| 11. |
- 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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| 12. |
- Sigurdsson, H, et al.
(författare)
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Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels
- 1990
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Ingår i: British Journal of Cancer. - 1532-1827. ; 62:5, s. 786-790
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Tidskriftsartikel (refereegranskat)abstract
- The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
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| 13. |
- Sigurdsson, H, et al.
(författare)
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Indicators of prognosis in node-negative breast cancer
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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