ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) are at increased risk
if a woman has had breast cancer, her risk of developing a second primary breast cancer is 2-6 times the risk seen in the general population of developing a primary breast cancer
PH breast irradiation:
radiotherapy for Hodgkin's lymphoma - doubles lifetime risk
CT scanning during pregnancy
the effect of radiation on the breast is strongly related to age at exposure ie the younger the woman is exposed the greater the excess risk.
hair dye
genetic mutations:
more common inherited germline genomic factors
it now seems there may be tens or hundreds of additional inherited germline gene variants that contribute risk and aggressiveness for each subtype of breast cancer via HLA-type and whether their HLA can detect an oncogene epitome and remove these cells and reduce risk of cancer, or whether they fail to do so an increase risk 1)
uncommon gene mutations:
BRCA1 - also assoc. with ovarian, bowel and prostate cancers and tends to cause triple negative breast cancer
BRCA2 - also assoc. with ovarian, pancreatic and prostate cancers
BRCA1 and BRCA2 - these occur in 1 in 500 women
rare familial disorders such as Li Fraumeni synd (TP53 gene mutation), Cowden's synd, Peutz-Jegher's synd., ataxia telangiectasia.
appears to be a correlation with severe acne which appears to have shared genetic causes
since breast cancer affects one woman in nine there will be many women who have a mother or sister with the disease. But only if there are several family members with early onset breast cancer is there a likelihood of a significant inherited predisposition to the disease
Higher expression levels of TLR-1, DNPH1, and LAYN and lower expression of LRRC37A2 and CD160 were found to be associated with an increase in breast cancer risk.2)
breast density:
higher density (less fat) is a risk factor, and appears mainly to be genetic, although menopausal status, parity and weight are factors.
women with denser breasts have 2-6 times the risk of breast cancer compared to women with less dense breasts
benign breast disease:
women who have had biopsies that showed proliferative breast disease without atypia have a 2-fold increased risk, while women with atypical hyperplasia have a 2-5 fold increased risk
alcohol intake:
increase of risk of 7% for each additional 10 grams of alcohol consumed on a daily basis
risk seems particularly an issue prior to 1st pregnancy as alcohol consumption is thought to reduce metabolism of oestrogen thereby causing high levels of oestrogen
no direct association between tobacco and breast cancer.
age:
the majority of breast cancer cases occur in women older than age 50.
risk of breast cancer in UK women:
aged < 25 years = 1 in 15,000
aged < 30 years = 1 in 1,900
aged < 40 years = 1 in 200
aged < 50 years = 1 in 50
aged < 60 years = 1 in 23
aged < 70 years = 1 in 15
aged < 80 years = 1 in 11
aged < 100 years = 1 in 9
additional risk factors for post-menopausal women:
body mass index if not on HRT
after the menopause, when the ovaries stop producing oestrogen, adipose tissue is the primary source of endogenous oestrogen so obese and overweight women are exposed to higher levels of oestrogen.
obesity is also associated with lower levels of sex hormone binding globulin (SHBG) which increases the amount of bioavailable oestradiol
30% increased risk if BMI > 28, and 2x death rate if BMI > 40
20% increased risk if BMI 25-30 when compared with women with BMI 20-25 at age 50-59 yearsuk_million_women_study_2010
age at natural menopause
for each year menopause is delayed, there is an approximate 3% increase in breast cancer risk
use of hormone replacement therapy
the risk increase of breast cancer for current users of HRT is 66%
the effect is substantially greater for oestrogen-progestagen combinations than for oestrogen only HRT. Risk increases with duration of use: the risk for current users of oestrogen-progestagen combinations for 10 or more years was 2.3 compared to 1.7 for 1-4 years of use.3)
risk decreases with cessation of use; past users have a similar risk to never users
prior false-positive mammogram
race:
Caucasians have higher risk of developing it than those of African descent or those from rural China or Japan.
height:
taller women are at slightly higher risk
relative risk for UK women 1.75 metres or taller compared with women shorter than 1.6 metres was 1.22 for all women and 1.28 for postmenopausal women
increase in relative risk of 7% for each additional 5 centimetres in height for postmenopausal women and 2% for premenopausal women.4)
age at menarche:
women who had their first menstrual period before age 12 have a slightly increased risk of breast cancer
relative risk for premenopausal breast cancer is reduced by an estimated 7% for each year that menarche is delayed after age 12 years, and by 3% for postmenopausal breast cancer
age at first live birth, breast feeding and FH breast cancer:
the relative risk of developing breast cancer increases by 3% for each year of delay of first live birth.
a woman has a 7% decreased risk of breast cancer per live birth after the 1st birth and her risk drops by a further 4% for every year of breastfeeding 5)
it is estimated that 5% of breast cancers could be prevented every year if women were to breastfeed their children for an extra six months.
tamoxifen and the osteoporosis agent, raloxifene have both been shown to substantially decrease the incidence of breast cancer by ~50% when used in post-menopausal women aged over 35 years 7).
it would seem women with a life time risk of breast cancer of 20% or more should be offered raloxifene as it has less adverse effects than tamoxifen while having the same 50% reduction in invasive breast cancer incidence.
screening mammograms:
women aged 40yrs and older should be offered screening mammogram every 1-2 years.
those younger than 50yrs may benefot more from digital rather than film mammography.
HPV vaccination:
(human papilloma virus (HPV)) type 18 has been detected in ~50% of breast cancers8), and although the evidence is not conclusive, if breast cancer is a sexually transmitted disease via hpv then HPV vaccination may decrease the incidence of breast cancer. It is thought that hpv is spread by touch from the genitals to the nipples.