Association between endometrial cancer and tamoxifen treatment of breast cancer

A retrospective cohortstudy in 4109 breast cancer patients was undertaken to determine how tamoxifen affected the risk of endometrial cancer. Data on 1701 tamoxifentreated women were analysed. Two thousand four hundred and eight nontamoxifen users served as control group. The occurrence of new primary uterine cancers was assessed by computerized linkage to the Austrian Cancer Registry. Twentyfive women who subsequently developed endometrial cancer were identified. Eight uterine cancers occurred in the tamoxifen group, whereas 17 uterine cancers were found in the control group. The estimate of the relative risk (RR) showed an increased risk to develop endometrial cancer for the tamoxifen group RR 1.136 (95% CI 0.71; 1.80). Analysis of relevant confounding variables did not show any differences in the two groups.In conclusion, this retrospective study demonstrated a nonsignificant increased risk of endometrial cancer in women receiving tamoxifen as treatment for breast cancer. However, the magnitude of RR and the absolute number of endometrial cancer cases in this long term observation demonstrate clearly that the clinical benefit of tamoxifen therapy greatly outweighs the risk.     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

Pre-existing diabetes and breast cancer prognosis among elderly women

Background:

The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis.

Methods:

Women (n=2833) with centrally confirmed invasive breast cancer in the Women''s Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality.

Results:

Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23–2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86–2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality.

Conclusions:

Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality.     

Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan

Raloxifene was approved for chemoprevention against breast cancer among high-risk women in addition to tamoxifen by the US Food and Drug Administration. This study aims to evaluate cost-effectiveness of these agents under Japan''s health system. A cost-effectiveness analysis with Markov model consisting of eight health states such as healthy, invasive breast cancer, and endometrial cancer is carried out. The model incorporated the findings of National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 trial, and key costs obtained from health insurance claim reviews. Favourable results, that is cost saving or cost-effective, are found by both tamoxifen and raloxifene for the introduction of chemoprevention among extremely high-risk women such as having a history of atypical hyperplasia, a history of lobular carcinoma in situ or a 5-year predicted breast cancer risk of ⩾5.01% starting at younger age, whereas unfavourable results, that is ‘cost more and gain less'' or cost-ineffective, are found for women with a 5-year predicted breast cancer risk of ⩽5.00%. Therapeutic policy switch from tamoxifen to raloxifene among postmenopausal women are implied cost-effective. Findings suggest that introduction of chemoprevention targeting extremely high-risk women in Japan can be justifiable as an efficient use of finite health-care resources, possibly contributing to cost containment.     

Randomized clinical trial of tamoxifen plus sequential CMF chemotherapy versus tamoxifen alone in postmenopausal women with advanced breast cancer

Summary Eighty-eight postmenopausal women with metastatic breast cancer, in whom estrogen receptors (ER) were positive or unknown, were treated on a controlled trial to determine the effectiveness of tamoxifen and to assess the therapeutic advantage of sequentially adding low-dose cyclophosphamide-methotrexate-5-fluorouracil (CMF) chemotherapy in tamoxifen responders. Patients with known ER negative status were not studied. After the initial 12-week treatment with tamoxifen alone, 60% of ER positive patients achieved complete or partial response as did 35% in whom ER were unknown. Response status further improved in 18% randomized to continue tamoxifen alone vs 31% in whom CMF was added to tamoxifen. There were no statistically significant differences in time to the development of progressive disease or survival between the ER positive and ER unknown patients or between the tamoxifen and tamoxifen plus CMF groups. We conclude that inability to determine ER status should not prejudice against the use of tamoxifen in postmenopausal patients with advanced breast cancer. No benefit has been demonstrated from the addition of CMF chemotherapy in tamoxifen responders. Address for reprints: J.H. Glick, M.D., Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104.     

Gender of offspring and long-term maternal breast cancer risk

Gender of offspring is influenced by maternal hormonal level during pregnancy, which is believed to influence the subsequent maternal breast cancer risk. However, analysing national birth and cancer registrations in a cohort of 998,499 women, we found no association between gender of offspring and subsequent breast cancer risk.     

Effect of tamoxifen on serum cholesterol in Japanese women with breast cancer

Background To investigate whether tamoxifen therapy has a favorable effect on plasma lipids, serum cholesterol levels were measured in 228 Japanese women with breast cancer (116 premenopausal women and 112 postmenopausal women). Methods These women were treated with tamoxifen or tamoxifen+chemotherapy (tamoxifen-treated group) or were given no therapy or chemotherapy alone (control group). Results There was no difference between cholesterol levels before treatment and after a 2-year follow-up period in these groups, except for the postmenopausal tamoxifen-treated group. In this particular group, the mean levels of serum cholesterol after 1 and 2 years of follow-up (197 and 188 mg/dL, respectively) were 8% and 12% lower than those before treatment (215 mg/dL,P<0.0001). In addition, the mean level of serum cholesterol after a 2-year follow-up period was significantly higher in the postmenopausal tamoxifen-treated group than in the postmenopausal control group (218 and 188 mg/dL, respectively,P=0.0066). Conclusions In multiple regression models that included age, body mass index, and chemohormonal therapy, only tamoxifen treatment appeared to predict the change between cholesterol levels before treatment and after 2-year follow-up in postmenopausal women. These results suggest that tamoxifen has the potential benefit of reducing the serum cholesterol level, which may be closely related to cardiovascular risk, in Japanese postmenopausal women.     

Increased prevalence of prior breast cancer in women with newly diagnosed diabetes

SummaryObjective There is growing evidence of a link between type 2 diabetes and breast cancer, possibly through insulin resistance and/or hyperinsulinemia. Because insulin levels are at their highest prior to the development of diabetes, breast cancer risk may be even greater during the pre-diabetes period.Research design and methods In this cross-sectional study, women aged 55–79 years living in Ontario, Canada, with newly diagnosed diabetes from 1994 to 2002 were identified from a validated, population-based database (N = 82,390). Prior history of breast cancer in this group was recorded from 1964 until their diabetes diagnosis from a linkable cancer registry, and was compared to a similarly aged comparison group without diabetes (N = 411,950).Results Prior breast cancers were identified in 3.7% of women with diabetes and in 3.1% women without diabetes (odds ratio, OR 1.22, 95% confidence interval, CI 1.17–1.27, p < 0.0001). The mean time from breast cancer diagnosis to diabetes diagnosis was 7.9 years. The likelihood of a breast cancer history remained significantly higher in women with diabetes after adjustment for age, income and physician visits (OR 1.13, 95% CI 1.09–1.18, p < 0.0001).Conclusions These results suggest that breast cancer risk may be increased in the pre-diabetes phase and may have implications for screening and prevention strategies. Further studies are required to better characterize the processes that link insulin resistance, diabetes and breast cancer.     

乳腺癌患者应用三苯氧胺导致的妇科并发症及其监测

三苯氧胺具有抗雌激素和雌激素的双重特性,长期持续使用可导致子宫内膜发生多种病理改变。临床应予以重视,并加以监测。本文就妇科并发症的发生和临床监测方面做一综述,以早发现、并减少并发症的发生。     

Birth outcome in women with breast cancer

We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95% confidence interval (CI): 3.8-17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0-2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3-6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients.     

The incidence of hepatocellular carcinoma in US white women with breast cancer after the introduction of tamoxifen in 1977

Summary It has been hypothesized that hepatocellular carcinoma might be a long-term adverse effect of tamoxifen therapy. Data from nine population-based cancer registries in the United States were used to investigate time trends in the incidence of hepatocellular carcinoma in white women previously diagnosed with invasive breast cancer during 1974–1987 and followed until 1989. Of particular interest were the rates after 1977, the year tamoxifen was licensed by the FDA. Compared to rates in all white women, no increased risk of hepatocellular carcinoma was found in women most likely to have received tamoxifen - those 50 years of age or more at diagnosis of breast cancer and diagnosed after 1977. These results suggest that tamoxifen does not cause a large increase in the incidence of hepatocellular carcinoma within the first decade after use. However, smaller and/or later increases in the risk for hepatocellular carcinoma are possible and warrant continued monitoring of women treated with tamoxifen.     

Risk for breast cancer among women with endometriosis

Although several risk factors are common to endometriosis and breast cancer, the results of observational studies of an association have so far been inconsistent. We evaluated the relationship between endometriosis and breast cancer on the basis of data on selected cancers and medical histories from the Danish nationwide cancer and hospital registries used in a large case-cohort study. A total of 114,327 women were included in the study of whom 1,978 women had received a diagnosis of endometriosis and 16,983 had had a diagnosis of breast cancer between 1978 and 1998. Of the women with endometriosis, 236 subsequently received a diagnosis of breast cancer. The crude overall rate ratio for breast cancer after endometriosis was 1.00 and after adjustment for reproductive factors, calendar-period, bilateral oophorectomy and benign breast disease, the rate ratio was 0.97 (95% confidence interval, 0.85-1.11). The risk for breast cancer increased with age at diagnosis of endometriosis, so that women in whom endometriosis was diagnosed at a young age (approximately <40 years) had a reduced risk for breast cancer and women in whom endometriosis was diagnosed at older ages (approximately > or =40 years) tended to have an increased risk for breast cancer. The reduced risks observed among young women may reflect their exposure to drugs with antiestrogenic effects. The increased risk associated with endometriosis among postmenopausal women may be due to common risk factors between postmenopausal endometriosis and breast cancer or an altered endogenous estrogen.     

Late risk of relapse and mortality among postmenopausal women with estrogen responsive early breast cancer after 5 years of tamoxifen.

BACKGROUND: Letrozole after 5 years of adjuvant tamoxifen results in a significant reduction in risk of recurrence from estrogen receptor (ER) positive breast cancer. An individualized estimate of the risk of relapse and death after 5 years of tamoxifen could improve decisions regarding extended hormonal therapy. METHODS: The British Columbia Breast Cancer Outcomes database was used to identify women aged 45 years or older at the time of diagnosis with early-stage (I-IIIA) breast cancer who received tamoxifen and were disease free 5 years after diagnosis. Ten-year breast cancer event rates and mortality were calculated as well as annualized hazard rates of recurrence. RESULTS: A total of 1086 women were identified with a median age of 64 years and follow-up of 10.5 years. The relative risk (RR) of death was 3.1 (P=0.003) and for recurrence was 1.7 (P=0.037) for N1 (one to three positive nodes) versus N0 (zero nodes positive) disease. N2 (four to nine nodes positive) had a RR of 5.8 (P<0.001) for death and 3.0 (P=0.002) for recurrence. Low tumor grade and high ER level subgroups had a more favorable prognosis. Annual breast cancer risk between years 6 and 10 was, respectively, 2.2%, 3.5% and 7.6% for N0, N1 and N2 disease and 2.6% and 4.5% for T1 and T2 breast cancer. CONCLUSION: T and N stages predicted late relapse and death from breast cancer in a population-based cohort of postmenopausal women. Risk estimates reported herein may be used to optimize decision making regarding adjuvant therapy after 5 years of tamoxifen.     

Risk of early recurrence among postmenopausal women with estrogen receptor-positive early breast cancer treated with adjuvant tamoxifen

BACKGROUND: Adjuvant aromatase inhibitors (AIs), instead of or after tamoxifen, are effective in decreasing recurrence in postmenopausal women with estrogen receptor (ER)-positive breast cancer. An understanding of which patients are at risk of early recurrence while they are receiving tamoxifen may improve clinical decision making. METHODS: The patients who were included in this study were women aged >or= 50 years with early-stage, ER-positive breast cancer diagnosed between 1986 and 1999 and had been treated with tamoxifen. Characteristics of the patients with early recurrences (within 2.5 years of diagnosis), late recurrences (between 2.5 years and 5 years) and no recurrence within 5 years were compared. Logistic regression analyses were conducted to identify which groups were at risk of early recurrence. RESULTS: Among 3844 women, 304 women (7.9%) developed disease recurrence within 2.5 years. Higher than average rates of recurrence within 2.5 years were observed in cohorts with lymph node (N)-positive tumors (11.5%), grade 3 histology (14.3%), or low-positive ER levels, ie, 10-49 fmol/mg or 10%-20% staining (14.9%). In multivariate analyses, only pathologically N-positive tumors (1-3 vs 0 positive lymph nodes: odds ratio [OR], 1.6; 4-9 vs 0 positive lymph nodes: OR, 2.23 [P= .03]) and low-positive ER status (OR, 2.04; P= .01) were associated with recurrence within 2.5 years compared with recurrence between 2.5 years and 5 years. Other clinical and pathologic variables were not predictive of early recurrence. CONCLUSIONS: Subgroups of women with early ER-positive breast cancer may be identified who are at increased risk of recurrence within 2.5 years of diagnosis despite tamoxifen. It remains to be proven whether upfront AI therapy results in an advantage to these women.     

Recent increase of breast cancer incidence among women under the age of forty

Using data from the Geneva Cancer Registry, we found that in 2002-2004, breast cancer incidence in women aged 25-39 years increased by 46.7% per year (95% CI: 7.1-74.0, P=0.015), which surveillance or detection bias may not fully explain.     

Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis

One hundred fiftyone postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred fortythree eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p=0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p=0.38). Duration of response and progressionfree survival were not found to be significantly different between DES and TAM (p=0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p=0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms.Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy.The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.     

Breast cancer mortality in relation to self-reported use of breast self-examination. A cohort study of 450,000 women

The benefits of breast self-examination (BSE) for reducingmortality from breast cancer are uncertain. We conductedan analysis of the relationship between self-reported practicingof BSE and mortality from breast cancer over13 years in a cohort of over 548,000women. The report of practicing BSE was unrelatedto breast cancer mortality. There was a smallbeneficial effect in those women who were thethinnest, but this effect was small and notstatistically significant. BSE was otherwise equally ineffective insubgroups defined by obesity level and family historyof breast cancer. We conclude that BSE, aspracticed by American women in 1959, did notreduce the risk of mortality from breast cancer.