Invasive breast carcinoma - IARC

nent only. There is often poor corre l a t i o n
between the tumour size determined by
g ross pathological examination and the
size of the invasive component as determined
by histological measure m e n t
{27}. The size of the invasive component
is clinically significant, and so the
pathological tumour size for classification
(pT) is a measurement of only the
invasive component {51}. There f o re ,
when there is a discrepancy between
the gross and the microscopic size of
the invasive component, the micro s c o p-
ic size takes precedence, and should
be indicated in the pathology re p o rt and
used for pathological staging.
Histological type
Some special histological types of
b reast cancer are associated with a
p a rticularly favourable clinical outcome
{771,2433}. These include tubular, invasive
cribriform, mucinous, and adenoid
cystic carcinomas. Some authors also
include tubulolobular and papillary carcinomas.
The 20-year re c u r re n c e - f re e
survival of special type tumours 1.1 to
3.0 cm in size is similar to that of invasive
ductal carcinomas of no special
type 1 cm and smaller (87% and 86%,
respectively) {2433}. The pro g n o s t i c
significance of medullary carc i n o m a
remains contro v e rtial and is discussed
e l s e w h e re (see medullary carc i n o m a ) .
Fig. 1.72 Carcinoma with central fibrosis. There is
extensive central fibrosis with only a rim of invasive
carcinoma left around the fibrotic area.
Histological grade
Grading is recommended for all invasive
carcinomas of the breast, re g a rdless
of morphological type {1984,
2216,2905}. This practice has been criticized
by some pathologists who feel
that grading is not appropriate for the
special histological types such as pure
t u b u l a r, invasive cribriform, mucinous,
m e d u l l a ry and infiltrating lobular carc i-
nomas. For example, most infiltrating
lobular carcinomas, especially those of
classical subtype, are assessed as
grade 2 and the overall survival curve of
lobular carcinoma overlies that of all
other types of grade 2 carcinoma. In
mucinous carcinoma and in carc i n o m a
of mixed morphological type, grading
p rovides a more appropriate estimate of
p rognosis than type alone {2216}. In
m e d u l l a ry carcinoma no additional
p rognostic value has been found.
Higher rates of distant metastasis and
p o o rer survival are seen in patients with
higher grade (poorly diff e rentiated) tumours,
independent of lymph node
status and tumour size {550,777,836,
868,886,1031,1763,2030,2434}. Tumour
grading has prognostic value
even in breast cancers 1 cm and smaller
{461}. The optimal grading method
{777} has been detailed earlier in this
c h a p t e r. The combination of histological
type and grade provides a more accurate
assessment of prognosis than does
histological type alone {2216}.
Histological grade may also pro v i d e
useful information with re g a rd to
response to chemotherapy and, theref
o re, be a predictive factor as well as a
p rognostic indicator. Several studies
have suggested that high histological
grade is associated with a better
response to certain chemotherapy re g i-
mens than low histological grade
{2254}. However, additional studies are
re q u i red to define this relationship more
clearly {612}.
Tumour cell proliferation
Markers of proliferation have been
extensively investigated to evaluate
p rognosis {886,1304}. Mitotic count is
p a rt of histological grading. Other
methods include DNA flow cytometry
m e a s u rement of S-phase fraction (SPF).
Many studies indicate that high SPF is
associated with inferior outcome.
Ki-67/MIB-1 is a labile, non-histone nuclear
protein detected in the G1 through
M phases of the cell cycle, but not in
resting cells and is therefore a direct indicator
of the growth fraction. The percentage
of Ki-67 positive cells can be used to
stratify patients into good and poor survivors.
Quantitative RT-PCR in detecting
the mRNA level has also been introduced
as well as array based quantification
of proliferation (see below).
Lymphatic and blood vessel invasion
Lymphatic vessel invasion has be e n
shown to be an important and independent
prognostic factor, part i c u-
larly in patients with T1, node-negative
breast cancers {461,1606,1623,
2433,2445,2452}. Its major value is
in identifying patients at increased
risk of axillary lymph node involvement
{627,839,1592,2253,2415} and
adverse outcome {186a,627,1623,
2415,2434}. As with histological grade,
the ability of pathologists to re p roducibly
identify lymphatic vessel invasion
has been challenged {998} but
can be improved if stringent criteria
a re employed {627,2109,2253,2415,
2452}. Lymphatic vessel invasion
must be distinguished from tumour
cell nests within artifactual tissue
spaces created by shrinkage or
retraction of the stroma during tissue
p rocessing.
Blood vessel invasion has been re p o rted
to have an adverse effect on clinical
outcome. However, there is a bro a d
range in the re p o rted incidence, fro m
under 5% to almost 50% {1470,1592,
2444,2445,2452, 3083}. This is due to
a variety of factors including the
patient population, the criteria and
methodology used, and difficulty in
identifying blood vessels.
Perineural invasion
Perineural invasion is sometimes observed
in invasive breast cancers, but it
has not been shown to be an independent
prognostic factor {2426}.
Tumour necrosis
In most studies {2452}, the presence of
n e c rosis has been associated with
an adverse effect on clinical outcome
{414, 877,999,2175}, although in one,
n e c rosis was associated with a worse
p rognosis only within the first two years
after diagnosis {999}.
Inflammatory cell infiltrates
The presence of a prominent mononuclear
cell infiltrate has been corre l a t e d
in some studies with high histological
grade {2030}. However, the pro g n o s t i c
significance of this finding is controversial,
with some studies noting an
adverse effect on clinical outcome
{67,286,2785} and others observing
either no significant effect or a beneficial
effect {635,1601,2445,2785}.
Invasive breast carcinoma
57