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