Invasive breast carcinoma - IARC

of synchronous cancers has been rep
o rted following the introduction of bilateral
mammography for the investigation
of symptomatic breast disease and
for population based breast scre e n i n g
{751,872,1491,1492}.
It is well recognized that a previous history
of breast cancer increases the risk of
subsequent breast cancer in the contralateral
breast. The re p o rted annual
hazard rates of between 0.5-1% per year
{448,872,1491,2383,2798} appear relatively
constant up to 15 years {1491} giving
a cumulative incidence rate for survivors
of around 5% at 10 years and 10%
at 15 years.
Family history {253,448,1219} and early
age of onset {35,1168,2798} have been
re p o rted to increase the risk of CBC
development in some studies but others
have found no such associations with
either early age of onset {252,253,872} or
family history {35,872}. One study has
re p o rted that family history, early age of
onset and lobular histology are independent
predictors of metachronous contralateral
breast cancer development {1492}.
These characteristics suggest a possible
genetic predisposition. Women with a
strong family history who develop breast
cancer at an early age are at considerable
risk of contralateral breast cancer
as a first event of recurrence particularly
if the first primary is of lobular histology
or is of favourable prognostic type {1491,
1492}.
Patients with metachronous CBC are
younger at the age of onset of the original
primary. Many, but not all, series
report that a higher percentage of the
tumours are of lobular type {35,252,872,
1219,1241,1492,2383}. This observation
does not imply that tumours of lobular
type, in isolation from other risk factors
such as young age and family history,
should be considered to have a higher
risk of bilateral breast involvement
{1491}. A greater frequency of multicentricity
in one or both breast tumours has
also been reported {355}. There does not
appear to be any association with histological
grade, other tumour types or the
stage of the disease {355,1491,1492}.
Prognosis and predictive features
T h e o retically women with synchro n o u s
CBC have a higher tumour burden than
women with unilateral disease which
may jeopardize their survival pro s p e c t s
{1035}. Indeed, synchronous CBC
appears to have a worse pro g n o s i s
than unilateral cohorts or women with
m e t a c h ronous CBC {164,1092,1233}.
Others have failed to demonstrate any
survival diff e rence between women with
unilateral and those with synchro n o u s
CBC {911,1053,2555}.
Tumour spread and staging
Tumour spread
Breast cancer may spread via lymphatic
and haematogenous routes and by direct
extension to adjacent structures. Spread
via the lymphatic route is most frequently
to the ipsilateral axillary lymph nodes,
but spread to internal mammary nodes
and to other regional nodal groups may
also occur. Although breast cancer may
metastasize to any site, the most common
are bone, lung, and liver. Unusual
sites of metastasis (e.g. peritoneal surfaces,
re t roperitoneum, gastro i n t e s t i n a l
tract, and re p roductive organs) and
unusual presentations of metastatic disease
are more often seen with invasive
lobular carcinomas than with other histological
types {319,704,1142,1578}.
Several models have been proposed to
explain the spread of breast cancer. The
Halsted model, assumes a spread from
the breast to regional lymph nodes and
from there to distant sites. This hypothesis
provided the rationale for radical en
bloc resection of the breast and regional
lymph nodes. Others suggest a systemic
disease from inception, which implies
that survival is unaffected by local treatment.
However, clinical behaviour suggests
that metastases occur as a function
of tumour growth and progression
{1181}. This concept is supported by the
results of axillary sentinel lymph nodes,
which show that metastatic axillary lymph
node involvement is a pro g re s s i v e
process.
Tumour staging
Both clinical and pathological staging is
used in breast carcinoma. Clinical staging
is based on information gathered
prior to first definitive treatment, including
data derived from physical examination,
imaging studies, biopsy, surgical
exploration, and other relevant findings.
Pathological staging is based on data
used for clinical staging supplemented
or modified by evidence obtained during
surgery, particularly from the pathological
examination of the resected primary
tumour, regional lymph nodes, and/or
more distant metastases, when relevant.
The staging system currently in most
widespread use is the TNM Classification
{51,2976}. The most recent edition is provided
at the beginning of this chapter.
The pathological tumour status ("pT") is a
measurement only of the invasive component.
The extent of the associated
intraductal component should not be
taken into consideration. In cases of
m i c roinvasive carcinoma (T1mic) in
which multiple foci of microinvasion are
present, multiplicity should be noted but
the size of only the largest focus is used,
i.e. the size of the individual foci should
not be added together. The pathological
node status ("pN") is based on information
derived from histological examination
of routine haematoxylin and eosinstained
sections. Cases with only isolated
tumour cells are classified as pNO
(see relevant footnote in the TNM Table
which also indicates how to designate
sentinel lymph node findings). A subclassification
of isolated tumour cells is
provided in TNM publications {51,1195,
2976}.
Measurement of tumour size
The microscopic invasive tumour size (I)
is used for TNM Classification (pT). The
dominant (largest) invasive tumour focus
is measured, except in multifocal
tumours where no such large single
focus is apparent. In these cases the
whole tumour size (w) is used.
Somatic genetics of invasive
breast cancer
As in other organ sites, it has become evident
that breast cancers develop thro u g h
a sequential accumulation of genetic
alterations, including activation of oncogenes
(e.g. by gene amplification), and
inactivation of tumour suppressor genes,
e.g. by gene mutations and deletions.
Cytogenetics
As yet no karyotypic hallmarks of breast
cancer have been identified, such as
the t(8;14) in chronic myelogenous
leukaemia (CML), or the i(12p) in testicular
cancer. There is not even a cytogenetic
marker for any of the histological
subtypes of breast cancer. One reason
for this is certainly the technical difficulty
of obtaining sufficient numbers of good
Invasive breast carcinoma
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