Incidence of female breast cancer in relation to prevalence of risk factors in Denmark

The extent to which changes in prevalence of risk determinants for female breast cancer could explain the temporal variation in incidence was examined using incidence figures from Denmark for the years 1943–1989. Significant increases in incidence were observed for more recent time periods and birth cohorts. Using deviance statistics from Poisson regression measures of variability explained, only a small proportion of the increase in incidence could be accounted for by fertility rates, average age at menarche and exposure to exogenous hormones. Dietary factors, on the other hand, accounted for the greater proportion of the variation observed by time period or birth cohort. In particular, there was a strong positive association of incidence with alcohol consumption and a negative association with carbohydrate intake.     

Early life factors in relation to breast cancer risk in postmenopausal women.

We evaluated the role of early life factors in a large, population-based, case-control study of breast cancer risk in postmenopausal women. Case women in Massachusetts, New Hampshire, and Wisconsin were ascertained through state cancer registries; control women were randomly selected from drivers license lists (50-65 years of age) or Medicare beneficiary lists (65-79 years of age). Information concerning factors of interest was obtained through structured telephone interviews. Overall, 83% of eligible cases and 78% of eligible controls participated, and data from more than 2900 women were available for this analysis. We observed a weak J-shaped relationship between birth weight and breast cancer risk; the increased risk was not statistically significant for either the lowest or the highest birth weight. Parental smoking during the pregnancy was not associated with risk of breast cancer in the adult daughter. Breast cancer risk increased significantly with father's education (P = 0.01). Risk also increased with greater age of the mother at the time of the subject's birth (P = 0.04). The subject's birth rank was inversely associated with risk (P = 0.03), as was the number of older sisters (P = 0.03), but the number of older brothers, number of younger siblings, sibship gender ratio, and total sibship size were unrelated to risk. Overall, our results are consistent with previous studies and suggest that these early life factors have a modest influence on breast cancer risk in postmenopausal women.     

Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer

At least four major categories of invasive breast cancer have been reproducibly identified by gene expression profiling: luminal A, luminal B, HER2-type, and basal-like. These subtypes have been shown to differ in their outcome and response to treatment. Whether this heterogeneity reflects the evolution of these subtypes through distinct etiologic pathways has not been clearly defined. We evaluated the association between traditional breast cancer risk factors and risk of previously defined molecular subtypes of breast cancer in the Nurses’ Health Study. This analysis included 2,022 invasive breast cancer cases for whom we were able to obtain archived breast cancer tissue specimens. Tissue microarrays (TMAs) were constructed, and slides were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR). Using immunostain results in combination with histologic grade, cases were grouped into molecularly defined subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed differences in the association between risk factors and subtypes of breast cancer. In general, many reproductive factors were most strongly associated with the luminal A subtype, although these differences were not statistically significant. Weight gain since age 18 showed significant differences in its association with molecular subtypes (P-heterogeneity = 0.05) and was most strongly associated with the luminal B subtype (P-trend 0.001). Although there was not significant heterogeneity for lactation across subtypes, an inverse association was strongest for basal-like tumors (HR = 0.6, 95% CI 0.4–0.8; P-heterogeneity = 0.88). These results support the hypothesis that different subtypes of breast cancer have different etiologies and should not be considered as a single group. Identifying risk factors for less common subtypes such as luminal B, HER2-type and basal-like tumors has important implications for prevention of these more aggressive subtypes.     

Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk

Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross-sectional studies have measured thyroid hormones/autoantibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause-effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of our study was to investigate prediagnostically measured levels of thyroid hormones, thyrotropin (TSH) and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free triiodothyronine (T3), free thyroxin (T4), TSH and thyroid peroxidase autoantibodies (TPO-Ab) levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10-1.77). This association was most pronounced in overweight women (1.51:1.07-2.12). Women with high levels of TPO-Ab had a lower risk of breast cancer, but only the analysis of TPO-Ab as a continuous variable reached statistical significance. Free T4 was in our study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO-Ab had a relatively low risk of breast cancer.     

Reproductive factors and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women

The associations between menstrual and reproductive factors and breast cancer risk in relation to estrogen/progesterone receptor (ER/PgR) status have been unclear in Japanese women. This case‐control study evaluated these associations, overall and separately, by menopausal status. A total of 1092 breast cancer cases and 3160 controls were selected from among female patients aged 30 years and over admitted to a single hospital in Miyagi Prefecture between 1997 and 2009. The receptor status distribution among the cases (missing: 8.4%) was 571 ER+/PgR+, 133 ER+/PgR?, 24 ER?/PgR+ and 271 ER?/PgR?. Menstrual and reproductive factors were assessed using a self‐administered questionnaire. Polytomous logistic regression and tests for heterogeneity across ER+/PgR+ and ER?/PgR? were conducted. Later age at menarche was significantly associated with a decreased risk of both ER+/PgR+ and ER?/PgR? cancer among women overall (P_trend = 0.0016 for ER+/PgR+; P_trend = 0.015 for ER?/PgR?) and among postmenopausal women (P_trend = 0.012 for ER+/PgR+; P_trend = 0.0056 for ER?/PgR?). Nulliparity was associated with an increased risk of ER+/PgR+, but not ER?/PgR? cancer among women overall (P_{heterogeneity} = 0.019) and among postmenopausal women (odds ratio for ER+/PgR+ = 2.56, 95% confidence interval = 1.61–4.07; P_{heterogeneity} = 0.0095). A longer duration of breastfeeding tended to be associated with a decreased risk in all subtypes among women overall. Later age at menarche has a protective effect against both ER+/PgR+ and ER?/PgR? cancer. However, parity might impact differently on various subtypes of breast cancer. Further studies are needed to clarify the etiology of the rare ER+/PgR? and ER?/PgR+ cancer subtypes.     

Histopathologic risk factors for breast cancer in women with benign breast disease

Mammary epithelial hyperplasia indicates an increased likelihood of carcinoma development as it does in other organs. Prospective studies have demonstrated that in the premammography era about 70% of women undergoing surgical biopsy had no increased risk of cancer and have little if any hyperplastic alteration. About 25% of women have well-developed hyperplastic changes and have a risk elevation, controlled for age, of 1.5-2 times that of the general population. Less than 5% of women have atypical hyperplasia demonstrating some histologic features of carcinoma in situ, which indicates a risk elevation of 4-5 times. This is about one half the risk associated with microscopic carcinoma in situ. Therapeutic implications of these premalignant lesions rest predominantly in their indication for the heightened intensity of subsequent breast cancer surveillance and screening.     

Case-control study of risk factors for breast cancer in Nigerian women

This study evaluated the potential risk factors for breast cancer in Nigerian women using a case-control design of 250 women with breast cancer and their age-matched female controls. Both cases and controls were recruited from 4 University Teaching Hospitals in Midwestern and Southeastern Nigeria. Data on the clinical and epidemiological characteristics were collected using interviewer-administered structured questionnaires. The mean age of the cases and controls were 46.1 and 47.1 years, respectively. Fifty-seven percent of the cases were premenopausal while 43% were postmenopausal. The association of risk factors with breast cancer was assessed using conditional logistic regression. Positive family history of breast cancer in first- and second-degree relatives (Odds ratio [OR] = 8.07, 95% confidence interval [CI], 1.003, 64.95, p = 0.04), education of high school level and above (OR = 1.35, 95% CI 1.04, 1.74, p = 0.0205), age at first fullterm pregnancy (FFTP) greater than 20 years (OR = 1.32 95% CI 1.01, 1.71, p = 0.0413) and waist/hip ratio (WHR) (OR = 1.98, 95% CI 1.27, 3.10, p = 0.0026) were associated with increased risk of breast cancer in the final multiple conditional logistic regression model. The findings from this study have shown that sociodemographic characteristics, reproductive variables and anthropometric measures are significant predictors of breast cancer risk in Nigerian women.     

Survival of breast cancer patients in relation to factors which affect the risk of developing breast cancer

In order to evaluate the prognostic significance of risk factors for developing breast cancer, a population-based study was conducted of 2,445 breast cancer patients diagnosed in Denmark, 1983-1984. Data on clinical and pathological characteristics of breast cancer were derived from the Danish Breast Cancer Cooperative Group and data on risk factors from a self-administered questionnaire. Among 1,744 patients (71%) with complete information, survival was determined primarily by size of the tumour, skin invasion, number of positive lymph nodes and grade. No significant association was found between survival and reproductive or hormonal risk factors, dietary variables, alcohol consumption and smoking. Low current body weight and weight loss indicated a poor prognosis, independent of the clinical characteristics of the tumour.     

Metabolic factors and breast cancer risk in Korean women

Purpose

Metabolic factors have been suggested to be associated with breast cancer. However, the findings are inconsistent among studies. We conducted a case–control study in Korean women to evaluate the association between metabolic factors and premenopausal and postmenopausal breast cancer.

Methods

Incident breast cancer cases (270 women) and their controls (540 women) matched by age and menopausal status were recruited from the recipients of a health examination at the same institution. Five relevant factors of metabolic syndrome were evaluated. Odds ratios (OR) and 95 % confidence intervals (CI) for the association were estimated by conditional logistic regression analysis.

Results

Proportions of cases and controls with each factors were 25.6 and 20.6 % for obesity (body mass index ≥ 25 kg/m²), 17.4 and 17.4 % for high fasting glucose (≥5.55 mmol/L or use of hypoglycemic medication), 13.0 and 18.9 % for high triglyceride (≥1.69 mmol/L), 26.3 % and 23.9 % for low high-density lipoprotein cholesterol (<1.29 mmol/L), and 29.6 and 30.6 % for high blood pressure (≥130/or 85 mmHg or use of antihypertensive medication), respectively. Although only the obesity was associated with an increased risk of postmenopausal breast cancer (OR = 2.24; 95 % CI 1.22–4.10) among individual metabolic factors, women with aggregation of three or more metabolic factors as defined by international diabetes federation criteria showed greater risk for postmenopausal breast cancer compared with women without any factor (OR = 2.36; 95 % CI 1.10–5.10).

Conclusions

Although obesity was the only metabolic factor associated with postmenopausal breast cancer, the presence of other metabolic factors may further increase the risk of postmenopausal breast cancer when combined with obesity.     

The relation of breast size to breast cancer risk in postmenopausal women (United States)

Objective: Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change.Methods: The data derive from a population-based case- control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n=2015) were identified through state tumor registries and controls (n=2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women.Results: We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P=0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger).Conclusion: Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women.     

Incidence of breast carcinoma in women with thyroid carcinoma

BACKGROUND: Breast carcinoma and differentiated thyroid carcinoma(the most common endocrine malignancy) occur predominantly in women. An association between the two tumors has been suggested by some investigators, but the potential impact of treatment of one of these diseases on the development of the other remains unclear. The authors examined the relation between the occurrence of these two tumors. METHODS: There were 41,686 patients with breast carcinoma and 3662 with thyroid carcinoma who registered at The University of Texas M. D. Anderson Cancer Center between March 1944 and April 1997. Women who received both diagnoses since 1976 were identified and incidence rates and relative risks of secondary tumor development were calculated. Surveillance, Epidemiology and End Results (SEER) program data on the age-adjusted incidences of these diseases during the same time period were used for the expected incidences in the same population. RESULTS: Among 18,931 women with a diagnosis of breast carcinoma since 1976, 11 developed differentiated thyroid carcinoma > or = 2 years after the diagnosis of breast carcinoma. These breast carcinoma patients contributed 129,336 person-years of follow-up; the observed incidence of thyroid carcinoma in this group was not different from that in a similar age group of women in the SEER database. Among 1013 women with a diagnosis of thyroid carcinoma since 1976, 24 developed breast carcinoma > or = 2 years after the diagnosis of thyroid carcinoma. These thyroid carcinoma patients contributed 8380 person-years of follow-up; the observed incidence of breast carcinoma in women ages 40-49 years was significantly higher than the expected incidence for women in the same age group in the SEER database. CONCLUSIONS: Breast carcinoma developing after thyroid carcinoma was diagnosed more frequently than expected in young adult women seen at the study institution since 1976. This potential association and plausible mechanisms of breast carcinoma development after thyroid carcinoma should be evaluated in larger cohorts of patients.     

Incidence and risk factors for axillary web syndrome after breast cancer surgery

The objective of the study is to estimate the incidence and risk factors of axillary web syndrome (AWS) in early postoperative period (45 days). From the prospective cohort of women undergoing breast cancer surgery, we collected the variables related to patient characteristics, treatment, tumor, and postoperative complications. We performed bivariate and logistic regression. A total of 193 patients are included with a mean age of 58.26 years, majority of which are women who are overweight or obese (72.3%). The incidence of AWS was 28.1%. The presence of pain in the ipsilateral upper-limb associated with AWS was reported in 5.4% of the patients, and the shoulder joint restriction was observed in 11.4%. When controlling for confounding between AWS and the factors that showed statistical significance in bivariate analysis, the variables that explain the occurrence of the AWS were the type of axillary surgery, where women who underwent sentinel lymph node biopsy showed 68% less risk compared with those that underwent axillary lymphadenectomy (AL) (RR = 0.32; 95% CI, 0.13−0.79; P value = 0.014) and numbness in the arm after an injury of the intercostobrachial nerve, which is 3.19 times the risk of the AWS (RR = 3.19; 95% CI, 1.40−7.29, P value = 0.006). From the above findings, we concluded that the incidence of AWS was 28.1%, and it was associated with AL and numbness in the arm after injury of the intercostobrachial nerve.     

Expression of risk factors for breast cancer in women younger than 49

The definition of women younger than 49 who are at increased risk for breast cancer would enable intensified efforts in surveillance and use of preventive measures for this group. In this survey of 32,123 members of Health Net, an increased risk for breast cancer was related to age, breast cancer in the immediate family (mother, sister), and previous biopsies for cystic lesions of the breast. No increased risk was related to menarche, nulliparity, first pregnancy after age 30, or breast feeding.     

Impact of established risk factors for breast cancer in nulligravid Japanese women

BACKGROUND: The mechanism by which pregnancy impacts breast cancer risk remains poorly understood. There is a need for detailed quantification of risk in nulliparous women. We therefore have undertaken a case-referent study of breast cancer employing data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan, examining the impact of reproductive and anthropometric factors on breast cancer risk among nulligravid women compared with their parous counterparts. METHODS: In total, 2032 breast cancer cases were included, and 17848 women, confirmed as free of cancer, were recruited as a reference group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. RESULTS: A protective effect of later age at menarche was observed among parous women, but it did not alter risk in nulligravid cases. The risk increment with a family history appeared to be most pronounced among premenopausal cases with no history of pregnancy (OR=2.68, 95% CI: 1.41-5.11). Among postmenopausal women, positive associations with height and current body mass index (BMI) in the nulligravid group were similar to those observed in the parous group. The present study indicated that age at menopause, family history in premenopausal women, and height and obesity in postmenopausal women seemed to exert more influence in nulligravid women. Formal tests for interaction between maternity status and these factors, however, did not prove statistically significant. CONCLUSION: Our findings suggest that established risk factors for breast cancer have an additive impact with nulligravid status. Thus, it is implied that obesity control for all women, including nulliparous individuals, is important from a practical viewpoint for primary breast cancer prevention.     

Cigarette smoking and other risk factors in relation to p53 expression in breast cancer among young women.

p53 mutations may be a fingerprint for cigarette smoking and other environmental carcinogens, including breast carcinogens. This study was undertaken to explore whether p53 mutations are associated with environmental or other suspected or established risk factors for breast cancer. p53 protein detection by immunohistochemistry (which is more easily quantified in large epidemiological studies than are mutations, and are highly correlated with them) was determined for 378 patients from a case-control study of breast cancer. In this population-based sample of women under the age of 45 years, 44.4% (168/378) of the cases had p53 protein detected by immunohistochemistry (p53+). Polytomous logistic regression was used to calculate the odds ratios (ORs) for p53+ and p53- breast cancer, as compared with the controls, in relation to cigarette smoking and other factors. The ratio of the ORs was used as an indicator of heterogeneity in risk for p53+ versus p53- cancer. The ratio of the ORs in a multivariate model was substantially elevated among women with a greater than high school education [2.39; 95% confidence interval (CI), 1.43-4.00], current cigarette smokers (1.96; 95% CI, 1.10-3.52), and users of electric blankets, water beds, or mattresses (1.78; 95% CI, 1.11-2.86). Nonsignificant heterogeneity was noted for family history of breast cancer and ethnicity but not for other known or suspected risk factors. Coupled with the strong biological plausibility of the association, our data support the hypothesis that in breast cancer, as with other tumors, p53 protein immunohistochemical detection may be associated with exposure to environmental carcinogens such as cigarette smoking.     

Menstrual and reproductive factors in relation to risk of endometrial cancer in Chinese women

Menstrual, reproductive and contraceptive factors have been associated with risk of endometrial cancer in populations where the incidence of this tumor is high. To investigate associations between these factors in a low-risk population with a low prevalence of hormone replacement therapy, we conducted a cohort study among 267,400 women employed in the textile industry in Shanghai, China. Menstrual, reproductive and other factors were ascertained at baseline in 1989–1991, and women were followed for incident endometrial cancer through 31 December 1998 (n = 206). Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Risk of endometrial cancer decreased with increasing age at menarche (p-trend = 0.004). Among menopausal women, risk increased with age at menopause and increasing years of menstruation. Compared to women with one live birth, risk was increased in relation to nulliparity (Hazard ratio = 3.95, 95% CI 1.43–10.86). Risk was decreased with increasing age at first live birth (p-trend = 0.03). There was a decreased risk associated with ever use of an intrauterine device (HR = 0.56, 95% CI 0.35–0.88) and use of oral contraceptives for ≥2 years (HR = 0.50, 95% CI 0.23–1.07). This prospective study confirms findings from previous case–control studies relating menstrual, reproductive, and contraceptive factors and endometrial carcinoma.     

Breast cancer risk factors in relation to breast density (United States)

Objectives Evaluate known breast cancer risk factors in relation to breast density. Methods We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Results Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. Conclusions The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.