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Reproduction (Semester 4) > 9.2 Breast disease > Flashcards

9.2 Breast disease Flashcards

1
Q

What do cyclical and diffuse pain in the breast area most likely indicate?

A

usually physiological conditions

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2
Q

What do non-cyclical and focal pain in the breast area most likely indicate? (3)

A

ruptured cysts, injury, inflammation

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3
Q

What is a palpable mass and what may this indicate if found in the breast?

A

A palpable mass is a lump in the breast that can be felt. It may represent normal nodularity hence cannot necessarily be used for diagnosis alone

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4
Q

When is a palpable mass concerning and what may this indicate?

A

Most worrying if mass is hard, craggy and fixed

Causes include: Invasive carcinomas, fibroadenomas, or cysts

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5
Q

What is the most significant presentation of breast cancer?

A

The appearance of a palatable mass

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6
Q

List 2 other clinical presentations (not palpable mass) that may be indicative of a breast conditions?

When would these be most concerning?

A

1) Nipple discharge: most concerning if it is spontaneous and unilateral
2) Skin changes that are associated with a palpable mass near the surface

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7
Q

If nipple discharge is milky what may this indicate?

A

endocrine disorders

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8
Q

If nipple discharge is bloody or serous what may this indicate?

A

benign lesions

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9
Q

What can be used to detect lesions in breasts

Does this work better on older or younger women

Who is eligible?

A

Mammography

Easier to detect lesions in breasts of older women

Women 50-70years (being extended to 47–73 years) are eligible for 2 view mammograms every 3 years in the UK

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10
Q

In a Mammogram what 3 features are concerning?

What may these indicate?

A

Asymmetric densities, calcifications and parenchymal deformities

Asymmetric densities may indicate: invasive carcinomas, fibroadenomas, cysts

Calcifications may indicate ductal carcinoma in situ (DCIS), benign changes

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11
Q

List 2 breast conditions characterised by disorders of development

A

1) milk line remnants “polythelia” (additional nipple)

2) accessory axillary breast tissue

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12
Q

List 3 Inflammatory conditions associated with breast conditions

A

1) Acute mastitis
2) Duct ectasia
3) Fat necrosis

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13
Q

List 3 breast conditions associated with benign epithelial lesions

A

1) Fibrocystic change
2) Epithelial hyperplasia
3) Papilloma

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14
Q

List 3 breast conditions associated with Stromal tumours

A

1) Fibroadenoma
2) phyllodes tumours
3) lipoma
4) leiomyoma
5) hamartoma

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15
Q

List 2 other breast conditions

A

1) Gynaecomastia

2) Breast carcinoma

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16
Q

What is Mastitis?

A

This is an acute inflammation of the breast often associated with breast feeding mothers

Usually only affects 1 breast, and symptoms often come on quickly

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17
Q

Give 5 common symptoms of Mastitis

A

1) a red, swollen area on the breast that may feel hot and painful to touch
2) a wedge-shaped breast lump or a hard area on the breast
4) a burning pain in the breast that might be constant or only when breastfeeding
5) nipple discharge, which may be white or contain streaks of blood
6) flu-like symptoms, such as aches, a high temperature, chills and tiredness (often associated with infection… NOT always)

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18
Q

Give 4 things that increase the risk of Mastitis

A

1) nipple damage
2) over-supply of breast milk
3) use of nipple shields
4) presence of S. aureus on the nipple or in breast milk

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19
Q

List a change in the breast that may mimic breast cancer and why

How does it differ from breast cancer?

What is this change usually due to?

A

Fibrocystic change: palpable mass or present with a mammogram abnormality

Unlike breast cancer the mass usually resolves on needle aspiration

These are usually associated with benign epithelial lesions

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20
Q

What is epithelial hyperplasia and what is a common presentation?

What does this increase you risk of?

A

Seen on histology as an expansion of the epithelial tissue in the ducts which can lead to a palpable mass.
The epithelia of the ducts can over proliferate and cause blockage to the duct which can lead to pain.

Presentation: palpable mass + pain

This isn’t invasive (expect into the lumen of the duct) however, this condition slightly increases your risk of breast cancer.

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21
Q

What is an intraductal papilloma?

It is malignant?

A

An intraductal papilloma is a wart-like lump that develops in one or more of the milk ducts in the breast and is usually close to the nipple

Intraductal papillomas are a benign breast condition.

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22
Q

What are the 2 most common stromal tumours of the breast?

What are they both associated with and what does this mean for examinations

At what age does each usually present?

A

Fibroadenomas and the Phyllodes tumours

These are both breast specific and associated with a mobile mass hence evades palpation when trying to touch the patient. Often called a “mouse breast lump”

Fibroadenomas are more commonly seen in younger age groups compared to Phyllodes tumours which are rarely seen before the age of 40

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23
Q

Give the appearance of a Fibroadenoma

Are they malignant

A

Mobile mass that is normally rounded, large and has a white appearance due to the surrounding stromal fat capsule

These tumours usually involve a combination of surrounding stroma and epithelium (it is the stromal proliferation that makes them so specific)

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24
Q

Give the appearance of a Phyllodes tumour

Are they malignant

A

Either a palpable mass or a mammogram presentation.

These are also very large

They involve both stromal and epithelial overgrowth BUT unlike the fibroadenoma, there is an aggressive local regrowth if the tumour is not completely excised.

Around 1/20 are malignant, so most of the time these are benign but, if they are malignant they can metastasis via the blood to other areas

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25
Q

What is Gynaecomastia and what is the general cause?
At what age is it usually seen?

What can this mimic and does this increase risk of cancer?

A

Enlargement of male breast that can be unilateral or bilateral caused by relative decrease in androgen effect or increase in oestrogen effect

It is often seen at puberty and in the elderly (can be seen in neonates due to excess circulation of hormones from pregnancy)

Can mimic male breast cancer especially if unilateral but does NOT increase risk of cancer

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26
Q

Give 3 conditions associated with Gynaecomastia and explain why

A

THINK it is caused by relative decrease in androgen effect or increase in oestrogen effect hence…

1) liver cirrhosis: because oestrogen cannot be metabolised (oestrogen excess)
2) testicular cancer: gonadotrophin excess
3) can often also be drug related (spironolactone and anabolic steroids)

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27
Q

What are the major risk factors related to for developing breast cancer?

At what age is diagnosis most prevelant?

A

Major risk factors are related to hormone exposure (mainly oestrogen and progesterone)

Majority of breast cancers are diagnosed from 50-75. The older you are the higher risk (younger women can still get it

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28
Q

Give 6 risk factors for developing breast cancer that relate to hormone exposure

A

1) Gender
2) Uninterrupted menses (mensuration)
3) Early menarche (< 11 years)
4) Late menopause
5) Reproductive history- parity and age at first full term pregnancy
6) Breast-feeding
7) Obesity and high fat diet
8) Exogenous oestrogens (HRT and possibly long term users of OCP possibly increase risk)

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29
Q

List 4 other risk factors (not related to hormones) that increase risk of breast cancer

A

1) Geographic influence- higher incidence in US and Europe (diet, physical activity, environmental factors?)
2) Atypical changes on previous biopsy
3) Previous breast cancer
4) Radiation (especially in childhood or adolescence), in particular mantle radiation used to treat Hodgkin’s lymphoma

30
Q

What breast cancer makes up for 10% of all breast cancers?

What gene causes this and what specific breast cancer is associated with it

A

Hereditary breast cancer

Attributed to mutations in BRCA1 BRCA2 associated specifically with familial breast carcinoma and ovarian cancer

31
Q

What does BRCA1 stand for and how can mutations in this gene lead to breast cancer

How can this therefore be treated prior to development of cancer…?

A

BReast CAncer associated gene 1 or 2

These are tumour suppressor genes and their proteins repair damaged DNA (repair double strand breaks)

Because they act like brakes on tumour growth, both alleles must be inactivated hence, they need “two hits” (one for each allele).

Mutations in the BRCA gene are often familial and hence the first hit is delivered through the germ-line, increasing risk of breast cancer development through a second hit

Carriers may undergo prophylactic mastectomies

32
Q

Give another gene involved in development of hereditary breast cancer?

A

p53 associated with Li-Fraumeni syndrome

33
Q

95% of all breast cancers are of what type?

What anatomical location do most breast tumours appear in?

A

Adenocarcinomas

Most common in the upper outer quadrant

34
Q

What is the main way we divide/classify carcinomas and what does this depend on?

How can we furthur divide most carcinomas?

A

Carcinomas can be classified as “in situ” or “invasive”
These depends on the morphological, microscopic subtypes.

Most can be further divided into ductal and lobular carcinomas based on their location

35
Q

What are the 4 main classifications of breast carcinomas

A

1) Ductal Carcinoma in situ (DCIS)
2) Lobular Carcinoma in situ (LCIS)
3) Invasive lobular carcinoma (ILC)
4) Invasive Ductal carcinoma (IDC)

36
Q

What is a DCIS?

A

Ductal Carcinoma in situ

A potential precursor to invasive carcinoma
There are 5 morphological subtypes and 3 grades

37
Q

What is a LCIS?

A

Lobular Carcinoma in situ

A potential precursor to invasive carcinoma
Lack of E-cadherin and β- catenin
Morphological grading

38
Q

What is a ILC?

A

Invasive lobular carcinoma

5%–15% of invasive breast carcinoma
usually affects older age group
women with ILC have five distinct histological variants

  • ILCs usually have a distinct pattern of metastasis, hence “odd sites” of metastasis are common
39
Q

What is a IDC?

A

15 histological subtypes cell types, cell amounts, cell number and types
Location and type of secretion
Histology architecture
IHC profile

40
Q

Describe an In situ carcinoma in terms of:

1) BM?
2) myoepithelial cells?
3) metastasis?

A

1) neoplastic population of cells limited to ducts and lobules by basement membrane (does NOT penetrate the BM)
2) myoepithelial cells are preserved
3) does not invade into vessels or lymph nodes and thus can NOT metastasise

41
Q

Give a disease that is a form of In situ carcinoma

Describe this disease and its presentations

A

Paget’s disease of the breast (NOT the same as Paget’s disease of the bone)

It is a form of In situ carcinoma where the cells can extend to nipple skin without crossing the BM. It is a special type of ISC because there is intra-epithelilal spread whilst still not crossing the BM

Presentation: unilateral, red and crusting nipple + expansion of nipple

42
Q

Should we be concerned about Eczematous or inflammatory conditions of the nipple, and why?

A

Eczematous or inflammatory conditions of the nipple should be regarded as suspicious and a biopsy should performed to exclude Paget’s disease

43
Q

Describe an Invasive carcinoma in terms of:

1) BM?
2) myoepithelial cells?
3) metastasis?

A

1) Invaded beyond BM into stroma
2) myoepithelial cells are NOT preserved
3) can invade into vessels, thus can metastasize to lymph nodes and other sites

44
Q

How do Invasive carcinomas present?

What is the problem with this?

A

Presents as a mass or as mammographic abnormality

BUT by the time a cancer is palpable more than half of the patients will have axillary lymph node metastases

“Peau d’orange” which is involvement of lymphatic drainage of skin (skin looks like orange peel due to lymphatic drainage)

45
Q

What is the name given to the appearance of skin when its phenotype resembles orange peel

Is this common in Invasive or In Situ carcinomas

What does this appearance indicate?

A

“Peau d’orange”

Seen in Invasive carcinomas

Indicates there is involvement/problems with lymphatic drainage of skin

46
Q

Give another visible SIGN of an Invasive carcinoma and what this indicates

A

An inverted nipple

This is a sign that there is disruption to the skin

47
Q

What is IHC?

How are these classified?

A

“Immunohistochemistry” is a type of molecular profiling that essentially classifies breast cancer types based on the presence or absence of a number of receptor types

This is done through the use of antibodies to see whether receptor is + or -

48
Q

What are the 3 main groups of IHC?

A

1) Hormone receptor positive: HR-positive
• Oestrogen receptor (ER)-positive,
• Progesterone receptor (PR)-positive

2) Human epidermal growth factor receptor 2
• (HER2) positive,

3) Triple-negative disease: no hormone or HER2
• (ER)-negative
• HER2-negative

49
Q

The 3 main groups of IHC have 4 main groups of molecular subtypes, what are these?

List in order of prognosis from best to worst

A

1) and 2) Luminal A and B groups:
• oestrogen and/or progesterone positive
• BUT a difference in the HER2 and the Ki-67

3) HER2/NEU phenotype:
• oestrogen and/or progesterone are negative
• HER2 positive

4) Basal-like cells: (these are the triple negatives)
• oestrogen and/or progesterone are negative
• HER2 and Ki-67 negative

50
Q

What is Ki-67 on IHC

A

Ki-67: is a marker of proliferation (how many times the cell is undergoing mitosis)

51
Q

What are the 5 main sites for a breast cancer to metastasise?

Why is metastasis so easy/common?

A

Main sites of metastasis in order

1) Bones (most common site)
2) Lung
3) Liver
3) Brain

+ Pancreas and Adrenal gland

The breast has large amounts of lymphatic drainage… Hence lots of potential lymph travel for the carcinoma in particular the ipsilateral axilla

52
Q

What are the 5 main lymph nodes in the ipsilateral axilla region?

A 
central 
axillary
pectoral
subcapsular
lateral nodes
53
Q

Invasive lobular carcinomas (ILC) usually have a distinct pattern of metastasis, hence “odd sites” of metastasis are common

Give 4 of these

A

peritoneum, retroperitoneum, leptomeninges, gastrointestinal tract, ovaries, uterus

54
Q

How do we diagnose breast cancer?

A

Using a Triple approach:

1) clinical: history, family history + examination (is there pain etc)
2) Radiographic imaging: mammogram + ultrasound (for the lobular invasive disease you can do a MRI due to the non typical pattern of metastasis)
3) Pathology: fine need aspiration cytology (FNAC) and core biopsy - provide material histological evaluation and IHC.

55
Q

What is the purpose of mammographic screening?

If abnormalities are found how can we further assess these?

Who is eligible and what has this screening shown to decrease the risk of?

A

Aim is to detect small impalpable cancers and pre-invasive cancer. It looks for asymmetric densities, parenchymal deformities and calcifications

Assess abnormalities using further imaging, FNAC and core biopsy

Women 50-70years (being extended to 47–73 years) are eligible for 2 view mammograms every 3 years in the UK

Shown to decrease the risk of DCIS

56
Q

If there is a high chance that the palpable mass on a patient is a carcinoma what test can be done?

What is this and if the results are negative what can be avoided?

A

A sentinel lymph node biopsy

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 (reduces the risk of postoperative morbidity)

57
Q

What test can examine the expression gene patterns in tissues from breast cancer patients?

What has recently been approved by NICE and how does this benefit patients?

A

Microarrays

A 17 marker gene panel that can correctly identify about 90% of women who would eventually develop metastases (allows more personalised care)

58
Q

Alongside microarrays what else is more broadly being done for patients with breast cancer and how is this beneficial?

A

Molecular profiling of different receptors is being used for the diagnosis of breast cancer (eg. through use of IHC)

People have a different prognosis dependent on their receptor profile

The triple negative subgroup have the poorest prognosis
(most BRAC1 patients have a triple negative disease)

59
Q

What does triple negative mean and in what type of breast cancer is it most common?

What implications does this have for the treatment of the patient?

A

Triple negative cancers do not express oestrogen receptor (ER), progesterone receptor (PR) or (HER2) receptors.

Therefore, these cancers do not respond to endocrine treatment or treatment with Herceptin.

However, they often show a better response to chemotherapy than some other breast cancers.

60
Q

List 3 methods of breast cancer treatment that are under local and regional control

Explain the options for each and some determining factors

A

1) Breast surgery:
• mastectomy (preventative or in response to diagnosis)
• breast conserving surgery (only affected part of breast is removed
The decision depends on patient choice, size and site of tumour and size of breast

2) Axillary surgery: extent depends on whether there are involved nodes (sentinel node sampling or axillary dissection)
3) Post-operative radiotherapy to chest and axilla: extra protective measure to ensure all malignant tissue has been removed

61
Q

List 3 methods of breast cancer treatment that are under Systemic control

A

1) Chemotherapy: only if benefits are thought to outweigh the risks
2) Hormonal treatment: e.g. tamoxifen: depending on oestrogen receptor status (80% of cancers are ER +)
3) Herceptin treatment: depends on HER2 receptor status (20% of cancers are Her2 positive)

62
Q

If chemotherapy is given BEFORE surgery what is this known as?

A

neoadjuvant

63
Q

Give a drug that is used to treat ER+ breast cancer

Give a drug that is used to treat HER2 + breast cancer

A

ER+ = Tamoxifen

Her2 + = Herceptin

64
Q

What is HER2 and what protein does it encode?

How would you treat?

A

Her2 is a member of the human epidermal growth factor receptor family

Encodes a transmembrane tyrosine kinase receptor

Treatment: Herceptin = trastuzumab which are humanised monoclonal antibodies against the Her2 protein

65
Q

How can triple negative breast cancer be treated?

A

Sub-divide into Lymph node (+) and (-) to decide the type of chemotherapy required (T= tumor size, abc)

If Lymph node (-)
• T1a < 0.5 cm = No chemo
• T1b 0.6-1.0 cm = consider chemo
• T1c > 1 cm = adjuvant chemo

If Lymph node (+)
• Adjuvant Anthracycline/ Taxane based chemo

66
Q

Give 5 factors that determine the prognosis of breast cancer

A

1) In situ disease or invasive carcinoma
2) histologic subtype: IDC and NST has poorer prognosis
3) tumour grade
4) tumour stage
5) gene expression profile

67
Q

What does NST stand for?

A

Invasive carcinoma of no special type (poor prognosis)

68
Q

What 4 things does breast cancer tumour staging look at?

MOD review: How is the stage worked out?

A

1) Tumour size
2) Locally advanced disease – invading into skin or skeletal muscle
3) Lymph node metastases
4) Distant metastases

TNM stage
T stage (T0-4), N stage (N1-3) and M stage (M0-1)
69
Q

MOD review

How are Breast carcinomas graded?

What 3 things does this look at and what do the scores indicate?

A

Using Bloom Richardson:

1) tubule formation (cell differentiation)
2) nuclear size (degree of pleomorphism)
3) mitotic count (rate of division)

Total scores indicate:
Grade I tumors have a total score of 3-5
Grade II tumors have a total score of 6-7
Grade III tumors have a total score of 8-9

70
Q

Give 4 ways we can improve survival from breast cancer

A

1) Early detection: awareness of disease, importance of family history, self-examination, mammographic screening
2) Neoadjuvant chemotherapy: early treatment of metastatic disease
3) Use of newer therapies: e.g. Herceptin
4) Gene expression profiles: ensure patient is given the right treatment upfront e.g. Oncotype DX, Mammaprint
5) 100K genome sequencing project: looks at breast cancer patients from various geographic locations in order to identify different groups of patients
6) Prevention in familial cases: genetic screening, prophylactic mastectomies

71
Q

What NHS tool can patients needing more information on their breast cancer use?

A

Predict: this is an online tool that helps patients and clinicians see how different treatments for early invasive breast cancer might improve survival rates after surgery.

Reproduction (Semester 4) (20 decks)

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