Breast cancer Flashcards
Epidemiology
Most common cancer in women
2nd deadliset cancer in UK
RFs
Increased hormone exposure
- Early menarche or late menopause
- Nulliparity or late first pregnancy
- Oral contraceptives or HRT
BRCA mutations (BRCA1/BRCA2)
Advancing age
Caucasian ethnicity
Obesity and lack of physical activity
Alcohol and tobacco use
History of breast cancer
Previous radiotherapy treatment
BC screening
3 yearly mammogram (x-ray)
caudal-cranial (CC) and mediolateral oblique (MLO) views for all women aged 50-70
Women over the age of 70 are able to self-refer for screening every 3 years if they wish.
2ww
They are ≥30yo with an unexplained breast mass (regardless of whether there is pain present or not)
They are ≥50yo or older presenting with nipple discharge, retraction or other concerning symptoms.
Consider referral if there are skin changes suggestive of breast cancer or if the patient is 30 years or older with an unexplained mass in the axilla
Histological subtypes
M/C: Ductal carcinoma or Lobular carcinoma
Either invasive or in-situ
Medullary carcinoma
Phyllodes tumour
Most common types of breast cancer
Invasive ductal carcinoma
Invasive lobular carcinoma
Ductal carcinoma-in-situ (DCIS)
Lobular carcinoma-in-situ (LCIS)
Ductal Carcinoma features
Most common form of breast tumour (75%)
Abnormal proliferation of ductal cells
The grade is considered higher as the ductal cells lose their acinar structure and their nuclei become abnormally large
If the basement membrane is NOT BREACHED then it is considered ductal carcinoma in situ (DCIS).
Lobular carcinoma
Makes up about 15% of breast cancers
More likely to be bilateral and multi-centric
Abnormal proliferation of lobular cells, which arrange themselves in single rows. The cells are often SMALL, BLAND AND UNIFORM
Due to the sparse distribution of the tumour cells, they are FREQUENTLY IMPALPABLE or not appreciable as a discrete lump
If the basement membrane is NOT BREACHED then it is considered lobular carcinoma in situ (LCIS). These are frequently multifocal and impalpable.
Medullary Carcinoma features
More common in younger patients and those with BRCA1 mutations
Composed of solid sheets of anaplastic cells with large pleomorphic nuclei, prominent nucleoli and frequent mitoses
There is also often significant lymphocytic infiltration surrounding the tumour
Often has a better prognosis than ductal tumours.
Phyllodes tumor
This is rare (1% of breast tumours)
Composed of epithelial and stromal tissue which grows in a “leaf-like” pattern
Also called cystosarcoma phyllodes
Most (75%) are benign, with 25% being malignant
Other forms of breast cancer
mucinous, tubular, papillary and lymphoma.
Paget’s disease of the nipple
eczematoid change of the nipple associated with an underlying breast malignancy and it is present in 1-2% of patients with breast cancer. In half of these patients, it is associated with an underlying mass lesion and 90% of such patients will have an invasive carcinoma. 30% of patients without a mass lesion will still be found to have an underlying carcinoma. The remainder will have carcinoma in situ.
Inflammatory breast cancer
Blocked lymph nodes
Familial BC
M/C: BRCA1 and BRCA2.
Other rarer mutations include TP53 (Li-Fraumeni syndrome). PTEN, MLH1, MLH2, and STK11.
BRCA 1 vs BRCA2
BRCA1
Found on Ch17
Autosomal dominant inheritance
LT risk: 65-85%.
Assoc: ovarian cancer & PCP
high grade triple negative cancers.
*bilateral salpingo-oopherectomy is prophylactic surgery
BRCA2
Found on Ch13
Autosomal dominant inheritance
LT risk: 40-85%
Also ovarian cancer, but lower risk than BRCA1
oestrogen and progesterone receptor positive tumours
Hormonal Receptors in Breast Cancer
Oestrogen (ER)
Progesterone (PR)
HER2 (human epidermal growth factor receptor type 2)
Absence of ER or PR is a poor prognostic factor
Being “triple negative” (ER/PR/HER2) is associated with a younger age of diagnosis and worse overall survival.
Mx
ER positive tumours
- Premenopausal - Tamoxifen (oestrogen receptor antagonist)
-post-menopausal - Anastrozole (aromatase inhibitor) if postmenopausal.
HER2 positive tumours –> Trastuzumab (Herceptin) (monoclonal antibody for HER2 receptor)
BC triple assessment (if suspicious of breast cancer)
- Clinical examination: of the breast and surrounding lymph nodes
- Radiological examination: m/c mammography, but possibly USS and MRI
- Biopsy: typically a core needle biopsy or fine needle aspirate (FNA)
If the lesion is large or there is suspicion of malignancy following mammography and/or ultrasound, the patient may be referred for a
core needle biopsy over a fine needle aspirate, which is capable of providing histological information as well as cytological.
Management: surgical
wide local excision (WLE) or mastectomy
WLE
- smaller, solitary lesions which are peripherally located. It depends on there being enough breast left behind to close the wound with acceptable cosmetic results
- DCIS <4cm
- Sentinel node biopsies
Axillary node clearance may be necessary if there are positive nodes
Sentinel node
the first lymph node to which cancer cells are most likely to spread from a primary tumor –> in BC it’s the axillary
Mx: radiotherapy
wide local excision OR mastectomy patients with higher cancer stages (i.e. T3 or 4 or positive nodes)
Mx: chemotherapy
hormone receptor negative and HER2 over-expressing patients
Sometimes neoadjuvant chemotherapy is given to downstage tumours before surgery.
Tamoxifen indications
Pro-drug –> afimoxifene and endoxifen (competitive oestrogen receptor antagonists)
Current recommendation is 5 years of Tamoxifen therapy following surgical treatment of oestrogen receptor positive breast cancer in premenopausal women.
Tamoxifen SEs
Hot flushes
Nausea
Vaginal bleeding and discharge
Weight gain
Increased risk of DVT/PE
Increased risk of endometrial cancer – the drug is a weak agonist on endometrial tissue
