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Hormone replacement therapy and biological aggressiveness of breast cancer

1997; Elsevier BV; Volume: 350; Issue: 9092 Linguagem: Inglês

10.1016/s0140-6736(05)64308-5

1474-547X

Kaija Holli, Jorma Isola, Jack Cuzick,

Cancer Risks and Factors

In the meta-analysis by the Collaborative Group on Hormonal Factors in Breast Cancer (Oct 11, p 1047)1Collaborative Group on Hormonal Factors in Breast Cancer Breast cancer and hormone replacement therapy:collaborative renalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer.Lancet. 1997; 350: 1047-1059Summary Full Text Full Text PDF PubMed Scopus (2485) Google Scholar hormone replacement therapy (HRT) was associated with an increased risk of breast cancer. In addition to this increased risk, the meta-analysis showed a tendency towards a higher proportion of localised tumours in HRT users. This is an important finding, because a less advanced clinical stage in breast cancer is usually associated with better survival and lower mortality. Thus the effect of HRT on breast cancer mortality (not examined in the meta-analysis) is probably less and may even be beneficial, as seen in two large cohort studies.2Willis DB Calle EE Miracle-McMahill H Heath C Estgrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States.Cancer Causes Control. 1996; 7: 449-457Crossref PubMed Scopus (202) Google Scholar, 3Grodstein F Stampfer M Colditz C et al.Postmenopausal hormone therapy and mortality.N Engl J Med. 1997; 336: 1769-1775Crossref PubMed Scopus (1142) Google Scholar The less advanced clinical stage in HRT users has been explained by selection or surveillance bias, and by a biological effect of HRT on breast tumours. The data on tumour biology in HRT users is scarce and we fully agree with the conclusion of the Collaborative Group that it should be the focus of future investigations. We have looked at the possible effect of HRT on tumour biology in a population-based cohort of 477 consecutive patients with breast cancer who were older than 50 years in the Tampere University Hospital district between 1992 and 1994. The use of HRT was determined by a structured interview and from prescriptions (171 [37%] of the patients had used HRT, of whom 44 [25%] were on oestrogen alone, 127 [73%] oestrogen and progestogen combination, and three [2%] on progestogen alone). Standard clinical and pathological information (age, tumour size, axillary nodal status, histological grade), and the method of diagnosis (screen detected or self-referral) were recorded for all patients. Indicators of biological aggressiveness included oestrogen and progesterone receptors, c-erbB2 oncoprotein, ploidy, and tumour proliferation rate. Our findings (table) indicated that tumours from HRT users are biologically less aggressive. Use of HRT was significantly associated with small tumour size and low tumour proliferation rate (S-phase fraction by DNA flow cytometry). The latter association was found only if HRT was used at the time when breast cancer was diagnosed. This finding suggests that the lower proliferation rate is a specific and immediate effect of HRT on established breast tumours. The primary tumours were also significantly smaller in HRT users, which is in accordance with the meta-analysis.1Collaborative Group on Hormonal Factors in Breast Cancer Breast cancer and hormone replacement therapy:collaborative renalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer.Lancet. 1997; 350: 1047-1059Summary Full Text Full Text PDF PubMed Scopus (2485) Google Scholar Adjusting for the method of detection (171 cancers detected by mammography screening vs 306 by self-referral) had a minimum effect on the association between tumour size, proliferation rate, and HRT, suggesting that the detection of smaller tumours in HRT users was not due to surveillance bias. Tumour size and proliferation rate were significantly correlated (p 2 cm vs <2 cm)0·47 (0·31–0·72)0·0005†χ2 test;Lymph-node status (−ve/+ve)0·73 (0·47–1·2)0·2†χ2 test;Histological grade (I vs II vs III)0·04‡χ2 test for trend;Oestrogen receptor0·76 (0·46–1·2)0·31†χ2 test;Progesterone receptor1·01 (0·85–1·5)0·99†χ2 test;C-erbB2 oncoprotein (−ve/+ve)1·60 (0·85–2·9)0·15†χ2 test;Ploidy (diploid vs aneuploid)0·69 (0·45–1·1)0·11†χ2 test;Tumour proliferation rate¶mean s-phase fraction (%) (SD).Never-user (n=228)Ex-users (n=27)Current users (n=91)10·3 (7·4)9·4 (5·8)7·8 (5·9)0·0001§Wilcoxon test for trend;Never-user=no use of HRT; ex-user=use of HRT for over 3 months but stopped at least 3 months before diagnosis of breast cancer; current user: use of HRT for over 3 months and until diagnosis of breast cancer; +ve=positive; –ve=negative.* Never-user vs HRT users;† χ2 test;‡ χ2 test for trend;§ Wilcoxon test for trend;¶ mean s-phase fraction (%) (SD). Open table in a new tab Never-user=no use of HRT; ex-user=use of HRT for over 3 months but stopped at least 3 months before diagnosis of breast cancer; current user: use of HRT for over 3 months and until diagnosis of breast cancer; +ve=positive; –ve=negative. Although HRT increases the risk of breast cancer,1Collaborative Group on Hormonal Factors in Breast Cancer Breast cancer and hormone replacement therapy:collaborative renalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer.Lancet. 1997; 350: 1047-1059Summary Full Text Full Text PDF PubMed Scopus (2485) Google Scholar the overall effect of HRT on breast carcinogenesis and tumour progression remains to be fully evaluated. There is growing evidence for a more favourable tumour biology in HRT users,4Harding C Knox W Faragher E Baildam A Bundred N Hormone replacement therapy and tumour grade in breast cancer: prospective study in screening unit.BMJ. 1996; 312: 1646-1647Crossref PubMed Scopus (67) Google Scholar, 5Salmon R Remvikos Y Ansquer Y Assealain B HRT and breast cancer.Lancet. 1995; 346: 1702-1703Abstract PubMed Google Scholar and there are at least two large studies reporting decreased mortality due to breast cancer in HRT users.2Willis DB Calle EE Miracle-McMahill H Heath C Estgrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States.Cancer Causes Control. 1996; 7: 449-457Crossref PubMed Scopus (202) Google Scholar, 3Grodstein F Stampfer M Colditz C et al.Postmenopausal hormone therapy and mortality.N Engl J Med. 1997; 336: 1769-1775Crossref PubMed Scopus (1142) Google Scholar