Breast anatomy and pathology

Question 1

Briefly describe breast anatomy

Answer 1

Each breast is divided into 15 -25 lobes that are separated by a fibrous septa. This fibrous septa forms the suspensory ligaments.
Each lobe is divided into many lobules in which are acini (aveoli) and fat cells.
Acini consist of milk-secreting cells arranged around a central lumen, draining into small ducts. Ducts unite to form successively larger structures as they pass toward the nipple.
Before opening to the surface, each of the ducts expand to form a sinus where milk accumulates during nursing.
Acini and ducts are surrounded by specialised smooth muscle cells known as myoepithelial cells. Contraction of these cells causes milk ejection.
The suspensory ligaments (ligaments of cooper) attach the mammary gland to the overlying skin. They are particularly well developed in the superior part of the gland to help support the lobes and lobules.

Question 2

Describe the breast during puberty

Answer 2

During puberty estrogen and progesterone stimulate the growth of ducts, and of acini. From puberty onwards growth of the breasts results from the deposition of fat.

Question 3

Describe the breast during reproductive years

Answer 3

During reproductive years the breast alters under the changing levels of oestrogen and progesterone in the blood that occur during the menstrual period. Towards the end of each cycle, the breast becomes engorged and oedematous; once menstruation has begun, the excess fluid is lost.

Question 4

Describe the breast during pregnancy

Answer 4

During pregnancy there is further development of alveoli and ducts under the influence of oestrogen, progesterone, prolactin and placental lactogen; and increased blood supply to the breasts

Question 5

Describe the breast after menopause

Answer 5

After menopause breasts tend to atrophy gradually, the amount of fat and glandular tissue is reduced and as such the proportion of fibrous tissue increases.

Question 6

Describe the function and occurrence of prolactin

Answer 6

Prolactin is an anterior pituitary hormone. It is first secreted during puberty under the influences of increasing levels of oestrogen. During pregnancy high levels of oestrogen again illicit high levels of prolactin secretion however the production of milk is prevented by the high levels of oestrogen and progesterone. After delivery lactation occurs under the influence of prolactin.
Prolactin also inhibits ovulation as long as suckling is frequent

Question 7

Describe the function and occurrence of Oxytocin

Answer 7

Oxytocin is a hypothalamic hormone secreted through the posterior pituitary gland that mediates milk ejection or ‘letdown’. It moves milk through the duct system to the nipple in response to suckling. Oxytocin secretion can also be triggered from the posterior pituitary by input from higher centres of the brain, for example, in response to a baby’s cry.
Oxytocin also causes contraction of uterine smooth muscle which helps to reduce bleeding from the site of the placenta soon after birth

Question 8

Compare the breast tissue of a pre and post-menopausal woman

Answer 8

Pre-menopausal – Largely consists of fat and glandular tissue.
Post-menopausal – Decreased fat and glandular tissue. Proportionally the breast is mainly fibrous tissue.

Question 9

List the lymphatic drainage of the breast-which lymph nodes drain the medial side of the breast?

Answer 9

Lymph passes from the nipple, areola and lobules of the gland through intramammary nodes and channels to the subareolar lymphatic plexus (Sappey’s Plexus).
From this plexus drainage takes place through three main routes that parallel venous tributarie

Axillary or lateral pathway
• Most lymph (>75%) especially from the lateral side of the breast, drains to the axillary lymph nodes.

Internal mammary pathway
• Most remaining lymph, particularly from the medial breast quadrants, drain to the parasternal lymph nodes or to the opposite breast.

Retromammary pathway
• Lymph from the deeper portion of the breast
• drains to the subclavicular plexus
Lymph from the inferior quadrants may pass deeply to the abdominal lymphnodes.

Question 10

What is a sentinel node

Answer 10

A sentinel node is defined as the first node in a reginal lymphatic basin that receives lymph flow from the primary tumour. it is the first lymph node to drain a malignant neoplasia

Question 11

List & describe the main features of fibrocystic disease

Answer 11

• Common benign condition
• Presentation 20-40years
• Often bilateral and multifocal
• Symptoms - painful, lumpy and tender breasts -especially in the upper outer quadrant.
• oestrogen dominance over progesterone is an important factor
• Cysts grow and symptoms are often worse just before menstruation
• Frequency decreases after menopause

Non-proliferative fibrocystic change
• The term non proliferative indicates that they are not associated with an increased risk of breast cancer

Proliferative fibrocystic change
• proliferative disease have a greater risk of breast cancer when compared with the general population
• atypical epithelial cell hyperplasias of the ducts or ductules
• Sclerosing adenosis (SA) is a benign proliferative condition of the terminal duct lobular units characterized by an increased number of acini and their glands.

Question 12

List & describe the main features of fibroadenoma

Answer 12

• Common benign condition
• results from the excess proliferation of connective tissue
• contain both stromal and epithelial cells
• most common benign breast neoplasm
• Presentation 20-35 years
• Symptoms – Lump that moves when touched. Usually painless.
• Can become painful just before menstruation
• Cause is relatively unknown
• Thought to be increased sensitivity to the hormone oestrogen

Question 13

What is the effect of oestrogen and progesterone on breast tissue? Why would symptoms be more noticeable just before menstruation?

Answer 13

Symptoms of soreness and tenderness and feeling of fullness are more noticeable in the mid to later part of the cycle as this is when the hormones are at their highest and have caused the breast tissue to swell.
Increased levels of oestrogen and progesterone during the menstrual cycle cause the breast to become engorged and oedematous.
Fibroadenomas respond to hormonal changes. Fibroadenomas develop from a lobule. The glandular tissue and ducts grow over the lobule and form a solid lump. So, the swelling of glandular tissue can cause pain.
Fibrocystic disease is associated with hormonal changes which cause the cysts to get bigger and painful just before menstruation.

Question 14

What is meant by proliferative epithelial change and ductal hyperplasia?

Answer 14

ductal hyperplasia - an overgrowth of the cells that line the ducts. Hyperplasia does not necessarily indicate the presence of breast carcinoma but it has the potential to become cancer.

proliferative epithelial change - epithelial cells appear to growing and accumulating more than normal. The epithelial cell layer appears thicker than normal

Question 15

List risk factors for breast malignancies

Answer 15

• modifiable: smoking, hormonal birth control,HRT, drinking, weight
• genetic: 5-10% of cases (BRCA1 and BRCA2 90%, p53, PTEN, STK11)
• Incidence increasing with increasing age
• Gender
• Family history
• Race/ethnicity
• beginning periods before age 12 or going through menopause after age 55
• Reproductive history (not having children or having your first child after age 35)
• Exposure to ionising radiation
• dense breasts

Question 16

What are the signs and symptoms of breast cancer?

Answer 16

Most breast cancers are detected as a palpable mass. In this case most are invasive and 2-3cm in size and half will have spread to regional lymphnodes.
Patients above 50 are screened and so about 60% of cancers are detected before signs and symptoms arise. Other presentations include;
• Change in breast size or shape
• Skin dimpling or skin changes (eg, thickening, swelling, or redness)
• Recent nipple inversion or skin change or other nipple abnormalities (eg, ulceration, retraction, or spontaneous bloody discharge)
• Nipple discharge, particularly if bloodstained
• Axillary lump
• contour change
• Skin tethering
• Dilated veins
• Ulceration
• Edema or peau d’orange
Note that pain is not a symptom typically associated with breast cancer.

Question 17

Where are breast cancers mainly located?

Answer 17

• upper outer quadrant (50%)
• central portion (20%)
• 4% of women have bilateral tumors or multiple tumors in the same breast.
• arises in the ductal or glandular epithelium of the breast lobule and excretory duct system.
  The tumour starts of as a proliferation of atypical epithelial cells. It will eventually fill and expand the lumen of the duct.

Question 18

What are some ways of classifying breast cancers?

Answer 18

• morphology
• hormone receptor status (ER, PR)
• histology (ductal, lobular)
• grade (low, intermediate, high)
• stage (TNM)
• DNA assays

Question 19

What are the three main hormone receptor statuses of breast cancer?

Answer 19

Breast cancer can be classified based on the expression of hormone receptors;

• oestrogen receptor ER
• progesterone receptor PR
• human epidermal growth factor receptor 2 HER2.

Question 20

What are the two morphological ways of describing breast cancer?

Answer 20

Breast cancers can be classified morphologically according to whether they have penetrated the basement membrane.
Those that remain within the boundary are carcinoma in situ.
Those that have spread through the membrane are invasive carcinoma.

Question 21

In relation to the breast, compare ductal carcinoma in situ with lobular carcinoma in situ. (4 marks)

Answer 21

ductal carcinoma in situ DCIS
- limited to the ducts with no extension beyond the basement membrane

• Accounts for approximately 15-20% of all detected breast cancers.
• Usually identified during routine mammographic screening
• If untreated 30 % would progress to invasive carcinoma.
• Treatment; mastectomy; excellent prognosis
• distorts the lobules into duct like spaces

lobular carcinoma in situ LCIS
- Malignant cells fill and distend the lobular acini and do not extend beyond the basement membrane.

• occurs predominantly in premenopausal women with a mean age of 45 years
• expands the involved lobules and is more likely to be multifocal and bilateral
• originates in the terminal ductal lobular unit (TDLU)
• usually incidentally-identified histologically in breast tissue biopsied for other reasons
• 1/3 of women with LCIS develop invasive carcinomas

Both ductal and lobular carcinoma are thought to arise from the cells in the terminal duct

Question 22

Why is DCIS more readily identified in mammograms?

Answer 22

A major difference between LCIS and DCIS is that DCIS is more likely to be associated with calcifications and hence are more readily identifiable through mammograms whereas LCIS is rarely associated with calcifications.

Question 23

Describe invasive breast carcinoma

Answer 23

• Invasive ductal carcinoma (includes all carcinomas that are not of a special type) 70-80%

• most common form of breast cancer
• usually manifests as a hard-fixed mass
• typically, firm with irregular margins

Question 24

Describe histological grading

Answer 24

Grading of breast cancer looks more at the histology of cancer cells. There are three grades of breast cancer. It looks at the aggressive potential of the tumour and can be used to calculate the survival rate at 10 years.

It takes into account three factors:

1. amount of gland formation - cell differentiation
2. nuclear features i.e. the degree of pleomorphism
3. mitotic activity 0 how much tumour cells are dividing or proliferating

each of these features is scored from 1-3 and then the scores are added to give a final score ranging from 3-9 to determine the grading. grade 1, 2 or 3

Question 25

Describe how breast cancer can spread

Answer 25

Invasive breast carcinoma spreads primarily thru the lymphatics to regional lymph nodes, including the axillary, internal mammary and supraclavicular nodes.
The probability of spread of to the axillary nodes is directly related to the size of the primary tumour
Breast cancer also spreads to distant sites, most commonly the lung and pleura, liver, bone, adrenals, skin and brain
Local spread of breast carcinoma includes adjacent tissue, overlying skin & deeply into pectoral muscles.
Lymphatic spread includes local lymphatics, (skin lymphatics; peau d’orange effect) axillary nodes and internal mammary chain
Vascular spread includes dissemination to distant sites- bone, lung, pleura and ovary.

Question 26

What is tumour staging?

Answer 26

Tumour staging is a measure of the extent of the tumour at the time of diagnosis and is based on the features of the primary tumour, involvement of regional lymph nodes and the presence of distant metastasis.

Question 27

Describe what is meant by inflammatory breast cancer

Answer 27

Inflammatory breast cancer is a rare and very aggressive disease in which cancer cells block lymph vessels in the skin of the breast. This type of breast cancer is called “inflammatory” because the breast often looks swollen and red, or inflamed.
Most inflammatory breast cancers are invasive ductal carcinomas. Inflammatory breast cancer progresses rapidly, often in a matter of weeks or months.
Symptoms of inflammatory breast cancer include swelling (edema) and redness (erythema) that affect a third or more of the breast. The skin of the breast may also appear pink, reddish purple, or bruised. In addition, the skin may have ridges or appear pitted, like the skin of an orange (called peau d’orange).
Symptoms are caused by the buildup of fluid (lymph) in the skin of the breast. This fluid buildup occurs because cancer cells have blocked lymph vessels in the skin, preventing the normal flow of lymph through the tissue.

Question 28

What does the term-‘peau-d’orange’ indicate?

Answer 28

A dimpled condition of the skin of the breast, resembling the skin of an orange, sometimes found in inflammatory breast cancer. Caused by cutaneous lymphatic edema, which causes swelling. However, some parts of the edematous skin is tethered by the hair follicles and the sweat glands such that it cannot swell, leading to an appearance like orange skin

Question 29

Which group has the higher percentage of breast cancer- those over or under 50 years of age?

Answer 29

Those over 50 years of age have a higher percentage of breast cancer.

Question 30

Which breast region tends to be diagnosed with more malignancy?

Answer 30

The upper outer quadrant (50%) and the central portion (20%)