如何預防、篩檢與診斷乳癌

2014.08.08 12:30-14:30

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復興航空澎湖空難 高雄丙烯輸管滲漏大爆炸

可以預防嗎? ◦ 系統性問題? ◦ 人一直會犯錯!

“Bathsheeba at her Toilet“

By Rembrandt, 17th century

10%: (BRCA1 BRCA2, TP53, PTEN

(90%)

)

:

( / 大陸 新加坡 南韓 越、菲、馬 台灣

)

/ 139(5.9%, 2.8%<35歲) 90 (18.9%<35歲) 206(18.4%) 4-10% 台大(4/11%)，高醫與彰基

12歲以前即有初潮，50歲以後停經 長期服用荷爾蒙藥物 未生育或很晚生育(30歲以後生第一胎) 肥胖 嗜好高熱量食物 曾罹乳癌的婦女 家中一或二等親有乳癌者 胸部曾接受過放射治療

HOW TO PREVENT BREAST CANCER

Life Style 1 Vitamins/Minerals

Selenium 250-300 Âľg daily

Natural vitamin A/C/E

Coenzyme Q10

Antioxidants: SeleniumçĄ&#x2019;

Important component of the antioxidant enzyme glutathione peroxidase Inhibit cell proliferation Individual selenium intake be not measured accurately by dietary assessment due to geographic area dependant 250-300 Âľg daily No association in prospective studies

-Carotenoids

Vitamin A

from animal sources

in fruits and vegetables Potent antioxidants Defense against reactive oxygen species that damage DNA

Vitamin A

(ATBC)

Cohort of Canadian women (519 women) (Rohan, 1993):

==intake

14 yrs F/U in Nurses’ Health Study(2697 cases), Zhang, 1999 == intake

marginally significant protection of breast cancer

Extended F/U of Canadian cohort(1452 cases) & Swedish cohort: not!

Total vitamin A, Preformed vitamin A, β-carotene

Inversely associated with BC risk β-carotene, utein/zeaxanthin

Vitamin A and Breast cancer

Vitamin A(retinol)

Measure vitamin A compounds in blood Low levels of carotenoids: twofold risk of BC

(Toniolo,2001)

-carotenoids in pre-MP women need randomized trial ◦ Women’s Health Study in 40000 women ◦ Terminated in 1996 due to increased risk of lung cancer in smoking men (Sato,2002)

Vit. E(tocopherol)

Inhibit mammary tumors in rodents the published prospective studies: none

Vit. C(ascorbic acid)

Block the formation of carcinogenic nitrosoamines No significant in prospective studies, even long-term use

Other antioxidants

Q（Coenzyme Q）

（Ubiquinone，縮寫為UQ） 是一種存在於自然界的脂溶性醌類化合物，其結構 與維生素K、維生素E與質體醌相似 「在人類身體細胞內參與能量製造及活化，是預防 動脈硬化形成最有效的抗氧化成份」 泛醌分子中含有一個由多個異戊二烯單位組成的、 與對苯醌母核相連的側鏈，該側鏈的長度根據泛醌 的來源而有不同，一般含有n＝6–10個異戊二烯單 位。 對於哺乳動物，n＝10，因此又稱輔酶Q10

Cancer Epidemiol Biomarkers Prev. 2011 Jun

Low plasma coenzyme Q(10) levels and breast cancer risk in Chinese women Cooney RV1, Dai Q, Gao YT, Chow WH, Franke AA, Shu XO, Li H, Ji B, Cai Q, Chai W, Zheng W. Office of Public Health Studies, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA.

BACKGROUND: Low circulating levels of coenzyme Q(10) (CoQ(10)) have been associated with increased cancer incidence and poor prognosis for a number of cancer types, while a recent prospective study observed a positive association for CoQ(10) with breast cancer risk.

METHODS: We prospectively examined the association of plasma CoQ(10) with breast cancer risk in a nested case-control study of Chinese women within the Shanghai Women's Health Study (SWHS). Prediagnostic plasma samples were obtained from 340 cases and 653 age-matched controls and analyzed for total CoQ(10).

RESULTS: A borderline significant inverse association for breast cancer incidence with plasma CoQ(10) level was observed by a conditional logistic regression model adjusted for age and age at first live birth, which became significant after elimination of cases diagnosed within 1 year of blood draw (P(trend) = 0.03). This association was independent of menopausal status. Plasma CoQ(10) levels were also observed to be significantly associated with circulating Îł-tocopherol (r = 0.50; P < 0.0001) and Îą-tocopherol (r = 0.38; P < 0.0001) levels.

CONCLUSIONS: Circulating levels of CoQ(10) were generally low in this population and the observed association with breast cancer risk may be limited to those women with exceptionally low values.

IMPACT: This study reports an inverse relationship between circulating CoQ(10) and breast cancer risk, while the only other prospective study of CoQ(10) and breast cancer to date found a positive association. Lower levels of CoQ(10) in the SWHS population suggest that the 2 studies may not be contradictory and indicate a possible nonlinear (U-shaped) association of CoQ(10) with risk.

Life Style 2食品包裝 多吃(天然)食物，少食(加工)食品 時常用的軟質塑膠

◦ 含Phthalates磷苯二甲酸鹽：仿女性荷爾蒙 雌激素 ◦ 此成分也常用於化妝品內涵成份中的防腐 劑

Life Style 3 Cooking 蔬菜洗淨，沸水川燙，時間盡量短，川 燙水留作蔬菜高湯 魚類與肉類慢火燉煮 清蒸魚肉及蔬菜 蔬果洗淨生吃 少微波及燒烤：free radicals

Life Style 4 pressure adaptation 正向思考的生活態度以面對情緒、挫折 與哀傷 個性：

吹毛求疵 追求完美

過程努力 接受結果

求快速 急性子 固執

凡事勿過度計較

自我膨脹 大頭病

讓時間解決一切

長期壓力會產生慢性身心疲勞

Life Style 5 Environment pollutants

PAHs 多環芳香族碳氫化合物 ◦ 燃燒不完全過程產生

戴奧辛(TCDD, PCDDs, PCDFs and 多 氯聯苯PCBs) ◦ 造紙時氯漂白與PVC製造過程

EDCs 內分泌干擾物 ◦ Galaxolide , tanolide, and Triclosan ◦ Detergents成份

Breast Cancer Site, USA

多吃(天然)食物，少食(加工)食品

LIFE STYLE 6 DIET

Cohort(prospective)studies No selection nor recall bias The results from postmenopausal breast cancer with >200 cases in table(next slide) 4980 breast cancer cases among 337,819 women

(Hunter, NEJM 1996)

No association between intake of total, saturated, monounsaturated or polyunsaturated fat and risk for breast cancer

Cohort studies: not significantly positive association with total fat intake

inverse

Cohort studies

No major relation exists between total dietary fat intake over a wide range during midlife and breast cancer incidence (Nursesâ&#x20AC;&#x2122; health study, Homes, JAMA 1999)

Systemic and random measurement error occurs â&#x2014;Ś when using food frequency questionnaires in cohort studies

2014 ASCO annual meeting

Childhood energy balance(1/3) •

The World War II Norwegian famine: human experiment (Tretli, 1996) – Female adolescents – 13% reduction in breast cancer risk

•

1944-45 Dutch famine (Elias,2004) – Short but severe (the timing and duration of nutrition deprivation) – Double in risk for breast cancer at 2-9 y/o

Energy-deprived children do not attain full height (Hunter, swanson, Vatten) ◦ as a proxy for childhood energy intake ◦ modest +tive association(4385 cases)

Childhood energy balance(2/3) van den Brandt PA, 2000

An increment of 5cm in height

RR= 1.02 for pre-MP RR= 1.07 for post-MP (no S.S.)

Childhood energy balance(3/3)

Age at menarche: â&#x2014;Ś an established breast cancer risk factor â&#x2014;Ś predicted by weight, height, and body fat (Meyer,1990; Merzennich, 1993)

At 12-13 y/o in western countries At 17-18 y/o in rural China( 200 years ago in western countries)

Adulthood energy balance 1.

2.

3.

Obese post-MP: nearly double estrogen levels of lean women Weight gain>attained weight (case-control & prospective): â&#x2020;&#x2014;25kg >18y/o â&#x2020;&#x2019; double HRT: obscures the variation in endogenous estrogens due to adiposity & elevates BC risk regardless of BW

Fruits and vegetables Inverse association in large number case-control studies • Weak/non significant association in pooled analysis of 8 large prospective studies(7377 cases in 351825 women) • RR= •

• 0.93 of F 0.96 of V 0.93 of F+V

Dietary fiber • •

High in fiber inhibit the reabsorption of biliary excreted estrogens Swedish cohort study(342 cases): • RR=0.58 • but others not support, may be particular fiber fractions than total fiber intake

•

Terry in Canadian national Breast Screening Study, 2002(89835 women): – total/soluble/insoluble cereal, fruits, vegetables fiber, lignin, cellulose – not associated with breast cancer

Carbohydrate quality

Swedish prospective study in 1328 cases: ◦ no association ◦ Western dietary pattern: refined grains and sweets ◦ Even stratified by 40-49 y/o vs. >50 y/o

Insulin resistance(IGF-1 higher level) Primarily in overweight women

Alcohol(1/2) •

Substantial evidence of increasing BC risk • 10g/D increase: 9% ↗ in pooled analysis of 6 largest cohort studies • All of Beer, wine, and liquor (Smith-Warner,1998; Reichman,1993)

•

0ne or two alcohol drinks per day increased estrogen levels in pre-MP and post-MP women (Ginsburg, 1995)

•

Protects against CVD?!

(Fuchs, NEJM, 1995)

Alcohol(2/2)

Folic acid In several large prospective studies Mitigate completely the excess risk for the breast cancer due to alcohol Recently confirmed using plasma folic acid levels Use the multivitamin if women alcohol drinking !

Caffeine In prospective studies: no increase

Phytoestrogens In soy Highly consumed in Asian countries low rates of cancer Isoflavone compounds Can bind ER, like Tamoxifen Soy intake during adolescence in Asian populations: lower BC risks

Phytoestrogens in Japan •

Three studies in 1988,1995 & 1999, one prospective in Japan:

•

High dose: increase E activity among postMP women (Marskarinec,,2001)

– little relation •

Another prospective study from Japan including 179 cases in 2003: (Yamamoto, 2003) – RR= 0.46 – Similar in misosoup group

•

More soy had more MMG dense breasts, a known risk of BC

•

Increased markers of cell proliferation of breasts (1998,1999)

Red meats reported sporadically UK nuns: little or no meat No association of red/white meat in pooled analysis of 7379 cases cohort studies Retrospectively in degree of cooking: associate ( no prospective)

Conclusion The role of specific dietary factors: no completely resolved 2. High-energy intake in relation to the physical activity, accelerates growth and menarche onset during childhood, leads to weight gain in middle life 3. The energy balance: account for international differences in BS rates 4. Alcohol intake: best established specific dietary risk factors for BC 1.

Life Style 7 Sleep

Insomnia common in breast cancer initially diagnosed patient Melatonin: 12-2am, wave Îą sleep Night-through work related to breast cancer, such as nurses

Life Style 8 Vitamine D and sunshine Vitamin D from sunshine(especially at noon) Breast cancer survivors and serum vitamin D level

Life Style 9 Hormone and Excercise

Long term infertility treatment HRT(E+P)>3 years, 2005: ◦ Breast cancer 26% ◦ CAD 23% ◦ Stroke 38%

Expert panel of International Agency for Research on Cancer of the WHO (Bianchini, 2002) ◦ 20-40% decreased among the most physically active women ◦ Regardless of menopausal status, type, or intensity of activity ◦ Lower levels of circulating ovarian hormones

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多吃深綠與色艷的蔬果 少食紅肉 避免常吃高熱量的精緻甜 食糖類與脂肪之加工食品 勿常飲酒 勿常吃被獸醫注射催熟及 催乳而殘留藥物(生長激 素、催乳劑)的肉雞雞肉 與鮮乳等相關製品

勿長期熬夜或晚睡 避免精神心理上長期處於 壓力(愛計較，追求完 美，過度扛責任且會隱忍) 身體勿慢性疲勞

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黃(大)豆 維生素A(紅蘿蔔等色艷的 蔬果，海魚) 葉黃素 蔓越莓 十字花科蔬菜 褪黑激素

運動(每周三次 每次30分 鐘) 作息正常 晚上11-12點前就寢

飲食(1)：多食物 攝均衡、天然、新鮮(少醃漬) 青果需充分清洗以減少殘餘農藥 纖維質的攝取 攝深綠或彩色蔬菜與水果(維生素 A與C) 降低脂肪的攝取(總熱量30%以下)

◦ 去皮肉，少吃奶油點心 ◦ 多蒸煮滷燉，少炸烤

飲食(2) ：少食品 避免含硝酸鹽或亞硝酸鹽類保存肉類 (培根、火腿、香腸) 避免有色添加物與人工甘味料 避免使用聚氯乙烯塑(PVC)膠膜或容器 來包裝儲存食物

生活型態(身與心靈)

規律的運動 ◦ 每周三次，每次30分鐘以上

減重(BMI: 20-25%) ◦ 體重（公斤）除身高（米）的平方，即 (kg/m2)

工作與家庭 ◦ 避免長期焦慮、疲勞與緊張

宗教信仰修行 ◦ 心靈的滋養有助身體的修復

體外環保衛教 勿長期暴露於具揮發性有機溶劑的室內 工作和生活環境 例如：染髮，染整布料，塑化生產加 工，屋內新裝潢與粉刷漆料，化學顏料 著色等 避免長期使用塑膠材質家具用品

HOW TO SCREEN AND DIAGNOSE BREAST CANCER

(2014~)

103.5.26

委辦計劃契約特色

預防保健與委辦計劃契約差異

Breast ultrasound(BUS) Mammography(MMG, XMG) Breast MRI 72

Mammography(MMG, XMG) 73

74

0

: :

1

: 2

1

2

75

3

(6-9 )

2%

4 4a: 4b: 4c:

2-10% 11-50% 51-80%

5

76

Breast ultrasound(BUS)

77

Schematic representation

0

Breast MRI

1

30-70

1

2 Simple cysts

79

3

(3

6

)

2%

4 4a: 4b: 4c:

2-10% 11-50% 51-80%

5

80

Breast MRI 81

Breast MRI 乳癌應該做磁振照影檢查嗎? *會有15-20%機會改變原乳癌手術計 劃。 *會有3%機會發現對側乳癌。 *目前無證據證實可降低復發率或有較 佳治療效果。 *會增加40%的假陽性診斷導致多做一 些額外的切片程序。

2.

83

1.

SonoSono-guided core needle biopsy

2.

3.

3-5

4.

5.

6.

7.

8.

(3mm) 9.

84

1.

MammoMammo-guided hook needle localization 2.

2 0.5-1 1

3.

4.

5.

85

*

1.

MammoMammo-guided sterotactic biopsy

2.

0.5-1.5

3.

4.

5. Encor 1.5-2 6.

(35mm)

7.

86

* MRIMRI-guided biopsy

1.

2.

3.

4.

Breast MRI

0.5-1.5

5.

11.5

6.

7.

(35mm)

8.

87

88

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