Pathophysiology
of breast cancer
of breast cancer
anatomy of breast
subtypes and rare variants
investigation and diagnosis
treatment and management
100
which tumour suppressor genes increase breast cancer risk when mutated ?
BRCA1, BRCA2, PTEN, PALB2
100
what are the main tissue layers of the breast
glandular (lobules)
fibrous (connective tissue)
adipose tissue
100
what is the most common subtype of invasive breast cancer ?
invasive ductal carcinoma
100
what age group is invited for mammograms and how frequently
in the UK women between the age 50-71 are invited every three years
100
what are the treatment options for breast cancer
- Mastectomy
-Lumpectomy
-chemotherapy
-radiotherapy
-hormone therapy
200
explain how BRCA1 and BRCA2 mutations lead to breast cancer
BRCA1 and BRCA2 repair double-strand DNA breaks via homologous recombination. Mutations disable repair → accumulation of mutations, chromosomal instability, and malignant transformation.
BRCA1 mutation - usually more aggressive cancer (triple negative)
BRCA2 mutation - less aggressive (triple positive)
200
what structure connects lobules to the nipple?
lactiferous ducts
200
what type of breast cancer presents with peau d'orange skin?
And what are other symptoms of this type of breast cancer
inflammatory breast cancer
- erythema
- swelling
- warmth
-pain
-nipple changes (flattened, inverted)
200
what are the clinical features of breast cancer
painless lump
nipple discharge
lumps
skin changes
general cancer symptoms e.g. weight loss, night sweats
200
how is tamoxifen used to treat hormone receptor positive breast cancer
tamoxifen is a selective estrogen receptor modulator, it binfs to estrogen receptors on breast cells and acts as an antagonists in breast tissue
300
why is obesity a risk factor for ER-positive breast cancer?
- adipose tissue can convert androgens into estrogen through an enzyme called aromatase.
- Increased aromatase in adipose tissue produces more oestrogen
- increases estrogen exposure increases ER-mediated transcription of growth genes, and estrogen metabolism produces reactive oxygen species that can damage DNA
300
which arteries supply the breast
internal thoracic (internal mammary) artery, particular from the second to fourth intercostal spaces supply the medial portion of the breast
the lateral thoracic artery, and branches from the axillary artery supply the lateral and superior portions
300
which subtype has the poorest prognosis and why?
triple negative - lacks targetable receptors, has high proliferation and early metastasis
300
Why is core needle biopsy preferred over fine needle aspiration for breast cancer diagnosis?
- it provides more and larger tissue samples, which increases the accuracy of the diagnosis and allows for necessary molecular testing like hormone receptor (HR) analysi.
- Preserves tissue architecture for receptor and grade assessment.
300
how is paclitaxel used to treat breast cancer
It is a chemotherapy drug. Paclitaxel is a taxane, it prevents dissasembly of microtubules in the cell blocking the G2/M phase leading to cell apoptosis. it targets rapidly dividing cells including cancer cells. often used in treating triple negative breast cancer
400
Why are ER-positive breast cancers more treatable but more likely to recur late (>5 years)?
They proliferate slowly but survive long-term under low-estrogen conditions via alternative signalling (e.g., growth factor pathways), leading to late recurrence after endocrine therapy.
400
what is the retromammary space, and how is it affected in breast cancer
this is the space between the breast and pectoral fascia.
if there is tumour invasion here this fixes the breast to the chest wall, reducing mobility on palpation. this is a sign of locally advanced disease.
this area is also used for breast reconstruction after a mastectomy
400
what are the different subtypes of breast cancer and their prognosis?
luminal A: ER+ and/or PR+, HER2-, ki-67 low (best prognosis and responds well to endocrine therapy)
Luminal B: ER+ and/or PR+, HER2-/+, ki-67 high (more aggressive, may require chemo +endocrine)
HER2- enriched: ER-/PR- , HER2+ (HER2 receptor targeted therapy)
triple negative: ER-/PR-, HER2- (agressive, chemotherapy and rediotherapy needed)
triple positive: ER+/PR+, HER2+ (better than triple negative but more aggressive than luminal A)
400
What clinical finding differentiates inflammatory breast cancer from mastitis in a non-lactating woman?
inflammatory breast cancer has a rapid onset, peau d'orange, changes to the nipple, usually only affects one breast,does not include fever and flu like symptoms and there will be a lack of response to antibiotics
400
what are the long term consequences and managements of mastectomy
consequences:
chronic pain, reduced shoulder mobility, numbness or altered sensation, pahntom breast sensation, scarring, loss of erotic sensation and sexual side effects, negatively effects body image, self esteem and femininity.
management:
breast reconstruction including: implant based reconstruction, autologous reconstruction, nipple-areola reconstruction.
phsyiotherapy for arm mobility and prevents lymphedema, counselling, support groups, sexual health therapy, special mastectomy bras and clothing, scar management, self-care
500
What is the role of PTEN in normal cells, and how does its loss contribute to oncogenesis?
PTEN dephosphorylates PIP3 → PIP2, turning off the PI3K/AKT pathway. Loss of PTEN leads to unchecked AKT activity, preventing apoptosis and promoting uncontrolled growth — common in hormone receptor–positive cancers.
500
draw a diagram including labels on a whiteboard
500
Explain the physiology behind Paget's disease of the breast
Paget cells (malignant glandular epithelial cells) migrate along the lactiferous ducts from an underlying ductal carcinoma to the skin of the nipple
these cells infiltrate the epidermis causing eczema like skin changes, causing redness,itching,pain,rash,discharge and nipple changes, which does not improve with topical steroids.
treatments include masectomy, and based of the underlying tumour hormonal, HER2 targeted or chemotherapy. And in rare cases where there isn't an underlying tumour central excision and radiotherapy.
500
A patient has a 2.5 cm ER+, HER2− , high Ki-67 tumour with 1 positive axillary node. What stage of breast cancer do they have? What subtype of breast cancer? and what treatment should they recieve?
T2 N1 M0
Luminal B (more proliferative and intermediate prognosis)
treatement:
mastectomy, axillary dissection, chemotherapy (e.g. paclitaxel) and radiotherapy. And hormone therapy e.g. tamoxifen
500
how is hormone therapy used to treat ER+/PR+ breast cancer
SERMs (selective estrogen receptor modulators) - e.g. tamoxifen blocks estrogen from activating in breast tissue
SERDs (selective estrogen receptor degraders) - e.g. fulvestrant binds to ER and casues receptor degradation
aromatase inhibitors - reduce estrogen production in peripheral tissues
ovarian supression - e.g. GnRH agonists, stops estrogen production in the ovaries