Outline of Key Learning Areas related to PBL week 16
‘Just my annual check-up’
Relevant Symptoms (incl. relevant negatives)
None on initial presentation – simply came in for a check-up: pap smear performed and referral provided for mammogram
Other Significant History
49 year-old nulliparous woman
LMP 6/12 ago - perimenopausal
Mother and aunt both died of breast cancer in their fifties (first-degree relatives)
Examination and Signs
Pap smear normal
Mammogram showed ‘suspicious area’; fine needle aspirate showed malignant cells (appear irregular compared to benign neoplasia)
Lymphovascular invasion
No lymph node involvement
Hormone receptor assay showed HER+ (positive receptor for oestrogen) and negative receptor for progesterone
Provisional Diagnosis
Differential Diagnoses
Initial: Grade III Ductal carcinoma
Fibroadenoma/ Breast cyst
Fibrocystic change of the breast is a non-specific term, commonly understood as a
Follow-up: Presented with back pain, lethargy, malaise,
continuum of physiological changes that expand to the pathological spectrum. It is
nausea and weight loss. These symptoms were
a condition characterised by "lumpy" breasts, associated with pain and tenderness
associated with pulmonary, bone and liver metastases,
that fluctuate with the menstrual cycle.
leading to severely impaired renal function
Mammographic calcifications that are large, are round, have sharp edges, and are
diffuse are typically benign
Risk Factors
Genetic:
BRCA1/BRCA2(tumour suppression and DNA repair) associated with 3% of breast cancers
p53 (CDK inhibitor)
CHEK2
1st degree family history of breast cancer
Hormonal – exposure to oestrogen
Female (99% of breast cancers occur in women)
Age of menarche/menopause
Nulliparity /Never lactating
HRT
Age
peak = 75-80 years old
Other
Radiation/carcinogen exposure
Aetiology
Oestrogen levels, which are higher in women than in men, stimulate proliferation of breast epithelial cells in the lobules and ducts. Spontaneous
mutations in epithelial cells, some of which provide a survival advantage to the cell, lead to precancerous changes. Further mutations lead to in
situ or invasive breast cancer.
)
1) Anatomy
3) Microbiology
nil
4) Pathophysiology
Carcinogenesis is a multi-step process (due to multiple
mutations – either inherited or acquired) which results in:




self-sufficient growth without external stimuli (protooncogenes mutate to oncogenes)
insensitivity to growth inhibitory signals
evasion of apoptosis
defects in DNA repair
Ductal carcinoma in situ (DCIS) is a potential precursor of
invasive carcinoma and suggests that cancer will become
invasive at that site.
Metastasis
Signifies the tumour is malignant
Routes of metastasis include
 lymphatics





Lymphatic drainage
Blood vessels
Direct extension
CNS spread
Transcoelomic
Field effect – exposure can cause multiple primary
tumours
Method of metastatic spread:
 Breach of ECM - breach of basement membrane and
migration of tumour cells
 Dissemination - Formation of tumour cell embolus and
adhesion to endothelium of a DISTANT site
 Formation of secondary deposit – digestion of basement
membrane and CT, proliferation of cells in new location
 Angiogenesis – support blood vessels to supply the new
growth.
Histopathology
Most breast cancers (95%) are adenocarcinomas
Divided into:
in situ carcinomas (neoplastic proliferation confined to the
ducts/lobules by the basement membrane – usually impalpable)
invasive carcinomas
Neoplasm that has penetrated the basement membrane and
can present with macroscopic changes
Tumour grading
Surface anatomy
2) Physiology/Biochemistry
The influence of oestrogen on breast tissue
Foetus/neonate
Mammary glands consist almost entirely of lactiferous ducts with few alveoli
Histologic
Grade
Grade 2.
Grade 1. Well moderately
Differentiated differentiated
, or low grade , or
intermediate
Grade 3.
Poorly
differentiated
, or high
grade
Puberty:
Under the influence of oestrogen, lactiferous ducts sprout and branch to
develop alveolar precursors
Breasts enlarge mostly due to fat deposition
Nipples become prominent
Resting adult:
Glandular part consists mostly of ducts – small lobules
When oestrogen levels peak in the menstrual cycle, duct cell proliferation
Increases
Pregnancy:
Large increase in breast size, mainly due to alveolar proliferation,
differentiation and duct branching
Amount of CT and fat stays the same but decreases relative to glandular
tissue
Lactation
Alveolar cells become smaller and low cuboidal - cytoplasm contains fat
droplets and may appear vacuolated
Secretion distends the alveoli and milk collects in the lactiferous ducts
Post-Menopause
The glandular component of the breast involutes and is replaced by fat and
CT
grade
Total
score of
each
parameter
A+B+C
3-5
6-7
8-9
Scoring Summary
Relative
Score or
each
parameter
1
2
3
A. Tubules
Assessmen
t in %
>75%= 1
10-75%=2
<10%=3
B. Nuclear
Grade
Assessmen
t
Uniform
Nuclei with
minimal
nuclear
variation in
size and
shape= 1
moderate
nuclear
variation in
size and
shape = 2
Marked
nuclear
variation and
bizarre nuclei
( sometimes
with
prominent
nuceloli ) = 3
C. Mitotic
Index
Assessmen
t
5-10 mitoses
=1
11-19 = 2
>20 = 3.
Cancer staging (TNM)
T = (Primary) Tumour Size
� T0 = impalpable
� T1 = 0-2cm
� T2 = 2-5cm
� T3 = ≥ 5cm ± fixation to
underlying muscle
� T4 = any size, with fixation
to chest wall or skin
o N = Lymph Node Status
� N1 = regional nodes involved
� N2,N3 = more distant nodal
Groups
o M = Metastases
� M0 = no detectable spread
� M1 = metastases present
(specify sites)
Investigations and Results
1) Blood tests
nil
2) Imaging
Mammogram (right)
A mammographic finding of clustered
calcifications, either focal or diffuse, and
absence of a soft tissue abnormality suggests
ductal carcinoma in situ (DCIS).
3) Other
Hormone receptor assay
Oestrogen and progesterone receptor status
is measured by immunohistochemical staining
of fixed tumour tissue. Results can help to
guide treatment.
ER + means the tumour relies on oestrogen
for growth
Diagnosis confirmed by triple test:
1)clinical – inspection and palpation
2) radiological – mammogram
3) Pathological – aspirate and histological assessment
Imaging con’d
Bone scan
Fine needle aspiration and biopsy (below)
Benign
Malignant
Showed multiple ‘hot spots’
Management Plan
Problem
Goal/desired outcome
Ductal carcinoma
Removal
Hormone-related growth of
neoplastic cells
Interruption of oestrogen growth
stimulus to prevent further growth of
Method (incl. patient
actions)
Excision of lump
(lumpectomy) and axillary
dissection
Oestrogen antagonist
administered
Resources/health
professional s involved
Oncologist
tumour
Locally invasive tumour
Radiotherapy
Potentially metastatic or recurring
tumour
Pain related to metastatic cancer
Prevention of metastatic spread/return
of cancer
Analgesia
Poor prognosis
Palliative care
Medications
Mode of action
Tamoxifen
Tumour cells that express the
oestrogen receptor ERα are sensitive
to hormone-based therapy, leading to
a good therapeutic outcome
Chemotherapy
Morphine administered for
pain associated with
metastases
Holistic approach
Family involvement
Symptom relief
Pain management
Multi-disciplinary approach
Side effects
Menopause-like symptoms
It is an oestrogen agonist/antagonist
(with the predominant effect
depending on the tissue). It is effective
in preventing disease recurrence in
oestrogen receptor-positive ductal
carcinoma in situ (DCIS) and invasive
breast cancers, as well as in
decreasing the risk of oestrogen
receptor-positive cancers developing
in the contralateral breast.
Chemotherapy
Duration of treatment is 5 years
drug therapy, usually given through I.V
line, which targets dividing cells
Oncologist, radiotherapist
Systemic symptoms
Palliative care team
Palliative care nurse
Any specific monitoring
required?
Consideration of preservation of
oocytes, fertility treatment
causing them to stop dividing and selfdestruct
regimes usually last 4-6 months,
require hospital stays and have
various side-effects
Radiotherapy
reduces the chance of breast cancer
returning by about 1/3
Uses high-powered radiation beams
which deliver radioactive particles or
X-rays to targeted tissue causing the
death of cells
Whole-breast radiotherapy is an
essential component of local therapy
following breast-conserving surgery
and has been shown to reduce 5-year
local recurrence.
skin changes like sunburn,
pigmentation of skin,
woodiness of breast tissue,
fatigue, depression, it rarely
can damage other organs
Other Psychosocial/ethical/legal/patient-centred considerations
Depression related to poor prognosis
Informed decision-making about end-of-life care
PPH/PPD implications
Screening
Mammogram
Early detection is highly effective in reducing mortality associated with breast cancer, with impalpable cancers being detected 1-2 years earlier
than relying on examination alone. Nonetheless, screening leads to over-diagnosis and over-treatment of breast disease in many women, and
women invited to screening should be informed of both the benefits and harms. In Australia, women are encouraged to have mammogram
screening every two years from age 50-70. If more than 2 risk factors are present, women can access mammogram screening earlier or even
elect to have a prophylactic mastectomy
Self-examination
All adult women can perform a monthly breast self-examination to detect lumps. However, ductal carcinoma in situ is generally detected by
mammography before it is palpable, so this physical examination of the breast is more likely to detect invasive cancer. Breast examination is
rarely of benefit to detect lobular carcinoma in situ.
Epidemiology
Breast cancer is the most common cancer in females, affecting 1 in 11-15 women in Australia
Resources used/discovered