GHANAIAN CANCER EPIDEMIOLOGY:Age Standardized Rates / 100,000 Females

Globocan 2002

CANCER INCIDENCE RATES CANCER INCIDENCE RATES FOR U.S. WOMEN, 1973-2005FOR U.S. WOMEN, 1973-2005

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CANCER DEATH RATES FOR U.S. WOMEN, 1930-2005CANCER DEATH RATES FOR U.S. WOMEN, 1930-2005A

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Cancer occurence in Women (USA)

Cancer mortality in Women (USA)

1

2

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

The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries.

By Region

In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows:

By Region

Nr World Region Incidence100,000

1 Eastern Asia 122 South Central Asia 223 Sub-Saharan Africa 224 South Eastern Asia 265 North Africa and Western Asia 286 South and Central America 427 Eastern Europe 498 Southern Europe 569 Northern Europe 7310 Oceania 7411 Western Europe 7912 North America 90

EU-27

>100/100,000

>20/100,000

Breast Cancer Incidence - USA

USABreast Cancer

Incidence & Mortality

White Femalesversus

Black Females

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

MEDITERRANEAN REGION

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

Older women are at higher risk, particularly women aged 50 – 69 are most at risk, predominantly those with a late menopause.

Breast cancer is strongly related to age, with only 5% of all breast cancers occurring in women under 40 years old

Breast cancer incidence by age in women(United Kingdom, 2006 – 2008

Female Breast Cancer – Age at diagnosis

Estimated risk of developing breast cancer by AgeFemales, 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

0

50

100

150

200

250

300

350

400

30 35 40 45 50 55 60 65 70

Age

Inci

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Menopauseage 45

Menopauseage 55

Colditz and Rosner, Am J Epidemiology 2000;152:950-64

44%

45

55

Age at Menopause

Pregnancy history

050

100150200250300350400450

30 34 38 42 46 50 54 58 62 66 70

Age

Inci

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00,0

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Age birth35Nulliparous

Age birth20,23,26,29

17%

27%

Pregnancy History

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

Age (years)at Starting Use

Cases Among Users

CasesAmong 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

Excess cases of breast cancer that would be generated in a population of 10,000 women using oral contraceptives

at different ages for 5 years.

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.

Genetic Factors (Heredity)

BRCA 1

BRCA 2

TP 53

CHEK2

The percentage of different genes with associated risk

Hereditary Breast Cancer

Hereditary Breast Cancer

• About 10% of breast cancers are inheritedAbout 10% of breast cancers are inherited• Approximately 40% of hereditary breast cancer is caused by Approximately 40% of hereditary breast cancer is caused by

mutations in the BRCA1 or BRCA2 genesmutations in the BRCA1 or BRCA2 genes• Women who inherit a BRCA mutation have a 50% to 85% Women who inherit a BRCA mutation have a 50% to 85%

chance of developing breast cancer in their lifetimechance of developing breast cancer in their lifetime• Women with a strong family history may consider preventive Women with a strong family history may consider preventive

surgery to remove breast tissue and/or chemopreventionsurgery to remove breast tissue and/or chemoprevention• Genetic counseling and testing is available for most Genetic counseling and testing is available for most

syndromessyndromes

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.

BREAST CANCER EPIDEMIOLOGY:Stage at diagnosis: United States vs. India

Sources: Sources: SEER Survival Monograph, 2007SEER Survival Monograph, 2007

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 disease 20% 4% 24% INDIA:

76% locally advanced or metastatic at

diagnosis

USA:90% DCIS or early staged

invasive disease at diagnosis

Female Breast Cancer – Age at diagnosis

Metastatic breast cancer is a heterogeneous disease with a variety of different clinical scenarios, ranging from solitary metastatic lesion to diffuse involvement.

Once metastases are detected, median survival ranges between 18 and 24 months, depending on number and site of metastatic lesions, and tumor characteristics.

Between 6 to 10% of breast cancer patients present with metastasis at diagnosis.

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

CA Cancer J Clin: 50:37, 2000CA Cancer J Clin: 50:37, 2000

0102030405060708090

North Americ

a

Northern Europe

Western Europe

Southern Europe

Southern Africa

Southeastern Asia

Northern Afric

a

South Central A

sia

INCIDENCE (per 100,000) 5-YEAR SURVIVAL (%)

Female Breast Cancer – Age at Death

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.