Qualitative age interactions in breast cancer studies: a mini-review

A qualitative age interaction is defined as the reversal of relative risks or rates according to age at onset, and is often evident in studies that examine the etiology, prognosis and treatment of breast cancer. For example, incidence rates (or risks) are higher for aggressive when compared with indolent breast cancers prior to age 40-50 years, after which rates are higher for indolent tumors. Nulliparity and obesity decrease breast cancer risk in younger women, but increase risk in older women. Curves depicting the annual hazard of breast cancer death are shaped differently for the early- and late-onset tumors. Clinical trials for mammography screening, fenretinide chemoprevention and neo-adjuvant chemotherapy show opposite effects in younger and older women. Finally, high-risk/early onset breast cancers are more common among African-American women than Caucasian women, and this may partly account for the racial survival disparities. Taken together, these examples imply that aging may modify breast cancer risk, prognosis and treatment. These qualitative age interactions (or effect modifications) are important because they suggest that high-risk/early-onset and low-risk/late-onset breast cancers are different diseases, derived from different carcinogenic pathways. When age interactions are suspected, breast cancer studies should be stratified by early versus late age of onset or analyzed age specifically.     

New criteria for selecting elderly patients for breast cancer adjuvant treatment studies

About 50% of breast cancers occur in women aged 65 years and older, and both the incidence and prevalence of breast cancer among older women are expected to increase in the future. Aging implies a reduction in life expectancy and tolerance to treatments that should be considered in elderly patients with early breast cancer. In fact, treatment options often carry short-term risks and toxicities that might be tempered by long-term survival gains. The choice of adjuvant treatment for elderly patients should be based on the same criteria that are currently used for younger patients: endocrine responsiveness and assessment of risk of relapse. Adjuvant endocrine therapy should be considered for women with endocrine-responsive disease, regardless of age. The value of adjuvant chemotherapy is controversial. Older women are frequently undertreated with adjuvant chemotherapy and are underrepresented in clinical trials. In particular, no convincing data are available on the role of adjuvant chemotherapy in endocrine nonresponsive tumors, partly because most of the time these tumors represent a relatively small subset in adjuvant studies focusing on the elderly population. Several phase III trials are currently ongoing in elderly patients with early breast cancer to evaluate different options of adjuvant treatments. Only one trial, coordinated by the International Breast Cancer Study Group, is investigating the role of adjuvant chemotherapy for postmenopausal women of advanced age with endocrine nonresponsive early breast cancer. Disclosure of potential conflicts of interest is found at the end of this article.     

A prospective study of body size and breast cancer in black women.

The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of >/=25 relative to <20 was associated with a reduced risk of breast cancer among both premenopausal women (IRR, 0.68; 95% confidence interval, 0.46-0.98) and postmenopausal women (IRR, 0.53; 95% confidence interval, 0.35-0.81). There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer, either overall or among never-users of hormone therapy. Weight gain was not associated with postmenopausal breast cancer risk. In analyses restricted to breast cancers that were estrogen and progesterone receptor positive, IRRs for current BMI and weight gain were elevated but not statistically significant. The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women. Understanding the reasons for the association may help elucidate the pathways through which adolescent exposures influence breast cancer risk. The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women.     

Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study

The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women (40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women.     

Effect of age at first childbirth on risk of developing specific histologic subtype of breast cancer

Epidemiologic variables related to breast cancer risk were assessed in a case-control study of 332 women with breast carcinoma and 1353 comparison women. Risk factors for breast cancer as a whole included nulliparity, late age at first childbirth, early age at menarche, late age at menopause, personal history of benign breast disease, family history of breast cancer, and among postmenopausal women, body weight. These risk factors were then analyzed with respect to histologic subtype of breast cancer involved, i.e., duct-derived or lobular tumors, to determine whether the association between any of the risk factors and breast cancer varied according to histopathologic subtype. Histologic subtype for the 316 cases reviewed included 284 duct cancers and 32 lobular carcinomas. Although slight differences were noted among some of the risk factors and the variety of cancer, none of the differences was marked except for the variable age at birth birth. For ductal carcinoma, the risk was highest among nulliparous women and decreased the younger a woman was at the time she gave birth to her first child. The risk of infiltrating lobular carcinoma, however, was lowest among nulliparous females or those who had given birth at a young age and increased the older a woman was when she gave birth to her first child.     

Breast cancer in black American women

A case-control study of breast cancer among Black American women was conducted in seven hospitals in New York City from 1969 to 1975. Results are reported for 127 cases and 317 controls. Compared to women with a first birth before age 19, those with a first birth after 25 had a relative incidence rate for breast cancer of 3.8 and 2.2 for the pre- and postmenopausal age-groups, respectively. Compared to nulliparous women, parous women had a relative incidence rate of 0.6 for premenopausal and 0.7 for postmenopausal women. The incidence rate of breast cancer for women with a menopause after age 49 was estimated to be 3.1 times that of women with a menopause before age 45. Thus, the known risk factors for breast cancer among Whites are also related to the etiology of the disease among Blacks. The incidence rate of breast cancer has increased among younger Blacks since 1947 and is now similar to that among younger Whites. However, among older women, the incidence rate is still appreciably higher for Whites. The most likely explanation of this pattern is that Black women born since about 1925 are being exposed at the same frequency as White women to the causes of breast cancer.     

Cancer and age

Age is the greatest risk factor for the development of cancer. For etiologic purposes, newly diagnosed cases of cancer among a defined population during a specified time (incidence) is the usual way of depicting cancer as it relates to age. Exposure to carcinogens in utero or perinatally can produce cancers soon after birth or years later. Cancers in older children have been related to growth factors and/or a single exposure to high doses of radiation. Hodgkin's disease occurring among young adults is different histologically, clinically, and prognostically than Hodgkin's disease among older adults. For the disease among young adults, the hypothesis is that clinical disease reflects the rare consequences of a prevalent infection of low pathogenicity; age of infection is determined by socioeconomic status. In older adults, it more closely resembles the lymphomas. This suggests dynamic trends associated with changing social environments related to etiologic factors. Among adults, the steady increase in colon cancer among both genders represents constant exposure to a carcinogen(s) starting in early life and persisting throughout older ages. Breast cancer is divided into pre- and postmenopausal phases on the basis of its age distribution. International differences in postmenopausal breast cancer suggest environmental factors in postmenopausal women and genetic and hormonal factors in premenopausal women. The age distribution of lung cancer increases linearly with the amount of cigarettes smoked and there is no indication of a threshold below which cigarette smoke is safe. The downturn among the oldest age groups results from competing causes of death or reflects a cohort effect of different exposure over time. Further, the pattern of lung cancer suggests exposure to a carcinogenic agent including substances that act principally as promoters.     

Dual effect of parity on breast cancer risk in African-American women

BACKGROUND: In the United States, breast cancer incidence is higher among African-American women than among white women before age 45 but lower at older ages. To explore whether differences in childbearing patterns can explain this observation, we assessed the relation of several childbearing variables to breast cancer risk in a large prospective cohort study of U.S. African-American women. METHODS: Black Women's Health Study participants were enrolled in 1995 and were followed by mailed questionnaires every 2 years (in 1997 and 1999). Of the 64,500 women enrolled, 56,725 (88%) completed at least one of the follow-up questionnaires. During 214,862 person-years of follow-up, participants reported 349 breast cancers, of which 128 were among women younger than 45 years and 221 were among women aged 45-70 years. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were derived from age-stratified Cox regression models that adjusted for each of the childbearing variables (parity, age at first birth, and time since last birth). RESULTS: Compared with primiparity, high parity was associated with an increased risk of breast cancer among women younger than 45 years (IRR for four or more births = 2.4, 95% CI = 1.1 to 5.1) and a decreased risk among women aged 45 years and older (IRR = 0.5, 95% CI = 0.3 to 0.9). The IRR for late age at first birth compared with early age was 2.5 (95% CI = 1.1 to 5.8) among the younger women and was not elevated among older women. We found no statistically significant association of time since last birth with breast cancer risk among either younger or older women. CONCLUSIONS: Parity has a dual association with breast cancer risk in African-American women; among women younger than 45 years, parity is associated with an increased risk and among women 45 years and older it is associated with a decreased risk. This dual effect may explain some of the observed differences in breast cancer incidence rates among African-American and white women.     

Age- and time-dependent changes in cancer incidence among immigrants to Sweden: colorectal, lung, breast and prostate cancers

To examine the role of gender, age at immigration and length of stay on incidence trends of common cancers, we studied risk of colorectal, lung, breast and prostate cancers in immigrants to Sweden from 1958 to 2008. The nationwide Swedish Family-Cancer Database was used to calculate standardized incidence ratios for common cancers among immigrants compared to Swedes. Immigrants were classified into "high-risk" countries when their risk was increased, into "low-risk" when their risk was decreased and into "other" when their risk was nonsignificant. Among those who immigrated at younger age (<30 years), we found an increasing trend for colorectal cancer risk in low-risk men and high-risk women. Among those who immigrated at older age (≥ 30 years), a decreasing lung cancer risk in high-risk men and an increasing breast cancer risk in low-risk women were observed. The increasing trend of prostate cancer risk was independent of age at immigration. The risk trends for "other" immigrants were between the risks of low- and high-risk countries. The gender-specific shifts in cancer risks in immigrants toward the risk in natives indicate a major role of sex, age at immigration and environmental exposures in colorectal and lung cancers risks. In contrast, the unchanged trend of breast cancer among those who immigrated at younger ages and an increasing trend for those who migrated at older ages may suggest a limited effect for environmental exposures, especially at younger age. Our study points out a role of age at immigration on the risk trend of cancer.     

Genetic implications of bilateral breast cancer: a population based cohort study

BACKGROUND: Women with breast cancer are at high risk of bilateral breast cancer. We aimed to assess the incidence of bilateral breast cancer in relation to age and time since diagnosis of first cancer. METHODS: We analysed a population-based cohort of 123757 women with a first primary breast cancer diagnosed in Sweden from 1970 to 2000 for frequency of bilateral breast cancers and deaths by means of record linkage. Second primary breast cancers were categorised as synchronous bilateral breast cancers if diagnosed within 3 months of the first primary cancer or as metachronous if diagnosed more than 3 months after diagnosis of first primary cancer. FINDINGS: We identified 6550 women who had developed bilateral breast cancer. Age-incidence patterns of synchronous and unilateral breast cancer were similar, although the absolute rates of synchronous bilateral cancer were 50-100 times lower than those of unilateral cancer. A woman aged 80 years or older is at least twice as likely to be diagnosed with synchronous bilateral breast cancer than is a woman younger than 40 years. In the first 20 years after diagnosis of primary breast cancer, incidence of metachronous bilateral cancer decreased from about 800 per 10(5) person-years to 400 per 10(5) person-years in patients diagnosed with primary breast cancer before the age of 45 years, whereas incidence remained at 500-600 per 10(5) person-years in those age 45 years or older at diagnosis. After 30 years' follow-up, cumulative risk of metachronous bilateral breast cancer was about 15% irrespective of age at first primary breast cancer. INTERPRETATION: The higher than expected risk of synchronous bilateral breast cancer could be explained by non-genetic factors. By contrast, incidence of metachronous bilateral cancer fits neither a model of highly penetrant genes nor aggregation of environmental risk factors.     

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.     

Ovarian volume: determinants and associations with cancer among postmenopausal women.

Clinical studies have reported associations between ovarian stromal hyperplasia and the diagnosis of hormonally related tumors such as endometrial cancer. To assess the hypothesis that characteristics of benign ovaries among postmenopausal women are related to risk for breast, endometrial, and colon cancer, we analyzed systematically collected transvaginal ultrasound data for participants enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Among women without cancer, median ovarian volume declined with age from 1.25 cm3 for women between ages 55 and 59 years to 1.0 cm3 for those between ages 65 and 69 years. African American and Caucasian women had larger median ovarian volumes than Asians. Larger ovarian volume was also associated with the highest quartiles of height and weight and ever having smoked. After adjusting for race, age, parity, body mass, smoking, and hormone use, women with median ovarian volumes >or=3.0 cm3 were at increased risk for breast cancer [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.11-1.70], endometrial cancer (OR, 1.97; 95% CI, 1.12-3.48), and colon cancer (OR, 2.00; 95% CI, 1.25-3.21). Significant trends of risk with increasing volume were found only for breast and endometrial cancers. We conclude that large ovaries among postmenopausal women may represent a marker of risk for hormonally related tumors. Confirmation of these findings in future studies, including analyses of serum hormone levels and tissues, may provide insights into hormonal carcinogenesis among older women.     

Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study

Background

Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women.

Methods

We examined relationships among 190,872 postmenopausal women, ages 50–71 years recruited during 1995–1996 for the NIH-AARP Diet and Health Study, in whom 7,384 incident invasive breast carcinomas were identified through 2006. Multivariable Cox regression hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated for breast cancer risk factors by age (50–59, 60–69, ≥70 years).

Results

The only factor showing significant statistical heterogeneity by age (p _het = 0.001) was menopausal hormone therapy duration, but trends were apparent across all ages and the strongest association prevailed among women 60–69 years. Although other risk factors did not show statistically significant heterogeneity by age, we did observe attenuated relations for parity and late age at first birth among older women [e.g., HR for age at first birth ≥30 vs. 20–24 = 1.62 (95 % CI 1.23–2.14) for women 50–59 years vs. 1.12 (0.96–1.31) for ≥70 years]. In contrast, risk estimates associated with alcohol consumption and BMI tended to be slightly stronger among the oldest subjects [e.g., HR for BMI ≥35 vs. 18.5–24.9 = 1.24 (95 % CI 0.97–1.58) for 50–59 years vs. 1.46 (1.26–1.70) for ≥70 years]. These differences were somewhat more pronounced for estrogen receptor positive and ductal cancers, tumors predominating among older women. Breast cancer family history, physical activity, and previous breast biopsies did not show divergent associations by age.

Conclusion

Although breast cancer risk factor differences among older women were not large, they may merit further consideration with respect to individualized risk prediction.     

Qualitative age-interactions in breast cancer: a tale of two diseases?

A qualitative age-interaction is defined as the reversal of relative risks or rates according to age at onset. Once thought rare, qualitative age-interactions are commonly reported in studies that examine the etiology, prognosis, and treatment of breast cancer. Thus, nulliparity, obesity, and oral contraceptives decrease breast cancer risk in younger women but increase risk in older women. High-risk tumors are more common in younger women, whereas low-risk tumors are more common among the elderly, with bimodal peak frequencies at ages 50 and 70, respectively. Curves depicting the annual hazard of breast cancer death for women with high-risk (early-onset) and low-risk (late-onset) tumors are shaped differently and move in opposite directions. Additionally, mammography screening and neo-adjuvant chemotherapy seem to have opposing effects in women with early and late-onset tumors. Taken together, these qualitative age-interactions may indicate that early and late-onset breast cancers are different diseases, derived from different pathways.     

Continued Breast Cancer Risk Reduction in Postmenopausal Women Treated with Raloxifene: 4-Year Results from the MORE Trial

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60mg/day, and 2,572 raloxifene 120mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.     

Qualitative age interactions (or effect modification) suggest different cancer pathways for early-onset and late-onset breast cancers

Background Prior to 1999–2000, breast cancer incidence rates had risen for decades, though more among older than younger women. Materials and methods To further explore the impact of advancing age-at-diagnosis upon breast cancer incidence, we used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program (1974–2003). Results Over time, we observed age interactions by tumor grade, stage, and race. For example, among women ages <40 years, high-grade lesions were more common than low-grade tumors for all time periods. Among women ages 40+ years, high-grade lesions were more common during early time periods then trend lines crossed, after which low-grade tumors were more common than high-grade lesions. Notably, the transition (crossover point) occurred earlier with advancing age-at-diagnosis. Conclusion The reversal (crossing) of incidence rates from high to low-grade tumors among women 40+ years is a qualitative age interaction, probably due to changing age-related risk factor and/or screening patterns, where mammography preferentially detected tumors of low malignant potential among older women. Though once thought to be rare or artifactual, qualitative age interactions suggest breast cancer heterogeneity. Indeed, if real, qualitative age interactions (effect modifications) imply different etiologic pathways for early-onset and late-onset types of breast cancer.     

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer

PURPOSE: To compare the efficacy, in regard to time to progression (TTP) and objective response rate (ORR), of letrozole (Femara; Novartis Pharma AG; Basel Switzerland), an oral aromatase inhibitor, with that of tamoxifen (Tamofen; Leiras OY; Turku, Finland) as first-line therapy in younger (<70 years) and older (>/=70 years) postmenopausal women with advanced breast cancer. MATERIALS AND METHODS: Nine hundred seven patients with advanced breast cancer were randomly assigned to receive 2.5 mg letrozole (n = 453) or 20 mg tamoxifen (n = 454) once daily in a double-blind, multicenter, international trial. Among the prospectively planned analyses were analyses of TTP and ORR by age (<70 and >/=70 years). The results of these prospectively planned analyses are reported here. RESULTS: Letrozole was as effective in older postmenopausal women (>/=70 years of age) as it was in younger postmenopausal women (<70 years of age). The overall ORR in the older subgroup was significantly higher in patients treated with letrozole (38%) than in patients treated with tamoxifen (18%). In the younger subgroup of postmenopausal patients, the ORRs were not significantly different (letrozole, 26%; tamoxifen, 22%). TTP was significantly longer for letrozole than for tamoxifen in both age groups (younger: letrozole median TTP, 8.8 months; tamoxifen, 6.0 months; older: letrozole median TTP, 12.2 months; tamoxifen, 5.8 months). Although age was independently prognostic of TTP, there was no significant effect of age on ORR in the presence of other factors. CONCLUSION: The data show that letrozole, 2.5 mg once daily, is as effective in older, postmenopausal women as it is in younger postmenopausal women with advanced breast cancer. In addition, letrozole was more effective than tamoxifen in both younger and older patients.     

Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States

Objectives: The purpose of the study was to describe the associations between height and body mass index (BMI) (wt/ht2) and breast cancer incidence and survival among female residents of Hawaii. Methods: The study sample is a randomly-selected, multi-ethnic cohort of 17,628 women. A total of 378 incident breast cancer cases were identified via linkage to the Hawaii Tumor Registry over an average follow-up period of 14.9 years. Using age 50 as a cut-point, 86 were considered premenopausal cases, and 292 were postmenopausal. Proportional hazards analysis was used to describe the risks associated with height and BMI, after adjustment for age, education, race/ ethnicity, and drinking status. For mortality analyses, there were 34 breast cancer deaths among the 365 breast cancer cases for which staging information was available. Results: The risk of postmenopausal breast cancer was found to increase progressively across approximate tertiles of the distribution of height (P = 0.02 for trend test), with a significantly excess risk among women in the tallest tertile (risk ratio [RR] = 1.5, 95 percent confidence interval [CI] = 1.1-2.1). Baseline levels of BMI were related positively to breast cancer incidence among postmenopausal women, after control for the above covariates (P = 0.01 for trend test). Among postmenopausal women in the highest quintile of the BMI distribution, the RR was 1.5 (CI = 1.0-2.3, P = 0.04). Further analyses indicated the association between BMI and postmenopausal breast cancer incidence was strongest among women aged 65 years and older. After statistical control for the above covariates and stage of disease, pre-morbid levels of BMI were significantly predictive of death from breast cancer, with an approximate nine percent increase in risk per unit increase in BMI (P = 0.01). Compared with women in the lowest two quartiles, the RR among the heaviest women was 2.2 (CI = 0.9-5.4, P = 0.08). Height was not associated with risk of breast cancer mortality. Conclusions: Relative weight may be an important modifiable risk factor for both breast cancer incidence and prognosis. The association between height and breast cancer incidence is more difficult to interpret, but may underscore the importance of early life exposures in the development of breast cancer.     

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

Breast cancer-specific mortality is static in older women despite having fallen in younger age groups, possibly due to lack of screening and differences in treatment. This study compared stage and treatment between two cohorts of postmenopausal women (55-69 vs >70 years) in a single cancer network over 6 months. A total of 378 patients were studied (>70: N=167, 55-69 years: N=210). Older women presented with more advanced disease (>70: metastatic/locally advanced 12%, 55-69 years: 3%, P<0.01). Those with operable cancer had a worse prognosis (Nottingham Prognostic Index (NPI) >70: median NPI 4.4, 55-69 years: 4.25, P<0.03). These stage differences were partially explained by higher screening rates in the younger cohort. Primary endocrine therapy was used in 42% of older patients compared with 3% in the younger group (P<0.001). Older women with cancers suitable for breast conservation were more likely to choose mastectomy (>70: 57.5% mastectomy rate vs 55-69 years: 20.6%, P<0.01). Nodal surgery was less frequent in older patients (>70: 6.7% no nodal surgery, 55-69 years: 0.5%, P<0.01) and was more likely to be inadequate (>70: 10.7% <4 nodes excised, 55-69 years: 3.4%, P<0.02). In summary, older women presented with more advanced breast cancer, than younger postmenopausal women and were treated less comprehensively.