NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

blocks collected in the ATAC trial indicated that HER2 amplification is a marker of relative endocrine resistance independent of type of endocrine therapy. 262 However, given the favorable toxicity profile of the available endocrine therapies, the panel recommends the use of adjuvant endocrine therapy in the majority of women with hormone receptor-positive breast cancer regardless of menopausal status, age, or HER2 status of the tumor. Possible exceptions to the recommendation of adjuvant endocrine therapy for patients with hormone receptor-positive disease are those patients with lymph node-negative cancers ≤0.5 cm or 0.6 to 1.0 cm in diameter with favorable prognostic features where the prognosis is so favorable that the benefits of adjuvant endocrine therapy are very small. The most firmly established adjuvant endocrine therapy is tamoxifen for both premenopausal and postmenopausal women. 3 In women with ER-positive breast cancer, adjuvant tamoxifen decreases the annual odds of recurrence by 39% and the annual odds of death by 31% irrespective of the use of chemotherapy, patient age, menopausal status, or ALN status. 3 In patients receiving both tamoxifen and chemotherapy, chemotherapy should be given first, followed by sequential tamoxifen. 252 Prospective, randomized trials have demonstrated that 5 years of tamoxifen is more effective than 1 to 2 years of tamoxifen. 263,264 The ATLAS trial randomly allocated 12,894 women to continue tamoxifen up to 10 years or to discontinue tamoxifen (control). The outcome analyses of 6846 women with ER-positive disease showed that by extending adjuvant treatment to 10 years, the risk of relapse and breast cancer-related mortality was reduced. 265 The risk of recurrence during years 5 to 14 was 21.4% for women receiving tamoxifen versus 25.1% for controls (absolute recurrence reduction 3.7%). Patients receiving tamoxifen beyond 10 years of treatment had a greater

Axillary Lymph Node-Positive Tumors Patients with lymph node-positive disease are candidates for chemotherapy and, if the tumor is hormone receptor-positive, for the addition of endocrine therapy (category 1). In postmenopausal women with hormone receptor-positive disease, an aromatase inhibitor should be utilized either as initial adjuvant therapy, sequential with tamoxifen, or as extended therapy following tamoxifen, unless a contraindication exists or the woman declines such therapy. In premenopausal women, adjuvant tamoxifen is recommended. If both chemotherapy and tamoxifen are administered, data from the Intergroup trial 0100 suggest that delaying initiation of tamoxifen until after completion of chemotherapy improves DFS compared with concomitant administration. 252 Consequently, chemotherapy followed by endocrine therapy should be the preferred therapy sequence. Stratification for Systemic Adjuvant Therapy The guidelines recognize subsets of patients with early breast cancer of the usual histologies based upon responsiveness to endocrine therapy and trastuzumab (ie, hormone receptor status, HER2 status). Patients are then further stratified based on risk of disease recurrence based on anatomic and pathologic characteristics (ie, tumor grade, tumor size, ALN status, angiolymphatic invasion). Adjuvant Endocrine Therapy The NCCN Guidelines call for the determination of ER and PR content in all primary invasive breast cancers. 15 Patients with invasive breast cancers that are ER- or PR-positive should be considered for adjuvant endocrine therapy regardless of patient age, lymph node status, or whether adjuvant chemotherapy is to be administered. 253 Selected studies suggest that HER2-positive breast cancers may be less sensitive to some endocrine therapies, although other studies have failed to confirm this finding. 217,254-261 A retrospective analysis of tumor

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