Download Breast Cancer - Wk 1-2

Breast Cancer
1. Outline the major recognised risk factors for cancers of the breast
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Sex (females 100 times more likely to get breast cancer)
Increasing age - uncommon < 25 years, then rises
Genetic predisposition
 < 10 % of breast cancer attributable to autosomal dominant gene
inheritance (maternal lineage)
 Strong FHx of breast/ovarian cancer particularly in premenopausal
women
 Genetic inheritance linked to BRCA1, BRCA2, p53, ATM
 Ashkenazi Jewish Ancestry
Proliferative breast disease
Carcinoma of contralateral breast or endometrium
Length of reproductive life & excess oestrogen levels - Risk increases with
early menarche & late menopause
Nulliparity (unremitting exposure to ovarian cycles) or age > 30 years at time
of first child
Radiation exposure - ↑ risk at younger age & high dose at exposure
Geographic influences eg. lower incidence in Asia versus rest Western world
Obesity
 Lower risk in obese women < 40 years (anovulatory cycles, lower
progesterone)
 Higher risk in postmenopausal obese (oestrogen synthesis in fat)
Hormone Replacement therapy > 5 years
2. Describe the histopathology of neoplasia of the breast
Clinical Features
 Hard lump (painless, palpable mass or abnormal mammogram with no mass)
 Non-mobile, skin tethering, inversion of nipple, Paget’s disease of nipple
(unilateral eczema), axillary node enlargement, peau d’orange (dimpling
caused by lymphoedema), ulceration through skin
Other Presenting Symptoms
 Colour changes, Nipple retraction, breast enlargement, axillary mass, bone
pain (rare), discharge
Macroscopic Appearances
 Circumscribed stellate mass (spiculated)
 Infiltrative border; retractive
 Firm to hard and gritty on sectioning
 Pale in colour with yellow flecks where there is tissue elastosis (cream or pale
tan in colour compared to normal yellow (fat) & white (fibrous) breast)
Histopathological/Microscopic Features
 Destruction of the normal lobular pattern
 Malignant cells invading normal structures such as the fat surrounding the
lobules
 Layer of myoepithelial cells disappears (underlying epithelial cells)
 Proliferation of tumour stroma derived from host connective tissue - this
stroma is collagen leading to clinical hardness
 Cords of undifferentiated cells with large nuclei containing prominent nucleoli
 Increased mitoses
Classification of Breast Cancers
 Almost all are adenocarcinomas
 Carcinomas are divided into in situ carcinomas + invasive carcinomas
 Calcification is visible within many tumours
 Cancers frequently arise in junction between lobules and ducts
Ductal: Arises from epithelial lining of large or intermediate-sized ducts
Lobular: Arises from epithelium of terminal ducts of lobules
3. Explain how breast cancer may spread
Breast cancer metastasis is occurs mostly via lymphatic spread (ie as carcinoma
prefers lymph, sarcoma prefers blood)
 Axilla (75%) » Sentinel node first » Anterior » Central » Apical nodes
 Infraclavicular, subscapular or supraclavicular nodes – 3rd most common site
of mets
 Parasternal nodes (25%)
 Contralateral breast
 Inferiorly to inferior phrenic plexus & abdominal wall
Pattern of lymphatic spread largely determined by location of mass – eg. upper outer
quadrant favours axillary; lower inner favours parasternal;
Distant metastases through bloodstream may affect virtually any organ of the body
 Favours lungs, bones, liver, adrenals ,skin, brain, meninges
4. Describe the impact that the biology of the tumour has on the
outcome of treatment
The outcome of treatment can also be considered as the prognosis for the condition.
Factors which influence prognosis include;
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Lymph Node metastases – involvement of axillary LNs worsens prognosis
(axillary node status is the most important prognostic factor)
Locally advanced disease – tumour invasion of skin/muscle correlates with
distant metastases
Tumour size : best if < 1- 2cm in diameter (96% 5 yr survival)
Histologic subtypes : Special types (Lobular, tubular, colloid, medullary)
associated with better prognosis than ductal
Tumour grade – Lower grade tumours have better prognosis (Grade I _ 80%
survive 16 years)
Oestrogen & progesterone receptors - 50-85% of tumours express oestrogen
receptors which have better prognosis (also with progesterone receptors)
 Can use Tamoxifen stain (hormone antagonist)
 ER+ve : usually lower grade (normal breast has these receptors),
metastases to bones
Lymphovascular invasion – tumour cells found in vascular spaces
(lymph/blood) surrounding tumours » suggests LN metastases, poor prognosis
Proliferative rate (high = poor prognosis)
DNA content (aneuploidy = worse prognosis)
Angiogenesis (increased vasculature in invasive cancers)
Proteases (eg cathepsin D help tumour invasion)
Expression of oncogenes (Her2/new, c-ras, c-myc), loss of expression of
tumour-suppressor genes (p53, RB)
5. Discuss the change in treatments for breast and other cancers over
time and the evidence on outcomes which have prompted these
changes in treatment choices.
PREVIOUS TREATMENTS
• Before radiation and chemotherapy, breast cancer treatment = mastectomy
 Removal of breast and underlying chest wall muscles and underarm contents
• Tumours were not picked up early before screening & only found when large and
metastatic
 only possible treatment was mastectomy = poor prognosis
• Surgery has moved from radical mastectomy » modified radical mastectomy »
lumpectomy
CURRENT TREATMENTS
• 2 main aims:
1. To cure disease
2. To maintain or improve quality of life
• Choice of which aim to pursue more thoroughly is made by patient
• Standard protocol: Lumpectomy + hormonal control (e.g. Tamoxifen),
chemotherapy and/or radiotherapy
LUMPECTOMY
 Involves removal of cancerous tissue and surrounding area of normal tissue
 Generally lymph nodes in armpit are sampled at same time
 If cancer is ductal and infiltrative or inflammatory then mastectomy is
performed (removal of entire breast but no other structures)
 If cancer is invasive, this surgery is not considered curative
 Common treatment for DCIS, and LCIS, non-invasive types of breast cancer
RADIATION THERAPY
 All removal of cancer today is followed with radiation therapy
 Radiation therapy is used to control local disease, especially when surgery has
been limited and included only lumpectomy
 It is usually given 5 days/week over 5-6 weeks and requires only a few
minutes/day
 Can be focused upon affected areas without systemic problems e.g.
chemotherapy
CHEMOTHERAPY
 As well as radiation most cancer treatment is followed with either or
chemotherapy and hormonal therapy
 Chemotherapy consists of administration of medicine, usually either orally or
IV, for treatment of cancer
 Chemotherapy and hormonal therapy are the only therapies that treat the entire
body and thus treat stray tumour cells that may have migrated from breast area
 In breast cancer, chemotherapy is given for 3 common reasons:
1. Adjuvant chemotherapy is given to women who have had curative treatment
for their breast cancers. It is given to ↓ possibility of recurrence
 Tamoxifen immediately following surgery for E/P receptor positive
disease
2. Pre-surgical chemotherapy is sometimes given prior to surgery to get better
control of disease at time of surgery and in an attempt to tumour size
3. Regular chemotherapy is routinely administered to women with breast
cancer that has spread beyond the breast