world cancer report - iarc

Markers of prognosis in breast cancer
Commonly assessed markers:
Number of positive axillary lymph nodes
Tumour size
Tumour TNM stage
Lymphatic and vascular invasion
Histological tumour type
Steroid hormone receptors (estrogen receptors ER-α, ER-β; progesterone receptor)
Growth factor receptor genes (epidermal growth factor gene, EGFR)
DNA ploidy (DNA histogram)
Proliferative indices (fraction of cells in S-phase; thymidine labelling index; mitotic index)
Less commonly assessed markers:
Proliferative indices (Ki67, PCNA, cyclins, thymidylate synthetase, MIB1)
Topoisomerase II
Histone H3
Transforming growth factors (TGF-α, TGF-β)
Epidermal growth factor (EGF)
Insulin-like growth factors and their binding proteins (IGF-I, IGF-II)
Oncogene products (c-erbB2, ras, c-myc, int2)
Markers of apoptosis (mutations of p53, Bcl-2 proteins, caspases, survirin, p21, R6 )
Markers of proteolysis (activation of urokinase-type plasminogen, cathepsin D, matrix metalloproteases)
Markers of cell adhesion (integrins, cadherins, CD-44 variants)
Markers of angiogenesis (endothelial markers: Factor VII, CD-31, CD34; angiogenic peptides e.g. VEGF)
Markers of cell mobility (cytokines)
Steroid hormones (estrogens, glucocorticoids, prolactin, progestins)
Tumour-associated antigens (carcinoembryogenic antigen, CEA; tissue polypeptide antigen, TPA; gross cystic
disease fluid protein, GCDP; mucin-like molecules, CA 15.3, MAM-6, MSA, MC)
pS2
NM23
Heat shock proteins
MDR1
Table 5.2 Prognostic indicators in breast cancer.
type, having a higher rate of proliferation,
being more aggressive and more
likely to be associated with areas of
microinvasion and with expression of
markers such as aneuploidy and overexpression
of p53, c-erbB2 and Bcl-2.
Lobular carcinoma in situ (Fig. 5.16),
unlike ductal carcinoma in situ, is not
readily detected clinically or mammographically,
is frequently multicentric
and bilateral, and occurs more commonly
in younger women. It is associated
with an increased risk for development
of cancer, but is not a precursor lesion.
Lobular carcinoma in situ is characterized
by a solid proliferation of small cells
with small uniform, round or oval nuclei,
which grow slowly, are usually estrogen
receptor positive and rarely overexpress
c-erbB2. The most frequent malignant
lesion (80%) is invasive ductal carcinoma
of no special type, with 20% of cancers
being lobular, tubular, medullary or other
special types (Fig. 5.17).
The most important genes identified in the
context of familial breast cancer are
BRCA1 and BRCA2 [12]. Inherited mutations
in these genes account for a very
high relative risk of breast and sometimes
ovarian cancer among carrier women [13],
although such instances of breast cancer
account for less than 5% of all cases
(Genetic susceptibility, p71). Other genetic
conditions suspected of playing a role
include heterozygosity of the ataxia telangiectasia
gene (Box: ATM and breast cancer,
p192) and germline mutations of p53
(the Li-Fraumeni syndrome) [14].
The most common genetic abnormality in
breast carcinoma tissue appears to be a
loss of heterogeneity at multiple loci. Such
change may determine the influence of a
mutated allele of a tumour suppressor
gene (Oncogenes and tumour suppressor
Fig. 5.20 Physician performing a sentinel lymph
node biopsy. With this state-of-the-art radio-guided
surgical equipment, the patient avoids complete
resection of the axillary lymphatic nodes and
the complications of lymphoedema.
Fig. 5.21 Five-year relative survival rates after
diagnosis of breast cancer.
genes, p96). Loss of heterogeneity on 13q
and 17p may involve the RB or p53 genes
respectively. Gene amplification is also
observed, the most studied gene in this
context being that encoding the growth
factor receptor c-erbB2. Although the
estrogen receptor cannot be clearly classified
as the product of an oncogene or
tumour suppressor, expression of this
gene mediates progression of breast cancer,
and the responsiveness of tumours to
hormone-based therapy.
Management
Successful management of a breast cancer
implies a multidisciplinary approach to
Breast cancer
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