Oncology - Breast Flashcards
What is the incidence of breast cancer?
- Most common cancer in women
- 1 in 8 women and 1 in 870 men will develop breast cancer
What are the 2 main types of breast carcinoma?
Beast cancers are typically adenocarcinomas
- Ductal carcinoma (85%) = epithelial lining of ducts
- Lobular carcinoma (15%) = epithelium of terminal ducts of lobule
Others: medullary, colloid, comedo and papillary.
Which breast carcinoma is more infiltrative?
Lobular carcinoma - it can present similarly to gynaecological cancers
What genes are associated with increased risk of breast cancer and what chromosomes are they found on?
BRCA1 - Chr17 (breast and ovarian cancer)
BRCA2 - Chr13 (early onset breast cancer and male breast cancer)
What risk factors associated with oestrogen exposure increase the risk of breast cancer?
Early menarche Late menopause HRT use Prolonged use of OCP? Obesity (especially post-menopause) Nullparity First child after 30
Where is oestrogen produced?
Premenopausal women – oestrogen produced in ovaries
Postmenopausal women – synthesis in fat cells (adipose tissue), skin, liver, muscle, breast
What is the most common presentation of breast cancer?
Breast lump
Hard, painless lump with irregular margins
Fixed to skin/chest wall
What are other common presentations of breast cancer aside from breast lump?
Breast pain Skin changes - peau d'orange, skin dimpling Nipple discharge Nipple changes - paget's disease Axillary lymphadenopathy
What causes peau d’orange?
Oedema due to lymphatic invasion from tumour
What questions are important to ask in a breast cancer history?
- How long?
- Change with cycle?
- Skin/nipple changes?
- Associated symptoms – discharge/pain?
- Related to menstrual cycle?
- Previous breast lumps? Previous cancer?
- Lumps under arm?
- Family history inc men
How do you investigate a suspected breast cancer?
Triple assessment
1) Examination - breast, axilla, supraclavicular fossa
2) Imaging
- bilateral mammogram
- targeted USS of the worrying area and axilla
3) Biopsy of the lump, and suspicious nodes (core biopsy done by USS)
- The biopsy will state if it is cancer, what type of cancer, grade of cancer, tumour markers
- Bone scan and full CT can be done if concerned about metastatic disease
- MRI instead of mammogram if a lot of breast tissue, or suspected lobular
What is the treatment of choice for LOCALISED disease in breast cancer?
Surgery
Either:
- Wide local excision/lumpectomy to remove lump with postoperative radiotherapy (always chemo after)
- Mastectomy to remove breast (chemo if high recurrence risk)
In breast cancer surgery, when would we clear the axilla?
Axilla clearance
- if the USS/biopsy show +LN involvement then clear axilla
- if the USS/biopsy show no LN involvement then do sentinel node biopsy day before surgery to check> if +ve then clear axilla
What is required in ALL breast cancer patients after CONSERVATIVE surgery (wide local excision/lumpectomy)?
- Adjuvant radiotherapy to residual breast tissue +/- lymph node areas
- Reduces risk of local relapse by HALF
- Monday-Friday for 3 WEEKS
- (40 Grey in 15 fractions over 3 weeks)
- Boost to tumour bed (10Gy in 5 fractions) in high risk disease
What adjuvant therapy is given to patients with breast cancer?
Adjuvant therapy for breast cancer depends on patient:
- Adjuvant chemotherapy-especially <50 years (Oncotype DX is a genomic test designed to predict benefit from chemotherapy)
- Targetted therapy (Herceptin/Trastuzamab) if HER2+
- Endocrine Therapy (Tamoxifen or Aromatase Inhibitors-postmenapausal) if ER/PR+
-Adjuvant radiotherapy
•all patients after CONSERVATIVE surgery
• some patients after mastectomy in those who have high risk occurrence (multiple lymph nodes, large tumours)
What endocrine therapy is only useful in post-menopausal women?
Why?
Aromatase inhibitors (Anastrozole, Letrozole, Exemestane )
They stop oestrogen production outside the ovaries by blocking the action of aromatase enzyme (prevents conversion of cholesterol to oestrogen in fat cells)
What are some side effects of aromatase inhibitors?
Aromatase inhibitors side effects (Anastrozole, Letrozole, Exemestane )
- Mood changes
- Vaginal dryness
- Loss of libido
- Muscle and joint pain (Myalgia, Arthralgia)
-Decreased bone density-osteoporosis- do a DEXA bone scan as a baseline before starting and monitor bone health (consider VitD, Ca supplements and bisphosphonates)
What endocrine therapy is ONLY useful in pre-menopausal women?
Ovarian ablation. This stops the ovaries from producing oestrogen. Can also use luteinizing hormone releasing hormone (LHRH) agonists.
What endocrine therapy can be used in pre- and post-menopausal breast cancer patients?
Oral Tamoxifen (give for 5 years)
What risk should you council patients about tamoxifen? (2)
Come back in if:
-Episode of post menopausal bleeding/abnormal bleeding (ENDOMETRIAL CANCER)
-Sudden onset leg pain/breathlessness (DVT/PE)
(although it has antioestrogenic activity, it also produces oestrogen-like effects at some receptors)
What is HER-2?
What is its relation to breast cancer?
HER-2 is an endothelial factor receptor oncoprotein that allow rapid multiplication of the cell
20% breast cancers overexpress HER-2
What drug can be used in HER2 positive breast cancers?
How does it work?
How is its given?/how long for?
Herceptin = transtazumab (monoclonal antibody)
what: Monoclonal Ab against Her-2 protein, blocks cell signalling pathways (not chemo)
how: Give IV or S/C every 3 weeks for 12 months
What is a risk of herceptin treatment?
How do we prevent this?
Cardiotoxicity
i.e. it makes the heart baggy
It is reversible
monitor cardiac function with MUGA scan
Which breast cancers are most responsive to chemotherapy?
ER-negative (EaRN)
HER2-positive (HERP)
What chemotherapy drugs are typically used in breast cancer?
How does the therapy change if no lymph nodes involved?
EC (epirubicin + cyclophosphamide) for 3 cycles
Docetaxel for 3 cycles
(if no lymph nodes involved, only EC for 6 cycles)
What chemotherapy agents can be given for breast cancer that is ER positive and HER2 negative?
CDK4/6 inhibitors (end in lib) (used alongside hormone therapy)
What are some poor prognostic indicators in breast cancer?
Triple negative (nothing to act on) HER2 positive (give chemo) ER/PR negative (give chemo) High TNM stage Lymph node involvement >5cm mass Higher grade (3>2>1)
What is TNM staging for breast cancer?
T0 No primary tumour Tis In situ disease, non invasive T1 Invasive tumour less than 2 cm T2 Tumour between 2 and 5 cm T3 Primary tumour greater than 5 cm T4 Skin involvement
N0 No lymph nodes N1 Mobile axillary nodes N2 Fixed axillary nodes N3 Internal mammary nodes
M0
No metastases
M1 Distant metastases
When would we give neo-adjuvant chemo (chemo before surgery) to patients with breast cancer?
Neoadjuvant chemotherapy is considered when:
○ The SIZE of the tumour makes initial surgery impossible - or it is the woman’s preference so that she might have a lumpectomy and not a mastectomy
○ Deemed the best way to preserve breast tissue
○HER2 positive or triple negative breast cancer (ER, PR and HER2 negative)
Side effects of tamoxifen?
tamoxifen causes post manopausal symptoms
- hot flushes
- mood changes
- loss of libido
- changes in vaginal discharge
- weight change
When are women screened for breast cancer?
Screening
- Women aged 50 - 70 years
- EVERY 3 YEARS
- MAMMOGRAM
- Screening is the route with the highest proportion of breast cancers diagnosed at an early stage
How is metastatic breast cancer managed?
If the patient presents with metastases or is placed in stage 4 after assessment, surgery is not part of the treatment unless to palliate some particular site of disease
Endocrine (tamoxifen, aromatase)
○ If ER/PR positive and the disease is slowly progressing
○ Best responce in soft tissue>bone mets>visceral mets
○Median duration of response is 1-2 years
Chemotherapy
○ Palliate symptoms to help improve quality/duration of life.
Radiotherapy
○Palliation of locally recurrent disease and controlling symptoms such as pain from bony mets
What is the predict tool?
Predicts how breast cancer will respond to therapies- 5 year survival
What is Paget’s disease of the breast?
Infiltrating carcinoma of nipple epithelium
Does the presence of HER2 mean it is a more/less aggressive disease?
More aggressive disease if HER2 (causes rapid multiplication of the cell)
