Breast pathology - malignant

Question 1

List the 4 main miscellaneous malignant breast tumours

Answer 1

1. Malignant Phyllodes tumour
2. Angiosarcoma
3. Lymphoma
4. Metastatic tumours

Question 2

What is the malignant change which occurs for a phyllodes tumour to become malignant and how often does this occur?

Answer 2

• Malignant change = stroma becomes sarcomatous (sarcoma)
• This occurs in 5% of cases

Question 3

What is an angiosarcoma and what is it associated with occuring after ?

Answer 3

• It is a malignant tumour of the inner lining of blood vessels
• They have an association of developing post radiotherapy

Question 4

Can a primary lymphoma occur in the breast ?

Answer 4

• Yes but uncommonly, they occur with diffuse large B-cell lymphoma being the most common

Involvement of the breast in disseminated lymphomas & in myeloid leukaemias is more common e.g. young feales with burkkets lymphoma may develop bilateral breast involvement

Question 5

What are the common metastatic tumours to the breast ?

Answer 5

1. Carcinomas - bronchial, ovarian serous carcinoma & clear cell carcinoma of the kidney
2. Malignant melanoma
3. Soft tissue tumouts - leiomysarcoma

Question 6

Define what a breast carcinoma is

Answer 6

A malignant tumour of breast epithelial cells arising in the glandular epithelium of the terminal duct lobular unit (TDLU)

Question 7

What are the signs and symptoms of breast cancer ?

Answer 7

• Dimpled or depressed skin
• Visible/ palpable lump
• Nipple change e.g. inversion
• Bloody discharge
• Texture change
• Skin change e.g. eczematous

Question 8

Pathologically what are all types of breast cancer ?

Answer 8

An adenocarcinoma

Question 9

What are the 2 main types of breast carcinomas?

Answer 9

Ductal or lobular carcinoma (arising from duct tissue or lobular tissue respectively)

Question 10

How can ductal & lobular breast cancer be further subdivided ?

Answer 10

Based on whether the cancer hasn’t spread beyond the local tissue (described as carcinoma-in-situ) or has spread (described as invasive).

Question 11

List the 4 main types of breast cancer

Answer 11

1. Invasive ductal carcinoma. (called no special type - NST)
2. Invasive lobular carcinoma
3. Ductal carcinoma-in-situ (DCIS)
4. Lobular carcinoma-in-situ (LCIS)

The other 3 types may be referred to as special types as they are less common

Question 12

Define what a carcinoma in situ is

Answer 12

This is where the cytological changes of malignancy are present in the epithelial cells but the basement membrane remains intact & no invasive is seen

==> invasive once the BM has been breached

Question 13

What are the 2 subtypes of lobular in situ neoplasia ?

Answer 13

1. Atypical Lobular Hyperplasia (ALH) where <50% of lobule involved
2. Lobular Carcinoma in situ (LCIS) where >50% of lobule involved

Question 14

What are the general characteristics of a malignant cell ?

Answer 14

• Increased nuclear size (with increased nuclear/cytoplasmic ratio–N/C ratio).
• Variation in nuclear or cell size (pleomorphism).
• Lack of differentiation (anaplasia).
• Increased nuclear DNA content with subsequent dark staining on H and E slides (hyperchromatism).
• Prominent nucleoli or irregular chomatin distribution within nuclei.
• Mitoses (especially irregular or bizarre mitoses).

Question 15

What are the characterisitc cells seen in lobular in situ neoplasia ?

Answer 15

• Small-intermediate sized nuclei
• Solid proliferation
• Intra-cytoplasmic lumens/vacuoles
• ER positive
• E-cadherin negative (due to deletion & mutation of CDH1 gene on Chr 16q22.1)

Question 16

What are the main presenting features of a lobular in situ neoplasia ?

Answer 16

• Frequently multifocal & often bilaterally affecting the breasts
• Not usually palpable or grossly visible so often incidental finding seen as calcification on mammography

Question 17

What happens to the incidence of lobular in situ neoplasia following menopause?

Answer 17

Its incidence increases

Question 18

What is the significance of lobular in situ neoplasia in terms of risk of invasive development ?

Answer 18

8x increased risk

Question 19

What is the management of a lobular in situ neoplasia ?

Answer 19

1. If discovered on core biopsy ==> proceed to exicision or vaccum biopsy to exclude higher grade lesion
2. If discovered on vaccum or excision biopsy ==> follow-up

Question 20

How do invasive lobular carcinomas typically present ?

Answer 20

• Often not apparent by either palpation or imaging until cancer is at an advanced stage
• Has typical histological ‘indian file patern’ (infiltrating tumour cells arrnaged in a single file)

Question 21

What are the ductal carcinoma precusor lesions ?

Answer 21

1. Epithelial hyperplasia of usual type
2. Columnar cell change
3. Atypical ductal hyperplasia
4. Ductal carcinoma in situ

Question 22

Where does a ductal carcinoma in situ arise ?

Answer 22

In the TDLU - characteristically affecting one duct system

Question 23

How do ductal carcinomas typically present ?

Answer 23

• Usually as a lump/mass
• Typically then find stellate (star like) solid mass or pleomorphic casting microcalcifications when investigated

Question 24

How is definitive diagnosis of a ductal carcinoma made?

Answer 24

By image guided tissue core-needle biopsy

Question 25

How do ductal in situ carcinomas typically present and what is seen on investigation ?

Answer 25

Usually present as non-palpable, but seen on screening XRM as malignant calcifications (pleomorphic & of the casting type - stellate)

Question 26

How is definitive diagnosis of a DCIS made ?

Answer 26

By vaccum assisted core-biopsy

Question 27

What are the pathological features of a ductal carcinoma in situ ?

Answer 27

* Cytologically malignant epithelial cells * Confined within basement membrane of duct * May involve lobules (cancerisation) * May involve nipple skin (Paget’s)

Question 28

Define what pagets disease of the nipple is

Answer 28

* It is a high grade DCIS extending along the ducts to reach the epidermis of the nipple. * It is still an in-situ carcinoma i.e. non-invasive as the BM has not been breached.

Question 29

What is the characterisitic appearance of pagets disease of the nipple?

Answer 29

Has a characterisitc eczematous appearance but can cause weeping which is percieved as nipple discharge

Question 30

What is a microinvasive breast carcinoma and how are they treated?

Answer 30

* This is a DCIS which has invaded \< 1mm * Treated as a high grade DCIS

Question 31

Define what an invasive breast carcinoma is

Answer 31

* **This is when malignant epithelial cells have breached the BM** * There is infiltration of normal tissues, with the risk of metastases

Question 32

Appreciate this about breast cancer: * It esp affects females * Its incidence increases with age * It is the 2nd highest cancer cause of death in females

Question 33

List the risk factors for breast cancer development

Answer 33

* Increasing age * Early menarche ≤ 12 * Nullipara (never given birth) * 1st pregnancy after 30 * Never breastfed * Later menopause \> 55 * Use of OCP or depo * Current HRT or used \> 5yrs * FH - relative \< 40 (otherwise not considered increased risk) * Previous DCIS/LCIS or breast cancer * Smoking & diabetes, increased BMI, alcohol consumption ≥ 1 per day * Genetics - BRCA 1/2 and TP53 * Radiation exposure

Question 34

What are the 2 main mutations which increase the risk of breast cancer ?

Answer 34

BRCA 1 and BRCA 2

Question 35

What are the places to which breast cancer commonly invades

Answer 35

* Local invasion (T) - Stroma of breast, Skin, Muscles of chest wall * Lymphatics (N) - to the Regional draining lymph nodes * Blood-borne (M) - predlictation to the Bone, liver, brain, lungs, abdominal viscera & female genital tract

Question 36

What 3 things are breast cancers classified based on ?

Answer 36

Based on: 1. Morphology - type and grade 2. Gene expression profiling 3. Homrone receptor expression - oestrogen receptor (ER), progesterone receptor (PR) & HER2

Question 37

Define what is meant by tumour grade ?

Answer 37

**This is a measure of tumour differentiation** * If a tumour is very similar to the original tissue it is described as well differentiated or low grade ==\> good prognosis * If a tumour is very different to the original tissue it is described as poorly differentiated or high grade ==\> poor prognosis

Question 38

Why is the grading of breast cancer important ?

Answer 38

Because it indicates prognosis - grade 1 \> 2 \> 3

Question 39

80% of breast cancers are oestrogen receptor (ER) +ve, what does this mean in terms of treatment options ?

Answer 39

It means the cancer may respond to anti-oestrogen therapies which include: * Oophorectomy * Tamoxifen * Aromatase inhibitors (Letrozole) * GnRH antagonists - (Goserilin [Zoladex])

Question 40

15% of breast cancers are HER2 +ve what does this mean in terms of treatment options ?

Answer 40

HER2 +ve may respond to Transtuzamab treatment (human monoclonal antibody)

Question 41

Referring to hormone receptor expression, what are good prognostic features ?

Answer 41

* If ER +ve rather than -ve * If PR +ve rather than -ve * If HER2 -ve rather than +ve These are all associated with increase survival rates

Question 42

How are breast carcinomas staged ?

Answer 42

TNM staging: Direct invasion of adjacent tissues * T0 - T4 Local tumour growth (size of tumour and extent of involvement of adjacent structures) Lymphatic spread * N0 - N3 Regional lymph nodes Blood-borne spread * M0 - M1 Distant metastasis

Question 43

State the different levels of local invasion of breast cancers (T component)

Answer 43

* T0 = no evidence of tumour * T1 = ≤ 2cm tumour * T2 = 2-5cm * T3 = \> 5cm * T4 = a) any sign of tumour invasion into chest wall, b) invasion of skin

Question 44

State the different levels of lymphatic spread of breast cancers (N component)

Answer 44

* N0 = no lymph node involvement * N1 = metastases to ipsilateral axillary nodes, but nodes are movable * N2 = a) metastases to ipsilateral axillary nodes, but nodes are not movable (stuck), b) metastases to ipsilateral mammary nodes without being in axillary nodes * N3 = a) mets in ipsilateral infraclavilcular nodes, b) mets in ipsilateral supraclavilculaar nodes, c) mets in ipsilateral axillary & mammary nodes

Question 45

State the different levels of metastatic spread (blood borne) of breast cancers (M component)

Answer 45

* M0 = no metastatic spread to a diff part of the body * M1 = cancer has spread to another part of the body

Question 46

What is used to determine prognosis following surgery for breast cancer?

Answer 46

Nottingham prognostic index

Question 47

Prior to surgery for any breast cancer (including DICS & pagets) what should be assessed?

Answer 47

Prior to surgery, the presence/absence of axillary lymphadenopathy: 1. women with no palpable axillary lymphadenopathy at presentation should have a pre-operative axillary U/S before their primary surgery. If positive then they should have SLNB to assess the nodal burden 2. In patients with breast cancer who present with clinically palpable lymphadenopathy or ≥ 4 +ve nodes on SLNB, axillary node clearance (ALND) is indicated at primary surgery, if this cant be done then adjuvant radiotherapy to axilla done

Question 48

What can axillary lymph node clearance lead to ?

Answer 48

Arm lymphedema and functional arm impairment

Question 49

What is the initial treatment of breast cancer?

Answer 49

Surgery + radiotherapy +/- adjuvant systemic therapy (hormonal, biological or chemo) Surgery is either: 1. WLE (breast conserving surgery) - solitary lesion, peripheral tumour, small lesion in large breast, DICS \< 4cm, pagets assessed as localised (also has removal of nipple-areloar complex) 2. Modified radical Masectomy - multifocal or central tumour, large lesion in small breast, DICS \> 4cm, pagets not localised

Question 50

What does modified radical masectomy involve ?

Answer 50

* This is removal of the entire breast inclduing the overlying skin & axillary lymph nodes. * The pectoralis major muscle is preserved however as this fascilitates improved wound healing & potentially allows for reconstruction surgery

Question 51

What should women be offered alongside surgery for breast cancer regardless of the type of operation they undergo?

Answer 51

Breast reconstruction to achieve a cosmetically suitable result regardless of the type of operation they have.

Question 52

What should always be discussed prior to masectomy ?

Answer 52

Breast reconstruction options and if they would like it done immediately, delayed or not at all following the surgery

Question 53

When is adjuvant radiotherapy offered to a women with breast cancer alongside surgery ?

Answer 53

1. Whole breast radiotherapy (3-6 weeks) + a boost dose targeted at the tumour bed is recommended after a woman has had a wide-local excision 2. For women who've had a mastectomy radiotherapy is offered for T3-T4 tumours and for those with three or more positive axillary nodes, positive surgical margins and/or tumors \> 5 cm.

Question 54

When is adjuvant chemotherapy used in breast cancer treatment ?

Answer 54

* Cytotoxic therapy may be used either prior to surgery ('neoadjuvanant' chemotherapy) to downstage a primary lesion or after surgery depending on the stage of the tumour, for example, if there is axillary node disease - FEC-D is used in this situation. * It should be considered for all patients with breast cancer where the benefit outweighs the risk

Question 55

Post-operatively what should be assessed to determine adjuvant treatment of breast cancer ?

Answer 55

Assess ER & HER2 status (PR status not routinley done)

Question 56

Who should be considered for adjuvant systemic therapy in breast cancer treatment ?

Answer 56

All those with early invasive breast cancer following surgery

Question 57

How soon after surgical treatment should adjuvant chemo or radiotherapy be initiated?

Answer 57

Within 3 days

Question 58

What should be offered for those \<50 with tripple -ve breast cancer (hormone receptors), but no family history of breast/ovarian cancer

Answer 58

BRCA 1/2 genetic testing

Question 59

What hormonal therapy should be used following surgery for ER +ve breast cancers ?

Answer 59

1. Tamoxifen is still used in pre- and peri-menopausal women. 2. In post-menopausal women, aromatase inhibitors such as anastrozole, letrozole

Question 60

When should hormonal therapy not be given for ER+ve early invasive breast cancer following surgery?

Answer 60

Do not give it for DICS following BCS (WLE)

Question 61

What targeted therapy is given for HER2+ve early invasive breast cancers following surgery?

Answer 61

Herceptin (Trastuzumab, TZ)

Question 62

When is the use of Trastuzumab contraindictated for use in HER2+ve breast cancer?

Answer 62

Cannot be used in patients with a history of heart disorders.

Question 63

What extra investigations should be done for advanced breast cancer?

Answer 63

Assessment for the presence or extent of metastases should be made using a combination of: (advanced means locally advanced so more likely to have metastases than early invasive) X-rays, U/S, CT & MRI

Question 64

What is the treatment of advanced ER+ve breast cancer ?

Answer 64

* 1st line = hormonal therapy (depending on if theyve undergone menopause or not) * Offer chemo 1st line if disease is immenitley life threatening or requires early relief of symptoms because of sig visceral ogran involvement, then followed by hormonal therapy

Question 65

What is used for advanced breast cancer if HER2+ve ?

Answer 65

Herceptin (Trastuzumab, TZ)

Question 66

What is the 1st line treatment of metastatic breast cancer ?

Answer 66

Biological therapy - bevacizumab