Invasive breast carcinoma - IARC

detected at a late stage as small
tumours are not felt in the pregnant
or lactating breast {91,311,1079}. Pre g-
nancy in women who have been tre a t e d
for breast cancer does not appear to
a ffect prognosis {119}.
Morphological factors
The traditional pathological factors of
lymph node status, tumour size, histological
type, and histological grade are
the most useful prognostic factors in
b reast cancer patients {886,1763},
although this is now challenged by gene
e x p ression pro f i l i n g .
Fig. 1.71 Lymphatic vessel invasion. Several tumour cell nests are present in endothelial lined spaces.
of breast cancer cases and that, as is
likely, these genes act in an additive
manner with the other loci involved in
familial aggregation, then we are left with
a residual familial risk of 1.8 to be
explained by other genes and/or correlated
family environment. There could be
several genes similar in action to BRCA1
and BRCA2, with lower breast cancer
risks, or a set of more common polymorphisms
in biologically relevant genes,
each associated with only a small
increased risk, or something in-between.
Genes are not the only factor which
could cause the observed familial
c o r relation. Shared lifestyle or enviro n-
mental risk factors would also cause
some degree of familial clustering,
however it can be demonstrated that
the known environmental risk factors
for breast cancer are unlkely to contribute
significantly to the overall familial
risk {1238}.
Based on a model of the contribution of
genetic variation to the overall familial
risk, it can be estimated that variation in
as few as 70 of the 30,000 genes in the
human genome may contribute to
b reast cancer susceptibility. Of course,
this model is based on a number of
unverifiable assumptions and does not
include potential gene-gene and genee
n v i ronment interactions, so should be
i n t e r p reted cautiously. However, it
seems clear that there are not going to
be hundreds of loci involved (or if there
a re, they will be impossible to find given
the weakness of the effects). Only until
m o re of these loci are identified, and
their interaction with known epidemiological
risk factors assessed, will we be
able to untangle the underlying causes
of the observed familial risk.
Prognosis and predictive factors
Clinical features
A g e
The prognostic significance of age and
menopausal status in patients with bre a s t
c a rcinoma is controversial. Yo u n g e r
patients have been found to have a poor
p rognosis {59,2029}, a favourable outcome
{2500} or no corre l a t i o n has been
found with age at all {1207}. These disc
repancies may be due to diff e rences in
patient selection, age grouping, and
other factors, including high grade, vascular
invasion, extensive in situ component,
steroid receptor negativity, high
p roliferation, T P 5 3 a b n o rmalities. An
increased incidence of node positivity
was found in two large studies of patients
under 35 years.
P r e g n a n c y
B reast cancer developing during pre g-
nancy is generally considered to have
an unfavourable prognosis. There is,
h o w e v e r, conflicting data as to whether
this is an independent factor. It may be
p a rt l y, or entire l y, due to the poor pro g-
nosis associated with young age and
also the fact that the cancer is often
Lymph node status
The status of the axillary lymph nodes is
the most important single pro g n o s t i c
factor for patients with breast cancer.
N u m e rous studies have shown that dise
a s e - f ree and overall survival rates
d e c rease as the number of positive
nodes increases {886}. The clinical significance
of micrometastases and isolated
tumour cells in the nodes, part i c u-
larly those identified exclusively by
i m m u n o h i s t o c h e m i s t ry, remains a matter
of debate {71,1655} although virt u a l-
ly all studies with more than 100
patients have shown that micro m e t a s-
tases are associated with a small but
significant decrease in disease-fre e
and/or overall survival {1655}.
A p p roximately 10-20% of patients cons
i d e red to be node-negative by ro u t i n e
pathological examination have identifiable
tumour cells as determined by serial
sectioning, immunohistochemical
staining for epithelial markers, or both.
H o w e v e r, at present, it appears pre m a-
t u re to recommend the routine use of
step sections and/or immunohistochem
i s t ry to evaluate sentinel or non-sentinel
lymph nodes {71}.
Tumour size
Tumour size is an important pro g n o s t i c
f a c t o r. Even among patients with bre a s t
cancers 1 cm and smaller (T1a and
T1b), size is an important pro g n o s t i c
factor for axillary lymph node involvement
and outcome {461}. However, the
manner in which the pathological
tumour size is re p o rted varies. Some
pathologists re p o rt the macro s c o p i c
size, some a microscopic size that
includes both the invasive and in situ
components, and others re p o rt the
m i c roscopic size of the invasive compo-
56 Tumours of the breast