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Epidemiology of breast cancer 2014 ap
Epidemiology of breast cancer 2014 ap
GHANAIAN CANCER EPIDEMIOLOGY: 
Age Standardized Rates / 100,000 Females 
Globocan 2002
Epidemiology of breast cancer 2014 ap
CANCER IINNCCIIDDEENNCCEE RRAATTEESS 
FFOORR UU..SS.. WWOOMMEENN,, 11997733--22000055 
AAggee--aaddjjuusstteedd IInncciiddeennccee RRaattee ppeerr 110000,,000000 FFeemmaalleess
CANCER DEATH RATES FOR U.SS.. WWOOMMEENN,, 11993300--22000055 
AAggee--aaddjjuusstteedd DDeeaatthh RRaattee ppeerr 110000,,000000 FFeemmaalleess
Cancer occurence in Women (USA)
Cancer mortality in Women (USA) 
1 
2
Epidemiology of breast cancer 2014 ap
Epidemiology of breast cancer 2014 ap
BREAST CANCER: 
Incidence and Mortality in the World 
• Third most frequent cancer in world (Male + Female) 
– 1990: 796,000 cases, 314,000 deaths 
– 2002: 1,152,000 cases, 411,000 deaths 
• Most common cancer among women worldwide 
– 2002: Most common cause female cancer deaths 
CA Cancer J Clin: 49:33, 1999 
Globocan 2002 (IARC)
 In 2008, breast cancer caused 458,503 deaths worldwide 
- 13.7% of cancer deaths in women and 
- 6.0% of all cancer deaths for men and women together.
Breast Cancer epidemiology 
Variation among countries 
Variation among populations 
Variation among ethnic groups
Epidemiology of breast cancer 2014 ap
Epidemiology of breast cancer 2014 ap
By Region 
 The incidence of breast cancer varies greatly 
around the world: it is lowest in less-developed 
countries and greatest in the more-developed 
countries.
Epidemiology of breast cancer 2014 ap
By Region 
 In the twelve world regions, the annual 
age-standardized incidence rates per 100,000 
women are as follows:
Nr World Region Incidence 
100,000 
1 Eastern Asia 12 
2 South Central Asia 22 
3 Sub-Saharan Africa 22 
4 South Eastern Asia 26 
5 North Africa and Western Asia 28 
6 South and Central America 42 
7 Eastern Europe 49 
8 Southern Europe 56 
9 Northern Europe 73 
10 Oceania 74 
11 Western Europe 79 
12 North America 90
Epidemiology of breast cancer 2014 ap
EU-27 
>100/100,000 
>20/100,000
Breast Cancer Incidence - USA
USA 
Breast Cancer 
Incidence & Mortality 
White Females 
versus 
Black Females
Epidemiology of breast cancer 2014 ap
MEDITERRANEAN REGION 
COUNTRY Incidence Mortality 
France 132 25 
Italy 116 25 
Spain 82 18 
Greece 62 22 
Albania 35 6.9 
Cyprus 90 21.0 
Turkey 33.3 8.1 
Algeria 18.8 6.23 
Tunisia 19.2 4.86 
Maroco 17.6 5.8 
Libya 18.6 5.6 
Egypt < 70 
Israel – Jews 92.2 
Israel – Non Jews 38.5
Epidemiology of breast cancer 2014 ap
Parameter: Race 
• Race 
• Gender 
• Age
Parameter: Race 
 It appears that there is no race with a special 
genetic predisposition. 
 It is the socioeconomic conditions and the life-style 
that make the difference.
Parameter: Gender 
 It is about 100 times more common in women 
than in men (Veto, et al., 2009).
Parameter: Age 
 Breast cancer is strongly related to age, 
with only 5% of all breast cancers occurring 
in women under 40 years old 
 Older women are at higher risk, 
particularly women aged 50 – 69 
are most at risk, predominantly 
those with a late menopause.
Breast cancer incidence by age in women 
(United Kingdom, 2006 – 2008
Female Breast Cancer – Age at diagnosis
Epidemiology of breast cancer 2014 ap
Estimated risk of developing breast cancer by Age 
Females, UK, 2008 
Adopted from: www.cancerresearch.uk
Reproductive Factors 
Endogenous Sex Hormones 
Oral Contraceptives 
Postmenopausal Hormone Use 
Dietary Factors and Energy Balance 
Genetic Factors 
Medical Factors
Reproductive Factors 
Age at menarche 
Pregnancy and age at first full-term pregnancy 
Number and spacing of births 
Lactation 
Spontaneous and induced abortion 
Age at menopause
Age at Menarche 
• Earlier age at menarche has been consistently associated 
with increased risk of both premenopausal and 
postmenopausal breast cancer. 
• Later age - lower risk 
• Age 15 vs age 11 gives 30% lower risk to age 70
Pregnancy and age at first 
full-term pregnancy 
• Nulliparous women are at more of a risk of breast cancer 
than parous women 
• The susceptibility of mammary tissue to carcinogens 
decreases after the first pregnancy, reflecting the 
differentiation of the mammary gland.
Number and spacing of births 
• A higher number of births is consistently related to lower 
risk of breast cancer; each additional birth beyond the 
first reduces long-term risk of breast cancer. 
• In addition to a protective effect of higher parity, more 
closely spaced births are associated with a lower lifetime 
risk of breast cancer.
Lactation 
• As early as 1926, it was proposed that a breast never used 
for lactation is more predisposed to cancer. 
• Research showed an overall 4% reduction in risk per 12 
months of breastfeeding for all parous women. 
• It is estimated that, if women in developed countries had 
the number of births and lifetime duration of 
breastfeeding of women in developing countries, the 
cumulative incidence of breast cancer by age 70 years 
would be reduced by as much as 60%
Spontaneous and induced abortion 
• It is hypothesized to increase a woman’s risk of 
developing breast cancer. 
• By far the strongest study to date on the association 
between breast cancer and abortion was a population-based 
cohort study made up of 1.5 million Danish 
women born April 1, 1935, through March 31, 1978.
Menopause 
• Early menopause reduces risk 
• Women who have undergone bilateral oophorectomy 
at a young age have a greatly reduced risk of breast 
cancer. 
• Women with bilateral oophorectomy before age 45 years 
have approximately half the risk (50%) of breast cancer 
compared to those with a natural menopause at age 55 
years or older. 
• On average, the risk of breast cancer increases by some 
3% per year of delay in age at menopause.
Age at Menopause 
Age at menopause 
400 
350 
300 
100,000 
250 
Incidence/200 
150 
100 
50 
0 
Age 44% 
45 
55 
30 35 40 45 50 55 60 65 70 
Menopause 
age 45 
Menopause 
age 55 
Colditz and Rosner, Am J Epidemiology 2000;152:950-64
Pregnancy history 
450 
400 
350 
300 
250 
200 
150 
100 
50 
0 
Pregnancy History 
30 
34 
38 
42 
46 
50 
54 
58 
62 
66 
70 
Age 
Incidence/100,000 
Age birth 
35 
Nulliparous 
Age birth 
20,23,26,29 
17% 
27% 
Birth at 35 = 17% increase risk to age 70 
Many births = 27% reduction in risk to age 70
Endogenous Sex Hormones 
Estrogens 
Androgens 
Prolactin 
Insulin-like Growth Factor
Estrogens 
• The risk of breast cancer increased with increasing 
estrogen levels
Androgens 
• Androgens have been hypothesized to increase breast 
cancer risk either directly, by increasing the growth 
and proliferation of breast cancer cells, or indirectly, 
by their conversion to estrogen.
Prolactin 
• Substantial laboratory evidence suggests that prolactin 
could play a role in breast carcinogenesis. 
• Prolactin receptors have been found on more than 50% of 
breast tumors, and prolactin increases the growth of both 
normal and malignant breast cells in vitro, although these 
findings have not been entirely consistent. 
• Prolactin administration is well documented to increase 
mammary tumor rates in mice.
Insulin-like Growth Factor 
• It is a polypeptide hormone with structural homology 
to insulin, and it is regulated primarily by growth 
hormone. 
• There is increasing evidence that the growth hormone- 
IGF-I axis stimulates proliferation of both breast cancer 
and normal breast epithelial cells.
Oral Contraceptives 
Any use of oral contraceptives 
Duration of use and time since last use 
Use before a first full-term pregnancy or at an early age 
Type and dosage of oral contraceptives 
Progestin-only contraceptives
Excess cases of breast cancer that would be generated in 
a population of 10,000 women using oral contraceptives 
Age (years) 
at Starting Use 
at different ages for 5 years. 
Cases 
Among Users 
Cases 
Among Nonusers 
Cumulative Excess 
Cases per 10,000 
16 – 19 4.5 4 0.5 
20 – 24 17.5 16 1.5 
25 – 29 48.7 44 4.7 
30 – 34 110 100 11.1 
35 – 39 180 160 21 
40 – 44 260 230 32 
Use before a first full-term pregnancy or at an early age
Oral Contraceptives 
• In several meta-analyses and a large pooled analysis,“ever” use of oral 
contraceptives was not associated with breast cancer risk 
• Most studies have observed no significant increase in breast cancer risk with 
long durations of use. 
• A slight increase in risk seen in some studies subsided within 10 years of 
stopping oral contraceptive use. 
• There is no evidence of a differential effect according to type or dose of either 
estrogen or progestin. 
• Data on specific formulations remain inconclusive 
• Progestin-only contraceptives users were observed to have either a similar or 
lower risk of breast cancer compared to never users
Oral Contraceptives 
• Results of more than 50 studies have provided 
considerable reassurance that there is little, if any, 
increase in risk with past oral contraceptive use in 
general, even among women who have used oral 
contraceptives for 10 or more years. In the pooled 
analysis, long-term use among young women was not 
independently associated with an increase in breast 
cancer risk, but current users and recent users (< 10 years 
since last use) had a modest elevation in risk compared to 
never users.
Post-menopausal hormonal use 
Any use 
Duration of use 
Recency of use 
Type, dosage, and mode of delivery of estrogen 
Use of estrogen plus progestin 
Receptor status and histologic subtypes of breast 
cancer
Post-menopausal Hormonal Use 
• In the meta-analyses, significant increases in risk of approximately 
30%-45% with more than 5 years of use have been observed. 
• RR for 10 or more years of use = 1.47; 95% CI, 1.22-1.76). 
• Risk is greater for users of estrogen plus progestin compared to 
users of estrogen alone.
Epidemiology of breast cancer 2014 ap
Epidemiology of breast cancer 2014 ap
Genetic Factors (Heredity) 
BRCA 1 
BRCA 2 
TP 53 
CHEK2
Hereditary Breast Cancer 
The percentage of different genes with associated risk
Hereditary Breast Cancer 
• About 10% ooff bbrreeaasstt ccaanncceerrss aarree iinnhheerriitteedd 
• AApppprrooxxiimmaatteellyy 4400%% ooff hheerreeddiittaarryy bbrreeaasstt ccaanncceerr iiss ccaauusseedd bbyy 
mmuuttaattiioonnss iinn tthhee BBRRCCAA11 oorr BBRRCCAA22 ggeenneess 
• WWoommeenn wwhhoo iinnhheerriitt aa BBRRCCAA mmuuttaattiioonn hhaavvee aa 5500%% ttoo 8855%% 
cchhaannccee ooff ddeevveellooppiinngg bbrreeaasstt ccaanncceerr iinn tthheeiirr lliiffeettiimmee 
• WWoommeenn wwiitthh aa ssttrroonngg ffaammiillyy hhiissttoorryy mmaayy ccoonnssiiddeerr pprreevveennttiivvee 
ssuurrggeerryy ttoo rreemmoovvee bbrreeaasstt ttiissssuuee aanndd//oorr cchheemmoopprreevveennttiioonn 
• GGeenneettiicc ccoouunnsseelliinngg aanndd tteessttiinngg iiss aavvaaiillaabbllee ffoorr mmoosstt 
ssyynnddrroommeess
Family History 
 A woman who has a family member with 
breast cancer increases to double the risk 
of getting breast cancer in comparison 
to a woman with no family history 
(Lancet, 2001)
Medical Factors 
Precursor neoplastic lesions 
Mammograms and breast density 
Antibiotic use 
Silicone breast implants 
Ionizing Radiation 
Electromagnetic fields 
Active and passive smoking
Precursor Neoplastic Lesions 
• 1/ Nonproliferative lesions 
• 2/ Proliferative lesions without atypia 
• 3/ Proliferative lesions with atypia
Precursor Neoplastic Lesions 
• 1/ Nonproliferative lesions (cysts) 
• Women with these lesions are at the 
same risk of breast cancer as women 
without a breast biopsy.
Precursor Neoplastic Lesions 
• 2/ Proliferative lesions without atypia 
(eg, intraductal papilloma, sclerosing adenosis, 
moderate hyperplasia of usual type) 
• These conditions are associated with a 1.5- to 2-fold 
increased risk of breast cancer compared to 
nonproliferative lesions.
Precursor Neoplastic Lesions 
• 3/ Proliferative lesions with atypia 
(Atypical ductal hyperplasia and atypical 
lobular hyperplasia) 
• These lesions are associated with a 3.5 – 6.0 
fold increased risk of subsequent breast cancer
Mammograms and Breast density 
• Mammographic density is the strongest risk factor for the 
development of breast cancer. 
• Women with dense breasts have 4 times the likelihood of 
developing breast cancer compared to women without dense 
breasts. 
• It is also well known that breast tissue density increases in about 
25%-30% of women who begin hormone replacement therapy and 
that, conversely, breast density decreases in some women who are 
placed on tamoxifen or raloxifene.
Antibiotic Use 
• No relation even with over a total of 1,000 days of use
Silicone Breast Implants 
• Most studies examining the relation of silicone breast 
implants with breast cancer risk have actually reported 
lower rates of breast cancer among women with 
implants. 
• Reported reductions in risk in some of these studies have 
been large (on the order of 50% or 60%). 
• There is strong epidemiologic evidence that breast 
implants do not lead to increased risk of breast cancer
Ionizig Radiation 
• Depends on dose and age at irradiation, being highest for 
women exposed before age ten years. (<10y) 
• For women exposed after age 40 years (>40y), there was 
no significant elevation in subsequent breast cancer risk.
Electromagnetic Fields 
• Electromagnetic fields (EMF) have been proposed to alter breast 
cancer risk, perhaps by altering melatonin secretion by the pineal 
gland. In case-control studies designed specifically to study 
occupational exposure to EMF and breast cancer in women, small 
increases in risk have been inconsistently observed.
Synthetic Chemicals 
• (Organochlorines, synthetic chemicals, DDT, Dioxins) 
• Many of these chemicals are weak estrogens and may act as 
estrogenic agents in breast tissue, thereby hypothesized to increase 
breast cancer risk by mimicking endogenous estradiol.
Smoking 
• No causal relationship between active smoking and 
breast cancer. 
• Same for passive smoking
Dietary Factors and Energy Balance 
Alcohol 
Caffeine 
Physical activity 
Obesity 
Height 
Weight and weight change during adulthood
Alcohol 
• Women consuming 35-44 g/day of alcohol (about 3 
drinks per day) have a RR of 1.32 compared to 
nondrinkers. 
• The risk increased by 7.1% for each 10 g/day. 
 One alcoholic drink each day increases the risk 
of breast cancer by around 12%
Caffeine & Tea 
• Most case-control studies have not observed evidence of 
a positive association with breast cancer. 
• In prospective studies, no increase in breast cancer risk 
has been seen. 
• Similarly, no evidence for an association between tea 
consumption and risk of breast cancer has been seen in 
epidemiologic studies.
Physical Activity 
• Among postmenopausal women, physical activity may 
lower breast cancer risk by reducing fat stores, which 
convert androstenedione to estrone. 
• Physical activity may also increase levels of sex hormone-binding 
globulin (SHBG), which would reduce 
bioavailable estrogens. 
• Increased physical activity also reduces insulin resistance 
and hyperinsulinemia, which has been hypothesized to be 
related to breast cancer. 
• Evidence was sufficient to establish that physical activity 
is protective against breast cancer. 
• Risk may be reduced by approximately 40% among those 
who were consistently most active.
Obesity 
• Postmenopausal adiposity is an established risk for 
postmenopausal breast cancer. 
• Components of energy balance have been evaluated in 
numerous studies indicting that highest energy intake, 
highest body mass index (BMI), and lowest energy 
expenditure may combine to more than double the 
risk of breast cancer. 
• 
 Obesity increases the risk of postmenopausal 
breast cancer by up to 30%, since levels of 
hormones rise with excess body fat.
Epidemiology of breast cancer 2014 ap
Epidemiology of breast cancer 2014 ap
BREAST CANCER EPIDEMIOLOGY: 
Stage at diagnosis: United States vs. India 
STAGE EXTENT 5 year 
SURVIVAL 
DISTRIBUTION 
USA INDIA 
0 Noninvasive 100% 16% ---- 
I Early stage 
disease 100% 40% 1% 
II Early stage 
disease 86% 34% 23% 
III Locally 
advanced 57% 6% 52% 
IV Metastatic 
USA: 
90% DCIS or 
early staged 
invasive 
disease at 
diagnosis 
disease 20% 4% 24% INDIA: 
SSoouurrcceess:: SSEEEERR SSuurrvviivvaall MMoonnooggrraapphh,, 22000077 
76% locally 
advanced or 
metastatic at 
diagnosis
Female Breast Cancer – Age at diagnosis
Epidemiology of breast cancer 2014 ap
 Metastatic breast cancer is a heterogeneous disease with 
a variety of different clinical scenarios, ranging from 
solitary metastatic lesion to diffuse involvement. 
 Between 6 to 10% of breast cancer patients present 
with metastasis at diagnosis. 
 Once metastases are detected, median survival ranges 
between 18 and 24 months, depending on number and 
site of metastatic lesions, and tumor characteristics. 
 The five-year overall survival rarely exceeds 20%. 
 Overall, survival of patients with MBC is slowly but steadily 
improving. This improvement is most probably related to 
the development and widespread availability of modern 
systemic therapies.
 Long term survival can be obtained in approximately 
50% of women with LABC who are treated with a 
multimodal approach. 
 The addition of systemic therapy to the traditional 
local treatment has improved prognosis. 
 Prognostic factors include age, histological type, 
grade, hormone receptor status and response to 
neoadjuvant therapy.
WORLD BREAST CANCER STATISTICS: 
Incidence and 5-Year Survival 
Southern Africa 
Southeastern Asia 
CA Cancer JJ CClliinn:: 5500::3377,, 22000000 
90 
80 
70 
60 
50 
40 
30 
20 
10 
0 
North America 
Northern Europe 
Western Europe 
Southern Europe 
Northern Africa 
South Central Asia 
INCIDENCE (per 100,000) 5-YEAR SURVIVAL (%)
Female Breast Cancer – Age at Death
Epidemiology of breast cancer 2014 ap
 Breast Cancer is a major Public Health problem. 
In several parts of the world, it remains the most 
common cancer among women. 
 Most breast cancer deaths occur in less 
developed countries
 The number of cases worldwide has 
significantly increased since the 1970s, 
a phenomenon partly attributed to the 
modern lifestyles
 Given the resources disparities between countries, 
impacting on both incidence and mortality, it is 
difficult to adopt a common strategy for cancer care. 
 However, efforts might be made to improve the 
health care system in every country, by facilitating 
the access to both care and screening structures.
Epidemiology of breast cancer 2014 ap
Epidemiology of breast cancer 2014 ap

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Epidemiology of breast cancer 2014 ap

  • 3. GHANAIAN CANCER EPIDEMIOLOGY: Age Standardized Rates / 100,000 Females Globocan 2002
  • 5. CANCER IINNCCIIDDEENNCCEE RRAATTEESS FFOORR UU..SS.. WWOOMMEENN,, 11997733--22000055 AAggee--aaddjjuusstteedd IInncciiddeennccee RRaattee ppeerr 110000,,000000 FFeemmaalleess
  • 6. CANCER DEATH RATES FOR U.SS.. WWOOMMEENN,, 11993300--22000055 AAggee--aaddjjuusstteedd DDeeaatthh RRaattee ppeerr 110000,,000000 FFeemmaalleess
  • 7. Cancer occurence in Women (USA)
  • 8. Cancer mortality in Women (USA) 1 2
  • 11. BREAST CANCER: Incidence and Mortality in the World • Third most frequent cancer in world (Male + Female) – 1990: 796,000 cases, 314,000 deaths – 2002: 1,152,000 cases, 411,000 deaths • Most common cancer among women worldwide – 2002: Most common cause female cancer deaths CA Cancer J Clin: 49:33, 1999 Globocan 2002 (IARC)
  • 12.  In 2008, breast cancer caused 458,503 deaths worldwide - 13.7% of cancer deaths in women and - 6.0% of all cancer deaths for men and women together.
  • 13. Breast Cancer epidemiology Variation among countries Variation among populations Variation among ethnic groups
  • 16. By Region  The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries.
  • 18. By Region  In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows:
  • 19. Nr World Region Incidence 100,000 1 Eastern Asia 12 2 South Central Asia 22 3 Sub-Saharan Africa 22 4 South Eastern Asia 26 5 North Africa and Western Asia 28 6 South and Central America 42 7 Eastern Europe 49 8 Southern Europe 56 9 Northern Europe 73 10 Oceania 74 11 Western Europe 79 12 North America 90
  • 23. USA Breast Cancer Incidence & Mortality White Females versus Black Females
  • 25. MEDITERRANEAN REGION COUNTRY Incidence Mortality France 132 25 Italy 116 25 Spain 82 18 Greece 62 22 Albania 35 6.9 Cyprus 90 21.0 Turkey 33.3 8.1 Algeria 18.8 6.23 Tunisia 19.2 4.86 Maroco 17.6 5.8 Libya 18.6 5.6 Egypt < 70 Israel – Jews 92.2 Israel – Non Jews 38.5
  • 27. Parameter: Race • Race • Gender • Age
  • 28. Parameter: Race  It appears that there is no race with a special genetic predisposition.  It is the socioeconomic conditions and the life-style that make the difference.
  • 29. Parameter: Gender  It is about 100 times more common in women than in men (Veto, et al., 2009).
  • 30. Parameter: Age  Breast cancer is strongly related to age, with only 5% of all breast cancers occurring in women under 40 years old  Older women are at higher risk, particularly women aged 50 – 69 are most at risk, predominantly those with a late menopause.
  • 31. Breast cancer incidence by age in women (United Kingdom, 2006 – 2008
  • 32. Female Breast Cancer – Age at diagnosis
  • 34. Estimated risk of developing breast cancer by Age Females, UK, 2008 Adopted from: www.cancerresearch.uk
  • 35. Reproductive Factors Endogenous Sex Hormones Oral Contraceptives Postmenopausal Hormone Use Dietary Factors and Energy Balance Genetic Factors Medical Factors
  • 36. Reproductive Factors Age at menarche Pregnancy and age at first full-term pregnancy Number and spacing of births Lactation Spontaneous and induced abortion Age at menopause
  • 37. Age at Menarche • Earlier age at menarche has been consistently associated with increased risk of both premenopausal and postmenopausal breast cancer. • Later age - lower risk • Age 15 vs age 11 gives 30% lower risk to age 70
  • 38. Pregnancy and age at first full-term pregnancy • Nulliparous women are at more of a risk of breast cancer than parous women • The susceptibility of mammary tissue to carcinogens decreases after the first pregnancy, reflecting the differentiation of the mammary gland.
  • 39. Number and spacing of births • A higher number of births is consistently related to lower risk of breast cancer; each additional birth beyond the first reduces long-term risk of breast cancer. • In addition to a protective effect of higher parity, more closely spaced births are associated with a lower lifetime risk of breast cancer.
  • 40. Lactation • As early as 1926, it was proposed that a breast never used for lactation is more predisposed to cancer. • Research showed an overall 4% reduction in risk per 12 months of breastfeeding for all parous women. • It is estimated that, if women in developed countries had the number of births and lifetime duration of breastfeeding of women in developing countries, the cumulative incidence of breast cancer by age 70 years would be reduced by as much as 60%
  • 41. Spontaneous and induced abortion • It is hypothesized to increase a woman’s risk of developing breast cancer. • By far the strongest study to date on the association between breast cancer and abortion was a population-based cohort study made up of 1.5 million Danish women born April 1, 1935, through March 31, 1978.
  • 42. Menopause • Early menopause reduces risk • Women who have undergone bilateral oophorectomy at a young age have a greatly reduced risk of breast cancer. • Women with bilateral oophorectomy before age 45 years have approximately half the risk (50%) of breast cancer compared to those with a natural menopause at age 55 years or older. • On average, the risk of breast cancer increases by some 3% per year of delay in age at menopause.
  • 43. Age at Menopause Age at menopause 400 350 300 100,000 250 Incidence/200 150 100 50 0 Age 44% 45 55 30 35 40 45 50 55 60 65 70 Menopause age 45 Menopause age 55 Colditz and Rosner, Am J Epidemiology 2000;152:950-64
  • 44. Pregnancy history 450 400 350 300 250 200 150 100 50 0 Pregnancy History 30 34 38 42 46 50 54 58 62 66 70 Age Incidence/100,000 Age birth 35 Nulliparous Age birth 20,23,26,29 17% 27% Birth at 35 = 17% increase risk to age 70 Many births = 27% reduction in risk to age 70
  • 45. Endogenous Sex Hormones Estrogens Androgens Prolactin Insulin-like Growth Factor
  • 46. Estrogens • The risk of breast cancer increased with increasing estrogen levels
  • 47. Androgens • Androgens have been hypothesized to increase breast cancer risk either directly, by increasing the growth and proliferation of breast cancer cells, or indirectly, by their conversion to estrogen.
  • 48. Prolactin • Substantial laboratory evidence suggests that prolactin could play a role in breast carcinogenesis. • Prolactin receptors have been found on more than 50% of breast tumors, and prolactin increases the growth of both normal and malignant breast cells in vitro, although these findings have not been entirely consistent. • Prolactin administration is well documented to increase mammary tumor rates in mice.
  • 49. Insulin-like Growth Factor • It is a polypeptide hormone with structural homology to insulin, and it is regulated primarily by growth hormone. • There is increasing evidence that the growth hormone- IGF-I axis stimulates proliferation of both breast cancer and normal breast epithelial cells.
  • 50. Oral Contraceptives Any use of oral contraceptives Duration of use and time since last use Use before a first full-term pregnancy or at an early age Type and dosage of oral contraceptives Progestin-only contraceptives
  • 51. Excess cases of breast cancer that would be generated in a population of 10,000 women using oral contraceptives Age (years) at Starting Use at different ages for 5 years. Cases Among Users Cases Among Nonusers Cumulative Excess Cases per 10,000 16 – 19 4.5 4 0.5 20 – 24 17.5 16 1.5 25 – 29 48.7 44 4.7 30 – 34 110 100 11.1 35 – 39 180 160 21 40 – 44 260 230 32 Use before a first full-term pregnancy or at an early age
  • 52. Oral Contraceptives • In several meta-analyses and a large pooled analysis,“ever” use of oral contraceptives was not associated with breast cancer risk • Most studies have observed no significant increase in breast cancer risk with long durations of use. • A slight increase in risk seen in some studies subsided within 10 years of stopping oral contraceptive use. • There is no evidence of a differential effect according to type or dose of either estrogen or progestin. • Data on specific formulations remain inconclusive • Progestin-only contraceptives users were observed to have either a similar or lower risk of breast cancer compared to never users
  • 53. Oral Contraceptives • Results of more than 50 studies have provided considerable reassurance that there is little, if any, increase in risk with past oral contraceptive use in general, even among women who have used oral contraceptives for 10 or more years. In the pooled analysis, long-term use among young women was not independently associated with an increase in breast cancer risk, but current users and recent users (< 10 years since last use) had a modest elevation in risk compared to never users.
  • 54. Post-menopausal hormonal use Any use Duration of use Recency of use Type, dosage, and mode of delivery of estrogen Use of estrogen plus progestin Receptor status and histologic subtypes of breast cancer
  • 55. Post-menopausal Hormonal Use • In the meta-analyses, significant increases in risk of approximately 30%-45% with more than 5 years of use have been observed. • RR for 10 or more years of use = 1.47; 95% CI, 1.22-1.76). • Risk is greater for users of estrogen plus progestin compared to users of estrogen alone.
  • 58. Genetic Factors (Heredity) BRCA 1 BRCA 2 TP 53 CHEK2
  • 59. Hereditary Breast Cancer The percentage of different genes with associated risk
  • 60. Hereditary Breast Cancer • About 10% ooff bbrreeaasstt ccaanncceerrss aarree iinnhheerriitteedd • AApppprrooxxiimmaatteellyy 4400%% ooff hheerreeddiittaarryy bbrreeaasstt ccaanncceerr iiss ccaauusseedd bbyy mmuuttaattiioonnss iinn tthhee BBRRCCAA11 oorr BBRRCCAA22 ggeenneess • WWoommeenn wwhhoo iinnhheerriitt aa BBRRCCAA mmuuttaattiioonn hhaavvee aa 5500%% ttoo 8855%% cchhaannccee ooff ddeevveellooppiinngg bbrreeaasstt ccaanncceerr iinn tthheeiirr lliiffeettiimmee • WWoommeenn wwiitthh aa ssttrroonngg ffaammiillyy hhiissttoorryy mmaayy ccoonnssiiddeerr pprreevveennttiivvee ssuurrggeerryy ttoo rreemmoovvee bbrreeaasstt ttiissssuuee aanndd//oorr cchheemmoopprreevveennttiioonn • GGeenneettiicc ccoouunnsseelliinngg aanndd tteessttiinngg iiss aavvaaiillaabbllee ffoorr mmoosstt ssyynnddrroommeess
  • 61. Family History  A woman who has a family member with breast cancer increases to double the risk of getting breast cancer in comparison to a woman with no family history (Lancet, 2001)
  • 62. Medical Factors Precursor neoplastic lesions Mammograms and breast density Antibiotic use Silicone breast implants Ionizing Radiation Electromagnetic fields Active and passive smoking
  • 63. Precursor Neoplastic Lesions • 1/ Nonproliferative lesions • 2/ Proliferative lesions without atypia • 3/ Proliferative lesions with atypia
  • 64. Precursor Neoplastic Lesions • 1/ Nonproliferative lesions (cysts) • Women with these lesions are at the same risk of breast cancer as women without a breast biopsy.
  • 65. Precursor Neoplastic Lesions • 2/ Proliferative lesions without atypia (eg, intraductal papilloma, sclerosing adenosis, moderate hyperplasia of usual type) • These conditions are associated with a 1.5- to 2-fold increased risk of breast cancer compared to nonproliferative lesions.
  • 66. Precursor Neoplastic Lesions • 3/ Proliferative lesions with atypia (Atypical ductal hyperplasia and atypical lobular hyperplasia) • These lesions are associated with a 3.5 – 6.0 fold increased risk of subsequent breast cancer
  • 67. Mammograms and Breast density • Mammographic density is the strongest risk factor for the development of breast cancer. • Women with dense breasts have 4 times the likelihood of developing breast cancer compared to women without dense breasts. • It is also well known that breast tissue density increases in about 25%-30% of women who begin hormone replacement therapy and that, conversely, breast density decreases in some women who are placed on tamoxifen or raloxifene.
  • 68. Antibiotic Use • No relation even with over a total of 1,000 days of use
  • 69. Silicone Breast Implants • Most studies examining the relation of silicone breast implants with breast cancer risk have actually reported lower rates of breast cancer among women with implants. • Reported reductions in risk in some of these studies have been large (on the order of 50% or 60%). • There is strong epidemiologic evidence that breast implants do not lead to increased risk of breast cancer
  • 70. Ionizig Radiation • Depends on dose and age at irradiation, being highest for women exposed before age ten years. (<10y) • For women exposed after age 40 years (>40y), there was no significant elevation in subsequent breast cancer risk.
  • 71. Electromagnetic Fields • Electromagnetic fields (EMF) have been proposed to alter breast cancer risk, perhaps by altering melatonin secretion by the pineal gland. In case-control studies designed specifically to study occupational exposure to EMF and breast cancer in women, small increases in risk have been inconsistently observed.
  • 72. Synthetic Chemicals • (Organochlorines, synthetic chemicals, DDT, Dioxins) • Many of these chemicals are weak estrogens and may act as estrogenic agents in breast tissue, thereby hypothesized to increase breast cancer risk by mimicking endogenous estradiol.
  • 73. Smoking • No causal relationship between active smoking and breast cancer. • Same for passive smoking
  • 74. Dietary Factors and Energy Balance Alcohol Caffeine Physical activity Obesity Height Weight and weight change during adulthood
  • 75. Alcohol • Women consuming 35-44 g/day of alcohol (about 3 drinks per day) have a RR of 1.32 compared to nondrinkers. • The risk increased by 7.1% for each 10 g/day.  One alcoholic drink each day increases the risk of breast cancer by around 12%
  • 76. Caffeine & Tea • Most case-control studies have not observed evidence of a positive association with breast cancer. • In prospective studies, no increase in breast cancer risk has been seen. • Similarly, no evidence for an association between tea consumption and risk of breast cancer has been seen in epidemiologic studies.
  • 77. Physical Activity • Among postmenopausal women, physical activity may lower breast cancer risk by reducing fat stores, which convert androstenedione to estrone. • Physical activity may also increase levels of sex hormone-binding globulin (SHBG), which would reduce bioavailable estrogens. • Increased physical activity also reduces insulin resistance and hyperinsulinemia, which has been hypothesized to be related to breast cancer. • Evidence was sufficient to establish that physical activity is protective against breast cancer. • Risk may be reduced by approximately 40% among those who were consistently most active.
  • 78. Obesity • Postmenopausal adiposity is an established risk for postmenopausal breast cancer. • Components of energy balance have been evaluated in numerous studies indicting that highest energy intake, highest body mass index (BMI), and lowest energy expenditure may combine to more than double the risk of breast cancer. •  Obesity increases the risk of postmenopausal breast cancer by up to 30%, since levels of hormones rise with excess body fat.
  • 81. BREAST CANCER EPIDEMIOLOGY: Stage at diagnosis: United States vs. India STAGE EXTENT 5 year SURVIVAL DISTRIBUTION USA INDIA 0 Noninvasive 100% 16% ---- I Early stage disease 100% 40% 1% II Early stage disease 86% 34% 23% III Locally advanced 57% 6% 52% IV Metastatic USA: 90% DCIS or early staged invasive disease at diagnosis disease 20% 4% 24% INDIA: SSoouurrcceess:: SSEEEERR SSuurrvviivvaall MMoonnooggrraapphh,, 22000077 76% locally advanced or metastatic at diagnosis
  • 82. Female Breast Cancer – Age at diagnosis
  • 84.  Metastatic breast cancer is a heterogeneous disease with a variety of different clinical scenarios, ranging from solitary metastatic lesion to diffuse involvement.  Between 6 to 10% of breast cancer patients present with metastasis at diagnosis.  Once metastases are detected, median survival ranges between 18 and 24 months, depending on number and site of metastatic lesions, and tumor characteristics.  The five-year overall survival rarely exceeds 20%.  Overall, survival of patients with MBC is slowly but steadily improving. This improvement is most probably related to the development and widespread availability of modern systemic therapies.
  • 85.  Long term survival can be obtained in approximately 50% of women with LABC who are treated with a multimodal approach.  The addition of systemic therapy to the traditional local treatment has improved prognosis.  Prognostic factors include age, histological type, grade, hormone receptor status and response to neoadjuvant therapy.
  • 86. WORLD BREAST CANCER STATISTICS: Incidence and 5-Year Survival Southern Africa Southeastern Asia CA Cancer JJ CClliinn:: 5500::3377,, 22000000 90 80 70 60 50 40 30 20 10 0 North America Northern Europe Western Europe Southern Europe Northern Africa South Central Asia INCIDENCE (per 100,000) 5-YEAR SURVIVAL (%)
  • 87. Female Breast Cancer – Age at Death
  • 89.  Breast Cancer is a major Public Health problem. In several parts of the world, it remains the most common cancer among women.  Most breast cancer deaths occur in less developed countries
  • 90.  The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles
  • 91.  Given the resources disparities between countries, impacting on both incidence and mortality, it is difficult to adopt a common strategy for cancer care.  However, efforts might be made to improve the health care system in every country, by facilitating the access to both care and screening structures.

Editor's Notes

  1. Mechanism of Action - Competitively block LHRH receptors in the pituitary - Initial stimulation of LHRH receptors followed by down-regulation of the receptor leading to a decreased production of FSH and LH - Estradiol and progesterone levels reduced
  2. Birth at 35 = 17% increase risk to age 70 Mult births = 27% reduction in risk to age 70
  3. Mechanism of Action - Competitively block LHRH receptors in the pituitary - Initial stimulation of LHRH receptors followed by down-regulation of the receptor leading to a decreased production of FSH and LH - Estradiol and progesterone levels reduced
  4. Sources: SEER Survival Monograph, 2007; Chopra, Cancer Institute Chennai, India, 2001