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What You Need to Know About Breast Cancer 熊立楷學經歷 :

乳房小葉乳腺管 Most breast cancers begin in the cells

浸潤,invasion) 甚至經由體內循環系統或淋巴系統轉移到身體其它部份 ( 遠端轉移 )

1 What You Need to Know About Breast Cancer 熊立楷學經歷 : 國防醫學院醫學系畢業陽明醫學院外科臨床講師現任 : 埔里基督教醫院外科主任 April 25, 2009 乳房小葉乳腺管 Most breast cancers begin in the cells that line the ducts (ductal cancer) Anatomy of the Breast 乳房淋巴系統 Cancer 癌癌症即是惡性腫瘤它是由控制細胞生長增殖機制的失常而引起癌細胞除了生長失控外, 還會局部侵入週遭正常組織 ( 浸潤,invasion) 甚至經由體內循環系統或淋巴系統轉移到身體其它部份 ( 遠端轉移 ) 癌症預防的目標就是減低癌症的發生包含減少接觸致癌物的機會, 改變飲食及生活習慣, 或是醫療技術的進步 ( 早期診治, 超音波,MRI 或 CT 掃描等檢驗 ) 1

Breast Cancer Continuum: intervention possibilities Breast cancer 5 year survival rates (UK, 1975) by stage at diagnosis Prevention of Recurrence Prevention of Progression Early breast cancer Women

1% Late Stage Cancer Recurrence of Breast Cancer Prevention of Clinically Detectable Breast Cancer Prevention of Contralateral Breast Cancer 3.

2 Breast Cancer Continuum: intervention possibilities Breast cancer 5 year survival rates (UK, 1975) by stage at diagnosis Prevention of Recurrence Prevention of Progression Early breast cancer Women at Increased Risk 1.7 % to 14% Pre- Malignant Conditions LCIS 6.5% ADH 5.1% Non- Invasive Cancer DCIS 7.2% Tumors < 1cm 11.8% Early Stage node neg 25.1% Early Stage node pos 47.1% Late Stage Cancer Recurrence of Breast Cancer Prevention of Clinically Detectable Breast Cancer Prevention of Contralateral Breast Cancer 3.2% 原位癌 VS 侵入癌零期乳癌原位癌 VS 侵入癌 Carcinoma In Situ (non invasive breast cancer) DCIS: ductal carcinoma in situ LCIS: lobular carcinoma in situ Invasive (Infiltrating) Carcinoma Invasive (infiltrating) ductal carcinoma (IDC) 80% Invasive (infiltrating) lobular carcinoma (ILC) 10% Inflammatory breast cancer (IBC) 1 3%: orange peel like skin breast caused by cancer cells blocking lymph vessels in the skin. Because there is no defined lump, it may not appear on a mammogram, which may make it even harder to catch it early. 評估乳癌的危險因子努力區別病人的乳房主訴症狀是惡性或良性時, 常以了解乳癌的危險因子, 找出病人的乳癌高危險因子為起點, 可使臨床醫師一開始就採取更積極的診斷作為, 不敢掉以輕心現今確認會增加乳癌風險機會的危險因子, 首為年齡增長, 這常被忽略乳癌病因? ( 危險因子 ) Risk Factors You Cannot Change Gender, Age, Genetic risk factors (BRCA1, BECA2: 80% chance), Family history, Race, Abnormal breast biopsy, Menstrual periods(before age 15 & after age 55), Early breast radiation, Treatment with DES. Breast Cancer Risk and Lifestyles Not having children or having them later in life(after age 30), Birth control pills(stop using 10 years), Postmenopausal hormone therapy(5 years stopping; ERT >10 years), Breast feeding and pregnancy(lasts yrs), Alcohol, Being overweight or obese, Exercise(The American Cancer Society suggests that you exercise for 45 to 60 minutes 5 or more days a week). Uncertain Risk Factors High fat diets(5 or more servings of vegetables and fruits each day), Pollution, Tobacco smoke, Night work. 2

Risk Factors for Breast Cancer Increasing age Caucasian race Age at menarche < 11 years Age at menopause > 55 years Nulliparity Age at first pregnancy > 30 years Absence of history

risk genes, BRCA1 & BRCA2, PTEN, & p53 Family Hx. of breast Ca. multi. relatives, early onset, bil. Family Hx. of ovarian ca: multi.

大多數婦女具有乳癌的危險因子, 卻未罹患乳癌 90% 的乳癌患者, 卻沒有乳癌的危險因子所以對於沒有任何乳癌危險因子的病人, 不能因此不做全面且完整的評估或對可疑病灶不做病理檢查切片 Screening Mammogram Clinical Breast Exam Breast Self Exam "The underlying premise is

Incidence In the UK in 1992, the incidence of breast cancer was 40% higher than in 1979 Incidence of breast cancer in the UK (age 50 64) increased steeply following the

3 Risk Factors for Breast Cancer Increasing age Caucasian race Age at menarche < 11 years Age at menopause > 55 years Nulliparity Age at first pregnancy > 30 years Absence of history of lactation? Prolonged oral contraceptives before 1 st pregnancy Use of postmenopausal estrogen Use of other hormones, fertility regimens, or diethylstilbestrol Breast ca. risk genes, BRCA1 & BRCA2, PTEN, & p53 Family Hx. of breast Ca. multi. relatives, early onset, bil. Family Hx. of ovarian ca: multi. affected relatives, early onset Pathologic indicate risk (e.g.: atypical hyperplasia, LCIS, proliferative fibrocystic disease) Previous breast cancer Previous breast problems Previous breast operations Previous exposure to radiation 危險因子? 大多數婦女具有乳癌的危險因子, 卻未罹患乳癌 90% 的乳癌患者, 卻沒有乳癌的危險因子所以對於沒有任何乳癌危險因子的病人, 不能因此不做全面且完整的評估或對可疑病灶不做病理檢查切片 Screening Mammogram Clinical Breast Exam Breast Self Exam "The underlying premise is that it allows for the detection of breast cancers before they become palpable. Incidence In the UK in 1992, the incidence of breast cancer was 40% higher than in 1979 Incidence of breast cancer in the UK (age 50 64) increased steeply following the introduction of screening in 1988 Changes in incidence and mortality from breast cancer (UK, 1994) Mortality Age-standardised mortality from breast cancer in women aged 55-69, England and Wales, Screening introduced Year Breast cancer screening Regular mammograms can decrease breast cancer mortality rates for women aged 50 to 69 years by 30%. Tabar and colleagues estimated that the deficit of 58 breast cancer death among women aged 50 to 69 years required 58,000 mammograms (1 death prevented per 1460 mammograms given) and 800 biopsies. Quinn M, et al. Br Med J 1995; 311:

4 Psychologic consequences of false positive Eddy and colleagues estimated that if a women has a mammogram every year between the ages 40 and 49 years, she has a 30% chance of receiving a false positive results. Women who test positive but who do not prove to have cancer may experience some important negative sequelae. Perhaps the most important is anxiety. Breast ca. screening guidelines, which of the following statements is correct for women at average risk? A). Women at average risk should begin mammography at age 35 years b). Women at average risk in their 20s and 30s should have a clinical breast examination every year c). Asymptomatic women at average risk aged 40 years and older should receive a clinical breast examination annually d). Breast self-examination should be strongly encouraged Breast cancer screening, which statement is correct? A). Mammograms are not indicated in women >65 years b). Women at high risk of breast cancer should be screened at shorter intervals c). Women at high h risk of breast cancer should have annual ultrasound or magnetic resonance imaging of both breasts d). As long as a woman is in reasonably good health and would be a candidate for treatment, she should continue to be screened with mammography regardless of her age 乳癌篩檢建議乳癌篩檢乳房自我檢查是無法取代定時的臨床乳房檢查及乳房攝影篩檢美國癌症學會的乳癌篩選準則, 指出 40 歲以上的婦女, 在年度健康檢查中必須包含乳房攝影及臨床乳房理學檢查此外醫療照護提供者必須說明乳房自我檢查的好處及有所不能, 強調對於各種乳房相關主訴症狀應儘速尋求醫療協助或諮詢, 而不只是每月做乳房自我檢查而已臨床乳房理學檢查 (Clinical breast examination) 臨床乳房理學檢查為經由專業的醫療照護者, 實行完整的全部乳房及腋下理學檢查相較於乳房自我檢查, 每年或每半年作一次臨床乳房檢查, 得到一些醫學文獻證據支持, 能夠增加乳癌篩選率大多數專家相信臨床乳房理學檢查對乳癌篩選是有意義的具體的說, 沒有任何乳房主訴症狀的婦女每年都應該作一次臨床乳房理學檢查 4

5 乳房攝影篩檢 (Screening mammography) 乳房攝影篩選的價值是常被討論的議題, 主要為醫生不能完全確定檢查結果的可靠性 ( 有假陽性 ) 及病患對檢查結果的迷惑雖然如此, 乳房攝影篩選仍然被許多專業醫學會推薦, 其中包含美國癌症學會及美國國家癌症協會目前最新的臨床建議為 : 一般婦女乳房攝影篩選由 40 歲開始 40 歲以上婦女每一至二年作一次乳房攝影篩選高風險婦女乳房攝影篩選依照專家建議採取較短的間隔一般婦女, 只要健康情況能夠接受治療, 不因年紀過高而不篩選有數篇醫學文獻佐證, 單做乳房攝影篩選有 78 % 乳癌篩選率, 而外加專業的臨床乳房理學檢查可提高乳癌篩選率至 82% 乳房攝影篩選使用頻率的增加, 造成臨床上無法觸摸到的乳房腫塊的病例增加, 作病理檢查的需求隨之增加同時臨床醫師被要求能夠評估異常的乳房攝影篩選結果 CBE, Mammography CBE may add 5% to 20% of the number of cancers detected when combined with mammography. Screening should include both mammography and highquality CBE for women aged 50 years and old. ACR Breast Imaging Reporting and Data System (BIRADS) Category Assessment Description/Recommendation 0 Additional Additional imaging recommended imaging evaluation required 1 Negative finding 2 Benign finding Nothing to comment on; routine screening recommended Negative mammogram, but interpreter may wish to describe a finding; routine screening recommended ACR Breast Imaging Reporting and Data System (BIRADS) Category Assessment Description/Recommendation 3 Probably benign finding 4 Suspicious abnormality 5 Abnormality highly suggestive of malignancy Very high probability of benignity; short-interval follow-up suggested to establish stability Probability of malignancy; biopsy should be considered High probability of cancer; appropriate action should be taken Benign versus Malignant Imaging Characteristics in Breast Cancer Circumscribed mass Fat containing lesion Microcalcifications Round, uniform density, large, age, coarse Widely scattered Long axis of the lesion is along the normal tissue planes Homogeneous internal echotexture Hyperechogenicity Smoothly marginated Spiculated mass Architectural distortion with no history of prior surgery Microcalcifications Linear, branching, pleomorphic, casting Tightly clustered Lesion is taller than it is wide Decreased hyperechogenicity Marked acoustical shadowing Spiculation Breast Complaints 5

6 高度的焦慮不安及急迫婦女一生中, 估計每兩位有一位, 會因為各種乳房相關主訴症狀而尋求醫療協助或諮詢, 這使現代臨床醫師必須對於各種常見乳房主訴症狀的評估及處理有基本概念雖然大多數的乳房主訴症狀最終都不是乳癌, 可是乳癌這個婦女癌症的頭號殺手, 卻會造成婦女在一旦在出現各種乳房相關主訴症狀時, 高度的焦慮不安及急迫想知道是否罹患了乳癌, 所以對一位婦女病人提出的乳房症狀必須有全面且完整的診療思路有下列症狀時請立即就醫? 乳房腫塊 ( 乳房似有似無的增厚或腫塊 29%; dominant, 3-D breast mass 36%) 乳頭異樣性分泌物, 尤其是帶血的分泌乳房外形改觀, 局部凹陷或凸出, 乳頭凹陷, 乳房皮膚有橘皮樣的變化, 紅腫或潰爛腋下有淋巴腫大評估及處理乳房主訴症狀 Breast Complaints 1. 臨床上觸摸到的乳房腫塊 Palpable mass 2. 不正常的乳房攝影篩選發現 Normal physical examination with abnormal mammogram 3. 乳房似有似無的增厚或腫塊 Vague thickening thickening or nodularity 4. 乳頭分泌物 Nipple discharge 5. 乳房疼痛 Breast pain 6. 乳房發炎 Breast infection of inflammation 舉例來說舉例來說, 一位停經後的婦女出現一個明確的乳房硬塊, 已經表示高度的惡性可能, 必須有立即而且直接的診斷作為相反狀況, 如一位停經前的婦女表現乳房似有似無的增厚或腫塊合併壓痛, 良性乳房疾病應該是最有可能臨床醫師應該要知道最重要的事是! 她們表現的症狀最終都有可能是惡性乳房腫瘤, 她們都需要做全面且完整的評估診斷伴隨可能的惡性機會 Common Presenting Symptoms of Breast Disease Symptom Palpable mass Abnormal mammogram with normal breast examination Vague thickening or nodularity Nipple discharge Breast pain Breast infection Likelihood of Malignancy Highest Lowest Risk of Missed Malignancy Lowest Highest Listen to BACH 事實上, 對一個通常是良性或者惡性機會較少的乳房臨床症狀, 才真正需要臨床醫師做出適當的臨床決斷 ; 當一個惡性乳房腫瘤主要表現出看似常見的良性臨床症狀時, 可能會誤導而延遲惡性腫瘤被診斷出來 Missed or delayed diagnosis of breast cancer is currently a major cause of malpractice claims and plaintiff awards. 6

Patient Presentation Approach to the Patient with a Breast Mass In 75% of breast cancers, the presenting symptom is a breast lump The presence of a breast lump does not always indicate

breast cancer cases diagnosed and age specific rates per 100,000 population, UK, 1999 Number 6000 450 Rate per of new number 400 100,000 cases 5000 rates population 350 4000 300 3000 250

7 Patient Presentation Approach to the Patient with a Breast Mass In 75% of breast cancers, the presenting symptom is a breast lump The presence of a breast lump does not always indicate cancer the majority (up to 90%) of breast lumps are benign Dominant Breast Mass 診斷及處理, 臨床上判斷一個臨床上觸摸到的乳房腫塊 ( 或描述為一個明顯的或 3-D 立體性的乳房腫塊 ), 主要依據婦女年齡乳房理學檢查的特徵及臨床病史作判斷臨床病史 : 危險因子 Number of new breast cancer cases diagnosed and age specific rates per 100,000 population, UK, 1999 Number Rate per of new number ,000 cases 5000 rates population Age at diagnosis Cancer Research UK, 2003 良及惡性乳房腫塊的理學檢查特徵 7

8 暗示可能的惡性病灶婦女年齡大於 40 歲某些理學檢查, 暗示可能的惡性病灶, 譬如乳房腫塊邊緣不規則腫塊較硬腫塊固定無法移動腫塊合併有皮膚病變皮膚凹陷和腋下淋巴結節腫大皆為惡性腫瘤高可能性的特徵但是不具備這些特徵, 仍然無法排除惡性病變可能 Signs that indicate a lump may be malignant include: findings of a radiological opacity (microcalcification) with radiating fibrous strands a change within the breast that is noticed by the patient signs of locally advanced or metastatic disease, including a large mass, tethering to the skin and/or chest wall, lymph node enlargement, peau d orange, nipple inversion and skin infiltration. Palpable mass Factors increasing suspicious of malignancy: Skin dimpling Palpable axillary nodes Mass with irregular borders Increasing age Determine whether mass is cystic or solid Mass is Cystic or Solid Cystic Mass If fluid is bloody or mass remains after aspiration, obtain tissue diagnosis. If not, follow up as for a simple cyst. Solid Mass Obtain tissue diagnosis by mean of fine needle needle aspiration. Coreneedle, or open surgical biopsy. 處理實心乳房腫塊 8

診斷性乳房攝影 Diagnostic Mammogram 診斷性乳房攝影不同於乳房攝影篩選, 它是在發現乳房異常時選擇的診斷工具 ; 它必須包含對側乳房攝影來尋找任何同時存在的病灶年齡大約 35 歲的婦女發現一個觸摸得到的腫塊時, 診斷性乳房攝影是用來尋找其他臨床上無法觸摸到同時存在的乳房腫塊乳房攝影確定無法偵測到

臨床上判斷為實心乳房腫塊, 常是經由乳房超音波診斷或嘗試乳房細針抽吸但抽不到液體而診斷, 此時病理組織檢查 (Tissue diagnosis) 是必要做的, 以排除惡性可能單靠臨床理學檢查不夠, 它對實心乳房腫塊是否為惡性的正確辨別率只有 60-85% 有一個研究顯示, 請四位有經驗的外科醫師, 對 15

9 診斷性乳房攝影 Diagnostic Mammogram 診斷性乳房攝影不同於乳房攝影篩選, 它是在發現乳房異常時選擇的診斷工具 ; 它必須包含對側乳房攝影來尋找任何同時存在的病灶年齡大約 35 歲的婦女發現一個觸摸得到的腫塊時, 診斷性乳房攝影是用來尋找其他臨床上無法觸摸到同時存在的乳房腫塊乳房攝影確定無法偵測到 % 臨床上觸摸得到的乳房惡性腫瘤, 對於小葉狀乳癌 (lobular breast cancer) 及放射學上緻密的乳房, 它的敏感率較低 ; 因此對一個臨床觸摸得的乳房腫塊, 不能因為陰性乳房攝影報告而影響必須作的乳房病理切片的臨床決斷病理組織檢查是必要做的明顯的或 3-D 立體性的, 臨床上判斷為實心乳房腫塊, 常是經由乳房超音波診斷或嘗試乳房細針抽吸但抽不到液體而診斷, 此時病理組織檢查 (Tissue diagnosis) 是必要做的, 以排除惡性可能單靠臨床理學檢查不夠, 它對實心乳房腫塊是否為惡性的正確辨別率只有 60-85% 有一個研究顯示, 請四位有經驗的外科醫師, 對 15 個臨床上觸摸到的乳房腫塊, 決定是否需要做病理組織切片檢查, 結果發現 4 個 (25%) 假陰性乳癌病人所謂病理組織檢查包含三種方式, 細針抽吸細胞學粗針切片及腫塊切除病理組織檢查 Breast cancer diagnosis Fine needle aspiration (FNA) Core needle biopsy Excision biopsy 9

overall, 10% to 15% false-negatives of mammogram.

10 Triple Assessment Triple diagnostic test approach to solid breast mass to breast cancer 1. Clinical breast examination 2. Mammogram 3. Needle biopsy Management of Solid Breast Masses by Triple Diagnosis (European) Suspicious by clinical breast examination (diagnostic accuracy 73%) Suspicious by mammogram (diagnostic accuracy 85%, overall, 10% to 15% false-negatives of mammogram.) FNAB fine-needle aspiration cytology (diagnostic accuracy 95%) Solid mass: use of triple diagnosis, An extensive review has documented a greater than 99% predictive value for benign disease when all three diagnostic components are benign. Breast mass should be evaluated by the same examiner at intervals for at least 1 year. Abnormal mammogram after normal breast examination Factors increasing suspicion of malignancy: Previous normal mammogram Localized soft tissue mass Stellate appearing lesion Clustered microcalcifications Abnormal mammogram after normal breast examination Mammogram is suspicious Perform biopsy (open or stereotactic or ultrasoundguided core needle). Mammogram is not suspicious Follow up with mammograms every 6mo for 2 yr. 10

11 Vague thickening or nodularity Factors increasing suspicion of malignancy Skin changes Asymmetry ybetween right and left breast No generic hormonal changes (e.g., pregnancy, beginning or ceasing contraception) Palpable axillary nodes. Order mammogram if patient is > 35 yr or >30 yr with a family history of breast cancer. Vague thickening or nodularity Thickening is suspicious malignancy, perform open biopsy (FNA is not appropriate). Thickening is not suspicious, reexamine patient after 2 menstrual cycles. If area resolves, provide routine follow up. If lesion persists or worsens, perform open biopsy. Nipple discharge Factors increasing suspicion of malignancy Bloody discharge Unilateral discharge Palpable mass Abnormal mammogram Nipple discharge Is suspicious Order mammogram. Perform biopsy of any lesions found. If a single duct is the source of the pathologic discharge, excise duct. If source of discharge can only be localized to a quadrant, excise ducts in that quadrant. Is not suspicious If discharge is physiologic, reassure patient, no further treatment is needed. If galactorrhea is present, initiate appropriate work (serum prolactin levels, thyroid function tests, and MRI if necessary). Breast pain Factors increasing suspicion of malignancy Abnormal skin changes Noncyclic pain Order mammogram if pain is noncyclic and patient is > 35 yr or > 30 yr with a family history of breast cancer. Breast pain Mammogram is abnormal, or palpable mass is detected Mammogram is normal, and physical examination yields normal result Offer comfort, reassure, and perform follow up examination in 2 mo. If pain resolves or there is still no palpable abnormality, reassure further and follow up routinely. If there is a palpable abnormality, obtain tissue diagnosis. 11

12 乳房超音波 (Ultrasonography) 主要價值是能區分囊腫性或實心性的乳房腫塊如果這個病灶在臨床上是觸摸得到的腫塊時, 最好的鑑別診斷方法是直接細針抽吸, 能夠同時做診斷及治療 ; 如果這個病灶在臨床上是觸摸不到的腫塊時, 乳房超音波能夠區分它是否為囊腫, 可能地減少其他的檢查或治療乳房超音波未經證實是有效的乳房篩選 ; 它無法偵測到乳房鈣化點, 找不出許多的惡性腫瘤, 而且將許多的正常乳房組織結構視為可疑結節然而它能夠幫助偵測得到的可疑結節, 作直接細針抽吸和粗針切片的定位 ; 它能夠幫助穿刺針即時性定位, 準確做在可疑結節上乳房篩檢工具乳房篩檢工具, 究竟應為乳房攝影或超音波, 是醫界長期爭論的議題除了品質穩定, 乳房攝影的最大優點為可偵測乳癌早期的顯微鈣化 (micro-calcifications), 但缺點為疼痛不適不適合密緻乳房無法區分腫瘤性質等等乳房超音波的最大好處為舒適方便, 但致命缺點為無法或困難偵測 microcalcifications, 且與操作者的技術有關因此目前仍以乳房攝影為乳癌篩檢的 gold standard, 超音波則為輔助性的工具台灣婦女的乳房多屬緻密性質, 此類型乳房在超音波檢查下常較乳房 X 光攝影易偵測到腫塊 Getting a Second Opinion 2nd Opinion Abnormal mammogram and biopsy or not. 12

Breast sparing surgery, Lumpectomy, Partial mastectomy Studies have found equal survival rates for breastsparing surgery with

sentinel lymph node biopsy Removal and examination of the sentinel node(s) (the first lymph node(s) to which cancer cells are

To identify the sentinel lymph node(s), the surgeon injects a radioactive substance, blue dye, or both near the tumor.

13 Breast sparing surgery, Lumpectomy, Partial mastectomy Studies have found equal survival rates for breastsparing surgery with radiation therapy, and mastectomy for Stage I and Stage II breast cancer. sentinel lymph node biopsy Removal and examination of the sentinel node(s) (the first lymph node(s) to which cancer cells are likely to spread from a primary tumor). To identify the sentinel lymph node(s), the surgeon injects a radioactive substance, blue dye, or both near the tumor. The surgeon then uses a scanner to find the sentinel lymph node(s) containing the radioactive substance or looks for the lymph node(s) stained with dye. The surgeon then removes the sentinel node(s) to check for the presence of cancer cells. Hormone therapy Radiotherapy Chemotherapy 13

14 Some Commonly Used Adjuvant Chemotherapy Regimens 14

Breast cancer demographics Proportion of patients (%) Mean age (years) Age at diagnosis (%) <50 50 Tumour size (%) >2.0 cm 2.

Breast Cancer Res Treat 2002; 76: 27 36 Treatment options for adjuvant therapy of hormone-sensitive breast cancer in premenopausal women St.

Chemotherapy tamoxifen OR Tamoxifen OR LHRHa (or ovarian ablation) Chemotherapy tamoxifen [± LHRHa] OR LHRHa (or ovarian ablation) + tamoxifen Luteinising hormone releasing hormone

J Clin Oncol 2003; 21: 3357 3365 Premenopausal oestrogen production Zoladex LHRH (hypothalamus) Gonadotrophins (FSH + LH) Ovary Pituitary gland Adrenal glands Androgens ACTH ACTH =

15 Breast cancer demographics Proportion of patients (%) Mean age (years) Age at diagnosis (%) <50 50 Tumour size (%) >2.0 cm 2.0 cm unknown ER = oestrogen receptor Patients (n=82,488) ER-positive ER-negative Anderson WF et al. Breast Cancer Res Treat 2002; 76: Treatment options for adjuvant therapy of hormone-sensitive breast cancer in premenopausal women St. Gallen consensus 2003 Risk group Treatment Node-negative Minimal risk Node-negative Average risk Node-positive Tamoxifen or none LHRHa (or ovarian ablation) + tamoxifen OR Chemotherapy tamoxifen OR Tamoxifen OR LHRHa (or ovarian ablation) Chemotherapy tamoxifen [± LHRHa] OR LHRHa (or ovarian ablation) + tamoxifen Luteinising hormone releasing hormone analogue (LHRHa) research was conducted using Zoladex Goldhirsch A et al. J Clin Oncol 2003; 21: Premenopausal oestrogen production Zoladex LHRH (hypothalamus) Gonadotrophins (FSH + LH) Ovary Pituitary gland Adrenal glands Androgens ACTH ACTH = adrenocorticotrophic hormone; FSH = follicle-stimulating hormone; LH = luteinising hormone; LHRH = LH-releasing hormone Tamoxifen Oestrogens Oestrogens Peripheral conversion (aromatase enzyme) Anastrozole Survival from time of tumour recurrence: in all patients with advanced breast cancer Cumulative Survival Months

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