BREAST Flashcards
1
Q
Where do we find the surface anatomy of the breasts?
A
They extend horizontally from the lateral border of the sternum to the mid-axillary line and vertically from the 2nd to 6th costal cartilages
2
Q
What muscles does breast tissue lie on top of?
A
Pectoralis major and serratus anterior
3
Q
What are the 2 regions of the breast?
A
Circular body
Axillary tail - runs along the inferior lateral edge of the pectoralis major towards the axillary fossa
4
Q
What surrounds the nipple?
A
The areola which is the circular dark-colored area of skin surrounding it
5
Q
What are the glands found in the areola?
A
Montgomery’s glands - sebaceous glands that lubricate and antibacterial
6
Q
What are mammary glands?
A
Modified sweat glands that produce milk - a series of ducts and secretory lobules which consist of many alveoli drained by a single lactiferous duct. These ducts converge at the nipple
7
Q
What attaches the breast to the dermis and underlying pectoral fascia?
A
The connective tissue stroma - the fibrous portion condenses to form the suspensory ligaments of Cooper
8
Q
What does the base of the breast lie on top of?
A
The pectoral fascia - a flat sheet of connective tissue associated with the pectoralis major muscle
9
Q
What is the retromammary space?
A
a loose areolar tissue that separates the breast from the pectoralis major muscle. The retromammary space is often the site of breast implantation due to its location away from key nerves and structures that support the breast.
10
Q
Whats the blood supply to the medial aspect of the breast?
A
The internal thoracic artery aka internal mammary artery (branch of subclavian artery)
11
Q
Whats the blood supply to the lateral part of the breast?
A
Lateral thoracic and thoracoacromial branches - from auxiliary artery
Lateral mammary branches - originate from posterior intercostal arteries from aorta
Mammary branch - from anterior intercostal artery
12
Q
What is the venous drainage from the breast?
A
Axillary and internal thoracic veins
13
Q
What are the 3 groups of lymph nodes that recieve lymph from breast tissue?
A
75% axillary nodes
20% parasternal nodes
5% posterior intercostal nodes
14
Q
Where does lymphatic drainage from the skin go?
A
drains to the axillary, inferior deep cervical and infraclavicular nodes
15
Q
Where does lymphatic drainage from the nipple and areola go?
A
drains to the subareolar lymphatic plexus.
16
Q
What innervates the breast?
A
anterior and lateral cutaneous branches of the 4th to 6th intercostal nerves
17
Q
Outline the embryological development of the breasts?
A
The mammary glands are derived from 2 thickened strips of epidermal ectoderm, the primitive mammary ridges/milk lines (week 6) The ridges extend from the axillae to the inguinal regions, but rapidly regress except in the thorax
Mammary buds that persist in the thoracic region penetrate the underlying mesenchyme and give rise to several secondary buds which develop into lactiferous ducts and their branches. These are canalized by the end of the prenatal life
The fibrous connective tissue and fat of the mammary gland develop from the surrounding mesenchym The lactiferous ducts form the small ducts and alveoli
Only the main ducts are found at birth, and the gland remains undeveloped until puberty
DURING THE LATE FETAL PERIOD, the epidermis becomes depressed to form an epithelial pit on which the ducts open
The lactiferous ducts at first open onto this epithelial pit which is formed by the original mammary line
Nipple itself forms during the perinatal period due to proliferation of the mesenchyme under the areola in the area of the mammary pit. The nipple is often depressed and poorly formed during infancy
AT PUBERTY, the female mammary glands enlarge rapidly as a result of the development of fat and connective tissue. The duct system also grows, stimulated by the estrogen and progesterone of the ovary
The glandular tissue remains completely undeveloped until pregnancy when the intralobular ducts rapidly develop, form buds, and become alveoli
The male glands undergo little postnatal development
18
Q
What regulates the let-down reflex?
A
Prolactin helps make the milk, while oxytocin causes the breast to push out the milk
19
Q
Whats the most common cancer in women who do not smoke?
A
Breast cancer
20
Q
Whats the prevalence of breast cancer?
A
1 in 8 women will develop it in their lifetime
21
Q
What causes physiological breast development?
A
At the time of menarche, oestrogen receptors in breast tissue react to ovarian oestrogen secretion which stimulates milk duct epithelial cells to divdide
22
Q
What are the risk factors of breast cancer?
A
Female
Increased oestrogen exposure - earlier onset of periods and late menopause
More dense breast tissue
Obesity
Smoking
Fhx first degree relatives
BRCA1/2 or p53 mutations
HRT, particularly combined HRT
Combined contraceptive pill causes a small increased risk
Previous treatment using radiation therapy
Exposure to the drug diethylstilbestrol
First pregnancy after 30
Not breastfeeding
Nulliparity
23
Q
What proportion of breast cancers are in females?
A
99%
24
Q
What proportion of pt with breast cancer have a genetic predisposition?
A
5%
25
What is the main genetic predisposition for breast cancer?
BRCA mutant carriers
26
What do the BRCA genes put you at risk of?
Breast and ovarian cancer
BRCA2 can also put you at risk of prostate cancer
27
What is the BRCA gene?
Tumour suppressor genes
28
Where are the BRCA genes found?
BRCA 1 gene on chromosome 17
BRCA 2 gene on chromosome 13
29
Outline the risks of being a BRCA 1 gene carrier?
70% will develop breast cancer by 80
50% will develop ovarian cancer
30
Outline the risks of being a BRCA 2 gene carrier?
Around 60% will develop breast cancer by aged 80
Around 20% will develop ovarian cancer
Increased risk of prostate cancer
31
What screening is available for breast cancer?
The NHS breast cancer screening program offers a mammogram every 3 years to women aged 50 – 70 years.
Screening aims to detect breast cancer early, which improves outcomes.
Roughly 1 in 100 women are diagnosed with breast cancer after going for a mammogram.
32
What is a mammogram?
X-ray images of the breast
33
Which groups of people are considered high risk patients for breast cancer?
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 or one first-degree and one second-degree relative diagnosed with breast cancer at any age
one first-degree or second-degree relative diagnosed with breast cancer at any age and one first-degree or second-degree relative diagnosed with ovarian cancer at any age
three first-degree or second-degree relatives diagnosed with breast cancer at any age
34
What are high-risk breast cancer patients offered for prevention?
Genetic counselling, pre-test counselling and genetic tests.
Annual mammogram screening potentially starting from the age of 30
Chemoprevention
Risk-reduced bilateral mastectomy or oophorectomy
35
What chemoprevention can be offered to women at high risk of breast cancer?
Tamoxifen if premenopausal
Anastrozole if postmenopausal (except with severe osteoporosis)
36
How does breast cancer present?
Typically a painless, increasing mass that may be associated with nipple discharge, skin tethering, ulceration and in inflammatory cancers, oedema and erythema
Lumps that are hard, irregular, painless or fixed in place
Lumps may be tethered to the skin or the chest wall
Nipple retraction
Skin dimpling or oedema (peau d’orange)
Lymphadenopathy, particularly in the axilla
37
What are the referral criteria for suspected breast cancer?
The NICE guidelines recommend a two week wait referral for suspected breast cancer for:
An unexplained breast lump in patients aged 30 or above
Unilateral nipple changes in patients aged 50 or above
The NICE guidelines recommend also considering a two week wait referral for:
An unexplained lump in the axilla in patients aged 30 or above
Skin changes suggestive of breast cancer
The NICE guidelines suggest considering non-urgent referral for unexplained breast lumps in patients< 30 years.
38
What are the types of breast cancer?
Non-invasive:
- ductal carcinoma in situ
- lobular carcinoma in situ
- Paget’s disease
Invasive
- invasive ductal cancer
- invasive lobular cancer
- metaplastic cancer
- medullary cancer
- inflammatory breast cancer
Other
- adenoid cystic, secretory and apocrine cancers
- Phyllodes tumours (sarcoma)
39
What type of breast cancer are most inflammatory breast cancers?
Invasive ductal carcinomas
40
Whats the most common type of breast cancer?
Invasive ductal carcinoma
41
What has invasive ductal carcinoma recently be renamed as?
No special type or not otherwise specified
42
What are the special types of breast cancer?
Lobular breast cancer
Medullary breast cancer
Mucinous (mucoid or colloid) breast cancer
Tubular breast cancer
Adenoid cystic carcinoma of the breast
Metaplastic breast cancer
Lymphoma of the breast
Basal type breast cancer
Phyllodes or cystosarcoma phyllodes
Papillary breast cancer
43
Whats the 5 year survival for beast cancer?
85%
44
What is breast carcinoma in situ?
a malignancy of the ductal tissue of the breast that is contained within the basement membran. I.e. have not spread into the surrounding breast tissue.
These carcinoma types represent a precursor to invasive breast cancer. They are rarely symptom acts
The 2 main types are DCIS and LCIS
45
Whats the most common type of non-invasive breast malignancy?
Ductal carcinoma in situ
46
What are the 5 major types of DCIS?
Based upon histolgical features:
Comedo, cribriform, micropapillary, papillary and solid types
(Most lesions are mixed)
47
What is lobular carcinoma in situ?
a non-invasive lesion of the secretory lobules of the breast that is contained within the basement membrane
Much rarer than DCIS but greater risk of developing invasive breast maliganncy - 30% of cases
48
When is lobular carcinoma in situ usually diagnosed?
Before menopause
49
Which type of DCIS is a high-grade type and has an increased risk of invasion?
Comedo DCIS
50
What proportion of invasive breast cancers are invasive ductal carcinomas?
70-80%
51
What proportion of invasive breast cancers are invasive lobular carcinomas?
5-10%
52
Which breast cancers cannot be seen on mammogram?
Lobular carcinoma in situ
Invasive lobular carcinomas (sometimes visible)
53
How does inflammatory breast cancer differ from other types of breast cancer?
It occurs in younger women i.e. <40
More common among women who are overweight
More aggressive
Always at a locally advanced stage (stage 3) when first diagnosed because breast cancer cells have grown into the skin
Presents similarly to a breast abscess or mastitis - Swollen, erythema over more than 1/3rd of the breast, warm, tender breast with pitting skin (peau d’orange)
Does not respond to antibiotics
Worse prognosis than other breast cancers
54
What is Paget’s disease of the nipple?
An erythematous scaly rash on the nipple or areola that looks like eczema
It indicates ductal carcinoma extending up through lactiferous ducts and onto the nipple area.(can be DCIS or invasive carcinoma) Present in 1-2% of pt with breast cancer
50% have an underlyign mass lesion with 90% of these having an invasive carcinoma
30% without a mass lesion will have an nderlyig carcinoma
20% will have a carcinoma in situ
55
What is done at the 2 week wait referral for suspected cancer?
Triple diagnostic assessment:
Clinical assessment
Imaging
Biopsy
56
What imaging should be done for suspicions of breast cancer?
Younger women i.e. <30 - USS
Older women - mammograms
MRI may be used
57
Why are USS used instead of mammograms in women <30 undergoing testing for breast cancer?
Younger women generally have more dense breasts with more glandular tissue. They are helpful in distinguishing solid lumps (e.g., fibroadenoma or cancer) from cystic (fluid-filled) lumps.
58
Why are mammograms better than USS for looking for signs of breast cancer?
Mammograms can capture microcalcifications whilst USS cannot
Mammograms are more effective in older woman
59
How are lymph nodes assessed when investigating for breast cancer?
All women are offered an ultrasound of the axilla and ultrasound-guided biopsy of any abnormal nodes.
A sentinel lymph node biopsy may be used during breast cancer surgery where the initial ultrasound does not show any abnormal nodes.
60
How is a sentinel lymph node biopsy done?
An isotope contrast and a blue dye are injected into the tumour area. The contrast and dye travel through the lymphatics to the first lymph node. The first node in the drainage of the tumour area shows up blue and on the isotope scanner. A biopsy can be performed on this node, and if cancer cells are found, the lymph nodes can be removed.
61
What are the 3 types of breast cancer receptors?
Oestrogen receptors
Progesterone receptors
Human epidermal growth factor (HER2)
62
What is triple-negative breast cancer and why does it carry a worse prognosis?
where the breast cancer cells do not express any of these three receptors.
This carries a worse prognosis as it limits the treatment options for targeting the cancer.
63
What is gene expression profiling?
assessing which genes are present within the breast cancer on a histology sample. This helps predict the probability that the breast cancer will reoccur as a distal metastasis (away from the original cancer site) within 10 years.
64
Who does NICE reccomend should undergo gene expression profiling?
women with early breast cancers that are ER positive but HER2 and lymph node negative. It helps guide whether to give additional chemotherapy.
65
Where does breast cancer typically metastasise to?
Lungs
Liver
Bones
Brain
66
How is staging done for breast cancer?
Triple assessment
Additional investigations may be required to stage the breast cancer:
Lymph node assessment and biopsy, MRI of the breast and axilla, Liver ultrasound for liver metastasis, CT of the thorax/abdomen/pelvis for lung/abdominal/pelvic metastasis, Isotope bone scan for bony metastasis
67
What system is used to stage breast cancer?
TNM staging
68
What are the options for managing breast cancer?
Surgery
Radiotherapy
Hormone therapy
Biological therapy
Chemotherapy
69
What are the surgical options for early breast cancer?
Wide local excision and segmental mastectomy with breast conservation for masses of <3cm in diameter
Simple mastectomy with or without reconstruction is used for larger tumours
70
What proportion of breast tumours are removed with wide-local excision?
2/3rds
71
What factors determine whether mastectomy or wide local excision is done for breast cancer?
Mastectomy is for multi focal tumours, centra tumours, large lesions in small breasts and DCIS >4cm
Wide local excision is best for a solitary lesions, peripheral tumours, small lesions in large breasts and DCIS <4cm
72
What is the risk with axillary clearance?
The greater the amount of axillary surgery, the greater the risk of postoperative lymphoedema
73
Who will require adjuvant radiotherapy in breast cancer?
Those undergoing breast-conserving surgery
Those with large, high-grade primary tumours
Those undergoing mastectomy who have disease close to resection margins
Lymph node metastasis
74
What are the common side effects of radiotherapy for breast cancer?
General fatigue from the radiation
Local skin and tissue irritation and swelling
Fibrosis of breast tissue
Shrinking of breast tissue
Long term skin colour changes (usually darker)
75
What is lymphoedema?
a chronic condition caused by impaired lymphatic drainage of an area. Lymphoedema can occur in an entire arm after breast cancer surgery on that side, with removal of the axillary lymph nodes in the armpit.
Areas of lymphoedema are prone to infection
76
Whats the non-surgical management for lymphoedema?
Massage techniques to manually drain the lymphatic system (manual lymphatic drainage)
Compression bandages
Specific lymphoedema exercises to improve lymph drainage
Weight loss if overweight
Good skin care
77
In what proportion of all breast cancers is Human Epidermal growth factor Receptor 2 overexpressed?
In 20% of all breast cancers
78
What do HER2-positive cancers respond to?
treatment with HER2 inhibitors such as trastuzumab and pertuzumab
79
What can be used to manage oestrogen receptor-positive disease?
Endocrine therapy. There are 2 strategies:
- oestrogen receptor blockade using tamoxifen or fulvestrant
- oestrogen deprivation using aromatase inhibitors such as anastrazole (post-menopausal)
80
Why are post-menopausal woman given aromatase inhibit so rather than tamoxifen for oestrogen receptor-positive breast cancer?
as aromatisation accounts for the majority of oestrogen production in post-menopausal women and therefore anastrozole is used for ER +ve breast cancer in this group.
81
What are the important side efefcts of tamoxifen?
increased risk of endometrial cancer, venous thromboembolism and menopausal symptoms.
82
Who cannot have trastuzumab?
patients with a history of heart disorders.
83
How may chemotherapy be used in the management of breast cancers?
Neoadjuvant therapy – intended to shrink the tumour before surgery
Adjuvant chemotherapy – given after surgery to reduce recurrence
Treatment of metastatic or recurrent breast cancer
84
Whats the moa of tamoxifen?
is a selective oestrogen receptor modulator (SERM).
It either blocks or stimulates oestrogen receptors, depending on the site of action.
It blocks oestrogen receptors in breast tissue, and stimulates oestrogen receptors in the uterus and bones. This means it helps prevent osteoporosis, but it does increase the risk of endometrial cancer.
85
Whats the moa of Trastuzumab (Herceptin)?
A monoclonal antibody that binds to an extracellular domain of this receptor and inhibits HER2 homodimerization, thereby preventing HER2-mediated signaling. It is also thought to facilitate antibody-dependent cellular cytotoxicity, leading to the death of cells that express HER2.
86
Whats the moa of pertuzumab?
A monoclonal antibody that binds to the extracellular domain II of HER2
87
What follow up should be done after treatment for breast cancer?
Surveillance mammograms yearly for 5 years (longer if not yet old enough for regular breast screening programme)
88
What are the 2 options for reconstructive surgery?
Immediate reconstruction, done at the time of the mastectomy
Delayed reconstruction, which can be delayed for months or years after the initial mastectomy
89
After breast-conserving surgery, reconstruction may not be required but what can be given if needed?
Partial reconstruction (using a flap or fat tissue to fill the gap)
Reduction and reshaping (removing tissue and reshaping both breasts to match)
90
After mastectomy what are the options for breast reconstruction?
Breast implants (inserting a synthetic implant)
Flap reconstruction (using tissue from another part of the body to reconstruct the breast)
91
What are the pros and cons of breast implants?
It gives an acceptable appearance but can feel less natural (e.g., cold, less mobile and static size and shape). There can also be long-term problems, such as hardening, leakage and shape change.
May need to be replaced after about 10 years
Body can have an inflammatory reaction to the implants
92
What can be used as flap reconstruction for breast cancer surgery?
Latissimus Dorsi
Rectus abdominis
Free flap - skin and subcutaneous fat from abdomen
93
What does pedicled mean?
refers to keeping the original blood supply and moving the tissue under the skin to a new location.
94
What is a free flap?
cutting the tissue away completely and transplanting it to a new location.
95
Whats a TRAM flap?
Transverse rectus abdominis flap
96
Whats the risk of a TRAM flap?
It poses a risk of developing an abdominal hernia due to the weakened abdominal wall.
97
Whats a DIEP flap?
Deep Inferior Epigastric Perforator Flap
98
Outline how a DIEP flap is done? (You have seen this in surgery in Hull!)
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.
Abdominal walls are left intact so less risk of hernia!
99
What are the pros and cons of immediate vs delayed breast reconstruction?
Immediate - better cosmetic outcomes, cheaper, psychoglocial benefit
Delayed - more time to consider options, adjuvant therapy, higher pt satisfaction rates
100
What is lipomodelling?
Autologous fat transfer
Fat removed from areas of excess by liposuction -> fat centrifuged in theatre to remove blood and dead cells -> fat re-injected into breast to augment reconstruction
101
What is a lumpectomy?
surgery to remove a breast cancer tumor and the margin
102
What findings can be seen on a mammogram in DCIS?
Microcalcifications
103
What is the Nottingham Prognostic index?
a prognostics measure that predicts operable primary breast cancer survival
104
How is the Nottingham Prognostic Index calculated?
Tumour size x 0.2 + lymph node score + grade score
Score 1 = 0 lymph nodes involved and grade 1
Score 2 = 1-3 lymph nodes involves and grade 2
Score 3 = >3 lymph nodes involved and grade 3
105
How do you interpret Nottingham prognostic index?
2-2.4 = 93% 5 year survival
2.5-3.4 = 85% 5 year survival
3.5-5.4 = 70% 5 year survival
>5.4 = 50% 5 year survival
106
Outline TNM staging for breast cancer?
Tx
Tis (DCIS) - ductal carcinoma in situ (pre-invasive breast cancer)
Tis (Paget) - Paget’s disease
T1 - tumour =/<2cm (divided into T1mi, T1a, T1b and T1c)
T2 - tumour 2cm-5cm
T3 - tumour >5cm
T4 - T4a means the tumour has spread into the chest wall, T4b means tumours spread into skin, T4c tumour spread to skin and chest wall, T4d means inflammatory carcinoma
N - clinical node staging and pathological node staging
M0 - no metastasis
CMo(i+) - no sign of the cancer on physical examination, scans or x-rays but cancer cells are found by lab tests
cM1 - cancer spread
PM1 - cancer measuring more than 0.2 mm across has spread to another part of the body
107
What proportion of DCIS will progress into invasive disease?
About 20%
108
How many lactiferous ducts are present in each breast?
15-20
109
How can Paget’s disease of the nipple be differentiated from eczema?
Paget’s disease only affects the nipple and eventually may include areola
Eczema usually involves the areola and spares the nipple
110
Whats the cause of inflammatory breast cancer?
Cancer cells block the lymphatic drainage of the breast leading to an inflamed looking breast O/E
111
Where should you signpost patients for information about breast cancer?
cancer research UK
Breast cancer now
112
What views of the breast does a mammogram do?
oblique
Cranio-caudal
113
Whats the difference between a core biopsy and a fine needle aspiration?
A core biopsy is for tumour grading, staging and looking for invasive disease. It takes longer but shows the full histology
Fine needle aspiration is very quick but only gives information on cytology. If abnormal the pt will have to undergo a core biopsy
114
Who does the breast MDT involve?
Diagnostic team -
Breast specialist clinician, specialist radiologist, pathologist, breast care nurse, nurse practitioner, clinic staff, administrative staff, MDT co-ordination
Cancer treatment team -
Clinical oncologist, medical oncologist, plastic and reconstructive surgeon, oncoplastic breast surgeon, medical geneticist, data management personnel, research nurse, lymphoedema specialist, medical prosthetist, clinical psychologist, palliative care team
115
Outline what you should do if you do and dont find palpable lymph nodes in axilla when examining for suspected breast cancer?
If they are present then use ultrasound-guided fine needle aspiration. If benign then do a sentinel node biopsy and if malignant then carry out axillary clearance.
If lymph nodes are not palpable then do a ultrasound scan. If lymph nodes are seen then do an US-guided FNA and follow steps above. If lymph nodes are not seen then do a sentinel lymph nodes biopsy
116
What additional things should you do when investigating for breast cancer?
CT for staging
Bone scan - for bone mets
CXR - for lung mets
117
What are the indications for a wide local excision when managing breast cancer?
Solitary, peripheral, small lesion
Or DCIS <4cm diameter
118
What are the indications for a mastectomy when managing breast cancer?
Multi focal, central, large lesion
Or DCIS >4cm diameter
119
Why is radiotherapy often given adjuvant to surgery when managing breast cancer?
To prevent recurrence
120
What should you ask about when eliciting a breast cancer history?
SOCRATES
Fluctuation in size with menstrual cycle
Associated symptoms e.g. nipple discharge, pain, inverted nipple., skin changes
Axillary lymphadenopathy
Weight loss, malaise etc
Risk factors
121
Why is a triple assessment for investigating breast cancer so important?
As a clinical examination has a sensitivity of 65-80% so triple assessment minimises the risk of missing a diagnosis
122
What are the 5 areas of the breast?
Upper inner area (UIA)
Lower inner area (LIA)
Lower outer area (LOA)
Upper outer area (UOA)
Nipple+ areaola region
(+axillary tail)
123
What does a breast cancer look like on USS?
Hypoechoic
Irregular shape is most common
Martian is not circumscribed
Frequently has posterior shadowing
May have microcalcifications in or outside the mass
124
What are the stages of breast cancer?
Stage 0 - Ductal carcinoma in situ (DCIS)
stage 1 – tumour measures <2cm and the lymph nodes in the armpit are not affected. No mets
stage 2 – tumour measures 2-5cm, axillary lymphadenopathy. No mets
stage 3 – tumour measures 2-5cm and may be attached to structures in the breast, such as skin or surrounding tissues, and the lymph nodes in the armpit are affected. No mets
stage 4 – the tumour is of any size and the cancer has metastasised
125
How is breast cancer cells graded?
ow grade (G1) – the cells, although abnormal, appear to be growing slowly
medium grade (G2) – the cells look more abnormal than low-grade cells and is growing faster than G1
high grade (G3) – the cells look even more abnormal and are more likely to grow quickly. This is more likely to metastasise.
126
What type of cancer are most breast cancers?
Adenocarcinoma
127
What are adenocarcinomas?
A maligannt tumour formed from glandular structures in epithelial tissue
128
Which area of the breast are most breast cancer lumps found?
UOQ
129
Which gene encodes HER2 receptors?
ERbB2 gene
130
Where are HER2 receptors found in a healthy individual?
In small amounts in the breast and ovarian tissues
(It’s the overexpression that causes cancer!)
131
In what proportion of breast cancers is erbB2 gene overexpressed?
30%
132
Which cancers are associated with overexpression of erbB2 gene?
Breast
Ovaries
Lung
Gastric
Salivary gland
133
Whats the prognosis for HER2 overexpression breast cancers?
Associated with more aggressive cancer, higher recurrence rate and shortened survival
(But more likely to respond to anti-HER2 monoclonal antibodies)
134
Why does ER-positive breast cancer respond best to aromatase inhibitors after menopause?
Because after menopause the main source of oestrogen is from adipose tissue converting androstenedione to estrone which is a weak oestrogen (using aromatase)
135
Which ethnicities are at the highest risk for breast cancer?
Caucasians
Black women have an increased risk of triple negative breast cancer
136
What are risk factors for breast cancer that are specific for men?
Klinefelter syndrome
BRCA2 gene mutations
Oestrogen treatment
Testicular conditions - undescended testicle, mumps as an adult, orchiectomy
137
What chemotherapy combination is used to treat breast cancer?
FEC
5 fluorouracil
Epirubicin
Cyclophosphamide
(Docetaxal can be added - FEC-D)
138
What is DCIS?
A mass of neoplastic epithelial cells in the terminal duct lobular unit
The cells can fill the lumen but do not invade the basement membrane
Usually 1 ductal system is affected but in extensive lesions it can spread to surrounding areas
139
What are the 2 categories of DCIS?
Comedo DCIS
Non-comedo DCIS
140
What is comedo DCIS?
Associated with pleomorphic high grade maligannt cells with central necrosis (comedonecrosis). These dead cells at the centre can calcify and form dystrophic calcifications which may eventually invade surrounding breast tissue and form a poorly define palpable mass (no mass until this stage when its invasive!!)
141
What is non-comedo DCIS?
Not associated with central necrosis
Relatively less aggressive
Types include papillary, cribiform and solid - describe how the cancer cells look in the lumen of the ducts
142
How is Paget’s disease of the nipple diagnosis?
Mammogram to look for underlying mass
Biopsy - shows Paget cells
143
What are Paget cells?
Intraepithelial adenocarcinoma cells
144
how is paget disease of the nipple treated?
Mastectomy or breast conserving therapy follow i Ed by whole-breast radiation
145
How does LCIS present differently to DCIS?
It doesnt present classically i.e. with a mass
It’s usually diagnosed as an incidental finding
(Remember: this is more likely to cause cancer in both breasts than DCIS is)
146
What causes the breast lump to be immobile?
If its infiltrated the pectoral muscles and deep fascia
147
What causes nipple retraction?
When the tumour infiltrates the central region of the breast, the duct behind the nipple and pulls it back
148
What causes retraction of the skin?
Infiltration of suspensory cooper ligaments
149
Whats the pathology of Peau d'orange?
It is due to invasion of the axillary lymphatics by tumour producing obstruction and subsequently, oedema of the overlying skin. This creates an orange peel appearance.
150
How do each type of invasive breast cancer masses present differently?
Invasive ductal breast cancer - unilateral, firm, fibrous, rock-hard, palpable, sharp margins
Invasive lobular breast cancer - bilateral often, not palpable always
Medullary breast carcinoma - well-circumscribed, palpable mass that can mimic benign lesions
Inflammatory breast cancer - no palpable mass, inflammation signs
151
what are the types of invasive ductal breast cancer?
Tubular
Mucinous
Medullary
152
Whats the histological findings of invasive ductal carcinoma NST?
Tumor cells are pleomorphic, with protruding nucleoli and numerous mitoses. Areas of necrosis and calcifications can be detected in more than half of the cases
153
Expression of ? Is associated with invasive lobular carcinoma?
Complete loss of E-cadherin expression (these are adhesion proteins that prevent cancer from spreading)
154
Whats the tumour marker for breast cancer?
CA15-3
155
What areas are affected by lymphoedema?
Extremities followed by genitalia
156
What causes lymphoedema?
Secondary to nematode infection, malignancy or cancer-related treatment e.g. axillary clearance
157
How does lymphoedema present?
painless unilateral limb swelling; pitting oedema is present in early disease, whereas non-pitting oedema is a sensitive but non-specific finding in advanced disease.
158
How is a lymphoedema diagnosis confirmed?
lymphoscintigraphy -
159
What are Fibroadenomas?
common benign tumours of stromal/epithelial breast duct tissue
160
How do Fibroadenomas present?
They are typically small and mobile within the breast tissue. They are sometimes called a “breast mouse”, as they move around within the breast tissue.
Painless
Smooth
Round
Well circumscribed (well-defined borders)
Firm
Mobile (moves freely under the skin and above the chest wall)
Usually up to 3cm diameter
161
Who do Fibroadenomas typically affect? And why?
They are more common in younger women, aged between 20 and 40 years. They respond to the female hormones (oestrogen and progesterone), which is why they are more common in younger women and often regress after menopause.
162
Whats the prognosis for Fibroadenomas?
50% regress spontaneously, 25% will remain unchanged and 25% will get bigger.
163
Whats the lifetime incidence of Fibroadenomas in women?
10%
164
What are the 3 types of Fibroadenomas?
Simple Fibroadenomas
Complex Fibroadenomas
Giant Fibroadenomas
165
What are the characteristics of simple Fibroadenomas?
These are small (1-3cm) lumps with classical features of a firm, mobile and painless lump. On histology they look the same all over
166
What are the characteristics of complex Fibroadenomas?
Complex appearance on histopathology - cells appear with different features. These have been associated with a slight increase in the risk of breast cancer.
167
What are the characteristics of giant Fibroadenomas?
Large fibroadenomas growing to a size of greater than 5cm.
Aka juvenile fibroadenoma when found in teenage girls
168
When may Fibroadenomas be triggered/increase in size?
during pregnancy or when taking hormone replacement therapy (HRT). This is because of the hormonal link
Note that <5% of Fibroadenomas increase in size and about 25% will get small or completely disappear
169
What genetic basis has been identified as a link to Fibroadenomas?
a mutation to MED12 found in around 60% of tumours.
MED12 has been implicated in many other conditions including uterine fibroids.
170
In what proportion of cases are there multiple Fibroadenomas affecting 1 or both breasts?
1/5
171
How are Fibroadenomas managed?
Core biopsy for any >4cm to exclude phyllodes tumour
Simple, small and asymptomatic, biopsy-proven fibroadenomas do not need further treatment. If appearances are classical in young patients (e.g. < 25) biopsy may be avoided and interval imaging considered.
Patients should be advised to re-present if the mass changes in size, if they develop pain or any other features that may indicate breast cancer (e.g. skin and nipple changes).
In certain circumstances excision may be discussed
172
What are the circumstances in which Fibroadenomas may be excised?
age >35 years
immobile or poorly circumscribed mass
size >3cm
biopsy not definitive for fibroadenoma
173
What proportion of breast lumps are Fibroadenomas?
13%
174
What causes Fibroadenomas?
Thought to be due to an increased sensitivity to hormones
It developers from a whole lobule not a single cell!
175
Do Fibroadenomas increase your risk of malignancy?
They aren’t cancerous and are not usually associated with an increased risk of developing breast cancer
But complex Fibroadenomas and a positive FHx of breast cancer may indicate a higher risk
176
What are fibrocystic breast changes?
Common benign change within the breast which lead to the development of cysts and fibrous tissue, which can make breasts feel tender, lumpy or ropy
These changes fluctuate with the menstrual cycle
177
What causes fibrocystic breast changes?
The connective tissues (stroma), ducts and lobules of the breast respond to the female sex hormones (oestrogen and progesterone). This is why its common in women of menstruating age and symptoms often occur prior to menstruating and resolve once menstruation begins. Symptoms usually improve or resolve after menopause
178
What are the symptoms of fibrocystic breast changes?
Symptoms can affect different areas of the breast, or both breasts, with:
Lumpiness
Breast pain or tenderness (mastalgia)
Fluctuation of breast size
179
What is mastalgia?
Breast pain
180
What are the 2 types of mastalgia?
Cyclical breast pain - linked to menstrual periods
Non-cyclical breast pain
181
How common is mastalgia and who does it affect?
70% of women at some point in their life
Common in women 35-50 (rare before 25)
182
How can you manage cyclical mastalgia?
Wearing a supportive bra
Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen
Avoiding caffeine is commonly recommended
Applying heat to the area
Hormonal treatments (e.g., danazol and tamoxifen) under specialist guidance
183
What is fibroadenosis?
Fibrocystic disease of the breast
184
What are breast cysts?
benign, individual, fluid-filled lumps
185
Whats the most common cause of breast lumps?
Breast cysts
186
Who do breast cysts tend to affect?
Women aged 30-50 - perimenopausal
187
How do breast cysts present?
They tend to be a smooth discrete lump. They can be painful and may fluctuate in size over the menstrual cycle.
O/E, breast cysts are:
Smooth
Well-circumscribed
Mobile
Possibly fluctuant
188
How should you manage breast cysts?
Breasts cysts require further assessment to exclude cancer, with imaging and potentially aspiration or excision. Aspiration can resolve symptoms in patients with pain.
189
Do breast cysts increase the risk of breast cancer?
Small increased risk of breast cancer (especially if younger)
190
What proportion of all western females will present with a breast cyst?
7%
191
What are lipomas?
benign tumours of adipocytes. They can occur almost anywhere on the body where there is adipose tissue, including the breasts.
192
How do breast lipomas present?
Soft
Painless
Mobile
Do not cause skin changes
193
How are lipomas managed?
They are typically treated conservatively with reassurance. Alternatively, they can be surgically removed.
194
Whats a rare complication of lipoma?
Liposarcoma
195
What are Galactoceles?
breast milk filled cysts that occur when the lactiferous duct is blocked, preventing the gland from draining milk
196
How do Galactoceles present?
with a firm, mobile, painless lump, usually beneath the areola
197
How do you manage Galactoceles?
They are benign and usually resolve without any treatment. It is possible to drain them with a needle. Rarely, they can become infected and require antibiotics.
198
How can a Galactocele be differentiated from an abscess?
a galactocele is usually painless, with no local or systemic signs of infection.
199
Who do Galactoceles tend to affect?
women who have recently stopped breastfeeding
200
What is a phyllodes tumour?
are tumours of the connective tissue (stroma) of the breast
They are large and fast-growing. They can be benign (~50%), borderline (~25%) or malignant (~25%). Malignant phyllodes tumours can metastasise.
201
Who do phyllodes tumours affect?
Those 40-50
202
What are duct papillomas?
Benign wart-like tumours that grow in the lacteriferous ducts of breasts
203
Who does duct papilloma affect typically and how does it present?
Pt who are premenopausal
Nipple discharge and bleeding. A small painful sub areola nodule is present in 30% of cases
204
Does duct papilloma increase your risk of breast cancer?
No
205
How are duct papillomas managed?
Microdochectomy (total duct excision) - a surgical procedure in which a single duct is removed from the nipple areolar complex
206
What causes breast fat necrosis?
Breast trauma 21-70%
Fine needle aspiration or biopsy
Anticoagulation treatment
Radiation
Breast infection
207
How does breast fat necrosis present?
Presents similarly to carcinoma
Initially inflammatory response lesion is firm and round but may develop into…
hard, irregular lump which may be tethered to the skin and accompanied by enlarged axillary lymph nodes. A history of trauma, evidence of injury, or shrinkage of the lump supports the diagnosis of fat necrosis.
208
How is breast fat necrosis managed?
Imaging and core biopsy to exclude cancer
Often harmless and you wont need any treatment
209
What is sclerosis adenosis?
Benign condition in which fibrous tissue is found in the breast lobules causes them to enlarge
210
How does sclerosisng adenosis present?
Usually presents as a breast lump or breast pain
211
What is breast hyperplasia?
An overgrowth of the cells that line the lobules or ducts inside the breast
Benign and usually found by chance
212
What is mammary duct ectasia?
Benign breast condition that occurs when there is dilatation of the intermediate and large breast ducts. As women progress through the menopause the breast ducts shorten and dilate. May also be associated with smoking.
This can cause the duct to become blocked and lead to a fluid build up
213
Who tends to get mammary duct ectasia?
Women around menopause
214
How does mammary duct ectasia present?
A dirty white, greenish or black nipple discharge from one or both nipples - often from several ducts
Tenderness in the nipple or surrounding breast tissue (areola)
Redness of the nipple and areolar tissue
A breast lump or thickening near the clogged duct
A nipple that's turned inward (inverted)
215
What is plasma cell mastitis?
When mammary duct ectasia ruptures and causes local inflammation
216
Who’s Most likely to get fat necrosis?
obese women with large breasts
217
Mastitis and breastfeeding problems
218
What is the commonest cause of blood stained nipple discharge in younger women?
Intraductal papilloma
219
What is the ‘snowstorm’ sign on ultrasound of axillary lymph nodes?
dense shadowing as seen with extracapsular silicone deposition in breast tissue and lymph nodes
220
How do duct papillomas present?
Single duct discharge that is clear or may be blood stained
Small lump felt right behind or next to the nipple
221
How is triple assessment graded?
Examination
E1 – Normal (no lump)
E2 – Benign lump
E3 – A lump
E4 – A suspicious lump
E5 – Probable cancer
Cytology
C1 – inadequate sample
C2 –Benign
C3 – Atypical features, but still likely benign
C4 –Atypical features, probably malignant
C5 –Malignant
Imaging
M1 / U1 – Normal
M2 / U2 –benign
M3 / U3 –Probably benign
M4 / U4 –Probably malignant
M5 / U5 –Malignant
222
How soon after stopping the combined contraceptive pill does the risk of breasts cancer return to normal?
10 years
223
Whats mastitis and what are the 2 types?
Inflammation of the breast tissue
Lactational and non-lactational
224
What is lactational mastitis?
Aka puerperal mastitis
It is seen in up to 1/3rd of breastfeeding women; it usually presents during the first 3 months of breastfeeding or during weaning
225
What can cause non-lactational mastitis?
Women with duct ectasia
Tobacco smoking
Nipple damage - psoriasis, eczema, Raynaud’s disease of the nipple
Those with depressed immune systems or diabetes
Breast implants
226
Why can smoking increase the risk of mastitis?
It can cause damage to the sub-areolar duct walls and predisposing to bacterial infection
227
What is periductal mastitis?
Inflammation of the ducts of the breast.
Strongly associated with cigarette smoking
Aka mammary duct ectasia
228
Whats the most common cause of mastitis?
Infection - typically S.aureus
Obstruction in ducts and accumulation of milk
229
How does mastitis present?
Breast pain and tenderness (unilateral)
Erythema in a focal area of breast tissue
Local warmth and inflammation
Nipple discharge
Fever and general malaise
230
Whats the pathophysiology of lactational mastitis?
In lactating women, milk stasis may occur due to blocked or reduced drainage of milk ducts. An inflammatory response occurs though this may not initially be infectious. However, static fluid eventually leads to bacterial proliferation.
231
What factors predispose pt to mastitis?
Diffiuclty breastfeeding - e.g. poor attachment of baby’s mouth to nipple - cleft palate, short frenulum
Reduced breast feeding - rapid weaning, unilateral feeding, breast tenderness
Pressure on breasts - seat belts, sleeping positions, tight bra
232
How can lactational mastitis be prevented?
Ensure skin to skin contact following birth and during inpatient stay
Effective positioning and attachment during breast-feeding
Frequent and baby-led feeding
Avoiding nipple trauma through effective technique
Promoting mother/baby bond
Avoid the use of dummies
Hand expression of breastmilk when needed
Avoiding pressure on the breast
Smoking cessation
233
At booking appointment, women who are at increased risk of lactational mastitis are identified. What are some risk factors?
Breast surgery (i.e. Augmentation/Reduction)
Problems relating to feeding her last baby
History of mastitis/breast abscess
History of Raynaud’s disease of the nipple, skin conditions on the breast or near the nipple area (e.g. psoriasis, eczema, nipple piercings)
Current un-investigated breast lump
Nipple piercing
Previous history of breast cancer/Paget's disease
234
How can you tell the difference between infective and non-infective mastitis?
If symptoms dont improve or worsen after 12-24 hours despite effective milk removal then its likely infective
Fissuring or evidence of nipple infection is indicative of infective lactational mastitis
Systemically unwell - Fever will be higher and pt will be more unwell in infective mastitis
Culture indicates infection
235
Whats the complication of mastitis?
Breast abscess
236
What investigations should you do for mastitis?
Investigations are not routine but any pt requiring hopsital admission will need…
FBC, renal function, CRP, LFTs, lactate
Breast milk culture (if mastitis or severe or recurrent, there is a risk of hospital-acquired infection or a deep burning indicative of ductal infection)
Blood cultures for inpatients with signs of systemic infection or routine in pt with immunosuppression
237
How should you image an occult abscess?
With breast ultrasound
238
How should simple lactational mastitis be managed?
Continued breast feeding
Expressing milk
Breast massage
Heat packs
Warm showers
Simple analgesia
239
How should infective mastitis be managed?
Antibiotics - flucloxacillin is first line for 10-14 days (erythromycin if allergic to penicillin)
Milk culture and sensitivities
Continue breast feeding or express (even on antibiotics)
240
Who needs urgent hopsital admission for mastitis?
In those with systemic signs of infection, immunosuppression or rapidly progressing symptoms
Breast abscess suspected or diagnosed
241
What are the 2 main surgical techniques to treat a breast abscess?
Incision and drainage
Needle aspiration
242
Why is flucloxacillin first line for mastitis?
Because the most likely cause is staph aureus (s aureus is gram-positive and flucloxacillin works by inhibiting synthesis of bacterial cell wall)
243
When might you get candida of the nipple?
Common after a course of antibiotics
244
How can candida of the nipple affect the baby you are breastfeeding?
They can get oral thrush or Candidal nappy rash
245
How does candida of the nipple present?
Sore nipples bilaterally, particularly after feeding
Nipple tenderness and itching
Cracked, flaky or shiny areola
Symptoms in the baby, such as white patches in the mouth and on the tongue, or candidal nappy rash
246
How does candida of the nipple get treated?
Both the mother and baby need treatment, or it will reoccur.
Treatment is with:
Topical miconazole 2% to the nipple, after each breastfeed
Treatment for the baby (e.g., oral miconazole gel or nystatin)
247
Whats the moa of miconazole?
inhibition of the CYP450 14α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.
248
What can cause breast pain during breast feeding?
Mastitis
Engorgement
Raynaud’s disease of the nipple
249
What is breast engorgement?
Breasts become overly full which causes pain in the first few days after the infant id born and almost always affects both breasts. The pain is typically worse just before a feed
250
What are the signs of breast engorgement?
Pain just before a feed
Infant finds it diffiuclt to attach and suckle
Fever may be present but usually settle within 24 hours
Breasts appear red
251
What are complications of breast engorgement?
blocked milk ducts, mastitis and difficulties with breastfeeding and, subsequently, milk supply.
252
How can you relieve the pain of breast engorgement?
Hand expression of milk
253
How does Raynaud’s disease of the nipple present?
Intermittent pain during and immediately after feeding
Blanching of the nipple followed by cyanosis and erythema
Nipple pain resolves when nipples return to a normal colour
254
How can Raynaud’s disease of the nipple be managed?
advice on minimising exposure to cold, use of heat packs following a breastfeed, avoiding caffeine and stopping smoking.
If symptoms persist consider specialist referral for a trial of oral nifedipine (off-license).
255
What is gynaecomastia?
The enlargement of the glandular breast tissue in males
256
Who is gynaecomastia common in?
Adolescence
Older men >50
Newborns due to circulating maternal hormones (resolves as maternal hormones are cleared)
257
What the pathophysiology of gynaecomastia?
caused by a hormonal imbalance between oestrogen and androgens (e.g., testosterone), with higher oestrogen and lower androgen levels. Raised oestrogen stimulates breast development, whilst androgens have an inhibitory effect on breast development.
258
What can cause gynaecomastia?
Hyperprolactinaemia
Dopamine antagonists
Idiopathic
Physiological in adolescence
Conditions that increase oestrogen:
Obesity
Testicular cancer
Liver cirrhosis and liver failure
Hyperthyroidism
HCG secreting tumour
Conditions that reduce testosterone:
Testosterone deficiency in older age
Hypothalamus or pituitary conditions that reduce LH or FSH e.g. tumours, radiotherapy, surgery
Klinefelter syndrome
Orchitis
Testicular damage
Meds
259
Why does hyperporlactinaemia cause gynaecomastia?
Prolactin can stimulate glandular breast tissue development as well as breast milk production
260
Why can dopamine antagonists cause gynaecomastia?
dopamine has an inhibitory effect on prolactin. Dopamine antagonists (e.g., antipsychotic medications) block dopamine production, which can allow prolactin levels to rise and cause gynaecomastia and galactorrhea (breast milk production).
261
Why can gynaecomastia be physiological?
in adolescents there can be proportionally higher oestrogen levels around puberty
262
Why can obesity cause gynaecomastia?
(aromatase is an enzyme found in adipose tissue that converts androgens to oestrogen
263
Why can testicular cancer cause gynaecomastia?
oestrogen secretion from a Leydig cell tumour
2% of people with gynaecomastia have a testicular tumour
264
Whats the most common HCG secreting tumour?
Small cell lung cancer
265
What medications can cause gynaecomastia?
Anabolic steroids - raise oestrogen levels
Antipsychotics - increase prolactin levels
Digoxin - stimulates oestrogen receptors
Spironolactone - inhibits testosterone production and blocks testosterone receptors
GnRH agonists e.g. goserelin
Opiates e.g. illicit heroin use
Marijuana
Alcohol
266
What is pseudo gynaecomastia?
Breast enlargement due to obesity
267
How can you differentiate between gynaecomastia and pseudo gynaecomastia?
On palpation, there will be firm tissue behind the areolas in gynaecomastia, representing growth of the gland and duct tissue. This is different to simple adipose (fat) tissue, which is soft and more evenly distributed.
268
What should you cover in the history for gynaecomastia?
Age of onset, duration and change over time
Associated sexual dysfunction- indicating low testosterone
Any palpable breast lumps or skin changes - exclude breast cancer
Associated symptoms that may indicate the cause (e.g., testicular lumps, symptoms of hyperthyroidism, symptoms of liver cirrhosis, previous surgeries, signs of HCG producing tumour)
Prescription medication (e.g., antipsychotics, spironolactone or GnRH agonists)
Use of anabolic steroids, illicit drugs or alcohol
269
What key parts should you cover in an examination for gynaecomastia?
True gynaecomastia versus simple adipose tissue
Unilateral or bilateral
Any palpable lumps, skin changes or lymphadenopathy (exclude breast cancer)
Body mass index (BMI)
Testicular examination (e.g., lumps, atrophy or absence)
Signs of testosterone deficiency (e.g., reduced body and pubic hair)
Signs of liver disease (e.g., jaundice, hepatomegaly, spider naevi and ascites)
Signs of hyperthyroidism (e.g., sweating, tachycardia and weight loss)
270
What investigations should you do for gynaecomastia?
Renal profile (U&Es)
Liver function tests (LFTs)
Thyroid function tests (TFTs)
Testosterone
Sex hormone-binding globulin (SHBG)
Oestrogen
Prolactin (hyperprolactinaemia)
Luteinising hormone (LH) and follicle-stimulating hormone (FSH)
Alpha-fetoprotein and beta-hCG (testicular cancer)
Genetic karyotyping (if Klinefelter’s syndrome is suspected)
Breast ultrasound to help assess the extent of gynaecomastia
Mammogram and biopsy if cancer is suspected
Testicular ultrasound if cancer is suspected
Chest X-ray if lung cancer is suspected
271
How should you manage gynaecomastia?
If in adolescence it commonly resolves over time
Stop causative drugs
Refer to specialist breast clinic if cause is unclear or cancer is suspected
Treatment options in problematic cases:
Tamoxifen (SERM that reduces the effect of oestrogen on breast tissue)
Surgery
272
What is Mondor's disease of the breast?
A localised thrombophlebitis of a breast vein.
