| 1. |
- Borg, Åke, et al.
(författare)
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ERBB2 amplification in breast cancer with a high rate of proliferation
- 1991
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Ingår i: Oncogene. - 1476-5594. ; 6:1, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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| 2. |
- Olsson, Håkan, et al.
(författare)
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DNA ploidy assessment of breast milk (colostrum) in primiparous women of different ages
- 1991
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Ingår i: Breast Disease. - 0888-6008. ; 4:3, s. 219-222
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies on breast cancer risk factors suggest that nursing may have a protective effect. The mechanism behind this is unknown. To investigate whether removal of tumorigenic epithelial cells in breast milk contributes to the reduced risk of developing breast cancer, DNA ploidy of cells in colostrum breast milk from 200 primiparous women was studied with flow cytometry. No woman displayed an abnormal DNA content of the shed epithelium in the milk. Although it cannot be excluded that tumor cells with a near-diploid DNA content are present, our results suggest that early shedding of a large clone of transformed aneuploid epithelium is not a common event and that the protective effect of nursing on breast cancer risk is due to other mechanisms, e.g., hormonal changes in the breast.
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| 3. |
- Olsson, Håkan, et al.
(författare)
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HER-2/neu and INT2 proto-oncogene amplification in malignant breast tumors in relation to reproductive factors and exposure to exogenous hormones
- 1991
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 83:20, s. 1483-1487
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Tidskriftsartikel (refereegranskat)abstract
- 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 ≦20 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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