causes of nipple discharge
- Duct ectasia>> greenish
- Intraduct papilloma
- Associated with a cyst
What does normal breast tissue look like histologically?
What is the breast tissue actually?
Modified sweat glands
•Non-functional except during lactation
•Lobules = acini and intralobular stroma
How can breast cancer present?
• Most common in the upper outer quadrant
(approximately 50% occur here)
– Most worrying if hard, craggy or fixed
– Bloody or serous (not milky) – Spontaneous and unilateral
Is breast cancer common?
average age at diagnosis?
Most common non-skin malignancy in women
- Accounts for 20% of all malignancies in women
- Incidence rises with age
- 77% occurs in women >50 years
- Average age at diagnosis is 64 years
- Rare before 25 years (except for some familial cases)
Male breast cancer
when do they have Increased risk?
1% of all cases of breast cancer
– Increased risk with Klinefelter’s syndrome, male to female transsexuals, men treated with oestrogen for prostate cancer
What are the risk factors for breast cancer?
what decreases risk for breast cancer?
• Major risk factors are related to hormone exposure
– Uninterrupted menses
– Early menarche (< 11 years)
– Late menopause
– Reproductive history - parity and age at first full term pregnancy
– Obesity and high fat diet
– Exogenous oestrogens – HRT slightly increases risk (1.2-1.7 times), long term users of OCP possibly have an increased risk
Higher incidence in which countries?
– Higher incidence in US and Europe
Hereditary breast cancer
what must carriers do?
Lifetime breast cancer risk for female carriers (%)
10% of breast cancers
– 3% of all breast cancers and 25% of familial cancers attributed to mutations in BRCA1 (BReast CAncer associated gene 1) or BRCA2
• Both tumour suppressor genes – their proteins repair damaged DNA
• 0.1% of population has BRCA1 germline mutations
• Lifetime breast cancer risk for female carriers is 60-85%
• Median age at diagnosis is approximately 20 years earlier than sporadic cases
• Carriers may undergo prophylactic mastectomies
How do we diagnose breast cancer?
• Triple approach
– Clinical – history, family history, examination
– Radiographic imaging – mammogram and ultrasound scan
– Pathology – core biopsy and fine needle aspiration cytology (FNAC)
How do we classify breast carcinoma?
Approximately 95% are adenocarcinomas
• Adenocarcinomas divided into in situ (ductal carcinoma in situ = DCIS) and invasive
• Invasive carcinomas classified by histological type:
– E.g., ductal, lobular, tubular, mucinous
What is DCIS?
- Neoplastic population of cells LIMITED to ducts and lobules by basement membrane, myoepithelial cells are preserved
- Does not invade into vessels and therefore cannot metastasise or kill the patient
- 3 grades showing increasing cytological atypia – low, intermediate and high
So why is ductal carcinoma in situ (DCIS) a problem then?
- Non-obligate precursor of invasive carcinoma
- High grade more likely to become invasive and produce a poor prognosis invasive tumour
- Can spread through ducts and lobules and be very extensive
How is DCIS likely to present histologically?
Histologically often shows central (comedo) necrosis with calcification
How is DCIS likely to present on a mammogram?
• Most often presents as mammographic calcifications
- clusters or linear and branching
- but can present as a mass
How does invasive carcinoma differ from DCIS?
What breast changes can you see with breast cancer?
How is invasive breast carcinoma classified?
What does invasive breast carcinoma look like?
Explain what u see?
what is this showing?
invasive LOBULAR carcinoma
what is this showing?
what is this showing?
How do we grade invasive Breast carcinoma
How does tumour grade effect survival?
How does breast cancer spread?
- Lymph nodes via lymphatics– usually in the ipsilateral axilla
- Distant metastases via blood vessels – bones (most frequent site), lungs, liver, brain
- Invasive lobular carcinoma can spread to odd sites – peritoneum, retroperitoneum, leptomeninges, gastrointestinal tract, ovaries, uterus
What factors determine prognosis in breast cancer?
• In situ disease or invasive carcinoma
• Tumour stage:
- Tumour size and locally advanced disease – invading into skin or skeletal muscle
- Lymph Node metastases
- Distant Metastases
• Tumour grade
• Histologic subtype – IDC NST has poorer prognosis
• Molecular classification and gene expression profile
What is a gene expression profile and why is it important in breast cancer?
Microarrays have been used to examine the
expression patterns of some 25,000 genes in tissues from breast cancer patients.
Computer cluster analysis of the patterns led to the identification of about 17 marker genes that can correctly identify about 90% of women who would eventually develop metastases.
What are the therapeutic approaches in breast cancer?
• Local and regional control – DCIS and invasive carcinoma
– Breast surgery – mastectomy or breast conserving surgery – decision depends on patient choice, size and site of tumour, number of tumours, size of breast
– Axillary surgery – extent depending on whether there are involved nodes (sentinel node sampling or axillary dissection)
– Post-operative radiotherapy to chest and axilla
- Systemic control – invasive carcinoma only
– Chemotherapy – if benefits thought to outweigh the risks; if given before surgery = neoadjuvant
– Hormonal treatment, e.g. tamoxifen – depending on oestrogen receptor status (approximately 80% of cancers are ER positive)
– Herceptin treatment – depending on Her2 receptor status (approximately 20% of cancers are Her2 positive)
what is Her2 ? Herceptiin?
Her2 is a member of the human epidermal growth factor receptor family
Encodes a transmembrane tyrosine kinase receptor
Herceptin = trastuzumab = humanised monoclonal antibodies against the Her2 protein
what do these show?