Invasive breast carcinoma - IARC

M a c r o s c o p y
The majority of male breast cancers
m e a s u re between 2 and 2.5 cm.
Multiple separate nodules are rare as is
involvement of the entire bre a s t .
H i s t o p a t h o l o g y
The histological classification and grading
of male and female invasive bre a s t
c a rcinoma are identical, but lobular carcinoma
does not usually occur in men
even in those exposed to endogenous
or exogenous hormonal stimulation
{1855,2521,2552} and should only be
diagnosed if E-cadherin expression is
absent {34}.
I m m u n o p ro f i l e
C o m p a red to breast carcinoma in
women, male breast carcinomas have a
somewhat higher frequency of ER positivity
in the 60-95% range, while PR positivity
occurs in 45-85% of cases {315,
578,1836,1917}. The concentrations are
independent of patient age and similar
to those found in postmenopausal
women {2297}. Androgen receptors are
e x p ressed in up to 95% of cases.
Prognosis and predictive factors
The prognosis and predictive factors
a re the same as for female breast cancer
at comparative stages.
Fig. 1.167 Male breast carcinoma, DCIS. The in situ
carcinomas are generally of the non-necrotic cribriform
or papillary types. Though necrosis develops in
some cases composed of either micropapillary or the
cribriform types, true comedo DCIS is rare.
Metastasis to the bre a s t
The ratio of primary breast cancer and a
metastasis from another primary site to
the breast is about 25:1. The most frequent
primaries are prostatic carc i n o-
ma, adenocarcinoma of the colon, carcinoma
of the urinary bladder, malignant
melanoma and malignant lymp
h o m a .
C a rcinoma and sarcoma secondary to
p revious treatment
As in women, carcinoma following previous
chemotherapy and/or irradiation
has been re p o rted {326,601}, as has
post irradiation sarcoma {2644}.
Carcinoma in situ
ICD-O code 8 5 0 0 / 2
Clinical features
In the absence of mammographic
s c reening in men, the two most fre q u e n t
symptoms are sero-sanguineous nipple
discharge and/or subareolar tumour.
H i s t o p a t h o l o g y
The histological features are in general
similar to those in the female breast but
two major studies have found that the
most frequent architectural pattern is
p a p i l l a ry, while comedo DCIS occurs
r a rely {602,1221}. Lobular intraepithelial
neoplasia is also extremely rare. Paget
disease may be relatively more common
among men compared to women due to
the shorter length of the duct system in
male bre a s t .
Other tumours
Almost all breast tumours which occur
in women have also, been re p o rted in
men, albeit rare l y.
Genetics in male breast cancer
Ve ry little is currently known about the
molecular events leading to the development
and pro g ression of sporadic
b reast cancer in males. Loss of hete
rozygosity (LOH) and comparative
genomic hybridisation (CGH) studies
and cytogenetic analysis have shown
that somatic genetic changes in sporadic
male breast carcinomas are quantitatively
and qualitatively similar to
those associated with sporadic female
b reast cancer {2532,2927,3134,3265}.
Tumour phenotypic markers, such as
ERBB2 and TP53 expression, are also
quite similar between the sexes {3129}.
Ki-ras mutations are not significantly
i n c reased in male breast cancer {636}.
LOH on chromosome 8p22 and 11q13
a re frequently identified in male bre a s t
cancer {490,1073} suggesting that the
p resence of one or more tumour supp
ressor genes in these regions may
play a role in the development or prog
ression of the disease. LOH at 11q13
is found more often in carcinomas with
positive nodal status than in carc i n o m a s
without lymph node metastasis {1073}.
F requent allelic losses on chro m o s o m e
13q are re p o rted in familial, as well as in
sporadic, male breast cancer {2296,
3134}. Chromosome 13q is the re g i o n
containing the B R C A 2, B R U S H - 1, and
retinoblastoma gene. Depending on the
population, studies demonstrated that
4-38% of all male breast cancers are
associated with B R C A 2 a l t e r a t i o n s
{918,1550, 2921}. Other putative target
genes are also situated here, including
p rotocadherin 9 and EMK (serine/thre o-
nine protein kinase). Possibly, multiple
tumour suppressor genes may influence
the observed pattern of loss of hete
rozygosity {1383}.
The role of aberrant hormone secre t i o n
or hormone receptor function in the
development or pro g ression of the disease
remains controversial. Horm o n a l
imbalances, such as those in Klinefelter
s y n d rome or Reifenstein syndro m e
(mutation of the androgen re c e p t o r
gene: Xq11-12) are known risk factors
for breast cancer in males {427,
1213,2484}. In three men, germ l i n e
mutations in the androgen re c e p t o r
gene was re p o rted including two
b rothers with Reifenstein syndro m e
{1686,3152}. However it has been
shown that mutations of the andro g e n
receptor are not obligatory for the
development of male breast cancer
{1213}.
Cytogenetic studies reveal clonal chromosomal
anomalies: Loss of the Y chromosome
and gain of an X chro m o s o m e ,
as well as the gain of chromosome 5,
a re all frequently observed {1213,2484}.
Taken together with previous data, the
p resent findings suggest close similarities
between the molecular pathogenesis
of male and female breast canc
e r s .
112 Tumours of the breast