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Pictorial Lesson on Breast
Cancer
Anatomy
Age-specific incidence of breast
cancer in the United States.
Timeline of breast cancer
•
Primary breast
cancers begin as
single (or more) cells
which have lost
normal regulation of
differentiation and
proliferation but
remain confined
within the basement
membrane of the
duct or lobule.
•
As these cells go
through several
doublings, at some
point they invade
through the
basement membrane
of the duct or lobule
and ultimately
metastasize to
distant organs.
Halsted theory of breast cancer
spread
• This theory suggests that
breast cancer originates in the
breast, eventually spreads to
local skin and/or lymph nodes
and then ultimately affects
distant organs.
• This theory maintains that
local/regional lymph nodes
serve as 'barriers' to the
spread of metastatic breast
cancer.
• The implication of this theory is
that more intensive local
therapy should lead to an
increased rate of cures.
Lymphatic spread of breast cancer.
•
Lymph node metastases are
present at the time of diagnosis
in up to 60% of cases.
•
In general, lateral lesions in the
breast metastasize to axillary
and supraclavicular nodes,
whereas medial tumors tend to
metastasize to the internal
mammary and mediastinal
lymph nodes, as well as the
supraclavicular nodes.
•
However, lymph node
involvement is merely a marker
for the probability that the
cancer has spread from the
breast.
•
A positive finding implies that
microdeposits of breast cancer
will likely be present in other
areas as well.
Breast cancer staging based on clinical characteristics (from AJCC: Manual for Staging of
Cancer, 4th edn. Lippincott, Philadelphia, 1993.)
Survival of breast cancer patients by stage at the time of diagnosis
Frequency of breast cancer
metastases
• The most common
first sites of
recurrent breast
cancer are the
chest wall, the
regional lymph
nodes and/or
bone.
• Liver, lung and
central nervous
system (CNS) are
less common sites
of recurrence.
Investigations
• Bilateral
mammograms:
• 45-year-old patient
with enlarged right
axillary nodes
(black arrow) but
no mammographic
abnormally within
either breast.
Investigations
• Sagittal MRI
• right breast with
fat saturation
prior to
administration of
gadolinium.
• A rounded
density
represents an
axillary node
(white arrow).
MRI
• Sagittal MRI
•
at the same location
after administration
of gadolinium enhancement of the
node is evident
(white arrow).
Sentinel node biopsy
(a) Axillary lymph mapping. (b) Injection of blue dye in the tumor cavity.
(c) Identification of the sentinel node (follow blue line).
An incisional biopsy makes a
definitive diagnosis
• Excisional
biopsies, although
diagnostic, can
also be
therapeutic by
eliminating the
need for further
breast surgery
when radiation
therapy is
performed.
Assays for steroid hormone
receptors.
ER staining
• In this frozen
section of an
infiltrating
ductal
carcinoma, a
brown stain
in the
nucleus
defines the
presence of
oestrogen
receptor
HER2 neu status
Two methods to
determine HER2
neu status:
i)immunohistochemistry
(IHC)
ii) fluorescent in
situ hybridization
(FISH).
Scores of +2 or
+3 are regarded
as positive
Pathology
Intraductal carcinoma (cribriform
type)
• (a) Low- and (b) highpower photomicrographs
demonstrate a cribriform
pattern composed of a
rather uniform tumour cell
population with distinct
cytoplasmic borders; the
cells are rigidly arranged
around crisp, circular
holes.
• With this pattern, the risk
for the subsequent
development of invasive
cancer increases 10-11fold.
Papillary carcinoma in situ.
• The architectural
features of this in
situ breast cancer
are similar to those
of a papilloma. The
normal two-cell-layer
epithelium covering
the fibrovascular
fronds is replaced by
a uniform
proliferation of cells
with hyperchromatic
nuclei.
Invasive lobular carcinoma
• The classic
presentation of this
tumour is marked by
a 'single file' pattern
of uniform malignant
cells infiltrating the
stroma.
• The invasive lesion
surrounds foci of in
situ tumour. (b)
Single file tumour
cells surround an
involved duct,
producing a targetlike pattern.
Cases
Stage I (T1N0) breast cancer
• Magnified view of a
screening
mammogram from a
52-year-old woman
who had no palpable
mass demonstrates
the classic clustered
microcalcifications of
several shapes and
sizes highly
suggestive of
carcinoma.
• Some exhibit linear
branching, which is
even more suggestive
of a ductal lesion.
Biopsy confirmed an
early invasive ductal
carcinoma.
Stage IIA (T2N0) breast cancer.
• This mammogram
from a 65-year-old
woman shows that
the breasts are not
too dense;
therefore, the 2.5
cm stellate mass in
the upper outer
quadrant of the
right breast was
easily palpated.
• Histological
examination
following resection
showed an
invasive ductal
carcinoma.
Stage IIIB (T4) breast cancer
• A common
presentation at this
stage is retraction,
dimpling and
thickening of the
skin surrounding the
nipple.
• This clinical finding
is designated 'peau
d'orange' a name
deriving from the
pitting and coloration
of the skin like
orange peel.
Stage IIIB (T4) breast cancer.
• Classically,
inflammatory
breast cancer does
not present as a
discrete mass, but
rather as
cutaneous
erythema with
overlying skin
warmth, as
illustrated in the left
breast of this 63year-old patient.
Stage IIIB (T4) breast cancer.
• Advanced primary
carcinomas can
present with skin
ulceration, as shown
in this mastectomy
specimen, in the area
above the nipple,
which is raised and
ulcerated by an
underlying tumour.
• Biopsy revealed an
adenocarcinoma.
Stage IIIB (T4) breast cancer.
• This 66-year-old patient
presented with a locally
advanced carcinoma
that had ulcerated
through the skin,
causing substantial
morbidity.
• She was treated
effectively with
chemotherapy and over
5 months the ulceration
decreased as the
tumour regressed.
Ultimately, the skin
healed completely.
Recurrence and Metastatic Disease
Recurrent breast cancer
• Locally recurrent
disease can
often present as
very subtle
subcutaneous
nodules along
the mastectomy
scar or as a
nodular
cutaneous rash.
Bone metastases
• Bone is one of the most
common sites of metastatic
breast disease.
• Although benign disorders,
such as osteoarthritis,
osteomyelitis, or benign
fractures, can cause a bone
scan to be positive, the
appearance of multiple 'hot
spots', especially in the axial
and thoracic skeleton, as
shown here is highly
suggestive of metastases.
Lytic vs blastic bone metastases
• In general, lytic bone
metastases are more
common than
osteoblastic lesions,
although many patients
exhibit mixed lytic
lesions with areas of
osteoblastic reaction.
• Diffuse lytic lesions can
be seen in this patient's
right femoral head and
ischial pubic ramus.
• Such lesions weaken
the cortex, often
resulting in pathologic
fracture.
Bone Mets
• Radiograph of the
pelvis of a 45-year-old
woman demonstrates
widespread foci of
increased bone density
representing
osteoblastic activity
surrounding bone
metastases of breast
cancer.
• It is interesting to note
that effective therapy
may alter the nature of
lytic bone metastases,
converting them to
sclerotic, blastic
lesions.
Spinal Cord Compression
• Large lytic lesion can be
seen involving about half
of the body of L2,
including the left pedicle
(arrow). In addition, a
soft tissue mass extends
into the spinal canal,
compressing the spinal
cord.
• Spinal cord compression
is classified as an
'oncologic emergency',
requiring either
immediate
decompression or
radiation therapy. It can
rapidly lead to
neurological deficits and
even paraplegia.
Intrathoracic metastases
• Intrathoracic
metastases can be
manifested in
several ways.
Among the more
common is
malignant pleural
effusion, as
demonstrated by
the large right
effusion on this CT.
• In addition, the
advanced right
breast cancer can
also be seen.
Brain metastases
• Metastases can be single,
multiple or meningeal.
• CT scan of the brain of a 62year-old woman, who
presented 6 years after having
undergone a mastectomy and
adjuvant chemotherapy for a
stage II breast carcinoma,
shows a well-circumscribed,
enhancing lesion with
surrounding oedema in the left
temporo-occipital region. She
also had pulmonary and
hepatic metastases. (b).
Post radiotherapy
• Repeat CT scan
taken 3 months after
completion of
successful
radiotherapy reveals
that the enhancing
lesion is no longer
evident and the
oedema has almost
completely resolved.
Her symptoms also
totally resolved
Disease Monitoring, Results
and Complications
Circulating tumour markers as
monitors of disease course
•
Tumour markers can also
correlate with clinical disease
course and can be useful in
monitoring patients during
therapy. In this figure, a patient
with metastatic breast cancer
to bone and lung (a) was
initially treated with
chemotherapy. Her symptoms
began to resolve during the
first 2 months of therapy, but
interpretations of her physical
examination, chest X-ray and
bone scans were equivocal
(b). However, her CA15-3
levels decreased from an initial
level of 200 U/ml to 50 U/ml.
Her chemotherapy was
continued and by the fourth
month of therapy she was
found to be responding, as
determined by history, bone
scan and chest X-ray findings
(c).
The cosmetic results
• This 70-year-old
patient had a stage I
carcinoma of the left
breast that was treated
by excisional biopsy
and primary irradiation.
• Although there is some
asymmetry of the
breast, as well as, on
close inspection, some
modest skin thickening
and retraction due to
the therapy, it is very
difficult to determine
which breast was
treated.
A patient with bilateral
mastectomies
Patient before and
after bilateral silicone
implants following
bilateral
mastectomies
Radiation recall reaction
A geometrically shaped area of
hyperpigmentation and
thickening of the chest wall
due to a radiation recall
reaction in the skin.
Adjuvant radiation to the chest
after mastectomy is no longer
indicated in most patients.
Although it decreases local
recurrence, it does not affect
survival and may be
associated with significant
morbidity.
Lymphoedema
• A 64-year-old patient
with significant arm
edema after a
radical mastectomy,
full axillary
dissection and
postoperative chest
wall and axillary
radiotherapy.
• The patient's left arm
is immensely
swollen in contrast
to her unaffected,
normal right arm.
• .
Radiation pneumonitis
Radiation therapy can be associated with local
tissue damage and toxicity. This patient presented
with a T2N3 breast cancer with supraclavicular
lymphadenopathy. She was treated by lumpectomy
and radiotherapy to the breast, as well as radiation
therapy to the supraclavicular fossa. At this time her
chest X-ray was normal (opposite).
Two years later the patient presented with dyspnoea
on exertion. A chest X-ray (below right)
demonstrated a nodular, right upper lobe density
and a CT scan (below) confirmed the presence of
these apical nodules.
Information
For more info:
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http://www.sign.ac.uk/pdf/qrg84.pdf
http://www.cancerresearchuk.org/
http://www.cancer.gov/
http://www.macmillan.org.uk/