Lecture 13- Breast cancer Flashcards
What does normal breast tissue look like histologically?
- Composed of ducts and acinar arranged into lobules
- Ductal cells are cuboidal surrounded by myoepithelial cells allowing contraction of the duct
Prepubertal breast
– few lobules (before puberty male and female breasts are identical)
Menarche
– increase in number of lobules, increased volume of interlobular stroma
Menstrual cycle
– follicular phase lobules quiescent, after ovulation cell proliferation and stromal oedema, with menstruation see decrease in size of lobules
Pregnancy
– increase in size and number of lobules, decrease in stroma, secretory changes
breast during pregnancy:
- Less fibromuscular stroma
- Luminal cells become bigger and paler due to containment of colostrum (large lipid filled cells)
Cessation of lactation-
atrophy of lobules but not to former level
- Increasing age
- terminal duct lobular units (TDLUs) decrease in number and size, interlobular stroma replaced by adipose tissue (mammograms easier to interpret)
How can breast conditions present?
- Pain
- Palpable mass
- Nipple discharge
- Skin changes
- Lumpiness
- Mammographic abnormalities
Which breast conditions cause pain
- Physiological
- Cyclical and diffuse pain
- Ruptured cysts, injury and inflammation
- Non-cyclical and focal
- Occasionally presenting complaint is breast cancer
Which breast conditions cause palpable mass
- Causes include
- Normal nodularity
- Invasive carcinoma
- Fibroadenoma
- Cysts
- Most worrying if hard, craggy and fixed
- No women should be allowed to have a lump in the breast without a firm diagnosis
Which breast conditions cause mammographic abnormalities
- Worrying findings include
- densities and calcifications
- Densities – invasive carcinomas, fibroadenomas, cysts
- Calcifications – ductal carcinoma in situ (DCIS), benign changes
who are invited for mammographic screening
- Women between 47-73 years invited every 3
- years
Easier to detect lesions in breasts of
older women because they have more adipose tissue and breast is less dense (also more likely statistically to have invasive carcinoma)
Are breast conditions common?
- Breast symptoms and signs are common
- Most breast symptoms and signs will be benign
- Fibroadenoma most common benign tumour
- Breast cancer most common non-skin malignancy in women
- Mammographic screening increases detection of small invasive tumours and in situ carcinomas
(1) Fibroadenomas
Can occur at any age during reproductive period
– Often <30 years
(2) Phyllodes tumours (very similar to fibroadenomas
- Most present in 6th decade
- Have potential to be malignant but present much later
(3) Breast cancer
- Rare before 25 years (except for some familial cases)
- Incidence rises with age
- 77% occurs in women >50 years
- Average age at diagnosis is 64 years
- In UK:
- 45,500 new female cases and 300 new male cases a year
- 12,500 deaths per year
How do we classify pathological conditions of the breast?
- Disorders of development
- E.g.Extra nipples
- Inflammatory conditions
- Benign epithelial lesions
- Stromal tumours
- Gynaecomastia
- Breast carcinoma
inflammatory conditions
acute mastitis
fat necrosis
(1) Acute mastitis
- Almost always occurs during lactation
- Usually Staphylococcus aureus infection from nipple cracks and fissures
- Erythematous painful breast, often pyrexia
- May produce breast abscesses
- Usually treated by expressing milk and antibiotics (stopping breast feeding)
2) Fat necrosis
- Presents as a mass, skin changes or mammographic abnormality
- Often history of trauma or surgery
- Can mimic carcinoma clinically and mammographically
Benign epithelial lesions
Fibrocystic change
- Commonest breast lesion
- May present as a mass or mammographic abnormality
- Mass often disappears after fine needle aspiration (FNA)
- Histology – cyst formation, fibrosis and apocrine metaplasia
- Can mimic carcinoma clinically and mammographically
- Dilated ducts
- Metaplasia- apocrine cell
stromal tumours e.g.
e.g., fibroadenoma, phyllodes tumours, lipoma, leiomyoma, hamartoma
Fibroadenomas
- Present with a mass, usually mobile, or mammographic abnormality
- ‘Breast mouse’ – mobile and elusive
- Can be multiple and bilateral
- Can grow very large and replace most of the breast
- Macroscopically - well circumscribed, rubbery, greyish/white
- Histology - composed of a mixture of stromal and epithelial elements
- Can mimic carcinoma clinically and mammographically
- Localised hyperplasia rather than true neoplasm
what do fibroadenomas look like
- Glandular and stromal elements
Gyaecomastia
- Enlargement of male breast
- Unilateral or bilateral
- Often seen at puberty and in the elderly
- Can mimic male breast cancer especially if unilateral
- No increased risk of cancer
gynaecomastia caused by
Caused by relative decrease in androgen (testosterone) effect or increase in oestrogen effect
What causes gynaecomastia
- Occurs in most neonates secondary to circulating maternal and placental oestrogens and progesterone
- Transient gynaecomastia affects more than half of boys in puberty as oestrogen production peaks earlier than that of testosterone
- Klinefelter’s syndrome
- Oestrogen excess - cirrhosis of the liver (when oestrogen not metabolised effectively)
- Gonadotrophin excess - functioning testicular tumour, e.g., Leydig and Sertoli cell tumours, testicular germ cell tumours
- Drug-related – spironolactone, chlorpromazine, digitalis, cimetidine, alcohol, marijuana, heroin , anabolic steroids
most type of breast cancers are
adenocarcinomas
- Most common in the upper outer quadrant (50%)
- Other malignant tumours are very rare e.g. primary sarcomas such as angiosarcoma
Risk factors of breast cancer
Major risk factors are related to hormone exposure
- Gender
- Uninterrupted menses
- Early menarche (< 11 years)
- Late menopause
- Reproductive history - parity and age at first full term pregnancy
- Breast-feeding
- Obesity and high fat diet
- Exogenous oestrogens – HRT slightly increases risk (1.2-1.7 times), long term users of COCP possibly have an increased risk
- Breast density
- Geographic influence
- Higher incidence in US and Europe
- Possible explanations include diet, physical activity, breast-feeding, environmental factors, alcohol consumption
- Atypical changes on previous biopsy (4-5 times)
- Previous breast cancer (10 times)
- Radiation
- Increased risk with previous exposure to therapeutic radiation (especially in childhood or adolescence), e.g. mantle radiation for Hodgkin’s lymphoma
- Genetics
NAME THE GENES ASSOCIATED WITH BREAST CANCER
- 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
- Another gene involved in hereditary breast cancer is P53 (Li-Fraumeni syndrome)
Li-Fraumeni syndrome
Another gene involved in hereditary breast cancer is p53
What is pagets disease?
- Cells can extend to nipple skin without crossing BM = Paget’s disease
- Unilateral red and crusting nipple
- Eczematous or inflammatory conditions of the nipple should be regarded as suspicious and biopsy performed to exclude Paget’s disease
- Requires further investigation
how do we classify breast carcinoma
- in situ
- invasive
- ductal
- lobular
In situ carcinoma
- Neoplastic population of cells limited to ducts and lobules by basement membrane (BM), myoepithelial cells are preserved
- Does not invade into vessels and therefore cannot metastasise or kill the patient
Whys is Ductal carcinoma in situ (DCIS) a problem?
- Non-obligate precursor of invasive carcinoma
- Presentation
- Mammographic calcifications (clusters or linear and rbanching and can be seen as a mass)
- Can spread through ducts and lobules and be very extensive
- Histologically often shows central necrosis with calcification
Invasive carcinoma
- Neoplastic cells have invaded beyond BM into stroma
- Can invade into vessels and can therefore metastasize to lymph nodes and other sites
- Usually presents as a mass or as mammographic abnormality
- By the time a cancer is palpable more than half of the patients will have axillary lymph node metastases
- Peau d’orange – involvment of lymphatic drainage of skin
why do we always refer if nipples inverted
tumour may be tethered to nipple
Carcinomas can be ductal or lobular:
- Invasive ductal carcinoma, no special type (Invasive ductal Carcinoma No special type (IDC NST))
- 70-80%
- Well-differentiated type – tubules lined by atypical cells
- Poorly differentiated type – sheets of pleomorphic cells
- 35-50% 10 year survival
Invasive lobular carcinoma
- 5-15%
- Infiltrating cells in a single file, cells lack cohesion
- Similar prognosis to IDC NST
other types of breast carcinoma
Other types, e.g. tubular (1-2%, excellent prognosis), mucinous (1-6%, excellent prognosis, often older women)
what does invasive breast carcinoma look like?
- Irregular
- Condensed part which tugs other tissue in e.g. inverted nipple or breast dimple
invasive ductal carcinoma NST histology
invasive lobular carcinoma histology
- Very small and can resemble lymphocytes
- Infiltrate very subtilty in the stroma
- Don’t always form a palpable mass
mucinous carcinoma histology
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
What factors determine prognosis in breast cancer?
- In situ disease (cant really be fatal) 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
which breast cancer has a poorer prognosis
IDC NST
Tumour grade
- Grade 3- doesn’t resemble tissue of origin- poorly differentiated
the higher the grade the less differentiated
molecular classififaction of breast carcinomas
oestrogen receptor postive and negative
both oestrogen receptor positive and negative carcinoma can be either
Her2 positive or negative
- Oestrogen receptor positive=
better prognosis
Her2 positive and oestrogen positive=
better prognosis (can have Herceptin)
Oestrogen receptor negative and HER2 negative =
poor prognosis and usually BRCA1
How do we investigate and diagnose breast cancer?
- Triple approach
- Clinical – history, family history, examination
- Radiographic imaging – mammogram (in older) and ultrasound scan (in younger)
- Pathology – core biopsy and fine needle aspiration cytology (FNAC)
What is mammographic screening?
- Started in the UK in the late 1980s
- Women 47–73 years
- 2 view mammograms every 3 years
- Aim is to detect small impalpable cancers and pre-invasive cancer (incidence of DCIS has increased from 5% of breast cancers to 25% in screened populations)
- Look for asymmetric densities, parenchymal deformities, calcifications
- Assess abnormalities using further imaging, core biopsy and FNAC
What are the therapeutic approaches in breast cancer?
Local and regional control
- breast surgery
- axillary treatment
- poster-operative radiotherapy to chest and axilla
Systemic control
- chemotherapy
- hormonal treatment
- herceptin
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)
What is sentinel lymph node biopsy?
- Reduces the risk of postoperative morbidity
- Intraoperative lymphatic mapping with dye and/or radioactivity of the draining or ‘sentinel’ lymph node(s) – the one most likely to contain breast cancer metastases
- If the sentinel node(s) is negative axillary dissection can be avoided – e.g. avoid lymphodema
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)
- 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
How do we improve survival from breast cancer?
- Early detection – awareness of disease, importance of family history, self-examination, mammographic screening
- Neoadjuvant chemotherapy – early treatment of metastatic disease
- Use of newer therapies – e.g. Herceptin
- Gene expression profiles
- Prevention in familial cases
- genetic screening, prophylactic mastectomies
