Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer.

PURPOSE: The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women. We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center. PATIENTS AND METHODS: We analyzed data after a median follow-up of 14.6 years (IQ range, 12.3-16.3 years) from 1739 women aged 30-70 (872 in the fenretinide arm and 867 in the observation arm), representing 60% of the initial cohort of 2867 women. The main efficacy endpoint was second primary breast cancer (contralateral or ipsilateral). RESULTS: The number of second breast cancers was 168 in the fenretinide arm and 190 in the control arm (hazard ratio = 0.83, 95% CI, 0.67-1.03). There were 83 events in the fenretinide arm and 126 in the observation arm in premenopausal women (HR = 0.62, 95% CI, 0.46-0.83), and 85 and 64 events in postmenopausal women (HR = 1.23, 95% CI, 0.63-2.40). The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023). There was no difference in cancers in other organs, distant metastases or survival. CONCLUSIONS: Fenretinide induces a significant risk reduction of second breast cancer in premenopausal women, which is remarkable at younger ages, and persists several years after treatment cessation. Since adverse events are limited, a trial in young women at high-risk is warranted.     

Relationships between plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3 and second breast cancer risk in a prevention trial of fenretinide.

PURPOSE: High circulating insulin-like growth factor (IGF) -I and/or low IGF-binding protein (IGFBP) -3 levels are associated with increased breast cancer risk in unaffected premenopausal women. We determined whether IGF-I and IGFBP-3 predict second breast cancer risk, and whether their changes during fenretinide explain observed reductions in second breast cancer in women 相似文献   

Long-term effects of fenretinide, a retinoic acid derivative, on the insulin-like growth factor system in women with early breast cancer.

High insulin-like growth factor-I (IGF-I) levels are associated with an increased risk of breast cancer in premenopausal women. Because the synthetic retinoid fenretinide showed a beneficial effect on second breast cancers in premenopausal women in a Phase III trial, we studied its long-term effects on IGF-I levels. We measured, at yearly intervals for up to 5 years, the circulating levels of IGF-I, IGF binding protein (BP)-3, and their molar ratio in 60 subjects < or = 50 years of age and 60 subjects > 50 years of age allocated either to fenretinide or no treatment. In women < or = 50 years of age, measurements of IGF-II, IGFBP-1, and IGFBP-2 were also performed. The associations between biomarkers and drug or metabolite plasma concentrations were also investigated. All biomarkers were relatively stable over 5 years in the control group. Compared with controls and after adjustment for baseline, treatment with fenretinide for 1 year induced the following changes: IGF-I, -13% [95% confidence interval (CI), -25 to 1%] in women < or = 50 years of age and -3% (95% CI, -16 to 13%) in women > 50 years of age; IGFBP-3, -4% (95% CI, -12 to 6%) in both age groups; IGF-I:IGFBP-3 molar ratio, -11% (95% CI, -22 to 1%) in women < or = 50 years of age and 1% (95% CI, -11 to 16%) in women > 50 years of age. These effects were apparently maintained for up to 5 years, although fewer samples were available as time progressed. No change in other IGF components was observed. Drug and metabolite concentrations were negatively correlated with IGF-I and IGF-I:IGFBP-3 molar ratio in women < or = 50 years of age. Fenretinide induces a moderate decline of IGF-I levels in women < or = 50 years of age. The association between IGF-I change and the reduction of second breast cancers in premenopausal women warrants further study.     

Obesity and outcomes in premenopausal and postmenopausal breast cancer.

PURPOSE: Obesity is associated with adverse outcomes in postmenopausal women with breast cancer. In premenopausal women, the association is less clear. METHODS: A population-based sample of 1,360 Australian women with breast cancer before the age of 60 years, 47% diagnosed before age 40, and 74% premenopausal, was studied prospectively for a median of 5 years (range, 0.2-10.8 years). Obesity was defined as a body mass index of > or =30 kg/m2. The hazard ratio (HR) for adverse clinical outcome associated with obesity was estimated using Cox proportional hazard survival models. RESULTS: Obesity increased with age (P < 0.001) and was associated with increased breast cancer recurrence (P = 0.02) and death (P = 0.06), larger tumors (P = 0.002), and more involved axillary nodes (P = 0.003) but not with hormone receptor status (P > or = 0.6) or with first cycle adjuvant chemotherapy dose reductions (P = 0.1). Adjusting for number of axillary nodes, age at diagnosis, tumor size, grade, and hormone receptor status, obese women of all ages were more likely than nonobese women to have disease recurrence [HR, 1.57; 95% confidence interval (95% CI), 1.11-2.22; P = 0.02] and to die from any cause during follow-up (HR, 1.56; 95% CI, 1.01-2.40; P = 0.05). In premenopausal women, the adjusted HRs were 1.50 (95% CI, 1.00-2.26; P = 0.06) and 1.71 (95% CI, 1.05-2.77; P = 0.04), respectively. CONCLUSIONS: Obesity is independently associated with poorer outcomes in premenopausal women, as it is in postmenopausal women, and this is not entirely explained by differences in tumor size or nodal status. Given the high and increasing prevalence of obesity in western countries, more research on improving the treatment of obese breast cancer patients is warranted.     

The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status

Soy food intake has previously been associated with reduced breast cancer risk. Epidemiological evidence for subgroups of breast cancer, particularly by menopausal and hormone receptor status, is less consistent. To evaluate the role of hormone receptor and menopausal status on the association between soy food intake and breast cancer risk, we measured usual soy food intake in adolescence and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40–70 years, recruited to the Shanghai Women's Health Study (1996–2000). After a median follow‐up of 13.2 years (range: 0.01–15.0), 1,034 incident breast cancer cases were identified. Using Cox models, we found that adult soy intake was inversely associated with breast cancer risk [hazard ratio (HR) for fifth versus first quintile soy protein intake = 0.78; 95% confidence interval (CI):0.63–0.97]. The association was predominantly seen in premenopausal women (HR = 0.46; 95% CI:0.29‐0.74). Analyses further stratified by hormone receptor status showed that adult soy intake was associated with significantly decreased risk of estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer in postmenopausal women (HR = 0.72; 95% CI:0.53–0.96) and decreased risk of ER?/PR? breast cancer in premenopausal women (HR = 0.46; 95% CI:0.22–0.97). The soy association did not vary by human epidermal growth factor‐2 (HER2) status. Furthermore, we found that high soy intake during adulthood and adolescence was associated with reduced premenopausal breast cancer risk (HR = 0.53; 95% CI: 0.32–0.88; comparing third vs. first tertile) while high adulthood soy intake was associated with postmenopausal breast cancer only when adolescent intake was low (HR = 0.63; 95% CI: 0.43–0.91). Our study suggests that hormonal status, menopausal status and time window of exposure are important factors influencing the soy‐breast cancer association.     

Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole

BackgroundMA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen.Patients and methodsExploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis.ResultsAt diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13–0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51–0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03–0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22–0.94; P = 0.03).ConclusionsExtended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.     

Soybean products and reduction of breast cancer risk: a case-control study in Japan

Components of the Japanese diet, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Since soybean products are widely consumed in Japan, a case-control study taking account of the menopausal status was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 167 breast cancer cases were included and 854 women confirmed as free of cancer were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. There were reductions in risk of breast cancer associated with high intake of soybean products among premenopausal women. Compared with women in the lowest tertile, the adjusted ORs for top tertile intake of tofu (soybean curd) was 0.49 (95% CI, 0.25-0.95). A significant decrease in premenopausal breast cancer risk was also observed for increasing consumption of isoflavones (OR=0.44; 95% CI, 0.22-0.89 for highest vs lowest tertile; P for trend=0.02). The present study found a statistically inverse association between tofu or isoflavone intake and risk of breast cancer in Japanese premenopausal women, while no statistically significant association was evident with the risk among postmenopausal women.     

A two-by-two factorial trial comparing oral with transdermal estrogen therapy and fenretinide with placebo on breast cancer biomarkers.

PURPOSE: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo. EXPERIMENTAL DESIGN: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 microg/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided. RESULTS: After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P < 0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39). CONCLUSIONS: Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies.     

Menstrual cycle characteristics and incidence of premenopausal breast cancer.

BACKGROUND: Epidemiologic studies have indicated that menstrual cycle characteristics such as age at menarche and age at menopause are associated with breast cancer risk. Anovulation, which is more common with long or irregular cycles, has been hypothesized to reduce the incidence of breast cancer. METHODS: We analyzed data from the Nurses' Health Study II, a cohort of 116,671 female registered nurses ages 25 to 42 years at baseline. Information on menstrual cycle characteristics was assessed in 1989 and 1993, and incident cases of premenopausal breast cancer were ascertained through 2001. RESULTS: During 1,135,496 person-years of follow-up (1989-2001), 1,163 incident cases of invasive premenopausal breast cancer were diagnosed. Overall, women with long menstrual cycles at ages 18 to 22 years (>32 days or too irregular to estimate) did not experience a significantly lower breast cancer risk compared with women with normal cycle lengths (26-31 days) at that age [covariate-adjusted hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.79-1.06]. Among women ages <40 years, those with menstrual cycles lasting >32 days or too irregular to estimate at ages 18 to 22 years had a decreased incidence of breast cancer (covariate-adjusted HR, 0.71; 95% CI, 0.53-0.97). Current menstrual cycle characteristics were not associated with breast cancer incidence. CONCLUSION: Overall, longer or irregular cycles at ages 18 to 22 years or in early adulthood were not associated with reduced premenopausal breast cancer risk. However, longer menstrual cycles at ages 18 to 22 years were associated with a lower incidence of premenopausal breast cancer before age 40.     

Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.     

Weight gain prior to diagnosis and survival from breast cancer.

BACKGROUND: To examine the effects of prediagnostic obesity and weight gain throughout the life course on survival after a breast cancer diagnosis, we conducted a follow-up study among a population-based sample of women diagnosed with first, primary invasive, and in situ breast cancer between 1996 and 1997 (n = 1,508). METHODS: In-person interviews were conducted shortly after diagnosis to obtain information on height and weight at each decade of life from age 20 years until 1 year before diagnosis. Patients were followed to determine all-cause (n = 196) and breast cancer-specific (n = 127) mortality through December 31, 2002. RESULTS: In multivariate Cox proportional hazards models, obese women had increased mortality due to breast cancer compared with ideal weight women among those who were premenopausal at diagnosis [hazard ratio (HR), 2.85; 95% confidence interval (95% CI), 1.30-6.23] and postmenopausal at diagnosis (HR, 1.91; 95% CI, 1.06-3.46). Among women diagnosed with premenopausal breast cancer, those who gained >16 kg between age 20 years and 1 year before diagnosis, compared with those whose weight remained stable (+/-3 kg), had more than a 2-fold elevation in all-cause (HR, 2.45; 95% CI, 0.96-6.27) and breast cancer-specific mortality (HR, 2.09; 95% CI, 0.80-5.48). Women diagnosed with postmenopausal breast cancer who gained more than 12.7 kg after age of 50 years up to the year before diagnosis had a 2- to 3-fold increased risk of death due to all-causes (HR, 2.69; 95% CI, 1.63-4.43) and breast cancer (HR, 2.95; 95% CI, 1.36-6.43). CONCLUSIONS: These results indicate that high levels of prediagnostic weight and substantial weight gain throughout life can decrease survival in premenopausal and postmenopausal breast cancer patients.     

Mammographic density and estrogen receptor status of breast cancer.

BACKGROUND: The density of breast tissue on a mammogram is a strong predictor of breast cancer risk and may reflect cumulative estrogen effect on breast tissue. Endogenous and exogenous estrogen exposure increases the risk of estrogen receptor (ER)-positive breast cancer. We determined if mammographic density is associated more strongly with ER-positive breast cancer than with ER-negative breast cancer.METHODS: We analyzed data from 44,811 participants in the San Francisco Mammography Registry of whom 701 developed invasive breast cancer. Mammographic density was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fat, 2 = scattered fibroglandular, 3 = heterogeneously dense, 4 = extremely dense). We tested for associations between mammographic density and ER-positive and ER-negative breast cancer separately. Analyses were adjusted for age, body mass index, postmenopausal hormone use, family history of breast cancer, menopausal status, parity, and race/ethnicity.RESULTS: Mammographic density was strongly associated with both ER-positive and ER-negative breast cancers. Compared with women with BI-RADS 2, women with BI-RADS 1 (lowest density) had a lower risk of ER-positive cancer [adjusted hazard ratio (HR), 0.28; 95% confidence interval (95% CI), 0.16-0.50] and ER-negative cancer (adjusted HR, 0.17; 95% CI, 0.04-0.70). Women with BI-RADS 4 (highest density) had an increased risk of ER-positive breast cancer (adjusted HR, 2.21; 95% CI, 1.64-3.04) and an increased risk of ER-negative breast cancer (adjusted HR, 2.21; 95% CI, 1.16-4.18).CONCLUSION: Surprisingly, women with high mammographic density have an increased risk of both ER-positive and ER-negative breast cancers. The association between mammographic density and breast cancer may be due to factors besides estrogen exposure.     

Contralateral Breast Cancer: a Clinico-pathological Study of Second Primaries in Opposite Breasts after Treatment of Breast Malignancy

Background: Breast cancer is by far the most frequent cancer of women (23 % of all cancers), ranking secondoverall when both sexes are considered together. Contralateral breast cancer (CBC) is becoming an importantpublic health issue because of the increased incidence of primary breast cancer and improved survival. The presentcommunication concerns a study to evaluate the role of various clinico-pathological factors on the occurrenceof contralateral breast cancer. Materials and Methods: A detailed analysis was carried out with respect to age,menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status,and use of chemotherapy or hormonal therapy. The diagnosis of CBC was confirmed on histopathology report.Relative risk with 95%CI was calculated for different risk factors of contralateral breast cancer development.Results: CBC was found in 24 (4.5%) out of 532 patients. Mean age of presentation was 43.2 years. Family historyof breast cancer was found in 37.5% of the patients. There was statistically significant higher rate (83.3%) ofCBC in patients in age group of 20-40 years with RR=11.3 (95% CI: 1.4, 89.4, p=0.006) seen in 20-30 years andRR=10.8 (95% CI:1.5-79.6, p=0.002) in 30-40 years as compared to older age of 60-70 years. Risk of developmentwas higher in premenopausal women (RR=8.6, 95% CI: 3.5-21.3, p≤0.001). Women with family history ofbreast cancer had highest rate (20.9%) of CBC (RR=5.4, 95% CI: 2.5-11.6, p≤0.001). Use of hormonal therapyin hormone receptor positive patients was protective factor in occurrence of CBC but not significant (RR=0.7,95% CI: 0.3-1.5, p=0.333). Conclusions: Younger age, premenopausal status, and presence of family history werefound to be significant risk factors for the development of CBC. Use of hormonal therapy in hormone receptorpositive patients might be protective against occurrence of CBC but did not reach significance.     

Influence of education level on breast cancer risk and survival in Sweden between 1990 and 2004

On account of limited recent data regarding the role of education in breast cancer risk and prognosis, we conducted this study to assess the association between education level and in situ and invasive breast cancer risk and invasive breast cancer survival, using the 2006 update of the Swedish Family-Cancer Database. Cox's proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) adjusted for age, time-period, parity, age at first birth, county of residence, and family history of breast cancer. Compared to women completing less than 9 years of education, university graduates were more likely to be diagnosed with in situ (HR = 1.44, 95% CI: 1.28-1.63) and invasive (HR = 1.28, 95% CI: 1.20-1.36) breast cancer, and the lack of homogeneity between these two HRs was statistically significant, p = 0.007. Further stratification revealed that the lack of homogeneity was greatest for breast cancers diagnosed before age 50. Compared to women completing less than 9 years of education, university graduates were associated with the highest survival following a breast cancer diagnosis (lowest fatality hazard ratio), HR = 0.68, 95% CI: 0.61-0.75. Further research is warranted to elucidate possible behaviors or characteristics associated with education that could explain the differences in incidence and survival, such as compliance with cancer screening.     

Meat consumption and risk of breast cancer in the UK Women's Cohort Study

We performed a survival analysis to assess the effect of meat consumption and meat type on the risk of breast cancer in the UK Women's Cohort Study. Between 1995 and 1998 a cohort of 35 372 women was recruited, aged between 35 and 69 years with a wide range of dietary intakes, assessed by a 217-item food frequency questionnaire. Hazard ratios (HRs) were estimated using Cox regression adjusted for known confounders. High consumption of total meat compared with none was associated with premenopausal breast cancer, HR=1.20 (95% CI: 0.86-1.68), and high non-processed meat intake compared with none, HR=1.20 (95% CI: 0.86-1.68). Larger effect sizes were found in postmenopausal women for all meat types, with significant associations with total, processed and red meat consumption. Processed meat showed the strongest HR=1.64 (95% CI: 1.14-2.37) for high consumption compared with none. Women, both pre- and postmenopausal, who consumed the most meat had the highest risk of breast cancer.     

Circulating hormones and breast cancer risk in premenopausal women: a randomized trial of low-dose tamoxifen and fenretinide

Tamoxifen and fenretinide have been extensively studied and exhibit breast cancer-preventing activity. We aimed to assess their effect on sex hormones, sex hormone binding globulin (SHBG) and retinol, and their association with mammographic density (MD) and breast cancer events. In a double-blind, placebo-controlled trial, premenopausal women at risk for breast cancer were randomized to tamoxifen 5 mg/day, fenretinide, both agents, or placebo for 2 years. We measured MD and circulating concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, testosterone, androstenedione, dehydro-epiandrosteronesulfate, prolactin, SHBG, and retinol at baseline and on yearly intervals. The associations with breast cancer events were evaluated through competing risk and Cox regression survival models. Low-dose tamoxifen markedly and enduringly increased SHBG, whereas the increases in testosterone, estradiol, and prolactin and reduction in LH weakened after 1 year. Fenretinide increased testosterone and androstenedione and decreased retinol. MD correlated directly with SHBG and inversely with retinol. After a median follow-up of 12 years, the 10-year cumulative incidence of breast cancer events was 37 % in women with SHBG ≤ 59.3 nmol/L, 22 % in women with SHBG between 59.3 and 101 nmol/L, and 19 % in women with SHBG > 101 nmol/L (P = 0.018). The difference among SHBG tertiles remained statistically significant at multivariable analysis: HR = 2.26 (95 % CI 1.04, 4.89) for the lowest versus the highest tertile. We conclude that low-dose tamoxifen or fenretinide exhibits favorable hormonal profiles as single agents, further supporting their administration for prevention of breast cancer in premenopause. Notably, SHBG levels were inversely associated with breast neoplastic events.     

Weight and weight changes in early adulthood and later breast cancer risk

Obesity is a well‐established cause of postmenopausal breast cancer. However, early life adiposity is inversely associated with breast cancer incidence. To understand these conflicting relations, we use validated measures to assess adiposity in childhood and late adolescence, as well as weight change, in relation to total invasive breast cancer incidence and receptor subtypes. We conducted a prospective observational study among 74,177 women from the Nurses’ Health Study from 1980–2012, with updated risk factors every 2 years during which 4,965 incident invasive breast cancers occurred. Overall, weight at age 18 was inversely associated with both premenopausal (HR per 30 kg = 0.52, 95% CI = 0.39–0.71) and postmenopausal (HR per 30 kg = 0.81, 95% CI = 0.72–0.92) breast cancer which was largely explained by adiposity at age 10. Long‐term weight gain from age 18 both during premenopause and postmenopause were positively associated with postmenopausal breast cancer risk. However, premenopausal weight gain was not related to premenopausal breast cancer risk. Furthermore, weight gain since age 18 was positively associated with ER+/PR+ postmenopausal breast cancer (HR per 30 kg = 1.50, 95% CI = 1.36–1.65) but not ER+/PR? (HR per 30 kg = 0.96, 95% CI = 0.78–1.19) or ER?/PR? (HR per 30 kg = 1.16, 95% CI = 0.95–1.42) postmenopausal breast cancer. Overall, 17% of ER+/PR+ postmenopausal breast cancer and 14% of total postmenopausal breast cancer are attributable to weight gain of > 5 kg since age 18.     

A prospective study of breast size and premenopausal breast cancer incidence

Studies of the association between breast size, as a proxy for mammary gland mass, and breast cancer risk have given equivocal results. Most have been case-control studies with limited statistical power. We conducted a prospective analysis of the relation between breast size as measured by self-reported bra cup size and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. Bra cup size at age 20 was assessed among 89,268 premenopausal women aged 29-47 in 1993. Subsequent incident cases of invasive breast cancer were assessed until 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model adjusting for potential confounders and risk factors for breast cancer. During 622,732 person-years of follow-up, 803 premenopausal women were newly diagnosed with invasive breast cancer. For women with a BMI below 25 kg/m2, those with a bra cup size of "D or larger" had a significantly higher incidence of breast cancer than women who reported "A or smaller" (covariate adjusted HR=1.80; 95% CI 1.13-2.88; ptrend=0.01). There was no significant association among women with a BMI of 25 kg/m2 or higher. Stratifying by BMI at age 18 at a cutoff point of 21 kg/m2 gave similar results. Larger bra cup size at a young age is associated with a higher incidence of premenopausal breast cancer, though this association is limited to leaner women.     

Longitudinal study of birthweight and the incidence of breast cancer in adulthood

A high birthweight has been associated with an increased risk of breast cancer later in life. The role of adult variables, possible effect modifiers and cancer characteristics has been little studied. We explored these in two large prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II). We collected information on birthweight from 152,608 female nurses participating in NHS and NHS II. During 10 years and 1.3 million person-years of follow-up, invasive breast cancer was newly diagnosed among 828 premenopausal and 2312 postmenopausal women. Data were analyzed using a Cox proportional hazards model. Premenopausal women with a birthweight of <5.5 lbs had a covariate-adjusted hazard ratio (HR) for breast cancer of 0.66 [95% confidence interval (CI) 0.47-0.93] compared with women born at 8.5 lbs or above. Adult height was the only factor explaining some of the association between birthweight and breast cancer incidence; after adjustment for height the HR was 0.73 (95% CI 0.51-1.03). The association between birthweight and the incidence of breast cancer was stronger among women with estrogen-receptor positive and progesterone-receptor positive breast cancer. Among postmenopausal women, no important association between the birthweight and the incidence of breast cancer was detected (HR comparing women with a birthweight of 5.5 lbs or less with women with a birthweight>8.5 lbs: 0.97; 95% CI 0.80-1.16). In these two large prospective cohorts, a low birthweight was associated with a decreased incidence of breast cancer among premenopausal women. This association was independent of other factors operating later in life, except for adult height.     

Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

PURPOSE: To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer. PATIENTS AND METHODS: Patients included 491 women with stage I or stage 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: The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v 相似文献