7 - Breast Flashcards
What are the risk factors for breast cancer?
THINK ABOUT OESTROGEN EXPOSURE
- Female gender
- Age
- Family history
- Personal history of breast cancer
- Genetic predispositions (e.g. BRCA 1, BRCA 2)
- Early menarche and late menopause
- Nulliparity
- Increased age of first pregnancy
- Multiparity (risk increased in period after birth, then protective later in life)
- Combined oral contraceptive
- Hormone replacement therapy
- White ethnicity
- Exposure to radiation
- Obesity
What type of HRT increases the risk of breast cancer?
Combined!!!!!
COCP also raises risk but risk back to normal after 10 years of stopping
What are the BRCA mutations and what do they increase the risk of?
BRCA 1
Mutation on chromosome 17
Breast cancer risk of 65-80%
Risk of ovarian cancer is 40-45%
BRCA 2
Mutation on chromosome 13
Breast cancer risk of 45-70%
Risk of ovarian cancer is 11-25%.
Baseline breast cancer risk is 12%
Base line ovarian cancer risk is 1.3%
Prostate and pancreatic cancer risk worse in BRCA 2
Also known to increase the risk of peritoneal, endometrial, fallopian, pancreatic and prostate cancer.
What type of genes are BRCA1 and 2 and what are some other genes that predispose to breast cancer?
Tumour suppressor genes
TP53 and PTEN genes
What are the different types of breast cancer and where in the breast do they arise from?
- Ductal carcinoma in situ
- Invasive ductal carcinoma (MOST COMMON)
- Lobular carcinoma in situ
- Invasive lobular carcinoma
- Inflammatory breast cancer
- Paget’s disease
- Medullary
- Mucinous
- Tubular
What is special type vs non-special type breast cancer?
- Non-special type is invasive ductal carcinoma
- Special type is any lobular carcinomas, any ductal carcinoma in situ and others
What is Paget’s disease of the nipple and inflammatory breast cancer?
Inflammatory Breast Cancer
- 1-3% of breast cancers
- Cancer cells block lymphatic drainage so inflammed swollen breast
- Presents similarly to a breast abscess or mastitis
- Swollen, warm, tender breast with pitting skin (peau d’orange)
- Does not respond to antibiotics
- Worse prognosis than other breast cancers
Paget’s Disease of the Nipple
- Looks like eczema of the nipple/areolar
- Erythematous, scaly rash
- Indicates breast cancer involving the nipple
- May represent DCIS or invasive breast cancer
- Requires biopsy, staging and treatment
What are the molecular subtypes of invasive breast cancer?
Depends on expression of oestrogen receptors, progesterone receptors, HER2 receptors and Ki67
- Luminal A
- Luminal B
- Basal
- HER2
Who in England is invited for breast cancer screening?
Women and trans-men/women aged 47-73 every 3 years (50-70 in the past)
May be invited younger if family history
What does breast screening involve and what are the different results?
Mammogram in caudal-cranial and mediolateral oblique views
- Satisfactory: no radiological evidence of breast cancer
- Abnormal: abnormality detected, further investigations needed. 25% of these will have cancer
- Unclear: results or imaging unclear or inadequate. Further investigations required
What are the pros and cons of breast cancer screening?
Pros
- Early detection of cancers
- Approximately 20% reduction in relative risk of death from breast cancer
- Can provide peace-of-mind for some patients
Cons
- Painful and undignified
- Not 100% sensitive (i.e. false negatives)
- Over treatment
- False positive results can be emotionally distressing for patients
- Exposure to radiation, with a very small risk of causing breast cancer
What patients are classed as being at ‘high-risk’ of breast cancer and need to be offered earlier screening?
- A first-degree relative with breast cancer under 40 years
- A first-degree male relative with breast cancer
- A first-degree relative with bilateral breast cancer, first diagnosed under 50 years
- Two first-degree relatives with breast cancer
What can people at high risk of breast cancer be offered?
- Genetic testing with pre-test counselling
- Annual mammogram potentially starting from aged 30
- Chemoprevention: Tamoxifen if premenopausal, Anastrozole if postmenopausal (except with severe osteoporosis)
- Risk-reducing bilateral mastectomy or bilateral oophorectomy
How may breast cancer present?
- Asymptomatic: picked up on screening
- Breast pain
- Axilla or breast lump
- Changes to skin on breast
- Changes to nipples: inversion, discharge
- Lymphadenopathy
- Metastatic complications: bone pain, headaches, seizures, SOB, jaundice etc
What is the referral criteria for a 2 week wait for breast cancer?
- >30 with unexplained breast lump with or without pain or
-
>50 with any of the following symptoms in one nipple only:
- Discharge
- Retraction
- Other changes of concern
- With skin changes that suggest breast cancer
- >30 with an unexplained lump in the axilla
What is the criteria for a non-urgent referral for breast changes?
Under 30 with unexplained breast lump with or without pain
What does in situ mean for a cancer?
Basement membrane is not breached
What investigations are done for a 2 week wait for breast cancer?
One Stop Clinic for triple assessment
- History and Examination
- Imaging: US if <40, mammogram if >40
- Histology: fine needle aspiration or core biopsy
What signs can a mammogram and US pick up that are suggestive of breast cancer?
- Mammogram: calcifications
- US: can tell cystic from solid lumps
If a triple assessment confirms breast cancer, what further investigations need to be done for the patient?
All with the aim to stage and look for metastases
Bloods
- FBC
- U+Es
- LFT
- Bone profile
Imaging
- CXR
- MRI breast: helps to guide treatment and plan surgery
- CT chest, abdo, pelvis
- CT brain: In symptomatic patients with suspected neurological spread.
- Contrast-enhanced liver USS
- Bone scan
Receptor Testing
- ER
- PR
- HER2 (human epidermal growth receptor)
Axilla Lymph Nodes
- FNA OR
- Sentinel node biopsy whilst having surgery
Genetic Testing
- If <50 and triple negative consider looking for BRCA½
What is gene expression profiling?
Assessing which genes are present within the breast cancer on a histology sample
Helps predict the probability that the breast cancer will reoccur as a distal metastasis (away from the original cancer site) within 10 years
Recommend this for women with early breast cancers that are ER positive but HER2 and lymph node negative. It helps guide whether to give additional chemotherapy
What are the main sites of metastases for breast cancer?
Liver
Lungs
Brain
Bones
How is breast cancer staged?
TNM
- Lymph node assessment and biopsy
- MRI of the breast and axilla
- Liver USfor liver metastasis
- CT of the thorax, abdomen and pelvis
- Isotope bone scan for bony metastasis
What are the principles of management for breast cancer?
MDT APPROACH
Treated as early-stage, locally advanced and advanced metastatic disease
Surgery is often used in treatment of early breast cancer. What are the different surgeries done?
Resection of tumour
- Conservative: wide local excision
- Mastectomy
Lymph Nodes
- Do sentinel lymph node biopsy
- Axillary clearance if above shows needed
Reconstruction
What needs to be done before resection surgery for breast cancer?
- If no palpable axillary lymph nodes: axilla US, if positive need sentinel lymph node biopsy in surgery
- If palpable axillary lymph nodes: do lymph node clearance regardless
What are the risks of axillary node clearance?
- Chronic lymphoedema
- Functional arm impairment
- Seroma formation
How can lymphedema from breast cancer surgery be managed?
- Massage techniques to manually drain the lymphatic system
- Compression bandages
- Specific lymphoedema exercises to improve lymph drainage
- Weight loss if overweight
- Good skin care
How do you decide between a mastectomy and wide local excision?
Wide Local Excision (WLE)
- Most common, need 1cm margin of macroscopically normal tissue with malignancy
- Only suitable for focal smaller cancers
- Dependent on location and relative size of breast
Mastectomy
- Indicated in cases of multifocal disease, high tumour:breast tissue ratio, disease recurrence, or patient choice
- Amount of skin left behind depends on type of reconstruction planned
What are the different types of reconstructive breast surgery?
Immediate or delayed
After breast-conserving surgery (WLE)
- Partial reconstruction (using a flap or fat tissue to fill the gap)
- Reduction and reshaping (removing tissue and reshaping both breasts to match)
After mastectomy:
- Breast implants
- Flap reconstruction (using tissue from another part of body to reconstruct breast)
What are the different types of flap reconstruction breast surgery?
Latissimus Dorsi Flap
“Pedicled”: keeping original blood supply and moving tissue under skin to new location
“Free flap”: cutting tissue away completely and transplanting it to new location
Transverse Rectus Abdominis Flap (TRAM Flap)
Pedicled or free flap
Risk of abdominal hernia
Deep Inferior Epigastric Perforator Flap (DIEP Flap)
Free flap. The deep inferior epigastric artery, with the associated fat, skin and veins, is transplanted from the abdomen to the breast. The vessels are attached to branches of the internal mammary artery and vein
This is a complex procedure involving microsurgery
Less risk of an abdominal wall hernia as abdominal wall muscles left intact
When is radiotherapy for breast cancer used?
Adjunct to surgery
WLE: given to all patients, whole breast if invasive, partial breast if in situ
After mastectomy: Offer only if positive resection margins, tumour size >5cm, or 4 or more pathological nodes in axilla (T3/T4)
Lymph nodes: not given if axilla was negative or after lymph node clearance
What is the aim of radiotherapy after breast surgery and what are the side effects of this?
Aim is to reduce recurrence, by around ⅔rds
- General fatigue from radiation
- Local skin and tissue irritation and swelling
- Fibrosis of breast tissue
- Shrinking of breast tissue
- Long term skin colour changes (usually darker)
When is chemotherapy given in breast cancer?
- Usually neoadjuvant before surgery to shrink primary tumour so can do breast-conserving surgery rather than mastectomy
- If given adjuvantly it is to try and prevent recurrence
What hormone therapy is given in breast cancer and how does it work as a treatment?
Patients with ER/PR positive disease are offered adjuvant endocrine therapy
- Tamoxifen: Selective Estrogen Receptor Modulator SERM used first-line in men and pre-menopausal women. It blocks oestrogen receptors in breast tissue, and stimulates oestrogen receptors in the uterus and bones. Therefore protective against osteoporosis
- Aromatase inhibitors (e.g. anastrozole): Used first-line in post-menopausal women who are at high or medium risk of disease recurrence. Inhibits peripheral conversion of androgens to oestrogens. Alone they are not effective in premenopausal women where oestrogens are primarily synthesised by the ovaries
What are some of the side effects of the hormone therapy for breast cancer and how long is hormone therapy used for?
Given after adjuvant chemotherapy, given for 5 years to try to prevent recurrence
Tamoxifen
- Blood clots
- Hot flushes
- Nausea
- Vaginal bleeding
- Endometrial cancer
- Should not become pregnant whilst on it or for 2 months post-treatment
Aromatase Inhibitors
- Menopausal symptoms
- Osteoporosis
- MSK pain
If a pre-menopausal woman has breast cancer that is ER+, what can be done other than giving her tamoxifen?
Ovarian function suppression:
- GnRH analogue (e.g. goserelin)
- Laparoscopic oophorectomy
- Fulvestrant (selective oestrogen receptor downregulator)
Give three examples of aromatase inhibitors?
- Letrozole
- Anastrozole
- Exemestane
What biologics (immunotherapy) can be used in breast cancer treatment and when?
Need to be HER2+ve
Trastuzumab (Herceptin): monoclonal antibody that targets the HER2 receptor
Pertuzumab (Perjeta) is another monoclonal antibody that targets the HER2 receptor
Neratinib (Nerlynx) is a tyrosine kinase inhibitor, reducing the growth of breast cancers. It may be used in patients with HER2 positive breast cancer
What are the side effects of Trastuzumab?
Given every 3 weeks for 1 year
- Cardiotoxic: cardiac function should be assessed prior to and during use
- Teratogenicity
How is metastatic breast cancer managed other than supportively?
Dependent on receptor status, ER, PR and HER2:
- Endocrine treatment with tamoxifen or anastrozole and targeted therapy with Herceptin may be used where receptor status is positive
Prevent lytic bone lesions, reduce bone pain and prevent fracture:
- Denosumab and bisphosphonates
What is the 5 year survival for breast cancer in general?
One Year
95.8%
Five years
85%
How is the prognosis of breast cancer calculated more accurately?
Nottingham Prognostic Index
Tumour Size x 0.2 + Lymph node score + Grade score
In this system the tumour size is weighted less heavily than other major prognostic parameters.
What factors determine prognosis in breast cancer?
- Tumour size
- Nodal involvement
- Grade
- Vascular invasion
- Receptor status
- Type of cancer
- Patient’s performance status and comorbidities
How are DCIS and LCIS usually diagnosed and how are they then managed?
DCIS
- Dx: detected as micro calcifications on screening
- Mx: Wide local excision
LCIS
- Dx: Incidental finding on biopsy of breast, no micro calcifications
- Mx: If low grade monitoring rather than excision
Why may an MRI instead of a mammogram be done in a triple assessment clinic?
Offer MRI to patients with invasive breast cancer:
– if there is discrepancy between the clinical and imaging assessment of disease extent
– if breast density precludes accurate mammographic assessment
– to assess tumour size if breast conserving surgery is being considered for invasive lobular cancer
What is the difference between FNA and core biopsy for breast cancer?
What is the histology of most breast cancers?
ADENOCARCINOMA
(ductal or lobular, in situ or invasive)
What is the blood supply and lymphatic drainage of the breasts?
Lymph node drainage to axillary or internal mammary chain
What questions can you ask someone with a previous history of breast cancer to screen for metastases?
Headaches?
How is hypercalcaemia from a malignancy managed?
What follow up care should be given to patients following breast cancer treatment?
Annual mammography for 5 years and open access
How should brain metastases in breast cancer be managed?
Surgery
Whole brain radiotherapy (if very poor prognosis and not suitable for surgery)
What are some differentials for a breast lump?
Malignancy
Fill in the following
