2023 - Between Philosophy and Practice: Introducing Yoga
Stressful life events and breast cancer risk
1. Stressful life events and breast cancer risk:
a hospital-based case-control study
Biljana Kocic
Sladjana Filipovic
Svetislav Vrbic
Ivica Pejcic
Natasa Rancic
Ana Cvetanovic
Dusan Milenkovic
輔大醫學四─流行病學第五組
簡淳羽、張齡元、柯皓禎、林俊燁
吳宜憲、楊智元、蘇聖維
指導老師
黃馨 老師
2. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Review
Disease
Known Unknown
Most commonly
occurring malignancy
in females in Serbia
• First-degree relative with
breast cancer
• Early menarche
• Late menopause
• Nulliparity or bearing of first
child at a later age
• Certain types of benign
breast diseases
• Smoking
• Certain aspects of nutrition
• Physical activity
• Psychological stress
Exposure
3. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Review
How to measure “stress”?
Molecular
biology
Epidemiology Physiology
• Provide inconsistent findings regarding relative contribution of stress
to breast cancer risk
• Probably due to the use of different measures of stress and other
study methods
4. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Review
─Hypothesis
Stressful life events Breast cancer
Quality?
Quantity?
Odds ratios?
Confounders?
5. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Participants
hospital-based
case-control study
120• Within two years
from diagnosis
(Case)
120• From the Clinic of Physical Medicine
and Orthopedic Clinic
• Non-occupational accidental injuries
• No breast cancer
• No benign breast disease
(Control)
matched by age
(± 2 years)
Interviewed by a
single interviewer
7. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Participants
─Scale
Paykel Life Events Scale(1971)
1 Death of child
2 Death of spouse
3 Jail sentence
4 Death of close family member (parent, sibling)
5 Spouse unfaithful
6 Major financial difficulties (very heavy debts, bankruptcy)
7 Business failure
8 Fired
9 Miscarriage or stillbirth
10 Divorce
11 Marital separation due to argument
12 Court appearance for serious legal violation
13 Unwanted pregnancy
14 Hospitalization of family member (serious illness)
15 Unemployed for one month
16 Death of close friend
17 Demotion
18 Major personal physical illness (hospitalization or one month off work)
19 Begin extramarital affair
20 Loss of personally valuable object
21 Lawsuit
22 Academic failure (important exam orcourse)
23 Child married against respondent's wishes
24 Break engagement
25 Increased arguments with spouse
26 Increased arguments with resident family member
27 Increased arguments with fiance or steady date
28 Take a large loan (more than one-half of a year's earnings)
29 Son drafted
30 Arguments with boss orco-worker
31 Argument with nonresident family member (in-laws, relatives)
32 Move to another country
33 Menopause
34 Moderate financial difficulties (bothersome but not serious, ie,
increased expenses, trouble from bill collectors)
35 Separation from significant person (close friend or relative)
36 Take important exam
37 Marital separation not due to argument
38 Change in work hours (much overtime, second job, much less than
usual)
39 New person in household
40 Retirement
41 Change in work conditions (new department, new boss,
bigreorganization)
42 Change in line of work
43 Cease steady dating (of at least three months)
44 Move to anothercity
45 Change in schools
46 Cease full-time education (graduate or drop out)
47 Child leaves home (eg, college)
48 Marital reconciliation (after one partner left home)
49 Minor legalviolation
50 Birth of live child (for mother)
51 Wife becomes pregnant
52 Marriage
53 Promotion
54 Minor personal physical illness (one that requires physician's
attention)
56 Birth of a child (father) or adoption
57 Begin education (full time or half-time)
58 Child becomes engaged
59 Become engaged
60 Wanted pregnancy
61 Child married with respondent's approval
8. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Participants
─Scale
Paykel Life Events Scale(1971)
1 Death of child
2 Death of spouse
3 Jail sentence
4 Death of close family member (parent, sibling)
5 Spouse unfaithful
6 Major financial difficulties (very heavy debts, bankruptcy)
7 Business failure
8 Fired
9 Miscarriage or stillbirth
10 Divorce
11 Marital separation due to argument
12 Court appearance for serious legal violation
13 Unwanted pregnancy
14 Hospitalization of family member (serious illness)
15 Unemployed for one month
16 Death of close friend
17 Demotion
18 Major personal physical illness (hospitalization or one month off work)
19 Begin extramarital affair
20 Loss of personally valuable object
21 Lawsuit
22 Academic failure (important exam orcourse)
23 Child married against respondent's wishes
24 Break engagement
25 Increased arguments with spouse
26 Increased arguments with resident family member
27 Increased arguments with fiance or steady date
28 Take a large loan (more than one-half of a year's earnings)
29 Son drafted
30 Arguments with boss orco-worker
31 Argument with nonresident family member (in-laws, relatives)
32 Move to another country
33 Menopause
34 Moderate financial difficulties (bothersome but not serious, ie,
increased expenses, trouble from bill collectors)
35 Separation from significant person (close friend or relative)
36 Take important exam
37 Marital separation not due to argument
38 Change in work hours (much overtime, second job, much less than
usual)
39 New person in household
40 Retirement
41 Change in work conditions (new department, new boss,
bigreorganization)
42 Change in line of work
43 Cease steady dating (of at least three months)
44 Move to anothercity
45 Change in schools
46 Cease full-time education (graduate or drop out)
47 Child leaves home (eg, college)
48 Marital reconciliation (after one partner left home)
49 Minor legalviolation
50 Birth of live child (for mother)
51 Wife becomes pregnant
52 Marriage
53 Promotion
54 Minor personal physical illness (one that requires physician's
attention)
56 Birth of a child (father) or adoption
57 Begin education (full time or half-time)
58 Child becomes engaged
59 Become engaged
60 Wanted pregnancy
61 Child married with respondent's approval
9. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Participants
─Scale
Paykel Life Events Scale(1971)
1 Death of child
2 Death of spouse
3 Jail sentence
4 Death of close family member (parent, sibling)
5 Spouse unfaithful
6 Major financial difficulties (very heavy debts, bankruptcy)
7 Business failure
8 Fired
9 Miscarriage or stillbirth
10 Divorce
11 Marital separation due to argument
12 Court appearance for serious legal violation
13 Unwanted pregnancy
14 Hospitalization of family member (serious illness)
15 Unemployed for one month
16 Death of close friend
17 Demotion
18 Major personal physical illness (hospitalization or one month off work)
19 Begin extramarital affair
20 Loss of personally valuable object
21 Lawsuit
22 Academic failure (important exam orcourse)
23 Child married against respondent's wishes
24 Break engagement
25 Increased arguments with spouse
26 Increased arguments with resident family member
27 Increased arguments with fiance or steady date
28 Take a large loan (more than one-half of a year's earnings)
29 Son drafted
30 Arguments with boss orco-worker
31 Argument with nonresident family member (in-laws, relatives)
32 Move to another country
33 Menopause
34 Moderate financial difficulties (bothersome but not serious, ie,
increased expenses, trouble from bill collectors)
35 Separation from significant person (close friend or relative)
36 Take important exam
37 Marital separation not due to argument
38 Change in work hours (much overtime, second job, much less than
usual)
39 New person in household
40 Retirement
41 Change in work conditions (new department, new boss,
bigreorganization)
42 Change in line of work
43 Cease steady dating (of at least three months)
44 Move to anothercity
45 Change in schools
46 Cease full-time education (graduate or drop out)
47 Child leaves home (eg, college)
48 Marital reconciliation (after one partner left home)
49 Minor legalviolation
50 Birth of live child (for mother)
51 Wife becomes pregnant
52 Marriage
53 Promotion
54 Minor personal physical illness (one that requires physician's
attention)
56 Birth of a child (father) or adoption
57 Begin education (full time or half-time)
58 Child becomes engaged
59 Become engaged
60 Wanted pregnancy
61 Child married with respondent's approval
• Experience of life events,
experience of severe life events
(first 5 life events from the scale)
• Experience of severe and moderate
threats (first 25 life events from
the scale)
11. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Result 1
Patients were statistically more likely to have a stressful life event in the
years prior to diagnosis, severe life events and severe and moderate life
events, compared to controls.
Variable Cases Controls p-value
Experience of
stressful life events
11.13 ± 2.66 8.79 ± 2.14 0.0000*
Experience of
severe life events
(first 5 from the scale)
1.33 ± 0.429 1.00 ± 0.000 0.0390*
Experience of
severe and moderate life events
(first 25 from the scale)
2.81 ± 1.29 1.54 ± 0.67 0.000*
12. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─Result 2
Multiple conditional logistic regression analysis revealed six independent
predictors of breast cancer risk:
Variable OR 95%CI p-value
Experience of severe
and moderate life events
3.15 2.01-4.93 0.0000*
Son’s
military service
6.09 4.17-12.37 0.0011*
Death of
close family member
7.98 2.18-9.14 0.0017*
Moderate
financial difficulties
3.26 1.24-8.56 0.0162*
Maternal death
in childhood
3.46 1.21-9.92 0.0209*
Serious
financial difficulties
3.55 1.20-10.52 0.0221*
13. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─壓力與罹患乳癌的關聯性
The plausibility of a stress–breast cancer association stems from two
important physiological roles of the stress hormone cortisol:
影響乳房發育及功能作用
在有壓力的情況下會更加強乳房
組織對cortisol的訊息作用
對乳房有特定似estrogen的活性
促進tumorigenic change
（尤其是在承受壓力之下）
Cortisol
Cortisol
Cortisol
Cortisol
Cortisol
Cortisol
Cortisol
Cortisol
Cortisol
(estrogen)
14. (1966~1997)
Meta-analytical review of epidemiologic studies A
1. 囊括了11篇針對喪偶與乳癌，6個case–control studies、5個limited prospective studies；
15篇針對其他life event與乳癌，8個case–control studies、7個limited prospective
studies
2. 測試a.喪偶(親)與乳癌、 b.其他life events與乳癌之間的關係 (探討以a為主)
3. 結果顯示在喪偶(親)跟乳癌之間是沒有相關性的（OR=1.06, 95% CI=0.95-1.18）
4. 但是在其他因素(total number of life events, major life changes, separation, war
experiences, serious illness, financial problems, and work problems)與乳癌之間具有高
度相關性（OR=2.63, 95% CI=2.34-2.96）
*OR比較：發現b結果比a高上了兩倍→這樣偏向其他因素的相關性較高
(1966～2002)
Meta-analytical review of epidemiologic studies B
1. 引用27篇paper，包括10篇retrospective control studies、4篇prospective case–control
studies、9篇limited prospective cohort studies、4篇prospective cohort studies
2. 測試stressful life event與乳癌風險之間的關係
3. 結果顯示與乳癌有顯著相關的因素如下：
• stressful life events（OR=1.77, 95% CI=1.31-2.40）
• death of a spouse（OR=1.37, 95% CI=1.10-1.71）
• death of a relative or friend（OR=1.35, 95% CI=1.09-1.68）
Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─與其他論文的呼應性
15. (1966~1997)
Meta-analytical review of epidemiologic studies A
1. 囊括了11篇針對喪偶與乳癌，6個case–control studies、5個limited prospective studies；
15篇針對其他life event與乳癌，8個case–control studies、7個limited prospective
studies
2. 測試a.喪偶(親)與乳癌、 b.其他life events與乳癌之間的關係 (探討以a為主)
3. 結果顯示在喪偶(親)跟乳癌之間是沒有相關性的（OR=1.06, 95% CI=0.95-1.18）
4. 但是在其他因素(total number of life events, major life changes, separation, war
experiences, serious illness, financial problems, and work problems)與乳癌之間具有高
度相關性（OR=2.63, 95% CI=2.34-2.96）
*OR比較：發現b結果比a高上了兩倍→這樣偏向其他因素的相關性較高
(1966～2002)
Meta-analytical review of epidemiologic studies B
1. 引用27篇paper，包括10篇retrospective control studies、4篇prospective case–control
studies、9篇limited prospective cohort studies、4篇prospective cohort studies
2. 測試stressful life event與乳癌風險之間的關係
3. 結果顯示與乳癌有顯著相關的因素如下：
• stressful life events（OR=1.77, 95% CI=1.31-2.40）
• death of a spouse（OR=1.37, 95% CI=1.10-1.71）
• death of a relative or friend（OR=1.35, 95% CI=1.09-1.68）
Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─與其他論文的呼應性
16. (1966~1997)
Meta-analytical review of epidemiologic studies A
1. 囊括了11篇針對喪偶與乳癌，6個case–control studies、5個limited prospective studies；
15篇針對其他life event與乳癌，8個case–control studies、7個limited prospective
studies
2. 測試a.喪偶(親)與乳癌、 b.其他life events與乳癌之間的關係 (探討以a為主)
3. 結果顯示在喪偶(親)跟乳癌之間是沒有相關性的（OR=1.06, 95% CI=0.95-1.18）
4. 但是在其他因素(total number of life events, major life changes, separation, war
experiences, serious illness, financial problems, and work problems)與乳癌之間具有高
度相關性（OR=2.63, 95% CI=2.34-2.96）
*OR比較：發現b結果比a高上了兩倍→這樣偏向其他因素的相關性較高
(1966～2002)
Meta-analytical review of epidemiologic studies B
1. 引用27篇paper，包括10篇retrospective control studies、4篇prospective case–control
studies、9篇limited prospective cohort studies、4篇prospective cohort studies
2. 測試stressful life event與乳癌風險之間的關係
3. 結果顯示與乳癌有顯著相關的因素如下：
• stressful life events（OR=1.77, 95% CI=1.31-2.40）
• death of a spouse（OR=1.37, 95% CI=1.10-1.71）
• death of a relative or friend（OR=1.35, 95% CI=1.09-1.68）
在第二個meta-analysis的探討
1. 因為有使用retrospective studies，可能會出現recall bias，導致研究之
誤差。(他們發現Prospective studies的OR值相對於Retrospective
studies是高的)
2. RF的選取已有先備知識的影響也很大
• well-established breast cancer risk factors v.s. non-control
(有先篩選過的OR值有顯著，但沒篩選過的OR卻不顯著)
Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─與其他論文的呼應性
17. (1966~1997)
Meta-analytical review of epidemiologic studies A
1. 囊括了11篇針對喪偶與乳癌，6個case–control studies、5個limited prospective studies；
15篇針對其他life event與乳癌，8個case–control studies、7個limited prospective
studies
2. 測試a.喪偶(親)與乳癌、 b.其他life events與乳癌之間的關係 (探討以a為主)
3. 結果顯示在喪偶(親)跟乳癌之間是沒有相關性的（OR=1.06, 95% CI=0.95-1.18）
4. 但是在其他因素(total number of life events, major life changes, separation, war
experiences, serious illness, financial problems, and work problems)與乳癌之間具有高
度相關性（OR=2.63, 95% CI=2.34-2.96）
*OR比較：發現b結果比a高上了兩倍→這樣偏向其他因素的相關性較高
(1966～2002)
Meta-analytical review of epidemiologic studies B
1. 引用27篇paper，包括10篇retrospective control studies、4篇prospective case–control
studies、9篇limited prospective cohort studies、4篇prospective cohort studies
2. 測試stressful life event與乳癌風險之間的關係
3. 結果顯示與乳癌有顯著相關的因素如下：
• stressful life events（OR=1.77, 95% CI=1.31-2.40）
• death of a spouse（OR=1.37, 95% CI=1.10-1.71）
• death of a relative or friend（OR=1.35, 95% CI=1.09-1.68）
Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─與其他論文的呼應性
18. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─與其他論文的呼應性
在本研究中，根據數據結果乳癌病患較傾向於發生以下幾點事件
在診斷乳癌數年前，與Control相比，Patient通常
會有發生過 stressful life events的狀況(也就是經
歷嚴重life events、經歷嚴重到中度life events)
→結論同論文A、B
發現以下三點會增加乳癌發展的風險
• 經歷過嚴重或中度威脅(first 25 from the scale)
(工作相關的、提供照顧相關的、每天的壓力都有可能)
• 親近家屬死亡→支持論文B
• 兒子從軍者
結論一
結論二
19. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─童年喪母與罹癌的關聯性
Variable OR 95%CI p-value
Experience of severe
and moderate life events
3.15 2.01-4.93 0.0000*
Son’s
military service
6.09 4.17-12.37 0.0011*
Death of
close family member
7.98 2.18-9.14 0.0017*
Moderate
financial difficulties
3.26 1.24-8.56 0.0162*
Maternal death
in childhood
3.46 1.21-9.92 0.0209*
Serious
financial difficulties
3.55 1.20-10.52 0.0221*
只有「童年喪母」並不是在探討近期壓力事件
Physiological hypothesis:
女性在幼年或青春期處於乳房發展階段遭遇重
大壓力事件，例如：喪母(根據prospective
cohort in the Baltimore Epidemiologic
Catchment Area Study)，會讓cortisol增加
影響此時的乳房發育
20. Introduction │ Method │ Result │ Discussion & Conclusion │ Critique
─研究限制
在壓力事件暴露與乳癌發生之間的潛伏時間長短是無法確知的
1. 在一般情況下乳癌的發展過程大約需要10~20年，再根據 a study
by Lillberg and colleagues發現，乳癌發生風險與確診乳癌當下前
11年發生的壓力事件最相關
2. 根據本研究，確診跟發生事件的時間間距並不相關於乳癌風險增加
3. 有鑒於在每個study的暴露的時間間距不盡相同，甚至有些暴露時間
已經超過生物有效時間，進而導致各個study不一樣的結果
經濟社會地位的困境可能與乳癌風險增加具相關性
但是無法得知是經濟社會地位直接導致乳癌風險增加；抑或是經濟社會地
位導致的壓力增加而使乳癌風險增加（此二種說法都有paper顯示可能性）
• 因此在做stress–breast cancer associations的分析時，要針對經濟
社會地位做matching以排除此confounder
