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JNCI Journal of the National Cancer Institute 1991 83(20):1483-1487; doi:10.1093/jnci/83.20.1483
© 1991 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 83, No. 20, 1483-1487, October 16, 1991
© 1991 Oxford University Press

Her-2/neu and INT2 Proto-oncogene Amplification in Malignant Breast Tumors in Relation to Reproductive Factors and Exposure to Exogenous Hormones

Håkan Olsson*,, Åke Borg, Mårten Fernö, Jonas Ranstam, Helgi Sigurdsson

Department of Oncology, University Hospital Lund, Sweden
Department of Community Health Science, Malmo General Hospital Malmo, Sweden

*Correspondence to: Hakan Olsson, M.D., Ph.D., Department of Oncology, University Hospital, Lund S-221 85, Sweden.

In previous studies in southern Sweden, early use of oral contraceptives has been found to be accompanied by an increased risk of developing premenopausal breast cancer, and the tumors developing in these patients have shown a more aggressive behavior. In the present study, amplification of the proto-oncogenes Her-2/neu (also known as ERBB2) and INT2 was studied in primary tumor specimens from 72 premenopausal women and was related to starting age of oral contraceptive use and other reproductive risk factors. Amplification of Her-2/neu was more common among early oral contraceptive users (i.e., those starting at less double equals20 years of age) than among nonusers or late users (odds ratio [OR], 53; 95% confidence interval [CI], 1.6–16.7), whereas INT2 amplification did not differ significantly among those groups (OR, 0.9; 95% CI, 0.1–5.0). The likelihood of INT2 amplification was greater among users of progestins and those with a history of abortions before the first full-term pregnancy (OR, 9.0; 95% CI, 1.3–51.7; and OR, 18.6; 95% CI, 2.2–165.8, respectively). No significant relationships were found between proto-on-cogene amplification and the variables of parity, age at first full-term pregnancy, or late abortion. The increased ORs persisted after adjustment for age at diagnosis and other risk factors. The findings suggest that the higher rate of Her-2/neu amplification among early oral contraceptive users is an effect of the oral contraceptive use per se rather than of the relative youth of the users. Moreover, the relationship between progestin use and early abortion and amplification of the INT2 gene is biologically plausible. [J Natl Cancer Inst 83: 1483–1487, 1991]


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