Genetic studies of 457 breast cancers. Clinicopathologic parameters compared with genetic alterations.
BACKGROUND
Human breast cancers frequently show loss of heterozygosity (LOH) and/or amplification at specific chromosomal regions.


METHODS
To investigate the roles of these genetic alterations during tumor development and/or progression, 457 cases of primary breast cancer were examined for LOH at chromosomal regions 16q24, 17p13.3, and 17q21, and for amplification of the erb-B2 locus at 17q11.2 and the c-myc locus at 8q24. The genetic changes then were compared with lymph node metastasis, histologic type, and tumor stage.


RESULTS
The LOH at 17q21 was observed more frequently in tumors of the solid, tubular type (41 of 75 [55%]) than in other types (48 of 187 [26%]) (P < 0.0001). The LOH at 17p13.3 was more frequent in scirrhous and solid, tubular tumors (77 of 141 [55%] and 48 of 88 [55%]) than in other types (29 of 89 [33%]) (P = 0.0004). Generally, mutations were seen more often in tumors with axillary lymph node metastases, undifferentiated tumors, and large or invasive tumors than in tumors considered less aggressive histopathologically. However, 22 tumors bearing three or more genetic alterations were found among 187 tumors histologically diagnosed as free of axillary lymph node metastasis; similarly, 12 of 122 t1 classification tumors and 4 of 89 histologically well differentiated tumors each contained three or more genetic alterations. Although these tumors would be regarded as having a relatively good prognosis on the basis of conventional clinicopathologic diagnosis, the authors suspect that, in fact, they do not.


CONCLUSIONS
Patients whose tumors contain multiple genetic alterations should be treated as a new high risk group with respect to operative and/or postoperative management.
Harada
Y
Y
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Katagiri
T
T
Ito
I
I
Akiyama
F
F
Sakamoto
G
G
Kasumi
F
F
Nakamura
Y
Y
Emi
M
M
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16; D002886:Chromosomes, Human, Pair 17; D002898:Chromosomes, Human, Pair 8; D004247:DNA / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D016259:Genes, myc; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D006801:Humans; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies
D004273:DNA, Neoplasm; D005819:Genetic Markers; D004247:DNA