Breast Cancer

Question 1

Where do most breast cancer arise from?

Answer 1

o The epithelial lining of ducts and are called ductal.

o From the epithelium of the terminal ducts of the lobules and are called lobular.

Question 2

Are all breast cancers invasive?

Answer 2

No.

Carcinoma can be invasive or in situ. Most cancers arise from intermediate ducts and are invasive.

Question 3

Can breast cancer occur in males?

Answer 3

Breast cancer in males is rare, contributing to about 1% of cases.

Question 4

What are the major risk factors for breast cancer in men?

Answer 4

clinical disorders carrying hormonal imbalances (especially gynaecomastia and cirrhosis)

radiation exposure

a positive family history and genetic predisposition.

Question 5

What are the two types of breast cancer?

Answer 5

Breast cancers can be divided into two main groups- the carcinomas and the sarcomas.

Question 6

What is breast carcinoma?

Answer 6

Carcinomas are cancers that arise from the epithelial component of the breast.

o The epithelial component consists of the cells that line the lobules and terminal ducts.

o Epithelial cells are responsible for making milk.

o Carcinomas comprise the vast majority of all breast cancers.

Question 7

What are sarcomas?

Answer 7

Sarcomas are rare cancers that arise from the stromal (connective tissue) components of the breast.

o These stromal component cells include myofibroblasts and blood vessel cells, and cancers arising from these ‘supportive’ cells include phyllodes tumours and angiosarcoma.
o Sarcoma account for less than 1% of primary breast cancers.

Question 8

What is in situ carcinoma?

Answer 8

In situ carcinoma is “pre-invasive” carcinoma that has not yet invaded the breast tissue. These in situ cancer cells grow inside of the pre-existing normal lobules or ducts.

Question 9

What are invasive cancers?

Answer 9

Invasive cancers have cancer cells that infiltrate outside of the normal breast lobules and ducts to grow into the breast connective tissue.

Invasive carcinomas have the potential to spread to other sites of the body, such as lymph nodes or other organs, in the form of metastases.

Question 10

What is the most common breast carcinoma?

Answer 10

Approximately 80% of breast carcinomas are invasive ductal carcinoma, followed by invasive lobular carcinomas which account for approximately 10-15% of cases.

Invasive ductal carcinomas and invasive lobular carcinomas have distinct pathologic features.

Question 11

What is the histology of lobular carcinomas?

Answer 11

Specifically, lobular carcinomas grow as single cells arranged individually, in single file, or in sheets, and they have different molecular and genetic aberrations that distinguish them from ductal carcinomas.

Question 12

What are the types of breast carcinoma?

Answer 12

DCIS 
Invasive ductal carcinoma 
Invasive lobular carcinoma 
Colloid (mucinous) carcinoma 
Medullary 
Micropapillary 
Papillary 
Tubular

Question 13

What are the risk factors for malignancy?

Answer 13

• Previous hx of malignancy.
• Risk increases with age.
• FHx of breast cancer in a first-degree relative. Between 6% and 19% of women will have a family history.
• Genetic factors
• Never having borne a child, or first child after age 30.
• Not having breast-fed (breastfeeding is protective)
• Early menarche and late menopause.
• Radiation to chest
• Obesity and alcohol
• HRT
• Combined oral contraception

Question 14

Which genetic mutations increases the risk of breast cancer?

Answer 14

o BRCA1, BRCA2 and TP53 mutations carry very high risk but only about 5% of all breast cancers are attributable to these genes.

o BRCA1 mutation on chromosome 17: lifetime risk of breast cancer for women with this mutation is 65-85%, and the lifetime risk of ovarian cancer is 40-50%; men with this mutation may also be at increased risk of breast cancer.

o BRCA2 mutation on chromosome 13: for women with this mutation, the lifetime risk of breast cancer is 40-85%, and the lifetime risk of ovarian cancer is 10-25%; for men with this mutation, the lifetime risk of breast cancer is 6%.

Question 15

How does breast cancer present?

Answer 15

• Most patients present having felt a lump, which is most often painless but may be associated with pain.
• Other presenting symptoms include nipple change, nipple discharge and skin contour changes.
• Breast pain/mastalgia alone is a very uncommon presentation.
• Intraduct carcinoma may present as a bloody discharge from the nipple.
• Other clinical symptoms that might be seen with breast cancer include skin changes, such as skin dimpling, redness, scaling, and ulceration, which may look like a large sore. Nipple changes such as scaling or new nipple inversion may also be seen.
• Other symptoms include a lump under the arm, lump in other regional lymph nodes and with retraction or inversion of the nipple.
• A suspicious mass may have been found at routine mammography (screening).
• Metastases may cause pain in bones or even pathological fractures.
• Metastases at other sites - for example, the liver, lung or brain - may cause symptoms.

Question 16

When should you refer patient for breast cancer in primary care?

Answer 16

• Refer people, using a suspected cancer pathway referral (for an appointment within 2 weeks), for breast cancer if they are aged 30 and over and have an unexplained breast lump with or without pain, or are aged 50 and over with any of the following symptoms in one nipple only: discharge, retraction or any other changes of concern.
• Consider a suspected cancer pathway referral in people with skin changes that suggest breast cancer, or for those aged 30 and over with an unexplained lump in the axilla.
• Consider non-urgent referral in people aged under 30 with an unexplained breast lump with or without pain.

Question 17

What are the imaging used to detect breast cancer?

Answer 17

• Imaging includes bilateral mammography and ultrasound of the breast and regional lymph nodes.

Question 18

Is MRI used in the imaging of breast cancer?

Answer 18

• An MRI of the breast is not routinely recommended but should be considered in cases of:

familial breast cancer associated with BRCA mutations.

breast implants.

lobular cancers.

suspicion of multifocality/multicentricity (particularly in lobular breast cancer).

large discrepancies between conventional imaging and clinical examination.

before and during neoadjuvant chemotherapy.

Question 19

When is ultrasound really effective in detecting breast cancer?

Answer 19

• Ultrasound is very effective (especially in younger women). It is particularly useful when breast tissue is dense. In young patients it can be diagnostically more useful than mammography.

Question 20

How do you diagnose breast cancer?

Answer 20

Triple assessment.

Question 21

What is biomarker testing in breast cancer?

Answer 21

One important aspect of the role of pathologists in the evaluation of breast cancer is biomarker testing, specifically the accurate assessment of:
the oestrogen receptor (ER)
the progesterone receptor (PR)
the HER-2 status of a patient’s breast cancer

Question 22

Why is it important to do biomarker testing?

Answer 22

o Biomarkers can be prognostic, predictive, or both.

o Prognostic biomarkers are independent measures of prognosis such that the presence or absence of the biomarker is associated with a patient’s overall clinical outcome (i.e., risk of recurrence and mortality).

o Predictive biomarkers, in contrast, predict whether or not a patient will respond to a given therapy.

Question 23

Why do you test for ER and PR?

Answer 23

Oestrogen and progesterone are endocrine hormones that drive the growth of most breast cancers.

Oestrogen and progesterone stimulate cancer cells to grow by binding their specific receptors, the oestrogen receptor (ER) and the progesterone receptor (PR).

Approximately 70% of breast cancers express ER and PR, which means that oestrogen and progesterone can
stimulate these cancers to grow.

ER and PR are weak prognostic biomarkers and strong predictive biomarkers.

A tumour that expresses ER and PR is called “ER and PR positive,” and these patients have a more favourable prognosis than if the tumour “ER and PR negative.”

In addition, the ER and PR expression predicts that the patient will likely benefit from endocrine therapy that targets the hormone receptor, such as tamoxifen and others.

Question 24

How do you test for ER and PR?

Answer 24

Testing for ER and PR is done by using an immunostatin which binds to ER and PR in the cancer nucleus and is detected by a positive brown colour.

Question 25

Why do you test for HER2?

Answer 25

HER-2/neu is the name of a gene that encodes the HER-2 protein, which acts as a “tyrosine kinase receptor” on the cell surface of the cancer cell.

When a cancer has an abnormally increased number of HER-2 genes and an abnormally high amount of HER-2 protein on its cell surface, the cancer cell can divide and grow more.

This feature makes the HER-2 gene called an “oncogene,” because when active or increased, it promotes the “oncogenesis” or cancer growth of the cell.

HER-2 overexpression is seen in approximately 15-20% of invasive breast cancers, and it is an example of both a strong prognostic and predictive biomarker.

HER-2 expression is associated with a diminished prognosis (e.g., higher risk of recurrence); however, it also predicts that a patient will more likely benefit from directed therapies that target HER-2 (such as trastuzamab and others).

Question 26

How do you test for HER-2?

Answer 26

HER-2 can be detected by immunostatin or fluorescence in situ hybridization (FISH).

Question 27

Should the biomarkers be tested again in the recurrence of breast cancer?

Answer 27

o All primary invasive breast carcinomas should be tested for ER, PR, and HER-2.

Since the ER, PR, and HER-2 status can change in a small percentage of breast recurrences or metastases, these markers should also be re-tested in subsequent recurrences and metastases.

Question 28

Apart from triple assessment and biomarker testing, which other investigations are done to assess breast cancer?

Answer 28

• Routine blood tests including LFTs.
• CXR.

• CT scans if metastases are suspected:
o CXR abnormal.
o Neurological symptoms.
o Hepatosplenomegaly or lymphadenopathy (supraclavicular).
o LFTs abnormal.

• Bone scintigraphy if:
o Distant metastases.
o Bone pain.
o Lymph node metastases.
o Advanced local disease.

• Positron emission tomography (PET):
o Can be used to detect distant metastases.
o Can fail to detect low-grade lesions and those less than 5 mm in diameter.

Question 29

What are the differential diagnosis for breast cancer?

Answer 29

Fibroadenoma
Paget’s disease
Breast cysts
Phylloides tumour

Question 30

How do you stage breast cancer?

Answer 30

o The pathologic stage of breast cancer is a measure of how advanced a patient’s tumour is. Breast cancer stage ranges from Stage 0 (pre-invasive disease) to Stage IV (metastatic disease).
o Stage is a prognostic factor, and in broad generalization, “low stage” cancers (Stages 0-II) tend to have better long-term outcome than “high stage” cancers (Stages III-IV). Understanding a patient’s stage helps the clinical team determine the right treatment.
o The “pathologic stage” of a cancer takes into consideration the characteristics of the tumor (“T”) and the presence of any lymph nodes metastases (“N”) or distant organ metastases (“M”).
o These features are assigned individual scores called the pathologic T stage (T0-4), N stage (N1-3) and M stage (M0-1) are combined to form a final overall pathology stage (stage 0-IV).

Question 31

Why do you grade breast cancer?

Answer 31

o The grade of a breast cancer is a prognostic factor and is representative of the “aggressive potential” of the tumour.

o In a broad generalization, “low grade” cancers tend to be less aggressive than “high grade” cancers.

o Determining the grade is thus very important, and clinicians use this information to help guide treatment options for patients.

Question 32

Which scoring system is most commonly used to grade breast cancer?

Answer 32

o There are different “scoring systems” available for determining the grade of a breast cancer. One of these systems is the Nottingham Histologic Score system (also termed “the Elston-Ellis modification of Scarff-Bloom-Richardson grading system”).

Question 33

How is the Nottingham histologic score system used to grade breast cancer?

Answer 33

In this scoring system, there are three factors that the pathologists take into consideration:

• the amount of gland formation (the cell “differentiation,” or how well the tumour cells are trying to recreate normal glands)
• the nuclear features (the degree of “pleomorphism” or how “ugly” the tumour cells look)
• the mitotic activity (how much the tumour cells are dividing, or proliferating)

Question 34

How is the grade of the breast cancer calculated from the Nottingham scoring system?

Answer 34

o Each of these features is scored from 1-3, and then the scores is added to give a final total score ranging from 3-9.

The final total score is used to determine the grade in the following way:
Grade I tumours have a total score of 3-5

Grade II tumours have a total score of 6-7

Grade III tumours have a total score of 8-9