Effect of family history,obesity and exercise on breast cancer risk among postmenopausal women

We examined effects of obesity and lifetime exercise patterns on postmenopausal breast cancer risk according to family history in a large population-based case control study conducted in Los Angeles County, California, because we hypothesized that both factors would affect risk through similar mechanistic pathways, and that their effects would be stronger among women with a family history. We studied 1883 postmenopausal breast cancer case subjects and 1628 postmenopausal control subjects ranging in age from 55-72 years. Cases were diagnosed with incident breast cancer in the late 1980s and 1990s. Controls were individually matched to case subjects on age, ethnic origin and neighborhood. In-person interviews determined known breast cancer risk factors including: height, weight, lifetime exercise, and family history of breast and other cancers. Breast cancer risk was raised among women who had at least 1 first-degree relative with breast cancer (odds ratio [OR] = 1.68; 95% confidence interval [CI] = 1.36-2.08). Risk increased with increasing levels of body-mass index (wt-kg/ht-m(2)) (p-trend = 0.005). Breast cancer risk was reduced among women who maintained, on average, 17.6 metabolic equivalent of energy expenditure (MET)-hr of activity/week from menarche onward (OR = 0.66; 95% CI = 0.48-0.90). Body-mass index, adjusted for lifetime exercise, was strongly associated with breast cancer risk among women with a positive family history of breast cancer (p-trend < 0.0001), but only weakly associated among women with no family history (p-trend = 0.08; homogeneity of trends p = 0.0005). In contrast, the risk reduction associated with exercise activity, adjusting for body-mass index, was limited to women without a family history of breast cancer (p-trend = 0.001; homogeneity of trends p = 0.005). Body-mass index and exercise activity, both modifiable risk factors for breast cancer, seem to have differential effects depending on a woman's family history of breast cancer, and may impact risk through different biological mechanisms.     

A case-control interview study of breast cancer among Japanese A-bomb survivors. I. Main effects

Women with breast cancer (cases=196) and without the disease (controls=566), selected from the Life Span Study sample of A-bomb survivors and nonexposed residents of Hiroshima and Nagasaki, Japan, and matched on age at the time of the bombings, city, and estimated radiation dose, were interviewed about reproductive and medical history. A primary purpose of the study was to identify strong breast cancer risk factors that could be investigated further for possible interactions with radiation dose. As expected, age at first full-term pregnancy was strongly and positively related to risk. Inverse associations were observed with number of births and total, cumulative period of breast feeding, even after adjustment for age at first full-term pregnancy. Histories of treatment for dysmenorrhea and for uterine or ovarian surgery were associated positively and significantly with risk at ages 55 or older, a finding that requires additional study. Other factors related to risk at older ages were the Quetelet index (weight [kg]/height [cm]²) at age 50, history of thyroid disease, and hypertension. Neither age at menarche nor age at menopause was associated significantly with risk. Subjects appeared to be poorly informed about history of breast cancer or other cancer in themselves or in their close relatives; this finding suggests that innovative strategies may be required when studying familial cancer patterns in Japanese populations.The Radiation Effects Research Foundation (RERF, formerly the Atomic Bomb Casualty Commission) was established in April 1975 as a private nonprofit Japanese Foundation, supported equally by the Government of Japan through the Ministry of Health and Welfare, and the Government of the United States through the National Academy of Sciences under contract with the Department of Energy. The present work was performed as part of a collaboration between RERF and the US National Cancer Institute.     

The effect of dietary fat on breast cancer survival among Caucasian and Japanese women in Hawaii

182 Japanese and 161 Caucasian breast cancer patients participated in an epidemiologic case-control study from 1975–1980. They were subsequently followed until the end of 1987 to determine their survival status. Among the Japanese, patients with regional or distant disease had a relative risk (RR) of death of 13.0 (95% Confidence Interval (CI), 4.3–39.1) compared to those within situ or localized disease, and obese patients had a RR of death of 3.5 (95% CI, 1.3–10.0) compared to non-obese subjects. Among the Caucasians, patients with advanced disease had a RR of death of 4.3 (95% CI, 1.8–10.5) compared to those within situ or localized disease, and patients with a high fat intake had a RR of 3.2 (95% CI, 1.2–8.6) compared to subjects with a low fat intake. Menopausal status (pre- or postmenopausal) and replacement estrogen use were not related to survival from breast cancer in either ethnic group. When Japanese and Caucasian patients were compared with each other, there was no significant difference in survival between them.     

A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose

Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the hombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor—age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births—conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early agefollowing exposure may be protective against radiation-related risk.The Radiation Effects Research Foundation (formerly the Atomic Bomb Casualty Commission) was established in April 1975 as a private nonprofit Japanese Foundation, supported equally by the Government of Japan through the Ministry of Health and Welfare, and the Government of the United States through the National Academy of Sciences under contract with the Department of Energy. The present work was performed as part of a collaboration between RERF and the US National Cancer Institute.     

Accuracy of breast screening among women with and without a family history of breast and/or ovarian cancer

SummaryObjectives To compare interval cancer rates, sensitivity and specificity of breast cancer screening between women with moderate or strong family history and women without a family history.Methods From 1996 to 1997, 115,460 women aged 50 to 69 screened by the Ontario Breast Screening Program, offering eligible women screening with mammography and clinical breast examination, were examined. Women were followed for up to 12 months after their screening examination. Family history definitions were based on the number of affected first degree relatives and their ages at diagnosis. Multivariate analysis was conducted to adjust for potential confounding variables.Results Interval cancer rates increased across family history groups and were greatest in women with a strong family history. The rate ratio (RR) for interval cancer rate in women with a strong family history compared to women without a family history approached significance (RR=2.28, 95% confidence interval (CI) 0.97–5.34), while for women with a moderate family history it did not (RR=1.37, 95% CI 0.62–3.04). A slightly but not significantly lower sensitivity was observed in women with a strong family history compared to women without a family history. There was little variation in specificity across family history groups.Conclusions Screening was able to detect a large proportion of invasive breast cancers in women with a family history, indicating their potential to benefit from regular breast cancer screening. However, due to increased interval cancer rates, screening with one-year intervals may be important even in an older population of women with a family history.     

Reproductive factors and family history of breast cancer in relation to plasma prolactin levels in premenopausal and postmenopausal women

Many reproductive factors are associated with breast cancer risk, potentially through a hormonal pathway. The peptide hormone prolactin is essential in mammary development and lactation and may be a link between risk factors and breast cancer. While higher prolactin levels are associated with increased breast cancer risk, few determinants of prolactin levels are known. We conducted a cross-sectional analysis among 1,089 premenopausal and 1,311 postmenopausal women within the Nurses' Health Study (NHS) and the NHS II to examine the associations of reproductive factors, benign breast disease and family history of breast cancer with plasma prolactin levels. Parous women had significantly lower prolactin levels than nulliparous women (parous vs. nulliparous multivariate-adjusted geometric means = 14.1 ng/mL vs. 16.6 ng/mL, p<0.001 for premenopausal and 9.1 vs. 10.1, p=0.04 for postmenopausal women), although levels did not decrease with increasing number of children for either premenopausal (p-trend = 0.23) or postmenopausal (p-trend = 0.07) parous women. Age at first birth was not associated with prolactin levels. The reduction in prolactin levels among parous premenopausal women appeared to attenuate with increasing time since first birth, but the trend was not statistically significant (p-trend = 0.12). Age at menarche, duration of lactation and benign breast disease were not associated with prolactin levels. Family history of breast cancer was associated with significantly higher prolactin levels when compared with no family history among premenopausal (15.9 ng/mL vs. 14.3 ng/mL, p=0.04) but not postmenopausal (p=0.73) women. In conclusion, the associations of parity and family history with breast cancer risk may be mediated, at least in part, by prolactin levels.     

Increased risk of pancreatic,thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.     

Correlations between family history and cancer characteristics in 2256 breast cancer patients

A comparison of 692 early invasive breast cancer with, and 1564 without, a family history of breast cancer showed that the former were younger at diagnosis (P=0.002), had smaller tumours (P=0.012), were more frequently oestrogen receptor positive (P=0.006) and diagnosed preclinically (P<0.001).     

Risk factors for breast cancer in Turkish women: a hospital-based case-control study

The aim of this study was to investigate the association between risk factors and breast cancer in Turkish women. In a hospital-based case-control study in Istanbul, 405 patients with histologically confirmed breast cancer were compared with 1050 controls, who were admitted to different departments of the same hospital. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor were obtained from logistic regression analyses. Risk factors for breast cancer were found to be early menarche age (OR 3.87, 95% CI 2.46-6.08), use of alcohol (OR 3.87, 95% CI 1.79-8.37), history of diabetes (OR 3.31, 95% CI 2.36-4.64) or hypertension (OR 3.44, 95% CI 2.07-5.71), oral contraceptive use (OR 1.98, 95% CI 1.38-2.85) and hormone replacement therapy (HRT) use (OR 1.94, 95% CI 1.15-3.29). The findings of the present study indicated that history of diabetes or hypertension, use of alcohol, oral contraceptive and HRT, never having breastfed and delayed age at first birth associated with changing of lifestyle led to an increased risk of breast cancer in Turkish women.     

Young women with family history of breast cancer and their risk factors for benign breast disease

BACKGROUND:

Breast cancer (BC) patients wonder how their daughters might reduce their risk. The authors investigated childhood/adolescent risk factors for benign breast disease (BBD), a well‐documented risk factor for BC, among girls with a family history.

METHODS:

GUTS (the Growing Up Today Study) includes females, aged 9 to 15 years in 1996, who completed annual questionnaires during 1996 to 2001, then in 2003, 2005, and 2007. Participants provided information regarding alcohol, menarche, height, and body mass index (BMI; kg/m²). Peak height growth velocity (PHV; in./y) was estimated from longitudinal heights. On 2005‐2007 surveys, 6888 women (18‐27 years old) reported whether they were diagnosed with biopsy‐confirmed BBD (n = 67 cases); 6741 women (noncases) reported no BBD. Participants' mothers reported their own biopsy‐confirmed BBD and BC, and BC in their sisters and mothers. Stratified by family history, logistic models investigated BBD risk factors.

RESULTS:

Young women whose mothers or aunts had BC were more likely to be diagnosed with BBD (odds ratio [OR], 2.34; P = .01), as were those with maternal BBD (OR, 1.59; P = .095). Adolescents with BC family history (mother, aunt, grandmother) who consumed alcohol (7 drinks/wk) doubled their BBD risk (OR, 2.28; P = .01), similar to those with maternal BBD (OR, 1.96; P = .02). Girls whose mother or aunt had BC saw their BBD risk elevated with higher PHV (OR, 1.82 [inch/yr]; P = .05). Among girls with no family history, BBD risk appeared to be related to other factors: childhood BMI, adolescent waist circumference, and adult height.

CONCLUSIONS:

Adolescents with family history may reduce their risk by avoiding alcohol. Separate risk factors were observed among girls with family history versus girls with no family history, possibly reflecting different causes of BC. Cancer 2011;. © 2011 American Cancer Society.     

Diagnosed with breast cancer while on a family history screening programme: an exploratory qualitative study

Mammographic screening is offered to many women under 50 in the UK who are at moderate or high risk of developing breast cancer because of their family history of the disease. Little is understood about the impact of screening on the emotional well-being of women with a family history of breast cancer. This qualitative study explores the value that women at increased risk placed on screening, both pre- and post-cancer diagnosis and the impact of the diagnosis. In-depth interviews were undertaken with 12 women, aged 35–50, diagnosed with breast cancer while on an annual mammographic screening programme. Women described the strong sense of reassurance gained from screening prior to diagnosis. This faith in screening was reinforced by early detection of their cancer. Reactions to diagnosis ranged from devastation to relief at having finally developed a long-expected condition. Despite their positive attitudes about screening, not all women wanted to continue with surveillance. For some, prophylactic mastectomy was preferable, to reduce future cancer risk and to alleviate anxieties about the detection of another cancer at each subsequent screen. This study illustrates the positive yet diverse attitudes towards mammographic screening in this group of women with a family history of breast cancer.     

雌激素受体表达与癌家族史阳性乳腺癌的关系

目的　为了探讨癌家族史阳性乳腺癌妇女ER水平是否高于非癌家族性乳腺癌者。方法　采用莹光组织化学法检测了本院 1985～ 1998年间 430例妇女可手术乳腺癌的新鲜组织ER水平 ,对其中癌家族史阳性乳腺癌ER与非癌家族性乳腺癌ER水平进行比较分析。结果　在 430例乳腺癌组织总的ER阳性率为 5 0 .2 % (2 16 / 430 ) ,其中绝经期前、后ER阳性率分别为 46 .3 % (6 8/ 14 7)和 5 0 .7% (10 7/ 2 11)。癌家族史阳性乳腺癌ER阳性率为 5 5 .1% (2 7/ 49) ;家族性乳腺癌ER阳性率为 72 .2 % (8/ 11) ;非癌家族性乳腺癌ER阳性率为 49.6 % (189/ 381)。结论　癌家族史阳性乳腺癌ER和家族性乳腺癌ER水平分别与非癌家族性乳腺癌ER相比 ,各呈明显增高倾向 ,但经统计学处理P >0 .0 5 ,认为无显著差异。本组乳腺癌病人中至少半数病例属于雌激素受体依赖性肿瘤 ,而且绝经期后水平略高于绝经期前者。     

A cohort study of reproductive factors and family history of breast cancer in southern Sweden

Background. Studies have been contradictory regarding the hypothesis that reproductive risk factors of breast cancer as parity and age at first full-term pregnancy (AFFP) operate differently in women with and without a family history of breast cancer. Methods. The overall tumour incidence and breast cancer incidence related to fertility factors were followed in a population based cohort of 29,508 women aged 25–65 when interviewed between 1990 and 1992 in south Sweden. At the end of the follow up in December 1999, the cohort constituted 226,611 person years. The risk of breast cancer in relation to reproductive factors were studied in women with at least one first degree relative with breast cancer and compared with women without a family history. Findings. A total of 1145 malignant tumours were seen and 1166.6 were expected (SIR = 0.98, 95% CI = 0.93–1.04). Slightly more breast cancer cases were seen 434 than expected 387.69 (SIR = 1.12, 95% CI = 1.02–1.23). A family history of breast cancer among a first degree relative was present in 1615 women. Forty-five breast cancers were seen among these women while 24.27 was expectecd (SIR = 1.85, 95% CI = 1.35–2.48). Nulliparous women with a family history of breast cancer had a higher risk of breast cancer, SIR = 1.76, 95% CI = 0.64–3.82, compared with nulliparous women without a family history, SIR = 1.13, 95% CI 0.99–1.29. Similarly women with parity 1–2 with a family history had a higher SIR = 1.81, 95% CI = 1.16–2.69 compared with women without a family history having 1–2 children, SIR = 1.13, 95% CI = 0.99–1.29. In women with 3 children those with a family history continued to have a high SIR = 1.98, 95% CI = 1.11–3.27 compared with women without a family history SIR = 0.90, 95% CI = 0.73–1.09. An early full-term pregnancy was protective in both groups. A higher risk than nulliparous women were seen after age 25 in the family history group and after age 30 in the sporadic cancer group. Interpretation. Women with a first degree family history of breast cancer do not experience the same protection from a high number of pregnancies as women without a family history. However, an early first full-term pregnancy seems to offer a substantial protection in the family history group if undertaken before age 20. This suggest that reproductive factors tend to operate differently in the two groups of women.     

Disparities in cancer screening in individuals with a family history of breast or colorectal cancer

BACKGROUND:

Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population‐based survey.

METHODS:

By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years.

RESULTS:

The authors found no significant BC screening disparities by race/ethnicity or income in the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino‐white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino‐white difference in CRC screening (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11‐0.60) was more substantial than that for individuals with no family history (OR, 0.74; 95% CI, 0.59‐0.92).

CONCLUSIONS:

Knowledge of their family history widened the Latino‐white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino‐white screening disparity in Latinos most susceptible to CRC. Cancer 2011;. © 2011 American Cancer Society.     

A comparison of reproductive risk factors for CIS lesions and invasive breast cancer

A differential effect of reproductive factors on the incidence of carcinoma in situ of the breast (CIS) and invasive cancer may indicate that hormonal factors related to reproductive history not only influence the initial steps towards breast cancer but also preinvasive malignant lesions. A comparison of reproductive factors was performed using a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1983 and 1998, 15,590 cases of invasive breast cancer and 871 cases of CIS were identified using a database with extensive clinical information. Number of births and age at first birth were similarly associated with the risk of being diagnosed with ductal carcinoma in situ (DCIS) compared to invasive breast cancer [RR(DCIS)(per birth)/RR(invasive)(per birth) = 1.03(0.93-1.14), RR(DCIS)(per 5yr) /RR(invasive)(per 5yr) = 1.06(0.96-1.17)]. Also, the short-term risk the first 10 years after birth was similar for DCIS and invasive cancer [RR(DCIS) /RR(invasive) = 0.90 (0.74-1.09)]. Additional analyses were performed according to characteristics of the DCIS lesion (size, malignancy grade, noncomedo or comedo type). In conclusion, our observations do not support the theory that reproductive history is associated with progression from noninvasive to invasive breast cancer.     

A case-control study on the dietary intake of mushrooms and breast cancer risk among Korean women

To evaluate the association between dietary mushroom intake and breast cancer risk, a total of 362 women between the ages of 30 and 65 years who were histologically confirmed to have breast cancer were matched to controls by age (+/-2 years) and menopausal status. Mushroom intake was measured via a food frequency questionnaire that was administered by well-trained interviewers. The associations between the daily intake and the average consumption frequency of mushrooms with breast cancer risk were evaluated using matched data analysis. Both the daily intake (5th vs. 1st quintile, OR = 0.48, 95% CI = 0.30-0.78, p for trend 0.030) and the average consumption frequency of mushrooms (4th vs. 1st quartile, OR = 0.54, 95% CI = 0.35-0.82, p for trend 0.008) were inversely associated with breast cancer risk after adjustment for education, family history of breast cancer, regular exercise [>or=22.5 MET (metabolic equivalent)-hr/week], BMI (body mass index, Kg/m(2)), number of children and whether they are currently smoking, drinking or using multivitamin supplements. Further adjustments were made for energy-adjusted carbohydrate, soy protein, folate and vitamin E levels, which tended to attenuate these results. After a stratification was performed according to menopausal status, a strong inverse association was found in postmenopausal women (OR = 0.16, 95% CI = 0.04-0.54, p for trend = 0.0058 for daily intake; OR = 0.17, 95% CI = 0.05-0.54, p for trend = 0.0037 for average frequency), but not in premenopausal women. In conclusion, the consumption of dietary mushrooms may decrease breast cancer risk in postmenopausal women.     

Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York,United States)

We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health, and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequencymatched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and -tocopherol; -tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio [OR]=0.01, 95 percent confidence interval [CI]=0.0–0.3). This association was much weaker for FH-women [OR=0.7, CI=0.4–1.2]. For FH-women, a significant inverse association was observed between -carotene and premenopausal breast-cancer risk (OR=0.4, CI=0.3–0.5), but not for FH+ women (OR=0.5, CI=0.1–4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH-women, and that -tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.This research was conducted by the Department of Social and preventive Medicine, State University of New York at Buffalo. This publication is supported in part by grants CA11535 and 5 R25 CA1820117 from the US National Cancer Institute and PDT-434 from the American Cancer Society. Dr Freudenheim is a recipient of a Research Career Development Award from the National Cancer Institute (CA01633). This work is solely the responsibility of the authors and does not necessarily represent the views of the NCI.