Mortality following development of breast cancer while using oestrogen or oestrogen plus progestin: A computer record-linkage study

Research and Evaluation Department, Kaiser Permanente Southern California, Pasadena, 91101, USA.
British Journal of Cancer (Impact Factor: 4.84). 09/2005; 93(4):392-8. DOI: 10.1038/sj.bjc.6602701
Source: PubMed


The literature on the relationship between breast cancer mortality and postmenopausal oestrogen and combined oestrogen/progestin therapy is seemingly contradictory. This study explored survival after exposure to oestrogen or oestrogen plus progestin at or in the year prior to breast cancer diagnosis. Information on patients first diagnosed with invasive breast cancer between 1993 and 1998 was linked with outpatient pharmacy data from 1992 to 2000. Patients were classified according to use of oestrogen alone or oestrogen plus progestin at or in the year prior to diagnosis. Compared to nonusers, and adjusting for age at diagnosis, race/ethnicity, tumour size and grade, oestrogen receptor status, surgery status, and chemotherapy and hormone therapy for breast cancer treatment, oestrogen plus progestin users had lower all-cause mortality (stage I hazard ratio (HR) = 0.69, 95% confidence interval (CI)= 0.48-0.99; stage II HR = 0.53, 95% CI = 0.39-0.72) and breast cancer mortality (stage I HR = 0.52, 95% CI = 0.26-1.04; stage II HR = 0.69, 95% CI = 0.48-0.98). Oestrogen users experienced little or no survival benefit for all-cause mortality (stage I HR = 1.04, 95% CI = 0.77-1.42; stage II HR = 0.86, 95% CI = 0.65-1.14) or breast cancer mortality (stage I HR = 1.23, 95% CI 0.72-2.10; stage II HR = 1.01, 95% CI 0.72-1.41). Our findings suggest, relative to nonusers, a lower risk of death from all causes and from breast cancer in patients who were diagnosed with breast cancer while exposed to oestrogen plus progestin, but not in patients exposed to oestrogen only.

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    • "In this regard, the pharmacology of digoxin would resemble that of estrogen-alone use, assuming it acts as an estrogen-agonist. Long-term survival appears to be better in those who develop breast cancer while using estrogen [20-23], perhaps because the tumors have better prognosis characteristics, but we did not examine survival in digoxin-users because of concern about the impact of co-morbidity from cardiac conditions. "
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    ABSTRACT: Introduction Digoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer. Methods Incident breast cancer cases in Danish women (n = 49,312; 1995 to 2008) were identified. Analyses were conducted in women 20 to 74 years old. Relapse hazard ratios (HR) were compared in women using and not using digoxin, adjusting for age, calendar period, protocol, tumor size, nodal involvement, histology grade, estrogen-receptor (ER) status, and anti-estrogen therapy in Cox regression models. Results At diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person-years); 24 relapses occurred in women later starting digoxin (384 person-years). Overall relapse risk HR in digoxin users was 1.13 (95% confidence interval: 0.88, 1.46) compared to non-users. Relapse risk in digoxin users was significantly increased in the first year (2.19; 1.26, 3.78) but not thereafter (0.99; 0.74, 1.32) (P = 0.02 for difference in HRs). First-year relapse hazard was high in digoxin-using women with ER+ tumors (2.51; 1.39, 4.55) but not ER- tumors (0.72; 0.10, 5.27). Recurrence hazard was not significantly changed among digoxin-using women also using tamoxifen. Conclusions Breast cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis.
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    • "Cancers discovered during HRT have a better prognosis, which could be due to a better differentiated histologic form. They are almost exclusively lobular or lobulo ductal cancers, with more hormone-sensitive forms (E3N) [13] [14] [15]. Their metastatic risk evaluated over 20 years is weaker, whatever the site [16]. "
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    ABSTRACT: Estrogens and artificial progestins used in hormone replacement therapy increase breast cancer risk. This seems to be due to a promoting and not initiating effect. A synergic effect of estradiol and hyperinsulinism has been shown. Insulin plays a role in the increase of breast cancer risk when associated with android obesity, sedentariness, type II diabetes, and high glycemic index food, alcohol and trans fatty acids intake. Natural menopause induces insulin resistance and does not induce a risk decrease. The role of insulin gives a new outlook on the influence of HRT in breast cancer pro-motion: estradiol alone, which improves insulin-sensitivity, does not increase breast cancer risk. Artificial progestins associated with estrogens increase the risk, whereas estrogens associated with progesterone do not. This could be due to the fact that artificial progestins increase insulin resistance, whereas natural progesterone does not. Adipose tissue, which is an endocrine gland, is insulin dependant. Breast cancer and its seriousness are correlated to adipocytokin circulating levels such as resistin, leptin, interleukin 1, adipocyte fatty acid-binding protein, and are inversely corre-lated to the level of adiponectin. Insulin could play a synergic role with sexual steroids by a direct effect and by in-creasing adipose tissue secretions.
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    • "Recent studies support the following conclusions: (1) an increase in breast cancer risk associated with hormone therapy is observed only in lean women; (2) the relative risk is higher with combinations of estrogen and progestin; (3) the effect is confined to ER+/PR+ tumors, mainly lobular cancers. A statistically significant reduced risk of breast cancer mortality was observed only in users of estrogen-progestin in a Kaiser cohort [10] "
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    ABSTRACT: There are good reasons why the use of postmenopausal hormone therapy is at a contemporary low level. But an analysis of these factors provides explanations that offer a basis for appropriate and renewed use. A more optimistic position is supported by an up-to-date appraisal of clinical studies.
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