BREAST CANCER RISK ASSESSMENT

Average population risk female breast cancer ~12% or 1 in 8

Genetic syndromes:
- BRCA1/2
o Tumour suppressor genes. Protein product involved in DNA repair.
o BRCA1:
 Female breast cancer 72% by age of 80 (general population 12%, contralateral 7%)
 Ovarian cancer 44% by age of 80 (general population 1.5%) (15% of women with
ovarian ca are BRCA+)
 Male breast cancer 1%
 Pancreatic cancer 1%
o BRCA 2:
 Female breast cancer 70% by age of 80
 Ovarian cancer 17% by age of 80
 Male breast cancer 7- 8% (15% of men with breast ca are BRCA2 carriers)
 Pancreas (~5%), bladder, prostate (~33% by age 65)
o Increased risk ipsilateral breast cancer (12% at 10yr) - NEW cancer rather than increased
local recurrence
o Increased risk contralateral breast cancer (10-30% at 10yr) [up to 63% at 25yr vs 7% gen
pop]
o Most BRCA1-associated breast cancers have triple negative and/or basal subtypes.
o Most BRCA2-associated breast cancers are hormone receptor (HR)–positive, although TNBCs
are also overrepresented in BRCA2 carriers
o Early onset, more commonly invasive, higher mitotic rates, ER/PR negative
- Li Freumeni (TP53)
o P53 = tumour suppressor gene
o Female breast cancer risk 50% by age 60. Mean age 35yrs
- PTEN Hamartoma Syndrome/Cowden (PTEN)
o PTEN tumour suppressor gene mutation
o Lifetime breast cancer risk 85.2%
- Peutz Jehgers (STK11)
o STK11 tumor suppressor gene
o Female breast cancer risk 55%. Mean age 37yrs
- Hereditary diffuse gastric cancer syndrome (CHD1)
o CDH1 gene mutation (cadherin 1)
o Highly invasive gastric cancers (usually signet ring)
o Lobular breast cancer risk up to 60%
- CHEK2
o ~37% breast cancer risk
- PALB2
o partner and localizer of BRCA2
o Breast ca risk = BRCA2 (33-58% depending on family history of breast cancer)
- ATM
- Lynch syndrome (MSH2, MSH6, MLH1, PMS2, or EPCAM)

Models for assessment of risk:

- Breast cancer risk assessment tool – BOADICEA, IBIS, Gail Model, BRCAPRO
- BOADICEA – better for personal or family hx of BRCA
- IBIS – better for patients with personal hx of LCIS or ADH and for women without a BC family history
 - CanRisk is web interface for BOADICEA
o Input: Personal details, lifestyle, women’s health, children, breast screening, medical hx,
family hx
o Outcome – risk of breast ca next 10 years, lifetime (80), specific risk of certain gene
mutations – BRCA, PALB2, CHEK2, ATM, BARD
- iPrevent (Peter Mac) uses both BOADICEA and IBIS
o Input: Personal details, women’s health, children, HRT/hormone exposure, family hx
o Outcome – 10 year cancer risk, life time cancer risk

7 important questions:
- Age
- Age at first merache
- Age at time of time of the birth of a first child (or has not given birth)
- Family history of breast cancer (mother, sister or daughter)
- Number of past breast biopsies
- Number of breast biopsies showing atypical hyperplasia
- Race/ethnicity

Who is at a risk of having inherited genetic conditions that cause BRCA1/2?

- Affected or unaffected individuals with BOADICEA/CanRisk risk score >10%
- Individuals with breast cancer:
o Age <40
o Bilateral breast cancer <50
o TNBC <60
o Male breast cancer
o Ashkenazi Jewish heritage
- High grade ovarian cancer at any age

Management of BRCA1/2 females?

Breast Medical Consider medication to reduce risk of developing breast cancer for women
not planning bilateral mastectomy within 3 years:
- Pre-menopausal women may consider tamoxifen
- Post-menopausal women may consider raloxifene, aromatase
inhibitors (anastrozole, letrozole, exemestane) or tamoxifen
Surveillance Begin screening from age 25-30 years
Age <40 - Annual MRI (US if MRI not possible)
Age 40-60 - Annual MRI + MMG (MMG + US if MRI not possible)
Age >60 - Annual MMG (consider MRI or US if over age 60 years with dense
breast tissue)
Surgical Consider bilateral risk-reducing mastectomy
Ovarian Surveillance Do not offer serum CA125 and/or transvaginal ultrasound
Surgical Recommend RRSO between the age of 35-40 years with peritoneal lavage and
histological examination
Uterine Surveillance Hysterectomy should not be recommended routinely
Pancreas Surveillance There is a lack of evidence of survival benefit from surveillance unless family
hx or exocrine pancreatic cancer

What to do on stratification by iPrevent or CanRisk into low, moderate or high risk for breast cancer?
- Low risk (gen pop):
 o 2 yearly MMG + US with BreastScreen
o Can opt for imaging from 40 years old

- Moderate risk:
o Women at moderately increased risk of breast cancer are those who have a lifetime risk of
greater than 17% but less than 30% to age 80 years using a validated risk model such as
CanRisk or iPrevent
- High risk:
o Women at greater than 30% lifetime risk of breast cancer (or greater than 8% risk between
age 40 and 50 years) using a validated risk model such as CanRisk or iPrevent

Moderate risk Medical Consider use of medication to reduce risk of developing breast cancer:
(17-30%): - Pre-menopausal women from age 35 years may consider
Exclusions: tamoxifen
BRCA, - Post-menopausal women may consider raloxifene, aromatase
Ashkenazi Jew inhibitors (anastrozole, letrozole, exemestane) or tamoxifen
Surveillance Age 40-50 - Recommend annual mammogram
Age >50 - Recommend mammogram every second year. Consider annual
mammogram in women with additional risk factors
Surgical Risk-reducing mastectomy is generally not recommended
High risk Medical Consider use of medication to reduce risk of developing breast cancer:
(>30%): - Pre-menopausal women from age 35 years may consider
Exclusions: tamoxifen
BRCA - Post-menopausal women may consider raloxifene, aromatase
inhibitors (anastrozole, letrozole, exemestane) or tamoxifen
Surveillance Age <40 – Annual MRI
Age >40 – Annual MMG+US, consider annual MRI if dense breasts
Surgical Discuss bilateral risk-reducing mastectomy

Who is eligible for breast MRI?

- High risk breast cancer gene mutation in patient or first degree relative
- Both:
o First or second degree relative diagnosed with breast cancer at age <45
o Another first or second degree relative on the same side diagnosed with bone or soft tissue
sarcoma at age <45
- Personal history of breast cancer <50 years old
- Personal history of mantle radiation
- Lifetime risk >30% on iPrevent or CanRisk

What type of mastectomy to offer BRCA and when?

- Immediate vs Delayed
- Implant vs Autologous

Immediate Delayed
Psychologically better Pathology known – plant adj tx
Risk of radiation may prevent immediate recon Two stage implant
Nipple preservation possible Preferred for autologous
Risks delay in adjuvant tx due to recovery

Implant Autologous
 Direct implant Use post radiation
2- stage with tissue expander Natural feel
Avoid in radiation Two donor sites - tummy tuck
Less natural feel Larger surgery and recovery
Replace 10 y

What are the indications for post mastectomy RT AND indications for nodal irradiation?
- pT3N+, pT4Nany, pTanyN2/3
- Consider for pT1-2N1, pT3N0 depending upon presence of additional risk factors.
o Presence of lymphovascular space invasion (LVI)
o High tumour grade
o Multifocal or multicentric tumours
o Nodal burden
o Young age
o ER negative
- Positive surgical margins
- Inflammatory breast cancer
- Postive nodal disease on ALNCD

Indications for adjuvant chemotherapy?

- All high risk patients where benefit>risks
- All HER2+ even ER+
- All TNBC
- T1a N0 – no chemotherapy
- T1b + N0 – chemotherapy

When to offer nipple sparing mastectomy vs skin sparing mastectomy in RRM?