Breast Cancer

What is the basic anatomy of the internal breast?

Network of lobules and ducts

• lobules = secretory units of the breast

• Adipose tissue and fibrous connective tissue support the lobes and lobules

What is the histology of breast lobules?

Made up of epithelial acini cells - secrete milk into series of ducts

What is the name of the ducts that empty milk into the surface of the nipple?

Lactiferous duct

Where do the lymphatics of the breast run?

In the sub-mamillary space - can drain into between 20-40 lymph nodes (mainly the axillary lymph nodes)

What is the standard triple assessment of a breast lump?

• Clinical assessment (exam & history)

• Imaging (mammogram/ultrasound)

• Histology (fine needle aspiration or core biopsy)

What clinical features might be suggestive of a breast cancer?

• Breast lump - hard, irregular, painless or fixed in place

• Lumps may be tethered to the skin or chest wall

• Nipple changes, retraction or discharge

• Lymphadenopathy

• Skin changes - dimpling or puckering of skin

• Peau d’orange

What is Paget’s disease?

Rough, dry, erythematous and ulcerated skin surrounding the nipple. It can look very similar to eczema - but is a sign of underlying in-situ or invasive cancer

What causes peau d’orange?

Skin that looks like the surface of an orange - occurs when the cancer cells block lymphatics draining the skin. Skin becomes oedematous

Which area of the breast do most breast cancers present in?

Upper outer quadrant

If breast cancer is suspected, what referral pathway is a patient put on?

Two week wait (2WW) pathway - given triple assessment

Who does NICE recommend the 2WW referral for?

• Unexplained axilla or breast lump in those 30+

• Unilateral nipple changes in patients 50+

• skin changes that suggest breast cancer

What are the NIC guidelines of unexplained breast lumps in patients under 30?

Consider a non-urgent referral

What are differential diagnosis for breast lumps?

• fibroadenoma

• breast cyst

• intraductal papilloma

• breast abscess

• fat necrosis

What is fibroadenoma?

Benign overgrowth of collagenous mesenchyme of one breast lobule

Firm, non-tender, highly mobile palpable lumps

breast cysts

Palpable, benign, fluid-filled rounded lumps that are not fixed to surrounding tissue

Intraductal papilloma

Benign, warty lesion usually located just behind the areola

Present as a small lump and a sticky, possibly blood-stained discharge may be noticed

Breast abscess

Most common in breastfeeding mothers

Presents with malaise and fever accompanied by a throbbing pain

The breast will be hot and red and may have tender ipsilateral lymphadenopathy in the axilla

Fat necrosis

Fibrosis and calcification of the breast tissue usually due to trauma and can present as an irregular craggy mass, skin tethering, nipple retraction, thus mimicking a cancer

What are the 2 classifications breast cancer is divided into?

• non-invasive breast cancer

• invasive breast cancer

What are the two non-invasive breast cancers?

• Ductal carcinoma in-situ

• lobular carcinoma in-situ

What does ductal carcinoma in-situ arise from?

Epithelial cells lining the ducts

What does lobular carcinoma in-situ arise from?

Epithelial cells inside the lobules, it is confined to the acini cells

What are the two types of invasive breast cancer?

• Invasive ductal carcinoma

• Invasive lobular carcinoma

What is the most common type of breast cancer?

Invasive ductal carcinoma

What is the main risk factor of breast cancer?

Increased oestrogen exposure

What can increase oestrogen exposure and therefore increase risk of breast cancer?

• Nulliparity and increasing age of first childbirth

• Early menarche

• late menopause

• HRT with oestrogen and progesterone

• Obesity - adipose tissue expresses enzyme aromatase = increased synthesis of oestrogen

What are non-oestrogen risk factors for breast cancer?

• increasing age

• female gender

• family/personal history

• Genetics: BRCA 1 and 2 mutations

• radiation therapy to chest

• not having breastfed

• lifestyle

Give a protective factor against breast cancer

Breastfeeding

Why is ultrasound used for imaging in younger women?

Under the age of 40 women tend to have denser breast tissue - making mammograms less sensitive for detecting breast cancers

What two angles are mammograms usually taken from?

• mediolateral oblique

• craniocaudal

What are the two methods used for biopsies?

• Fine needle aspiration

• Core biopsy

Fine needle biopsy

Single fine needle used to collect cells

• used for smaller more cystic lumps under ultrasound guidance

Core biopsy

Wider needle used under ultrasound guidance.

• it takes a core of tissue = providing more information about cancer and the involvement of surrounding tissue

• Has a much higher diagnostic yield than FNA

What age is breast cancer screening available to?

Women ages 50-70

• involves a two view mammogram every 3 yrs.

What are the 3 hormone receptors important in breast cancer?

• oestrogen receptors (ER)

• progesterone receptors (PR)

• HER-2 receptors

What effect do ER and PR have on cells?

Have proliferative effects on cells and are driven by hormone

What is triple negative breast cancer - implications?

Where cancer is negative for ER, PR and HER-2 receptors

• This limits treatment options and often leads to poor prognosis

What are the different medical management options for breast cancer?

• endocrine therapy

• Biologics

• Chemotherapy

• Radiotherapy

Endocrine therapy - who is tamoxifen used for?

Used in premenopausal women with ER+ cancer, and works by blocking oestrogen receptors

Endocrine therapy - who are aromatase inhibitors for?

Only used in postmenopausal women with ER+ cancer

• block enzyme aromatase that converts androgens to oestrogen

What is the target of biologic drug trastuzumab?

HER-2 receptors

How can we divide up chemotherapy?

Into neoadjuvant and adjuvant

Neoadjuvant chemotherapy

Used prior to surgery to help shrink the cancer to allow for breast conserving surgery

Adjuvant chemotherapy

Used after surgery to try and prevent the recurrence of cancer and increase survival

Oncotype DX breast recurrence score assay

Involves the genetic testing of breast cancer cells to decide if adjuvant therapy is warranted.

• produces a score of 0-100

• aims to help patients avoid chemotherapy that wouldn’t benefit them

Who is radiotherapy recommended for?

Recommended for most patients with breast cancer

Wide local excision

Removes the breast cancer with a margin of healthy tissue around the cancer - used when cancer is small.

• favoured because it conserves the breast.

Mastectomy

Removal of the entire breast and the skin overlying it

• used for much larger and multifocal breast cancers where a wide range excision would not be possible

What is sentinel node sampling?

To rule out lymphatic involvement the first (sentinel) lymph node is located by blue dye and radioactive technetium.

• the lymph node is then removed and sent to the lab for analysis.

What happens in the sentinel node shows evidence of metastasis?

The axillary lymph nodes will need to be surgically removed

Why is ovarian ablation performed?

To stop oestrogen synthesis (rarely performed because preventing oestrogen synthesis can be achieved through drugs or radiotherapy)

. It is most often used in women with a BRCA1 or BRCA2 mutation as this also predisposes them to ovarian cancer.

What are the 3 methods of metastasis?

• Direct spread

• Lymphatic spread

• Haematogenous spread

Where does breast cancer directly spread to?

skin and muscle

Lymphatic spread of breast cancer

To axillary nodes

haematogenous spread of breast cancer

Blood-borne metastasis often in the lungs, bones, liver and brain

Why is breast cancer more common in women?

Exposure to oestrogen has an impact on mutations

What are BRCA1 and BRCA2?

They are anti-oncogenes that both code for tumour suppressor proteins, which, when functioning normally, reduce the risk of breast cancer.

• mutations in these genes therefore increase the risk of breast and ovarian cancer

What is the roles of HER-2 receptors?

Transmembrane glycoprotein that plays a key role in cell survival, proliferation and differentiation and thus is an important oncogene in breast cancer when it is overexpressed.