Leg length, sitting height and postmenopausal breast cancer risk

Background:

Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height.

Methods:

From the prospective Danish cohort ‘Diet, Cancer and Health'', 23 864 postmenopausal women enrolled during 1993–1997 were followed for a diagnosis of breast cancer in the Danish Cancer Registry through 2009.

Results:

The incidence rate ratios for breast cancer were 1.11 (95% CI=1.06–1.16) for each 5 cm increase in total height and 1.09 (95% CI=1.01–1.17) and 1.14 (95% CI=1.04–1.25) for each 5 cm increase in leg length and sitting height, respectively. There was no statistical significant difference between the associations for leg length and sitting height (P=0.47).

Conclusion:

Leg length does not seem to be more strongly associated with breast cancer among postmenopausal women than sitting height.     

Low-to-moderate alcohol intake and breast cancer risk in Chinese women

Background:

Despite extensive investigation of the association between alcohol consumption and breast cancer risk, effect of low-to-moderate alcohol intake on breast cancer incidence has been inconsistent.

Methods:

A case–control study was conducted in China, 2004–2005 to examine the association by menopausal status, oestrogen (ER) and progesterone receptor (PR) status of the tumour. There were 1009 incident cases with histologically confirmed breast cancer and 1009 age-matched controls recruited. We assessed alcohol consumption by face-to-face interview using a validated questionnaire and obtained tumour ER and PR status from pathology reports.

Results:

Low-to-moderate alcohol consumption was inversely associated with breast cancer risk. Compared with nondrinkers, the adjusted odds ratios (ORs) for alcohol <5 g per day were 0.41 (95% confidence interval 0.27–0.62) and 0.62 (0.48–0.79) in postmenopausal and premenopausal women, respectively. The inverse association was consistent for alcohol <15 g per day across hormone receptor status groups with ORs of 0.36–0.56 in postmenopausal women and 0.57–0.64 in premenopausal women. An exception was that alcohol ⩾15 g per day appeared to increase the risk of breast cancers with discordant receptor status in postmenopausal women, that is, ER+/PR− or ER−/PR+ (4.27, 1.57–11.65).

Conclusion:

We found that low-to-moderate alcohol intake was not associated with increased risk of breast cancer in pre- or postmenopausal Chinese women. Future studies are required to understand differences in effect of alcohol on breast cancers by tumour hormone receptor status.     

Birth intervals and breast cancer risk

Background:

The interval between successive births (birth interval) may affect breast cancer risk, whereas interval from last birth to cancer onset may modify its behaviour.

Methods:

The study cohort consisted of 29 488 Finnish grand multiparous (GM) women, including 628 women with breast cancer. Conditional logistic regression for case–control design nested within the cohort was used to estimate proportional hazards (referred as relative risks, RR). Age at first birth and parity were co-variables.

Results:

Short interval (<1 year) between first and second birth increased the risk of advanced ductal breast cancer at ages < 50 years (RR=5.29; 95% CI 2.00–14.0) as compared to interval 3+ years. The risk of advanced ductal cancer was also large (RR = 4.00; 95% CI 1.19–13.4) shortly (<3 years) after last birth as compared with the period 15+ years.

Conclusions:

Short birth interval-associated excess breast cancer risk may be related to stimulatory effects of female steroid hormones produced during two closely connected pregnancies, or defective breast maturation owing to failures in breastfeeding.     

Joint effects of nulliparity and other breast cancer risk factors

Background:

Pregnancy may reduce breast cancer risk through induction of persistent changes of the mammary gland that make the breast less susceptible to carcinogenic factors. It is not known to what extent the effects of parity are independent of other breast cancer risk factors.

Methods:

In a Norwegian cohort of 58 191 women (2890 breast cancers), we assessed whether the effects of parity on postmenopausal breast cancer risk may be modified by menstrual and anthropometric factors. We calculated attributable proportions due to interaction as a measure of synergism.

Results:

Parity, height, body mass index (BMI), age at menarche and menopause were all associated with breast cancer risk in the expected directions. For BMI, follow-up was stratified into two age groups because of non-proportional hazards. We found that nulliparity and overweight may amplify each other''s effect on breast cancer risk among women after 70 years of age (attributable proportion 0.21, 95% confidence interval 0.04–0.39). There was some indication that parity and age at menopause may antagonise each other''s effect. Effects of parity were largely unaffected by age at menarche and height.

Conclusion:

Nulliparity and overweight may have a synergistic effect on breast cancer risk in elderly women. If confirmed by others, the findings may help disentangle the interplay of different causes of breast cancer.     

Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study

Background:

Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors.

Methods:

Within the Breakthrough Generations Study cohort, we conducted a case–control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus.

Results:

Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89–21.1) for oestradiol and 4.57 (95% CI: 1.75–11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50–69 years and 19.4% at ages 20–79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density.

Conclusions:

Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis.     

Effects of annual vs triennial mammography interval on breast cancer incidence and mortality in ages 40-49 in Finland

Background:

The aim of this study was to evaluate the effects of mammography screening invitation interval on breast cancer mortality in women aged 40–49 years.

Methods:

Since 1987 in Turku, Finland, women aged 40–49 years and born in even calendar years were invited for mammography screening annually and those born in odd years triennially. The female cohorts born during 1945–1955 were followed for up to 10 years for incident breast cancers and thereafter for an additional 3 years for mortality.

Results:

Among 14 765 women free of breast cancer at age 40, there were 207 incident primary invasive breast cancers diagnosed before the age of 50. Of these, 36 women died of breast cancer. The mean follow-up time for cancer incidence was 9.8 years and for mortality 12.8 years. The incidence of breast cancer was similar in the annual and triennial invitation groups (RR: 0.98, 95% confidence interval (CI): 0.75–1.29). Further, there were no significant differences in overall mortality (RR: 1.20, 95% CI: 0.99–1.46) or in incidence-based breast cancer mortality (RR: 1.14, 95% CI: 0.59–1.27) between the annual and triennial invitation groups.

Conclusions:

There were no differences in the incidence of breast cancer or incidence-based breast cancer mortality between the women who were invited for screening annually or triennially.     

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis

Background:

Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause.

Methods:

We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies.

Results:

Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27).

Conclusion:

Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk.     

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

Background:

No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.

Methods:

A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.

Results:

In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day⁻¹, 95% CI: 0.98–1.18, P_trend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, P_trend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, P_trend=0.99).

Conclusions:

There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.     

Hypertensive diseases in pregnancy and breast cancer risk

Background:

Hypertensive diseases in pregnancy may be associated with a reduced risk of breast cancer. Most previous studies are small and have shown conflicting results.

Methods:

In a cohort of 919 712 women who gave their first birth between 1967 and 2008, with linkage of information from two national registries, we assessed whether women with pregnancy hypertensive diseases are at reduced breast cancer risk. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (CI).

Results:

Compared with women with a normotensive first pregnancy, women with hypertension or preeclampsia in their first pregnancy had a reduced breast cancer risk (HR 0.83, 95% CI 0.77, 0.90). A reduced risk was consistently observed for hypertensive disease in any pregnancy, for recurrent hypertensive disease in pregnancy, and before and after 50 years of age at breast cancer diagnosis. The association was strongest for women with hypertension in pregnancy, who delivered at term/post-term (HR 0.81, 95% CI 0.75, 0.88) or had a child of average birth weight (HR 0.77, 95% CI 0.69, 0.85).

Conclusion:

Women with pregnancy hypertensive diseases are at reduced breast cancer risk. Whether this association can be attributed to pregnancy-specific events or to underlying biological traits remains unclear.     

Postmenopausal endometrial cancer risk and body size in early life and middle age: prospective cohort study

Background:

Greater adiposity in early life has been linked to increased endometrial cancer risk in later life, but the extent to which this association is mediated through adiposity in later life is unclear.

Methods:

Among postmenopausal women who had never used menopausal hormone therapies and reported not having had a hysterectomy, adjusted relative risks (RRs) of endometrial cancer were estimated using Cox regression.

Results:

Among 249 791 postmenopausal women with 7.3 years of follow-up on average (1.8 million person-years), endometrial cancer risk (n=1410 cases) was strongly associated with current body mass index (BMI) at baseline (RR=1.87 per 5 kg m⁻² increase in BMI, 95% confidence interval (CI): 1.77–1.96). Compared with women thinner than average at age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09–1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77–1.06). Similarly, compared with women with clothes size 12 or less at age 20, the increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61–2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88–1.22).

Conclusion:

Among women who have never used hormone therapy for menopause, the association between body size in early life and endometrial cancer risk in postmenopausal women can be largely explained by women''s current BMI.     

Breast cancer awareness and barriers to symptomatic presentation among women from different ethnic groups in East London

Background:

During 2001 to 2005, 1-year breast cancer survival was low in ethnically diverse East London. We hypothesised that this was due to low breast cancer awareness and barriers to symptomatic presentation, leading to late stage at diagnosis in women from ethnic minorities. We examined ethnic differences in breast cancer awareness and barriers to symptomatic presentation in East London.

Methods:

We carried out a population-based survey of 1515 women aged 30+ using the Cancer Research UK Breast Cancer Awareness Measure. We analysed the data using logistic regression adjusting for age group and level of deprivation.

Results:

South Asian and black women had lower breast cancer awareness than white women. South Asian women, but not black women, reported more emotional barriers to seeking medical help than white women. White women were more likely than non-white women to report worry about wasting the doctor''s time as a barrier to symptomatic presentation.

Conclusion:

Interventions to promote early presentation of breast cancer for South Asian and black women should promote knowledge of symptoms and skills to detect changes, and tackle emotional barriers to symptomatic presentation and for white women tackle the idea that going to the doctor to discuss a breast symptom will waste the doctor''s time.     

Age of onset in familial breast cancer as background data for medical surveillance

Background:

Familial breast cancers are known to be of early onset. This article provides differences in the age of onset of breast cancer and death by breast cancer between women with and without a family history.

Methods:

The Swedish Family-Cancer Database was used to estimate the cumulative risk of breast cancer and death by breast cancer according to family history with a stratified Cox model. Family history was defined separately for affected mother or sister considering their diagnostic ages.

Results:

The age to reach the same cumulative incidence as women without family history decreased with decreasing diagnostic age of the affected relative. Women with a maternal history reached the risk of women lacking a family history at the age of 50 years between 12.3 (mother affected <40 years) and 3.3 years (mother affected >82 years) earlier. The trend for breast cancer mortality was essentially similar.

Conclusions:

Women with mother or sister affected by breast cancer are diagnosed and die at earlier ages than do women without family history. The differences depend on the diagnostic age of the affected relative. The present data may provide a rationale to derive recommendations for the starting age of screening in women with affected family members.     

Loss of partner and breast cancer prognosis - a population-based study, Denmark, 1994-2010

Background:

The extent to which experiencing a stressful life event influences breast cancer prognosis remains unknown, as the findings of the few previous epidemiological studies are inconsistent. This large population-based study examines the association between a common major life event, loss of a partner and breast cancer recurrence and all-cause mortality.

Methods:

N=21 213 women diagnosed with a first primary breast cancer 1994–2006, who had a cohabiting partner in the 4 years before their breast cancer diagnosis, were followed for death and recurrence in population-based registers and clinical databases. Information on education, disposable income, comorbidity and prognostic risk factors were included in Cox regression analyses.

Results:

Women who had lost a partner either before diagnosis or in subsequent years were not at significantly higher risk of recurrence or dying than women who had not lost a partner.

Conclusion:

Our results do not support the concern that experiencing a stressful life event, the loss of a partner, negatively affects prognosis of breast cancer.     

A promoting early presentation intervention increases breast cancer awareness in older women after 2 years: a randomised controlled trial

Background:

We have developed the Promoting Early Presentation (PEP) Intervention to equip older women with the knowledge, skills, confidence and motivation to present promptly with breast symptoms, and thereby improve survival from breast cancer. The PEP Intervention consists of a 10-min interaction between a radiographer and an older woman, supported by a booklet. Our previous report showed that at 1 year, the PEP intervention increased the proportion who were breast cancer aware compared with usual care.

Methods:

We randomised 867 women aged 67–70 years attending for their final routine appointment on the National Health Service Breast Screening Programme to receive the PEP Intervention, a booklet alone or usual care. The primary outcome was breast cancer awareness measured using a validated questionnaire asking about knowledge of breast cancer symptoms, knowledge that the risk of breast cancer increases with age and breast checking behaviour.

Results:

At 2 years, the PEP Intervention increased the proportion who were breast cancer aware compared with usual care (21 vs 6% odds ratio 8.1, 95% confidence interval 2.7–25.0).

Conclusions:

The uniquely large and sustained effect of the PEP Intervention on breast cancer awareness increases the likelihood that a woman will present promptly should she develop breast cancer symptoms up to many years later.     

Increasingly strong reduction in breast cancer mortality due to screening

Background:

Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008.

Methods:

In Nijmegen, the Netherlands, 55 529 women received an invitation for screening between 1975 and 2008. We designed a case–referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50–69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women.

Results:

The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49–0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975–1991 (OR=0.72; 95% CI=0.47–1.09) to 65% in the period 1992–2008 (OR=0.35; 95% CI=0.19–0.64).

Conclusion:

Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening.     

Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Purpose:

The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk.

Patients and methods:

Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

Results:

Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8% P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36% P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30–0.76; P=0.002).

Conclusion:

The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.     

Adolescent endogenous sex hormones and breast density in early adulthood

Introduction

During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer.

Methods

Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV.

Results

Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all P_trend ≤0.03) but not when measured in postmenarche samples (all P_trend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all P_trend ≥0.16).

Conclusions

Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown.

Clinical trials registration

ClinicalTrials.gov Identifier, {"type":"clinical-trial","attrs":{"text":"NCT00458588","term_id":"NCT00458588"}}NCT00458588 April 9, 2007; {"type":"clinical-trial","attrs":{"text":"NCT00000459","term_id":"NCT00000459"}}NCT00000459 October 27, 1999     

Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT study of Norway

Background:

Adult weight gain is associated with increased risk of postmenopausal breast cancer. Most previous studies are limited by using recalled or self-reported data, and it is not known if age-specific weight changes are important for breast cancer risk.

Methods:

In a Norwegian cohort of 28 153 women (and 900 incident breast cancers) with longitudinal anthropometric measurements over up to 30 years, we studied both overall and age-related weight changes in adulthood and risk of postmenopausal breast cancer.

Results:

Overall, weight gain in adulthood was associated with increased breast cancer risk (hazard ratio (HR) per kg per year 1.31, 95% confidence interval (CI) 1.11–1.54). Weight gain before (HR per kg per year 1.38, 95% CI 1.09–1.75) or around menopause (1.69, 95% CI 1.32–2.16) was associated with increased risk, but there was no clear risk increase associated with later weight gain (HR per kg per year 0.92, 95% CI 0.73–1.18).

Conclusion:

Weight gain in adulthood was associated with increased risk of breast cancer. Our results suggest that weight gain before and around menopausal age may be particularly important for breast cancer risk among postmenopausal women.     

Adiposity, adult weight change and breast cancer risk in postmenopausal Japanese women: the Miyagi Cohort Study

Background:

The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women.

Methods:

A total of 10 106 postmenopausal women aged 40–64 years (the Miyagi Cohort) were followed from 1990 to 2003, and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years.

Results:

Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05).

Conclusion:

Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk.     

Population-based mammography screening below age 50: balancing radiation-induced vs prevented breast cancer deaths

Introduction:

Exposure to ionizing radiation at mammography screening may cause breast cancer. Because the radiation risk increases with lower exposure age, advancing the lower age limit may affect the balance between screening benefits and risks. The present study explores the benefit–risk ratio of screening before age 50.

Methods:

The benefits of biennial mammography screening, starting at various ages between 40 and 50, and continuing up to age 74 were examined using micro-simulation. In contrast with previous studies that commonly used excess relative risk models, we assessed the radiation risks using the latest BEIR-VII excess absolute rate exposure-risk model.

Results:

The estimated radiation risk is lower than previously assessed. At a mean glandular dose of 1.3 mGy per view that was recently measured in the Netherlands, biennial mammography screening between age 50 and 74 was predicted to induce 1.6 breast cancer deaths per 100 000 women aged 0–100 (range 1.3–6.3 extra deaths at a glandular dose of 1–5 mGy per view), against 1121 avoided deaths in this population. Advancing the lower age limit for screening to include women aged 40–74 was predicted to induce 3.7 breast cancer deaths per 100 000 women aged 0–100 (range 2.9–14.4) at biennial screening, but would also prevent 1302 deaths.

Conclusion:

The benefits of mammography screening between age 40 and 74 were predicted to outweigh the radiation risks.