乳癌診療指引 乳癌多專科團隊擬定 修訂 修訂 修訂 修訂 修訂 修訂 修訂 修訂 修訂

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1 乳癌診療指引 乳癌多專科團隊擬定 修訂 修訂 修訂 修訂 修訂 修訂 修訂 修訂 修訂

2 前言 乳癌為我國婦女發生率第 1 位之癌症, 發生高峰約在 歲之間, 且日趨年輕化, 約為每十萬名婦女 人 依據衛生福利部死因統計及國民健康署癌症登記資料顯示, 女性乳癌標準化發生率及死亡率分別為 65.9 及 11.9 ( 每十萬人口 ), 每年有逾萬位婦女罹患乳癌, 逾 2,000 名婦女死於乳癌, 相當於每天有 29 位婦女被診斷罹患乳癌 6 位婦女因乳癌而失去寶貴性命 近年來由於醫學進步, 乳癌如能早期發現, 經由適當的治療, 不僅可做乳房保留手術, 乳癌第零期的五年存活率為 97%, 第一期乳癌的存活率則高達 95%, 整體存活率也有 85% 本院自民國 91 年召集相關次專科制定乳癌治療指引, 並於民國 92 年起陸續修訂 每年度藉由 多專科醫師參與團隊會議共同討論 的機制, 參酌 NCCN 指引及國內外相關文獻, 進行指引改版修訂, 以期更貼近國內民情及國際乳癌診療潮流, 提供乳癌個案更完整適切的治療計畫及更好的治療品質 1

3 乳癌診療指引修訂紀錄 版本生效日期 新訂定 修訂 tumor>5cm 先 C/T 文件制定記錄 修訂低 low risk( 低危險群的定義 ) 1. 修訂腫瘤大小 1 公分 年齡 35 歲 low risk( 低危險群的定義 ) 備註說明前哨淋巴結定義及增加前哨淋巴結切除術定義 3. 新增化學治療藥物 -Herceptin 適應症 1.stage I 新增 Wide excision +SLNB 2. 修正 satage II 個案淋巴結 3 顆 R/T 適應症 強調 tumor 5cm 以化學治療為主 4 備註說明 Her-2(+++) 化學藥物至少各一種 : Epirubicin Taxane Herceptin 修訂術前檢查中乳房攝影 - 備註男性視狀況 2. 新增放射線治療劑量 cGy 1. 依據 NCCN 2010Breast cancer treatment guideline 重新修訂 StageI 腫瘤大小之輔助性治 療 2.StageII 增加 >2mm Mico-axillary LN meta 2

4 版本生效日期 文件制定記錄 1. 新增 Tubular Colloid Medullary Mucinous Papillary 2. 將 Radiotherapy 獨立出來 3. 刪除 new van nuys prognostic index scoring system 刪除 tumor 1-2cm>35 歲 C/T(optional)+Herceptin 的年齡限制 5. 新增 local only recurrence 的手術治療 6. 新增 Lymph nodes 的放射線治療 7. 新增 Boost treatment for scar 修改放射線治療劑量 Gy 2. 刪除 Boost treatment for scar 增加 stagei ER orpr(+)her2(-):pn1mico:hormone Tx+C/T (option). 2. 改 Chemotherapy 備註 : 請詳見參考本院通用抗癌藥物處方. 3. 增加 Hormone therapy 備註. 4.R/T 部份 :1-3postive axillary nodes 電療需加強 chest wall+ infraclavicular and supraclavicular +internal mammary nodes. 5.LN meta 1# 就需要電療, 予刪除 Indications for post-mastectomy Radiotherapy 第三項 postive axillary lymph node 4 及第七項 Axillary lymph node1-3 postive had 3 risk factor,(suclear Grade2 or 3,LVI(+),EIC(+),tumor>2cm,age<40,ER(-). 6. 將 Colloid(Mucinous) 診療臨床指引改至 stageι*histology 欄位. 3

5 版本生效日期 文件制定記錄 1. 於 LCIS 增加備註 2 一些多形性 LCIS 型態 (pleomorphic LCIS) 類似 DCIS, 可考慮完全切除並且 margins 需 negative 2. 於 DCIS 備註 3.high risk recurrence:larger size 由團隊共識定為 5cm; 新增備註 4.SLND (option) 視個案情況決定 3. 此次將 medullary and papillary 納入 Ductal 型態 4. 於 stagei-iiia 新增 Her2(+),LN(+) 及 Her2(-),LN(+) 治療方式 ; 增加備註 ( 詳見治療指引流程圖 ) 5. 此次將 Tubular Mucinous 治療方式獨立出來 ( 詳見治療指引流程圖 ) 6. 多增加有關 Adjuvant endocrine therapy 及備註 ( 詳見治療指引流程圖 ) 4

6 版本生效日期 文件制定記錄 1. 在 Tubular 和 Mucinous 部份 ( 之前未詳述 ), 予增加治療 BCT+R/T& MRM+R/T/LN(+) 包括 macrometastase/close margins 2. 為更精確診斷乳癌疾病於 Tubular Mucinous LCIS DCIS 部份增加備註 : 診斷確診方式以 core biopsy 為主,cytology 不能作為標準 3. 根據 The use of MRI has not been shown to increase likelihood of negative margins or decrease conversion to mastectomy. Data to support improved long-term outcomes are lacking; 予增加 DCIS 乳癌 I II III 初期 IIIA 以上 ->Breast MRI(option) 4. 根據 BINV-11Preoperative Systemic Therapy Breast and Axillary Evaluation->Clinically negative axillary lymph node(s),should have axillary ultrasound;suspicious nodes should be sampled by FNA or core biopsy and clipped with image-detectable marker; positive clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy;clinically positive axillary lymph node(s) should be sampled by FNA or core biopsy and clipped with image-detectable marker; positive clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy; 此次暫不予新增 Axillary Evaluation 5. 根據 BINV-19 ER(+) PR(+) Her2(-), 停經前婦女增加使用停經針劑 (leuplin-depot) 健保條文規定 : 停經前 ( 或更年期前 ) 之早期乳癌, 且須完全符合以下六點 :(100/2/1) Ⅰ 與 tamoxifen 合併使用, 作為手術後取代化學治療之輔助療法 Ⅱ 荷爾蒙接受體為強陽性 :ER/PR 為 2+ 或 3+ III.Her-2 Fish 檢測為陰性或 IHC 為 1+ IV. 淋巴結轉移數目須 3 個 V. 使用期限 :goserelin 使用 3 年,tamoxifen 使用 5 年 VI. 須事前審查 ( 訂於初次病理報告出來時 ), 並於申請時說明無法接受化學治療之原因 6. 新增 Chemotherapy palliative Chemotherapy Regimes: 請詳見參考本院通用抗癌藥物處方 5

7 版本生效日期 文件制定記錄 1. 追蹤共識 : 理學檢查及乳房超音波每年追蹤 2-4 次,5 年後改每年一次 2.Women on an aromatase inhibitor or experience ovarian failure to treatment should monitor bone mineral density 3.DCIS work up 新增 Estrogen receptor status 4.DCIS primary treatment 修改刪除 ± SLND or ALND;Wide excision 併入 Partial mastectomy 5.Invasive breast cancer work up 新增 ALK-phosphatase, ER/PR/Her-2 status, Chest CT(optional) 檢查項目 6. Stage I II III Adujvant Treatment ER or PR(+) Her-2(+) LN(-): Tumor 0.5cm this Group 新增 ± (Chemotherapy+ Herceptin) And if LN(+) Her-2(+) 新增 + Herceptin use 7.Recurrence/Stage IV disease work up 新增 Her-2 status Liver function and ALK-phosphatase or PET 檢查項目 8.Recurrence/ Stage IV disease systemic disease or denovo stage IV status renew treatment rule and salvage treatment : 請詳見診療指引流程圖 1.Tubular Mucinous primary treatment,part1.er or PR(+); Tumor<1cm group 刪改 No adjuvant therapy 為 Consider adjuvant endocrine therapy for risk reduction 2. 各期別 Work-UP 新增 Genetic counseling if patient is high risk for hereditary breast cancer(optional) and Counseling for fertility concerns if premenopausale (optional) 3.DCIS Partial mastectomy 刪除備註 3 說明 4.Adjuvant endocrine therapy post suppression or ablation, 原 consider Aromatase inhibitor for 5 y 改為加入此項治療 5.Post surgery Radiotherapy Salvage treatment 放射線治療部位內容依照 NCCN(BINV-2,3) 陳述內容修正 6.Recurrence/stage IV disease Radiotherapy Salvage treatment 放射線治療部位內容刪除 6

8 版本生效日期 文件制定記錄 1.Work-UP 修改 CA-153(optional) 為抽血必要項目 2. 各期別 Work-UP 新增 pregnancy test in all women of childbearing potential(optional) 3.CIS-1:Footnote "b", changed "with negative margins" to "to clear margins." 原 negative margins 修改為 clear margins. 4. 新增 Adjuvant chemotherapy with trastuzumab + pertuzumab (optional) 7

9 目錄 一 乳癌診療指引流程圖 二 放射腫瘤科乳癌治療指引 三 診斷共識 四 治療共識 五 追蹤共識 六 乳癌院內通用抗癌藥物處方 七 參考資料

10 一 乳癌診療指引流程圖 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : DIAGNOSIS WORK-UP PRIMARY TREATMENT FOLLOW-UP Tubular Mucinous CBC CEA CA153 Liver function test Chest x-ray Bilateral mammography Breast echo Pathology review Abd sona (optional) Bone scan (optional) PET (optional) Partial mastectomy +SLND or ALND (if SLN positive) +R/T Modified radical mastectomy +SLND or ALND (if SLN positive) ± reconstructive surgery +R/T(if LN(+)/macrometastase/ close margins) 1. ER or PR(+) and PT1 T2 T3 and No or N1 mico 2 mm : Tumor<1cm: Consider adjuvant endocrine therapy for risk reduction Tumor1-2.9cm: Consider adjuvant endocrine therapy Tumor 3cm:Adjuvant endocrine therapy 2.ER or PR(+) and Node positive (one or more metastasis>2mm to one or more ipsilateral axillary lymph nodes) : Adjuvant endocrine therapy ± adjuvant CT *Physical examination and Breast echo 2-4 times / year for 5 y then annually *Mammography every 12 mo *Chest x-ray or Chest CT every 12 mo *Bone Scan (Optional) *Abdominal Ultrasound (Optional) *Women on Hormone Tx pelvic examination every 12 mo *Women on an aromatase inhibitor or experience ovarian failure to treatment should monitor bone mineral density at baseline and periodically thereafter (optional) X621 健保未給付鼓勵個案作!! 註 :1. 乳房攝影男性視狀況執行 2.Radiotherapy: 參考放射腫瘤科乳癌治療指引 3. 診斷確診方式以 core biopsy 為主,cytology 不能作為標準 3.ER and PR(-) Treat as usual breast cancer histology 參考資料 : 一 2017.V4 NCCN 9

11 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : DIAGNOSIS WORK-UP PRIMARY TREATMENT FOLLOW-UP Lobular Carcinoma in Situ (LCIS) Diagnostic bilateral mammogram Breast echo Pathology review Observation after surgical excision (preferred)( 註 2) *Yearly physical examination *Yearly mammography and /or Breast echo *HRT 5 years for ER(+) (option) 註 :1. 乳房攝影男性視狀況執行 2. 一些多形性 LCIS 型態 (pleomorphic LCIS) 類似 DCIS, 可考慮完全切除並且 clear margins. 3. 診斷確診方式以 core biopsy 為主,cytology 不能作為標準 參考資料 : 一 2017.V4 NCCN 10

12 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : DIAGNOSIS WORK-UP PRIMARY TREATMENT FOLLOW-UP Ductal Carcinoma in Situ (DCIS) Diagnostic bilateral mammogram Breast echo Pathology review Estrogen receptor (ER) status Total mastectomy ± SLND ± reconstructive surgery Physical examination and Breast echo every 6-12 mo for 5y, then annually Mammography every 12 mo Breast MRI (optional) Genetic counseling if patient is highrisk for hereditary breast cancer (optional) Partial mastectomy Radiotherapy HRT 5 years for ER / PR(+) on BCT (option) 備註 :1. 乳房攝影男性視狀況執行 2.Radiotherapy: 參考放射腫瘤科乳癌治療指引 3.SLND (option) 視個案情況決定 4. 診斷確診方式以 core biopsy 為主,cytology 不能作為標準 參考資料 : 一 2017.V4 NCCN 11

13 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : DIAGNOSIS WORK-UP PRIMARY TREATMENT ADJUVANT TREATMENT FOLLOW-UP Stage I,IIA IIB,IIIA T1N0M0 T0N1M0 T1N1M0 T2N0M0 T2N1M0 T3N0M0 T3N1M0 CBC CEA CA153 ALK-phosphatase Liver function test Chest x-ray Bilateral mammography Breast echo Pathology review ER/PR/Her-2 status Abd echo (optional) Bone scan (optional) PET (optional) Breast MRI (optional) Chest CT (optional).genetic counseling if patient is high-risk for hereditary breast cancer(optional).counseling for fertility concerns if premenopausale;pregnancy test in all women of childbearing potentialf (optional) LN(-) Partial mastectomy + SLND or ALND (if SLN positive) Modified radical mastectomy + SLND or ALND ( if SLN positive) ± reconstructive surgery Mastecctomy + SLND or ALND (if SLN positive) *Histology: Ductal (Medullary,papillary) Lobular Mixed Metaplastic 1.ER or PR(+) Her-2(+) LN(-) and No or N1 mico 2 mm : Tumor 0.5cm / Microinvasive :pn0 : ± Hormone Tx ± (Chemotherapy +Herceptin) Tumor 0.5cm / Microinvasive: pn1 mico: Hormone Tx ± ( Chemotherapy +Herceptin ) Tumor 0.6-1cm: Hormone Tx ± ( Chemotherapy + Herceptin ) Tumor >1 cm: Hormone Tx + ( Chemotherapy +Herceptin ) 2.ER(-) and PR(-) Her-2(+) and No or N1 mico 2 mm : Tumor 0.5cm:N0 or N1 mico: ± ( Chemotherapy + Herceptin ) Tumor cm: ± ( Chemotherapy + Herceptin ) Tumor > 1 cm:+ ( Chemotherapy + Herceptin ) 3.ER or PR (+) Her-2(-), and N0 or N1mico( 2 mm) : Tumor 0.5cm / Microinvasive :pn0 : ±Hormone Tx Tumor 0.5cm / pn1mico :Hormone Tx ± C/T Tumor >0.5cm : Hormone Tx ± ( Chemotherapy ) 4.ER and PR (-) Her-2(-), and N0. or N1mico ( 2 mm): Tumor 0.5cm / Microinvasive :pn0 :No adjuvant therapy Tumor 0.5cm / pn1mico : ± Chemotherapy Tumor cm : ± Chemotherapy Tumor >1 cm : Chemotherapy R/T (for Partial mastectomy/ LN(+)/ Tumor>5cm/T3 ) *Physical examination and Breast echo 2-4 times / year for 5 y then annually *Mammography every 12 mo *Chest x-ray or Chest CT every 12 mo *Bone Scan (Optional) *Abdominal Ultrasound (Optional) *Women on Hormone Tx pelvic examination every 12 mo *Women on an aromatase inhibitor or experience ovarian failure to treatment should monitor bone mineral density at baseline and periodically thereafter (optional) X621 健保未給付鼓勵個案作!! 註 :1. 乳房攝影男性視狀況執行 2. 申請 PET/CT 需符合健保適應症, 未符合適應症需請病人自費 3.Herceptin: 考慮健保給付條規, 後面予加 (optional) 4.Chemotherapy: 請參考本院通過抗癌藥物處方 5.Radiotherapy: 參考放射腫瘤科乳癌治療指引 LN(+) Her-2(+) LN postive (one or more metastases >2mm Herceptin(or ± Perjeta) ER(+):Chemotherapy +Hormone Tx ER (-):Chemotherapy Her-2(-) LN postive (one or more metastases >2mm ER(+):Chemotherapy+Hormone Tx ER (-):Chemotherapy 參考資料 : 一 2017.V4 NCCN 12

14 DIAGNOSIS WORK-UP Breast Cancer Treatment Guideline PRIMARY TREATMENT ADJUVANT TREATMENT 初版日期 :91.09 最後更新日 : FOLLOW-UP Clinical stage IIIA ( 以上 ) T0N2M0 T1N2M0 T2N2M0 T3N2M0 T4 any N M0 Any T N3 Mo CBC CEA; CA153 ALK-phosphatase Liver function test Chest x-ray Bilateral mammography Breast echo Pathology review ER/PR/Her-2 status Abd echo (optional) Bone scan (optional) Chest CT; PET (optional).breast MRI (optional).genetic counseling if patient is high risk for hereditary breast cancer (optional).counseling for fertility concerns if premenopausale ;pregnancy test in all women of childbearing Potentialf (optional) Operable Induction chemotherapy with anthracycline-based regimen for 3-4 cycles Modified radical Mastectomy ± ALND Modified radical Mastectomy ± ALND (Respones preferred) If no response:individualized therapy Chemotherapy + R/T + Hormone Tx if ER(+) +Targeted theraphy if HER2 postive *Physical examination and Breast echo 2-4 times / year for 5 y then annually *Mammography every 12 mo *Chest x-ray or Chest CT every 12 mo *Bone Scan (Optional) *Abdominal Ultrasound (Optional) *Women on Hormone Tx pelvic examination every 12 mo *Women on an aromatase inhibitor or experience ovarian failure to treatment should monitor bone mineral density at baseline and periodically thereafter (optional) X621 健保未給付鼓勵個案作!! Clinical stage IV Any T any N M1 參考資料 : 一 2017.V4 NCCN.CBC.CEA ; CA15-3.Liver function test and.alk-phosphatase.chest x-ray.bilateral mammography ±breast echo.pathology review.er/pr/her-2 status.abd echo.bone scan or PET/CT.Biopsy documentation of distant metastasis if possible.metastatic site CT scan or MRI (optional).genetic counseling if patient is high risk for hereditary breast cancer (optional) SYSTEMIC TREATMENT Systemic chemotherapy and/or hormonal therapy ± radiotherapy* / surgery 13

15 Adjuvant endocrine therapy Premenopausal at diagnosis Tamoxifen for 5-10 y ovarian suppression or ablation ( 備註 D) Breast Cancer Treatment Guideline Postmenopausal Premenopausal +Aromatase inhibitor for 5 y Aromatase inhibitor ( 合計 5 年 ) or ± tamoxifen for an additional 5-10y 初版日期 :91.09 最後更新日 : ± Tamoxifen for an additional 5-10y or no further endocrine therapy Postmenopausal at diagnosis Aromatase inhibitor for 5 y or Tamoxifen +Aromatase inhibitor for 5 y Women with a contraindication to aromatase inhibitors, who decline aromatase inhibitors, or who are intolerant of the aromatase inhibitors Aromatase inhibitor to complete 5 y of endocrine therapy or up to 5 y of an aromatase inhibitor Tamoxifen to complete 5-10y of endocrine therapy Tamoxifen for 5-10 y or ± tamoxifen for up to 10 y 備註 : A. 更年期定義 : 停經條件包括 1.Prior bilateral oophorectomy 2.Age 60 y 3. 年齡 <60 歲和停經為 12 個月或以上在沒有化療及服用 tamoxifen or toremifene, 或卵巢抑制和 FSH 和 LH E2 在停經後範圍.4. 如果服用 tamoxifen or toremifene, 和年齡 <60 歲, 那麼 FSH 和 LH E2 在停經後範圍 ( 參考 BINV-L) B.Femara( 針對健保條文 102 年 8 月 1 日生效 ) 1. 停經後且荷爾蒙接受體呈陽性, 有淋巴結轉移之乳癌病人, 作為 tamoxifen 治療五年後的延伸治療, 且不得與其他 aromatase inhibitor 併用 ; 使用時需同時符合下列規定 (1) 手術後大於等於 11 年且無復發者不得使用 (2) 每日最大劑量 2.5mg, 使用不得超過四年 2. 停經後且荷爾蒙接受體呈陽性之早期乳癌病人, 經外科手術切除後之輔助治療, 且不得與 tamoxifen 或其他 aromatase inhibitor 併用 ; 使用時需同時符合下列規定 (1) 每日最大劑量 2.5mg, 使用不得超過五年 (2) 若由 tamoxifen 轉換使用本品, 則使用期限合計不得超過 5 年 (3) 病歷上應詳細記載手術資料 病理報告 ( 應包含 ER PR 之檢測結果且無復發現象 ) 及用藥紀錄 ( 如 tamoxifen 使用五年證明 ) C.Tamoxifen 於此次建議延長 10 年, 在健保部份未明文規定是否給付, 故可適個案情況而定 ; 予更改 Tamoxifen for 5-10 y D.leuplin-DEPOT 健保條文規定 : 停經前 ( 或更年期前 ) 之早期乳癌, 且須完全符合以下六點 :(100/2/1)->I 與 tamoxifen 合併使用, 作為手術後取代化學治療之輔助療法 Ⅱ 荷爾蒙接受體為強陽性 :ER/PR 為 2+ 或 3+ III.Her-2 Fish 檢測為陰性或 IHC 為 1+ IV. 淋巴結轉移數目須 3 個 V. 使用期限 :goserelin 使用 3 年,tamoxifen 使用 5 年 VI. 須事前審查 ( 訂於初次病理報告出來時 ), 並於申請時說明無法接受化學治療之原因 參考資料 : 2017.V4 NCCN 14

16 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : LOCALREGIONAL TREAMENT STATUS SALVAGE TREATMENT 4 positive axillary nodes Radiation therapy to whole breast with or without boost to, infraclavicular region and supraclavicular area, internal mammary nodes, and any part of the axillary bed at risk (category 1). strongly Consider radiation therapy to internal mammary nodes. Radiation therapy should follow chemotherapy when chemotherapy is indicated. Lumpectomy with surgical axillary staging 1-3 positive axillary nodes Radiation therapy to whole breast with or without boost to. Strongly consider radiation therapy to infraclavicular region, supraclavicular area, internal mammary nodes, and any part of the axillary bed at risk. Radiation therapy should follow chemotherapy when chemotherapy indicated. Negative axillary nodes Radiation therapy to whole breast with or without boost to or consideration of partial breast irradiation (PBI) in selected patients. Radiation therapy should follow chemotherapy when chemotherapy indicated. *Radiotherapy: 詳見本院放射線治療指引 參考資料 : 一 2017.V4 NCCN 15

17 LOCALREGIONAL TREAMENT Breast Cancer Treatment Guideline STATUS SALVAGE TREATMENT 初版日期 :91.09 最後更新日 : positive axillary nodesl Radiation therapyr to chest wall + infraclavicular region, supraclavicular area, internal mammary nodes, and any part of the axillary bed at risk. (category 1) Radiation therapy should follow chemotherapy when chemotherapy indicated. 1-3 positive axillary nodes Strongly consider radiation therapy to chest wall ± infraclavicular region, ± supraclavicular area, ± internal mammary nodes and any part of the axillary bed at risk. Radiation therapy should follow chemotherapy when chemotherapy indicated. Total mastectomy with surgical axillary staging (category 1) ± reconstruction Negative axillary nodes and tumor > 5 cm or margins positive Consider radiation therapy to chest wall ± infraclavicular region, ± supraclavicular area, ± internal mammary nodes and any part of the axillary bed at risk. Radiation therapy should follow chemotherapy when chemotherapy indicated. Negative axillary nodes and tumor 5 cm And negative margins but < 1 mm Consider radiation therapy to chest wall. Radiation therapy should follow chemotherapy when chemotherapy indicated. *Radiotherapy: 詳見本院放射線治療指引 Negative axillary nodes and tumor 5 cm and margins 1 mm No radiation therapy 參考資料 : 一 2017.V4 NCCN 16

18 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : RECURRENCE / STAGE IV DISEASE WORK-UP STATUS SALVAGE TREATMENT Biopsy documentation of first recurrence if possible Mammography ER/PR and Her-2 status CBC Blood chemistry CEA and CA15-3 Liver function and ALK-phosphatase Whole body bone scan or PET Chest x-ray Ultrasonography of liver CT scan or MRI of symptomatic areas Genetic counseling if patient is high risk for hereditary breast cancer (optional) Local recurrence only Initial treatment with lumpectomy + radiation therapy Initial treatment with mastectomy + level I/II axillary dissection and prior radiation therapy Initial treatment with mastectomy no prior radiation therapy Regional only or Local regional recurrence Axillary recurrence Supraclacivular recurrence Internal mammary node recurrence Post breast-conserving surgery alone Post breast-conserving surgery + radiotherapy* Post mastectomy Post mastectomy + radiotherapy* Total mastectomy + axillary lymph node staging if level I/II axillary dissection not previously done + systemic therapy Surgical resection if possible + systemic therapy Surgical resection if possible + radiotherapy + systemic therapy Surgical resection if possible + radiotherapy if possible + systemic therapy Radiotherapy if possible + systemic therapy Radiotherapy if possible + systemic therapy Salvage mastectomy + systemic therapy ± radiotherapy* Salvage mastectomy + systemic therapy Surgical resection if possible + radiotherapy* + systemic therapy Surgical excision if possible + systemic therapy ± radiotherapy* *Radiotherapy: 詳見乳癌治療指引 參考資料 : 一 2017.V4 NCCN 17

19 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : RECURRENCE / STAGE IV DISEASE WORK-UP STATUS SALVAGE TREATMENT Biopsy documentation of first recurrence if possible Mammography ER/PR and Her-2 status CBC Blood chemistry CEA and CA15-3 Liver function and ALKphosphatase Whole body bone scan or PET Chest x-ray Ultrasonography of liver CT scan or MRI of symptomatic areas.genetic counseling if patient is high risk for hereditary breast cancer (optional) Systemic disease or denovo stage IV Hormone-sensitive; Her-2 negative Hormone-sensitive; Her-2 positive Prior endocrine therapy within 1 y No prior endocrine therapy within 1 y Premenopausal Postmenopausal Visceral crisis Premenopausal Postmenopausal Ovarian ablation or suppression, plus endocrine therapy as for postmenopausal women or chemotherapy shift endocrine therapy or chemotherapy Initial chemotherapy or Anti Her-2 ((for Her-2 (+)) or shift Hormone Tx Ovarian ablation or suppression, plus endocrine therapy as for postmenopausal women or Selective ER modulators or chemotherapy Aromatase inhibitor or Selective ER modulators or ER down-regulator or chemotherapy P.D. Chemotherapy or shift endocrine therapy or Palliative care Visceral crisis Initial chemotherapy or Anti Her-2 ((for Her-2 (+)) or Hormone Tx * Radiotherapy: 詳見乳癌治療指引 參考資料 : 一 2017.V4 NCCN 18

20 Breast Cancer Treatment Guideline 初版日期 :91.09 最後更新日 : RECURRENCE / STAGE IV DISEASE WORK-UP STATUS SALVAGE TREATMENT Systemic disease or denovo stage IV Biopsy documentation of first recurrence if possible Mammography ER/PR and Her-2 status CBC Blood chemistry CEA and CA15-3 Liver function and ALK-phosphatase Whole body bone scan or PET Chest x-ray Ultrasonography of liver CT scan or MRI of symptomatic areas Genetic counseling if patient is high risk for hereditary breast cancer(optional) ER and PR negative; or ER and/or PR positive and endocrine refractory; and HER2 negative ER and PR negative; or ER and/or PR positive and endocrine refractory; And HER2 positive ; ; Bone/soft tissue only or Asymptomatic visceral (No other metastatic conditions) Bone/soft tissue only or Asymptomatic visceral (No other metastatic conditions) Y N Y N Consider Chemotherapy or trial of endocrine therapy Chemotherapy Anti Her-2 agent(s) + Chemotherapy or Anti Her-2 agent(s) + trial of endocrine therapy Anti Her-2 agent(s) ± Chemotherapy P.D. P.D. C/T or Palliative care Anti Her-2 or C/T ± Anti Her-2 or Palliative care 參考資料 : 一 2017.V4 NCCN 19

21 二 放射腫瘤科乳癌治療指引 初版日期 :91.09 最後更新日 : 目的 : 制定乳癌 (breast cancer) 放射治療指引與執行規範 2. 適用範圍 : 適用於根治性乳癌病患之放射治療 3. 分期依照 AJCC th edition 4. 需接受放射治療之適應症 (indication) : (1) 凡接受乳房保留手術後之病患應接受手術後之全乳含或不含局部淋巴區域放射治療 ( 照射範圍請看第 6 點詳述 ) (2) 凡接受全乳切除手術後之病患應接受前胸壁含或不含局部淋巴區域放射治療 ( 照射範圍請看第 6 點詳述 ) 5. 模擬定位 : (1) 在電腦斷層掃描定位室, 請病患依指定姿勢躺在已製作好的固定模具上, 並根據病患皮膚標記點對到定位雷射 (2) 在病患之皮膚上, 貼上金屬標記, 在影像上呈現中心點之位置 (3) 如果有手術後之刀疤 (surgical scar), 應在刀疤貼上金屬標記 ; 另建議將乳房之上下左右邊緣貼上金屬標記定位用 (4) 電腦斷層之掃描範圍及條件為由頸部至乳房下緣二指幅處, 切片厚度 4~5 毫米 (5) 一般的病人不需要透過靜脈注射顯影劑, 除非懷疑有腫瘤殘存才會要求病人打顯影劑來加強判讀腫瘤侵犯之範圍 6. 靶體積定義 (Target Volume Definition) 及放射治療計畫規劃 (Radiation Therapy Planning): (1) 全乳房照射 (Whole Breast Irradiation) a. 經乳房保留手術 (Breast-Conserving Surgery) 之病患,GTV 應包含原來腫瘤部位之範圍 CTV 包含整個患側之乳房 + 淋巴結區域,PTV 為 CTV 加上 0.5~1.5 公分之範圍 b. 劑量 : 腫瘤部位 () Gy/25-28frs + 同步或非同步 boost Gy; 患側乳房 Gy/ 25-28frs 或 Gy/15-16frs (5 times per week); 淋巴結區域 Gy/25-28frs(5 times per week) c. 內乳淋巴腺是否接受照射由原發腫瘤部位及臨床狀況決定 20

22 d. 治療天數應由病況決定, 合理範圍 : 天 Guideline suggestion for Clinical target volume (CTV) selection after conservative breast surgery Target area for whole breast; Superior margin: clavicle head; Inferior margin: infra-mammary fold two- finger width; Inner margin: mid-sternum ; Outer margin: mid-axillary line Tumor location Axillary area pn0 pn1mi pn1a-c pn2-pn3 Inner Quadrant Central Area Outer Quadrant T1-2 T3-4 T1-2 T3-4 T1-2 T3-4 whole breast * *: internal mammary chain whole breast +/- whole breast +/- +/- whole breast +/- +/- +/- whole breast +/- whole breast +/- +/- 21

23 (2) 胸壁及局部淋巴線照射 (Chest Wall and Regional Lymph Nodes Irradiation) a. CTV 包含整個患側之胸壁 全乳房手術後之傷疤 + 腋下淋巴腺 (Axillary Lymph Nodes) 及上及下鎖骨窩淋巴腺 (Supra/infraclavicular Lymph Nodes),PTV 為 CTV 加上 0.5~1.5 公分之範圍 b. 劑量 : 胸壁及淋巴結區域 Gy/25-28frs (5 times per week) c. 內乳淋巴腺是否接受照射由原發腫瘤部位及臨床狀況決定 d. 治療天數應由病況決定, 合理範圍 : 天 Guideline suggestion for Clinical target volume (CTV) selection after Mastectomy Target area for chest wall Superior margin: clavicle head Inferior margin: infra-mammary fold two- finger width Inner margin: mid-sternum Outer margin: mid-axillary line 22

24 MRM+ALND Tumor location Axillary area pn0 pn1mi (=SN+) * pn1a-c pn2-pn3 *: internal mammary chain Inner Quadrant Central Area Outer Quadrant T1-2 T3-4 T1-2 T3-4 T1-2 T3-4 +/- +/- +/- 23 +/- +/- +/- +/- +/- +/- 7. 危急器官定義之劑量限制 : (1) 脊索 (Spinal cord) 劑量限制 : 最高劑量 < 45 Gy (2) 肺 (Lung) 劑量限制 : 平均劑量建議 <20 Gy 整個肺部之 V20Gy < 35% (20 Gy 劑量之體積, 應低於肺總體積之 35%), 如肺功能較差之病患, 整個肺部之 V20Gy <30% 與患側同邊之肺部 : 平均劑量建議 < 20 Gy V20Gy < 35% 在患側對側之肺部 :V5Gy < 15%, 盡量合理抑低 (3) 胸腔之食道 (Thoracic Esophagus) 劑量限制 : 平均劑量 < 35 Gy (4) 對側之乳房組織 (Contralateral Breast) 劑量限制 : 盡量合理抑低 (5) 心臟 (Heart) 劑量限制 :1/3 之體積應低於 60 Gy 2/3 之體積應低於 45 Gy 所有體積應低於 40 Gy

25 8. 治療驗證 (Treatment Verification) (1) 三度空間放射治療或強度調控放射治療或銳速刀 : 治療前由放射師拍攝正交之驗證片 (orthogonal verification films) 來驗證照野之中心點 (2) 影像導引放射治療 (IGRT: OBI 或 CBCT): 如需要影像導引放射治療, 治療前應由放射師拍攝電腦斷層影像或正交之驗證片確認治療範圍, 治療期間應由醫師決定再次驗證的時間及頻率 24

26 三 診斷共識 病人自我檢查 初版日期 :91.09 最後更新日 : 醫師理學檢查 可摸到乳房腫瘤 乳房超音波 ± 乳房 X 光攝影 ± 細針抽吸細胞學檢查 ± 粗針切片檢查 異常腫塊 (Category 4 以上 ) 纖維腺瘤良性結節纖維囊腫變化 活體組織切片檢查 切片檢查或定期追蹤 定期追蹤 定期追蹤 確診乳癌 良性 依據乳癌流程分期 定期追蹤 25

27 備註 : 1. 乳超 : 台灣婦女的乳房多屬緻密性質, 故在乳房超音波下檢查較乳房 x 光攝影下易偵測到, 小於 35 歲婦女, 由於放射線影響可能較大, 宜先做超音波檢查 2. 細針抽吸細胞學檢查 : 方便易做, 不需麻醉, 以空針細針頭刺入腫塊, 做多次收吸, 取得細胞檢體, 診斷率相當高, 但仍有偽陰性和偽陽性情形可能, 若為上述情形, 應做組織切片檢查 3. 粗針切片檢查 : 目的為確定病理診斷, 及檢測乳癌預後因子, 如 ER PR Her-2/neu 過度表現, 以做為治療參考 乳癌確診後相關檢查 1. 腫瘤標記 (CEA CA153):CA153 為乳癌腫瘤指標, 通常只在乳癌擴散轉移時才升高, 初期檢驗以便於再後續追蹤時做比較 2. 胸部 X 光 : 診斷乳癌轉移可能性 3. 腹部超音波 : 檢查肝臟轉移可能性 4. 骨骼攝影掃描 : 骨骼掃描是目前唯一可以進行全身骨骼癌症轉移的篩檢工具, 其敏感度比 X- 光高 30-40%, 且發現病灶的時間可以比 X- 光提早 3-6 個月 X- 光必須要骨密度改變 50% 左右才會顯示出異常, 而骨骼掃描則在疾病早期血流增加或成骨活動增強時就可以清楚看到, 是各種癌症骨轉移的最佳篩檢工具 5. 正子造影檢查 : 為最新型 16 切 PET/CT, 非侵入性高科技診斷, 低輻射劑量安全性高的全身性造影檢查, 對癌症具有高度診斷力 ( 解像力高達 2mm), 可早期發現潛藏癌症 6. 電腦斷層檢查 : 適情況而定 乳癌分期 1. 零期乳癌 : 即原位癌, 為最早期乳癌, 癌細胞仍在乳腺管基底層內 2. 第一期乳癌 : 腫瘤小於兩公分以下的浸潤癌且腋下淋巴結無癌轉移 ; 或腫瘤小於兩公分但腋下淋巴結有小於兩毫米癌轉移 3. 第二期乳癌 : 腫瘤在兩公分至五公分之間的浸潤癌 ; 或腫瘤小於兩公分但腋下淋巴結有 1-3 顆癌轉移 4. 第三期乳癌 : 局部廣泛性乳癌, 腫瘤大於五公分的浸潤癌且腋下淋巴結有任何癌轉移或有胸壁皮膚的浸潤乳癌, 或鎖骨上淋巴結轉移, 或腋下淋巴結 4 顆以上轉移 5. 第四期乳癌 : 轉移性乳癌, 已有遠處器官轉移 ( 如肝 肺 骨 ) 等 26

28 四 治療共識 ( 一 ) 乳癌外科治療 : 1. 改良型乳房根除手術 : 適用於任何沒有胸大肌侵犯或非第四期轉移性乳癌的患者, 為目前最常使用的手術 術式包含腋下淋巴結廓清術 2. 乳房保留手術 : 適用於乳房腫瘤小於 3 公分, 非於乳頭或乳暈下方 ( 距離乳暈 2cm 以上 ), 而且無多發病灶的第一 二期乳癌患者 術式包含部分乳房組織切除術及腋下淋巴結廓清術, 通常術後需放射線治療 3. 單純性全乳房切除手術 : 適用於乳房腺管原位癌乳癌患者, 術式不包含腋下淋巴結廓清術 4. 部分乳房組織切除術 : 可用於小而非粉刺型的乳房腺管原位癌 粉刺型原位癌若採用此手術, 宜加放射線治療 5. 腋下淋巴結廓清術 : 腋下淋巴結被癌細胞侵犯的狀況, 為乳癌預後最重要的指標之一, 因此腋下淋巴結廓清術兼具有診斷及治療的目的 ( 註 : 目前前哨淋巴結摘除術可取代部分腋下淋巴結廓清術, 但此項手術之安全性及可靠性仍在臨床研究中 ) 6. 前哨淋巴結摘除術 : 適用於原位癌及臨床檢查無淋巴轉移第一期個案, 在手術進行中將前哨淋巴結摘除並做切片檢查, 視其是否已轉移再決定給予腋下淋巴結廓清術與否, 對無轉移乳癌患者而言, 則可省去不必要之淋巴切除, 目的為減少因淋巴切除所導致上臂淋巴水腫 感覺麻痺 手臂活動不適等後遺症的發生 27

29 ( 二 ) 術後輔助性治療 : 期別 治療方式 零期第一期第二期第三期第四期 外科手術 v v v v 視需要 化學治療視需要 v v 視需要 放射線治療視需要視需要視需要 v 視需要 荷爾蒙治療視需要視需要視需要視需要視需要 標靶治療視需要視需要視需要視需要 復發 :( 請參照本院乳癌治療指引流程圖 ) 轉移 :( 請參照本院乳癌治療指引流程圖 ) 備註 : 1. 荷爾蒙療法 : 是腫瘤細胞有雌性激素受體 (Estrogen Receptor, 以下簡稱 ER) 或是黃體素受體 (Progesterone Receptor, 以下簡稱 PR) 之表現呈現陽性可使用, 目前本院用藥為 Tamoxifen Femara( 目前已證實 Tamoxifen 當作術後之輔助治療, 五年是最佳之治療期程 ) 2. 標靶藥物 : HER-2 過度表現呈現 3+ FISH(+), 目前本院用藥為 賀癌平 (Herceptin), 學名為 Trastuzumab( 健保給付於早期 HER-2 過度表現且淋巴結陽性乳癌之輔助性治療, 及轉移性乳癌病人合併紫杉醇類化療第一線使用或第一線化療失敗後單獨使用 ) 3. 放射線治療 : a. 原來乳房腫瘤大於 5 公分 b. 術前已經出現皮膚侵犯現象 c. 手術邊緣有殘存癌細胞或癌細胞靠近手術切口 (margin<2mm) d. 癌細胞轉移 1 個以上的腋窩下淋巴 4. 化學治療 :( 參考本院化療處方 ) 28

30 五 追蹤共識 時間兩年內三至五年內第六年起 檢查項目及頻率 1. 理學檢查 ( 血液腫瘤標記 ) 2-4 次 / 每年 2. 乳房超音波 2-4 次 / 每年 3. 胸部 x 光及腹部超音波 每半年 4. 乳房攝影檢查及全身骨骼掃描 每年 1. 理學檢查 ( 血液腫瘤標記 ) 2-4 次 / 每年 2. 乳房超音波 2-4 次 / 每年 3. 胸部 x 光及腹部超音波 每半年 4. 乳房攝影檢查及全身骨骼掃描 每年 1. 理學檢查 ( 血液腫瘤標記 ) 每年 2. 乳房超音波 每年 3. 胸部 x 光及腹部超音波 每年 4. 乳房攝影檢查及全身骨骼掃描 視需要而定 29

31 六 乳癌院內通用抗癌藥物處方 最初出版日期 :95.03 最後更新日期 : 癌症類別 Neoadjuvant( 術前 ) (3-4 cycles) Adjuvant( 術後 ) (6 cycles) Palliative( 無法手術 ) 乳癌 (1)CEF: Endoxan 600mg/ m 2 (N/S 300 c.c.; 2hrs) + Epirubicin 60mg/ m 2 (N/S 100 c.c.; 1hr) + 5-FU 600mg/ m 2 (N/S 500 c.c.; 3hrs) (Epi: 50mg/ m 2 (JCO 1988;6:679-88) 60mg/ m 2 (Br J Cancer 1995Mar ;71(3)587-91) (2)TEC Epirubicin 60mg/ m 2 +Endoxan 600mg/ m 2 + Docetaxel 60,75mg / m 2 (N/S 100 c.c.; 1hr) or Epirubicin 60mg/ m 2 + Docetaxel 35,40mg (N/S 100 c.c; 1hr) Endoxan 600mg/ m 2 + Docetaxel 35,40mg (Breast J 2007 May-Jun; 13(3):274-80) (3) Herceptin 4mg/kg/2wks (or 6 mg/kg/3wks or 8 mg/kg/4 wks) + TEC (as above) (1)CEF: 如左 (2) TEC 如左 (3)CMF: Endoxan 600mg/ m 2 + MTX 60mg/ m 2 (N/S 100 c.c.; 1hr) + 5-FU 600mg / m 2 (NEJM 1976; 294; ) (4) Epirubicin 80 mg/ m 2 (N/S 100 c.c.; 1hr) IV CMF IV (Annals of Oncology Vol.16 Nov. 2005, pp ) (5)EC IV T IV Endoxan 600mg/ m 2 + Epirubicin 80 mg/m 2 Docetaxel 60,75mg / m 2 or biweekly 35,40mg / m 2 or (Paclitaxel 135 mg/ m 2 (N/S 500 c.c.; 3 hrs) or biweekly 85 mg/ m 2 (N/S 300 c.c.; 2hrs) )(Anticancer Res 2009 May; 29(5): ) (6) 以上處方可考慮 combined with Herceptin 4mg/kg/2wks (or 6 mg/kg/3wks or 8 mg/kg/4 wks) (1)CEF q3-4 wks (2)Navelbine (p.o) mg/m 2 q2 wks(breast Cancer Res. 2005;7 (Suppl 1):S25) (3)Navelbine (v.) mg/m 2 (N/S 50 c.c.; 10 mins) q2 wks (Ann Oncol May; 5(5):423-6) (4)UFUR(324 mg) mg/ m 2 qd ( 健保條例 ) (5)Paclitaxel 85 mg/ m 2,q2 wks ( 健保條例 ) (6)Gemcitabine 1000 mg / m 2 (N/S 100 c.c.; 30 mins) +Paclitaxel ( 同上 ) q2wks( 健保條例 ) (7)Docetaxel 35,40 mg / m 2 q2wks( 健保條例 ) (8)Xeloda mg/m 2 (2:1 or 5:2) ( 健保條例 ) (11) Avastin 5mg/kg q3-4wks(the Oncologist Jan 15, 2004) (12)Perjeta(pertuzumab) 840 mg 420mg (N/S 300 c.c.; 2hrs) & Herceptin 6-8mg/kg (N/S 300 c.c.; 2hrs)(Am NIH Feb ) (13)Kadcyla(TDM-1) 3.6mg/kg (N/S 300 c.c.; 2hrs) q3-4 wks(ther Adv Med Oncol Sep;615): ) (14)Halaven mg/m 2 (N/S 50 c.c.; 5 mins) II/cycle( 健保條例 ) (15)Lapatinib (Am NIH Jan ) 30

32 七 參考資料 ( 一 ) 診療指引參考文獻 1.NCCN Clinical Practice in Oncology: Breast cancer V 國家衛生研究院 ( 二 ) 抗癌藥物處方參考文獻 1. Breast J 2007 May-Jun; 13(3): NEJM 1976; 294; Annals of Oncology Vol.16 Nov. 2005, pp Anticancer Res 2009 May; 29(5): Breast Cancer Res. 2005;7 (Suppl 1):S25 6. Ann Oncol May; 5(5): The Oncologist Jan 15, Am NIH Feb Ther Adv Med Oncol Sep;615): Am NIH Jan Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N. Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol 2005;23(22): Levine MN, Bramwell VH, Pritchard KI et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1998;16(8): Ferreira Filho AF, Di LA, Paesmans M et al. The feasibility of classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for pre- and post-menopausal node-positive breast cancer patients in a Belgian multicentric trial: a study of consistency in relative dose intensity (RDI) and cumulative doses across institutions. Ann Oncol 2002;13(3):

33 14. Piccart MJ, Di LA, Beauduin M et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol 2001;19(12): Mamounas EP, Bryant J, Lembersky B et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol 2005;23(16): Martin M, Pienkowski T, Mackey J et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352(22): Buzdar AU, Valero V, Ibrahim NK et al. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 2007;13(1): NCCN version Jones S,Holmes F,O Shaughness J,et al. Extended follow-up and analysis by age of the US oncology Adjuvant Trial 9735: Docetaxwl/cyclophosphamide is associated with an overall survival benefit compared to doxorubicin/ cyclophosphamide And is well toleranted in women 65 or older.san Antonio Breast cancer Symposium,2007(abstr). 20. Piccart-Gebhart MJ,Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353: Slamon D,Eiermann W,Robert N,et al.adjuvant trastuzumab in HER2-postive breast canecr.n Engl J Med 2011; 365: ( 三 ) 放射線治療指引參考文獻 1. National Comprehensive Cancer Network (NCCN) guidelines in oncology-2017 version 4 2. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 2013; 14: Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer. N Engl J Med 2010; 362: Handbook of evidence-based radiation oncology, second edition 5. Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet Nov;378(9804): Epub 2011 Oct Clarke M, Collins R, Darby S, Davies C et al: Effects of radiotherapy and of differences in the extent of surgery for early 32

34 breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503): Whelan TJ, Julian J, Wright J et al: Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol. 2000;18(6): Overgaard M, Hansen PS, Overgaard J et al: Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337(14): Overgaard M, Jensen MB, Overgaard J et al: Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999; 353(9165): Breast treatment guidelines of radiation oncology of Taichung Veterans general hospital 11. Breast treatment guidelines of radiation oncology of Kaohsiung Veterans general hospital 33