HER2 positivity or triple-negative status high 21-gene RS, high-risk 70-gene signature involvement of more than three lymph nodes choice of chemotherapy regimen desire to preserve fertility, avoidance of alopecia, presence of co-morbidities but not intrinsic subtype or the presence or BRCA1 or BRCA2 mutation

Panel deliberations (6) Anti-HER2 therapies Trastuzumab therapy : tumours >5 mm or any size Concurrently with a taxane but not with an anthracycline duration of trastuzumab should be 1 year Neoadjuvant cytotoxic chemotherapy The Panel was split about whether neoadjuvant chemotherapy had benefits beyond local downstaging Neoadjuvant anti-HER2 therapy With HER2-positive disease, use of chemotherapy plus trastuzumab alone Neoadjuvant endocrine therapy endocrine therapy alone : postmenopausal, strongly positive hormone receptors, low proliferating disease