Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study

Increasing use of HRT over the last 2 decades could have contributed to the increasing incidence of cancer in women. Our aim was to investigate the relation between use of HRT and risk of hormone-dependent cancers in a Norwegian cohort of women. The Norwegian Women and Cancer (NOWAC) study is a representative, national, population-based cohort study. This report includes 35,456 postmenopausal women aged 45-64 years who answered a postal questionnaire in 1996-1998 providing information on reproduction, lifestyle and use of HRT. The women were followed up for cancer incidence. The main analyses were restricted to 31,451 postmenopausal women with complete information. Ever use of HRT was reported by 43.5% and current use, by 35% of the women. Current users had an increased risk of breast cancer (adjusted RR=2.1, 95% CI 1.5-2.5). The risk increased with increasing duration of use (ptrend < 0.0001). Using a regimen of continuous estrogen-progestagen implied an increased risk. Adjusted RRs associated with <5 and > or =5 years' duration of use were 2.6 (95% CI 1.9-3.7) and 3.2 (95% CI 2.2-4.6), respectively. The population-attributable risk of breast cancer due to current use of HRT was 27%. We found no significant increase in risk of ovarian cancer. Neither did we find users of estrogen-progestagen preparations to have any increase in risk of endometrial cancer. Our results suggest that HRT could be considered a major determinant for the increasing incidence of breast cancer in Norway.     

Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study

Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.     

Long-term oral contraceptive use increases breast cancer risk in women over 55 years of age: the DOM cohort

The role of past oral contraceptive use in the development of breast cancer is unclear, particularly in postmenopausal women. The authors investigated this relationship among pre- and postmenopausal middle-aged women in a nested case-control study within the population-based DOM cohort, Utrecht, the Netherlands. Among a total population of 12,184 women followed up for an average of 7.5 years, 309 breast cancer cases aged 42 to 63 years, diagnosed from November 1982 through May 1996, and 610 controls were examined. Overall, duration of oral contraceptive use was not clearly related to breast cancer. In women older than 55 years, however, oral contraceptive use for more than 10 years was associated with a 2-fold increased risk of breast cancer (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0). We conclude that long duration of oral contraceptive use increases the risk of breast cancer in women over 55 years of age but not in younger women.     

Risk of second non-hematological malignancies among 376,825 breast cancer survivors

Breast cancer survivors are at increased risk of treatment-related second cancers. This study is the first to examine risk 30 or more years after diagnosis and to present absolute risks of second cancer which accounts for competing mortality. We identified 23,158 second non-hematological malignancies excluding breast in a population-based cohort of 376,825 one-year survivors of breast cancer diagnosed from 1943 to 2002 and reported to four Scandinavian cancer registries. We calculated standardized incidence ratios (SIR) and utilized a competing-risk model to calculate absolute risk of developing second cancers. The overall SIR for second cancers was 1.15 (95% confidence interval [CI] = 1.14–1.17). The SIR for potentially radiotherapy-associated cancers 30 or more years after breast cancer diagnosis was 2.19 (95% CI = 1.87–2.55). However, the largest SIRs were observed for women aged <40 years followed for 1–9 years. At 20 years after breast cancer diagnosis, the absolute risk of developing a second cancer ranged from 0.6 to 10.3%, depending on stage and age; the difference in the absolute risk compared to the background population was greatest for women aged <40 years with localized disease, 2.3%. At 30 years post breast cancer diagnosis, this difference reached 3.2%. These risks were small compared to the corresponding risk of dying from breast cancer. Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease.     

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).     

A population-based cohort study of HRT use and breast cancer in southern Sweden

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI 1.32-2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use.     

Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden

BACKGROUND: The authors previously reported an increased risk of breast carcinoma with longer duration of hormone replacement therapy (HRT) use. It is unclear if different types of HRT confer different risks. METHODS: In this study, a population-based cohort of 29,508 women were interviewed during 1990-1992 to determine whether there are any differences in breast carcinoma risk according to different types and duration of HRT use. RESULTS: At the end of the follow-up period in December 2001, the cohort constituted 298,649 person-years. Slightly more breast carcinoma cases were seen (n = 556) than expected (n = 508.37; standardized morbidity ratio =1.09, 95% confidence interval [CI] = 1.00-1.19). Approximately 3663 women had ever used HRT. In Cox regression models, time to breast carcinoma in relation to duration and type of HRT use was analyzed, adjusting for age at menarche, age at first full-term pregnancy, parity, age at menopause, family history of breast carcinoma, and age at interview. In women with a natural menopause, a significantly higher risk was observed for longer duration of combined continuous HRT use compared with never users (hazard ratio [HR] = 4.60, 95% CI = 2.39-8.84). Nonsignificant elevated risks also were observed for longer combined sequential (HR = 2.23, 95% CI = 0.90-5.56), gestagen only (HR = 3.74,9 5% CI = 0.94-14.97), and estriol use (HR = 1.89, 95% CI = 0.81-4.39). No increased risk was seen in women after 5 years of nonuse. When studying women who ever used only one type of HRT, even more elevated HRs for gestagen-containing preparations were seen. The highest risks were associated with the combined continuous and gestagen-only therapy in women with >/= 48 months of use. Use of estradiol without progestins did not increase breast carcinoma risk significantly. The authors estimated the cumulative risk of breast carcinoma in a 50-year-old woman with gestagen-containing therapies for >/= 48 months, with a follow-up of 10 years, to be 7% (95% CI = 5.4-11.4%) compared with 2% (95% CI = 1.6%-2.9%) for never-users of HRT. CONCLUSIONS: Longer use of HRT containing progestins significantly elevates breast carcinoma risk whereas estradiol use does not. Continued use of progestins rendered the highest risks. The yearly risk of breast carcinoma for long-term users of progestins is of the magnitude of 50% the risk of a BRCA1 mutation carrier.     

Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast.

Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer, and it is possible that this reflects a positive association between HRT use and risk of proliferative forms of benign breast disease (BBD), conditions which are thought to have pre-malignant potential. The purpose of the present investigation was to study the association between HRT use and risk of benign proliferative epithelial disorders of the breast (BPED). The study was undertaken using the 56,837 women within the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) During the course of the follow-up period, a total of 691 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a sub-cohort consisting of a random sample of 5681 women (including 65 of the subjects with BPED) was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 691 cases and 5443 non-cases. In post-menopausal women, in whom most of the reported use occurred, there was a positive association between duration of HRT use and risk of BPED, the adjusted incidence rate ratio (95% confidence interval) in those who had used HRT for more than 8 years being 1.70 (1.06-2.72). There were too few cases of atypical BPED for meaningful analysis, but results for those whose BPED showed no atypia were similar to the overall results. Further analyses conducted separately in the screened and control arms of the NBSS were similar to those observed overall, as were those conducted separately for screen-detected and interval-detected BPED.     

Is a dense mammographic parenchymal pattern a contraindication to hormonal replacement therapy?

The aim of the study was to find out whether the effect of hormonal replacement therapy (HRT) is modified by the mammographic parenchymal patterns on the risk of breast cancer. Subjects were 4163 Finnish women aged 40-47 years at entry who were invited to breast cancer screening every second year from 1982 to 1990. Mammographic parenchymal patterns (Wolfe's classification) were recorded at each screening round. The information, on use of HRT, was recorded from 1984. The follow-up ended in 1993 and up until that time 68 new breast cancers were diagnosed. A Poisson regression model was used in the analysis of the data. Use of HRT was not related to the risk of breast cancer (RR = 0.7, 95% CI 0.4-1.4), whereas mammographic parenchymal pattern was statistically significantly associated with risk of breast cancer. The age-adjusted relative risk of breast cancer among women with P2 versus N1 pattern was 2.5 (95%CI 1.3-4.8) and with DY versus N1 pattern 4.9 (95%CI 1.6-15.1). Women using HRT and with DY pattern were at substantially increased risk of breast cancer (RR = 11.6, 95%CI 2.5-53.6) compared with women not using HRT and with N1 pattern. There was an increased risk of breast cancer among women with DY mammographic parenchymal pattern who used HRT, which was consistent with a synergistic joint effect.     

Hormone replacement therapy and the breast

Increasing numbers of women are using hormone replacement therapy (HRT) in their 50s and 60s. Oestrogen alone or oestrogen and progestogen combined given in this age group increase breast density and this has the effect of reducing both the sensitivity and specificity of breast screening in HRT users. HRT significantly increases the risk of developing breast cancer with combinations of oestrogen and progestogens increasing the risk to a greater degree than oestrogen alone. The longer HRT is used the greater the risk with 5 years use being associated with risks of 1.05-1.16 for oestrogen alone and 1.24-1.45 for oestrogen and progestogen combined. No consistent effect of HRT on breast cancer mortality has been demonstrated. Two studies have reported that more than 5 years HRT use is associated with an increased risk of death from breast cancer. A variety of non-oestrogenic agents are available to control menopausal symptoms and these may be of particular value in breast cancer survivors. HRT has been used in breast cancer survivors and although published data are reassuring, none have included sufficient patient numbers to detect small effects of HRT on breast cancer outcome. Prospective randomised trials are underway but are unlikely to include sufficient numbers to exclude a small adverse influence of HRT on breast cancer mortality. Tibolone, a gonadomemetic agent which has been used to control menopausal symptoms, appears to have less direct effects on the breast and is being evaluated as an alternative to oestrogen in breast cancer survivors who develop significant menopausal symptoms resistant to non-hormonal therapies. There is clear evidence that HRT causes breast cancer and the challenge for the physician is to control the menopausal symptoms using HRT or alternatives while at the same time limiting the risks associated with this treatment.     

Hormone replacement treatment and breast cancer risk: a cooperative Italian study.

The relationship between hormone replacement treatment (HRT) and breast cancer risk was analysed using data from a case-control study conducted between June 1991 and February 1994 in six Italian centres on 2569 patients aged below 75 with histologically confirmed breast cancer and 2588 controls admitted to hospital for a wide spectrum of acute, non-neoplastic, non hormone-related diseases. Ever HRT use was reported by 7.5% of cases and 7.5% of controls, corresponding to a multivariate odds ratio (OR) of 1.2 [95% confidence interval (CI), 0.9-1.5]. The risk increased with increasing duration of use: the ORs were 1.0 for use lasting less than 1 year, 1.3 for 1-4 years and 1.5 for 5 years or more. There was no clear pattern of risk with reference to time since starting use, but the OR was significantly elevated (OR = 2.0, 95% CI 1.3-2.9) for women who had stopped HRT within the last 10 years. No association was observed in those who had stopped HRT more than 10 years ago (OR = 1.0). The increased OR for women who had stopped HRT within the last 10 years was consistent across strata of identified covariates, and was significantly related to duration of use. This study confirms the absence of a strong association between HRT and breast cancer risk, although the risk estimate was above unity for women who had used HRT for 5 years or longer. However, the risk was significantly elevated in the short to medium term after use, particularly for long-term use. This short-term increased risk is consistent with an effect of HRT on one of the later stages of the process of breast carcinogenesis. The flattening of risk with increasing time since stopping, and hence the absence of a long-term cumulative excess in breast cancer risk after stopping HRT exposure, has relevant implications on individual risk assessment and public health.     

Decline in breast cancer incidence after decrease in utilisation of hormone replacement therapy

Hormone replacement therapy (HRT) has been implicated as a risk factor for breast cancer and the use of HRT has decreased substantially in general population over the last years. Recently, there are first indications that breast cancer incidence has started declining. We examined recent breast cancer incidence and actual data on HRT utilisation in Schleswig-Holstein, Germany, to find out population based evidence on decreasing breast cancer incidence and its possible relationship with reduced HRT usage. Breast cancer incidence is taken from the population based cancer registry of Schleswig-Holstein. HRT data was extracted from a cohort of 102,000 women taking part in a quality assurance project in breast cancer diagnosis for the years 2001–2005. The annual percentage change in incidence of breast cancer and HRT utilisation was measured by linear regression. There is a linear decline in HRT utilisation among less than 50 years group, 50–69 years group and all age group women between the years 2001 and 2005. Breast cancer incidence decreased between the years 2001 and 2005 for more than 50 years old and all age group, but not in the younger than 50 years women. The decline of breast cancer incidence started about two years after the HRT decline. Breast cancer incidence decline and decreased HRT utilisation showed a high correlation. A drastic change in age-incidence relationship in breast cancer has taken place, the change is likely to continue and in future it has to be monitored closely with HRT use and other possible explanations.     

Hormone replacement therapy and the risk of breast cancer. Nested case-control study in a cohort of Swedish women attending mammography screening

There is concern that hormone replacement therapy (HRT) increases the risk of breast cancer. We undertook a case-control study of this risk relationship within a cohort of 40- to 74-year-old women in Uppsala County, Sweden, who participated in mammography screening. Incident cases of breast cancer were ascertained during 5 years of follow-up. In all, 435 cases (87% invasive, 13% in situ cancers) were detected, 313 through screening and 122 through clinical diagnosis. As controls, 1,740 women were selected randomly. Information on risk factors and use of HRT was obtained through interviews before the start of follow-up. Multivariate analyses revealed an increased risk among users of any type of HRT for more than 10 years, the odds ratio (OR) being 2.1 (95% confidence interval [CI] 1.1–4.0), as well as when restricting analyses to cases diagnosed through mammography screening. After stratification for compound type, risk estimates were apparently higher among women reporting estradiol–progestin combined treatment vs. estradiol or conjugated estrogens alone, with ORs for more than 10 years of intake being 2.4 (95% CI 0.7–8.6) and 1.3 (95% CI 0.5–3.7), respectively. Analyses through a model including both compound type and length of hormone intake confirmed a significant excess risk linked to treatment for more than 10 years, OR = 2.6 (95% CI 1.3–5.1). Our results indicate a moderately increased risk of breast cancer after many years of HRT and, hypothetically, a further enhancement of the risk with added progestins. Int. J. Cancer 72:758–761, 1997. © 1997 Wiley-Liss, Inc.     

Duration of Hormone Replacement Therapy, Breast Tumour Size and Grade in a Screening Programme

One of the primary adverse effects of long-term use of hormone replacement therapy (HRT) is a modest increase in the risk of breast cancer. Breast tumours that develop in women using HRT have been shown to have prognostically favourable histological features but it is unclear if this is the case for both short- and long-term use. Methods. We evaluated the association between HRT use with tumour size and histologic grade in a cohort of women aged over 55 years (n = 2200) diagnosed with invasive breast cancer at subsequent screen in BreastScreen Victoria (BSV), Australia between 1993 and 2000. BSV biennially screens women aged over 40 years with the target age group 50–69 years. Multiple linear regression was used to examine predictors of log-transformed tumour size and multinomial logistic regression was used to evaluate associations of HRT with tumour grade. Results. Short-term users of HRT (5 years), were approximately 50% less likely to develop poorly-differentiated breast tumours OR 0.48 95%CI (0.28–0.82) or node-positive tumours OR 0.57 95%CI (0.35–0.94) than non-users. Long-term users of HRT (5 years) were also less likely to develop poorly-differentiated tumours OR 0.36 95%CI (0.24–0.56) but were not more likely to be node-positive than women not on HRT. Duration of HRT use was not significantly associated with tumour size. Conclusion. HRT use, regardless of duration, was associated with breast tumours that were better differentiated and not significantly larger than women not on HRT, although only short-term use was associated with fewer node-positive tumours.     

Decline in breast cancer incidence in the Flemish region of Belgium after a decline in hormonal replacement therapy

BackgroundBreast cancer incidence rate in Belgian women was as high as 152.7 for 100 000 in 2003 (adjusted on European population). We made an estimation of the contribution of hormone replacement therapy (HRT) on breast cancer incidence from 1999 to 2005 in women aged 50–69 years in Flanders.MethodsBreast cancer data were extracted from the Belgium Cancer Registry. Drug consumption was computed from drug sales data. The fraction of breast cancers attributable to HRT was calculated by year, using the relative risks of the Million Women Study in the UK.ResultsThe proportion of women aged 50–69 years using HRT in Flanders increased since 1992, peaked at 20% in 2001, then decreased to 8% in 2008. The incidence of breast cancer in 100 000 women aged 50–69 years in Flanders increased from 332.8 in 1999 to 407.9 in 2003, then decreased to 366.1 in 2005; the variations were mostly noticeable for tumors <20 mm in size. The fraction of breast cancers attributed to HRT peaked at 11% in 2001 and decreased afterward.ConclusionThe high level of breast cancer observed in the years 2001–2003 in Flanders can be partly attributed to the use of HRT. Since participation to mammography screening of Flemish women aged 50–69 years was still on the rise in 2003 and never exceeds 62%, the decrease in breast cancer incidence was likely to be due to the decrease in HRT use and not to screening saturation.     

Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing

Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.     

Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project

The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.     

Do younger female breast cancer patients have a poorer prognosis? Results from a population‐based survival analysis

Younger women who develop breast cancer are hypothesized to have poorer survival rates than women who develop it at a later stage in life. Several studies have suggested that differences in biologic characteristics of breast cancer in younger (premenopausal) and older (postmenopausal) women may account for the prognostic variation. This population-based cohort study reports on survival rates of breast cancer in Singapore and examines the hypothesis that younger breast cancer patients have a poorer prognosis. A total of 6,397 breast cancer patients diagnosed from 1968 to 1992 were identified from the population-based cancer registry and followed up through 1997. Outcome measures were relative survival rates (RSRs) calculated using Hakulinen's method and excess hazards ratios (HRs) derived from a regression model based on relative survival. The 2-, 5- and 10-year RSRs were worse among those aged > 75 (65%, 48% and 39%, respectively). The best survival rates were seen among those aged 40-44 (84%, 67% and 56%). Patients younger than 35 years faired reasonably well (79%, 60% and 50%). When the data were stratified according to clinical stage and calendar year, the highest risk of excess deaths was found in women > or = 75 years old. In patients with localized cancer and/or regional metastases, those in the 35-39 age group had the lowest excess risk. In patients with distant metastases, those younger than 35 years of age had the lowest excess risk of death. At the population level, younger women (< 45 years) with breast cancer in Singapore have higher relative survival rates.