Chronic preoperative pain and psychological robustness predict acute postoperative pain outcomes after surgery for breast cancer

Background:Few epidemiological studies have prospectively investigated preoperative and surgical risk factors for acute postoperative pain after surgery for breast cancer. We investigated demographic, psychological, pain-related and surgical risk factors in women undergoing resectional surgery for breast cancer.Methods:Primary outcomes were pain severity, at rest (PAR) and movement-evoked pain (MEP), in the first postoperative week.Results:In 338 women undergoing surgery, those with chronic preoperative pain were three times more likely to report moderate to severe MEP after breast cancer surgery (OR 3.18, 95% CI 1.45-6.99). Increased psychological 'robustness', a composite variable representing positive affect and dispositional optimism, was associated with lower intensity acute postoperative PAR (OR 0.63, 95% CI 0.48-0.82) and MEP (OR 0.71, 95% CI 0.54-0.93). Sentinel lymph node biopsy (SLNB) and intraoperative nerve division were associated with reduced postoperative pain. No relationship was found between preoperative neuropathic pain and acute pain outcomes; altered sensations and numbness postoperatively were more common after axillary sample or clearance compared with SLNB.Conclusion:Chronic preoperative pain, axillary surgery and psychological robustness significantly predicted acute pain outcomes after surgery for breast cancer. Preoperative identification and targeted intervention of subgroups at risk could enhance the recovery trajectory in cancer survivors.     

Non-standard management of breast cancer increases with age in the UK: a population based cohort of women > or =65 years

Evidence suggests that compared to younger women, older women are less likely to receive standard management for breast cancer. Whether this disparity persists once differences in tumour characteristics have been adjusted for has not been investigated in the UK. A retrospective cohort study involving case note review was undertaken, based on the North Western Cancer Registry database of women aged > or =65 years, resident in Greater Manchester with invasive breast cancer registered over a 1-year period (n=480). Adjusting for tumour characteristics associated with age by logistic regression analyses, older women were less likely to receive standard management than younger women for all indicators investigated. Compared to women aged 65-69 years, women aged > or =80 years with operable (stage 1-3a) breast cancer have increased odds of not receiving triple assessment (OR=5.5, 95% confidence interval (CI): 2.1-14.5), not receiving primary surgery (OR=43.0, 95% CI: 9.7-191.3), not undergoing axillary node surgery (OR=27.6, 95% CI: 5.6-135.9) and not undergoing tests for steroid receptors (OR=3.0, 95% CI: 1.7-5.5). Women aged 75-79 years have increased odds of not receiving radiotherapy following breast-conserving surgery compared to women aged 65-69 years (OR=11.0, 95% CI: 2.0-61.6). These results demonstrate that older women in the UK are less likely to receive standard management for breast cancer, compared to younger women and this disparity cannot be explained by differences in tumour characteristics.     

The relation between socioeconomic and demographic factors and tumour stage in women diagnosed with breast cancer in Denmark, 1983-1999

The authors investigated the association between socioeconomic position and stage of breast cancer at the time of diagnosis in a nationwide Danish study. All 28 765 women with a primary invasive breast cancer diagnosed between 1983 and 1999 were identified in a nationwide clinical database and information on socioeconomic variables was obtained from Statistics Denmark. The risk of being diagnosed with a high-risk breast cancer, that is size >20 mm, lymph-node positive, ductal histology/high histologic grade and hormone receptor negative, was analysed by multivariate logistic regression. The adjusted odds ratio (OR) for high-risk breast cancer was reduced with longer education with a 12% reduced risk (95% confidence interval (CI), 0.80,0.96) in women with higher education and increased with reduced disposable income (low income group: OR, 1.22; 95% CI, 1.10,1.34). There was an urban-rural gradient, with higher risk among rural women (OR 1.10; 95 % CI, 1.02, 1.18) and lower risk among women in the capital suburbs (OR, 0.85; 95% CI, 0.78, 0.93) and capital area (OR, 0.93; 95% CI, 0.84-1.02). These factors were significant only for postmenopausal women, although similar patterns were observed among the premenopausal women, suggesting a subgroup of aggressive premenopausal breast cancers less influenced by socioeconomic factors.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women: a case-control study

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR = 0.45, 95% CI = 0.30-0.66; OR = 0.34, 95% CI = 0.22-0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR = 0.36, 95% CI = 0.14-0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

克拉玛依市区女性乳腺癌危险因素的病例对照研究

 目的　探讨克拉玛依市区女性乳腺癌的危险因素。方法　用病例对照研究方法调查129例女性乳腺癌和对应的129名对照者,用Logistic回归模型进行乳腺癌危险因素分析。结果　乳腺癌的危险因素有乳腺癌家族史（OR＝2.744,95 % CI＝1.884～4.674）、乳腺增生症（OR＝1.423,95 % CI＝1.160～1.810）、 乳腺炎（OR＝2.363,95 % CI＝2.039～3.934）、子宫肌瘤（OR＝1.623,95 % CI＝1.263～2.024）、 流产（OR＝1.723,95 % CI＝1.143～2.600）、 饮酒（OR＝1.243,95 % CI＝1.040～1.483）、精神创伤（OR＝2.184,95 % CI＝1.753～3.025）、长期接触电离辐射（OR＝1.374,95 % CI＝1.152～1.699）; 保护因素有初潮年龄增大（OR＝0.773,95 % CI＝0.674～0.956）、累计哺乳时间（OR＝0.672,95 % CI＝0.480～0.941）、坚持运动（OR＝0.572,95 % CI＝0.391～0.837）。结论　以上11个因素为克拉玛依市区女性乳腺癌重要的危险因素和保护因素。     

Obesity,Diet and Physical Inactivity and Risk of Breast Cancer in Thai Women

To evaluate the relationship between obesity, diet, physical activity and breast cancer in Thai women, weconducted a case control study with 1,130 cases and 1,142 controls. Informed consent was obtained from allparticipants and a structured questionnaire was performed by trained interviewers to collect information ondemographic and anthropometric data, reproductive and medical history, residential history, physical activityand occupation as well as dietary habits. A significant positive association with an increased risk of breast cancerwas observed in women body mass index (BMI) of ≥25 mg/m2 (OR=1.33, 95%CI 1.07-1.65), the risk beinghigher in postmenopausal women (OR=1.67, 95%CI 1.24-2.25). In addition, underweight BMI at ages 10 and 20years showed an inverse association in all women (OR=0.70, 95%CI 0.56-0.88 and OR=0.74, 95%CI 0.59-0.93,respectively) and in those with a premenopausal status (OR=0.69, 95%CI 0.51-0.93 and OR=0.76, 95%CI 0.56-0.99, respectively). Regular exercise was associated with a decreased risk of breast cancer (OR=0.78, 95%CI0.68-0.98). Interestingly, analysis by type of activity revealed significant protective effects for women who reportedthe highest levels of walking for shopping (OR=0.58, 95%CI 0.38-0.88). High consumption of vegetables andfruit were associated with a decreased risk of breast cancer, while high consumption of animal fat showed anincreased risk in postmenopausal women. In conclusion, our results indicate that obesity and high consumptionof animal fat are associated with breast cancer risk, particularly in postmenopausal women, while recreationalphysical activity has protective effects. It seems that primary prevention of breast cancer should be promotedin an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles.     

Risk factors,prevalence, and course of severe fatigue after breast cancer treatment: a meta-analysis involving 12 327 breast cancer survivors

BackgroundThis meta-analysis aimed to (i) examine demographic, disease-related, and treatment-related risk factors, (ii) estimate the prevalence, and (iii) describe the course of severe fatigue following breast cancer (BC) treatment.MethodsPubMed, PsycINFO, Cochrane, CINAHL, and Web of Science were systematically searched from inception up to 23 November 2015. Risk factors and prevalence rates were analyzed with inverse variance random-effects analyses. Heterogeneity was studied with sensitivity analyses.ResultsTwenty-seven studies were included (N = 12 327). Breast cancer survivors (BCS) with a partner were at lower risk for severe fatigue than survivors without a partner [risk ratio (RR) 0.96, 95% confidence interval (CI) 0.93–0.98]. Survivors with stage II or III cancer, and survivors treated with chemotherapy were at higher risk for severe fatigue than survivors with stage 0 or I cancer and without chemotherapy (RR respectively 1.18, 95% CI 1.08–1.28; 1.12, 95% CI 1.06–1.19). Survivors treated with surgery, radiotherapy, and chemotherapy, and survivors with this combination plus hormone therapy were at higher risk than survivors with other treatment combinations (RR respectively 1.18, 95% CI 1.05–1.33; 1.38, 95% CI 1.15–1.66). Survivors treated with surgery and surgery plus radiotherapy were at lower risk than survivors with additional treatments (RR respectively 0.83, 95% CI 0.70–0.98; 0.87, 95% CI 0.78–0.96). Hormone and targeted therapy were no significant risk factors. The pooled prevalence of severe fatigue was 26.9% (95% CI 23.2–31.0), but this should be interpreted with caution because of high heterogeneity. A relatively large decrease in the prevalence of severe fatigue seemed to occur in the first half year after treatment completion.ConclusionsApproximately one in four BCS suffer from severe fatigue. Risk factors of severe fatigue were higher disease stages, chemotherapy and receiving the combination of surgery, radiotherapy, and chemotherapy, both with and without hormone therapy. Having a partner, receiving only surgery, and surgery plus radiotherapy decreased the risk.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR=0.45, 95% CI=0.30–0.66; OR=0.34, 95% CI=0.22–0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR=0.36, 95% CI=0.14–0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Early-life physical activity and postmenopausal breast cancer: effect of body size and weight change.

It is not yet known whether early-life physical activity reduces the risk of developing breast cancer. Subgroup analyses according to menopausal status and body mass may help clarify this association. Data from a population-based case-control study of female residents of Wisconsin, Massachusetts, Maine, and New Hampshire were used to examine associations between body mass and breast cancer risk. Cases (n = 4614) were identified by each state's tumor registry; controls (n = 5817) were randomly selected from population lists. Frequency of participation in strenuous physical activity when 14-22 years of age, weight at age 18 and 5 years before interview, height, and other factors were ascertained through structured telephone interviews. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression. Reductions in postmenopausal breast cancer risk associated with strenuous physical activity were greatest for women in the fourth quartile of body mass index at age 18; the OR for women with the highest activity frequency on average (> or =once/day) was 0.45 (95% CI = 0.26-0.79). Associations with frequency of activity also varied by weight change. Compared to women with no activity and little adult weight gain, frequent physical activity was associated with reduced postmenopausal breast cancer risk in women who had lost weight since age 18 (OR = 0.19, 95% CI = 0.05-0.70) or had gained little or modest amounts of weight (weight gain: first tertile, OR = 0.36, 95% CI = 0.05-0.85; second tertile, OR = 0.31, 95% CI = 0.14-0.66). Weighted MET score analyses yielded similar but less inverse results. These findings suggest that the reduced risk of postmenopausal breast cancer associated with frequent, early-life physical activity may be greatest in women who, over the adult years, either lost weight or gained only modest amounts.     

Risk Factors for breast cancer among japanese women: A case-control study in Ibaraki, Japan

BACKGROUND: The number of epidemiologic studies on breast cancer risk factorsin Japanese women is still quite limited. Our objective was to clarify the relationship between lifestyle, body size and breast cancer risk. METHODS: A matched case-control study was conducted in Ibaraki, Japan. The participants were 148 women aged 26-69 diagnosed with breast cancer at Tsukuba University Hospital or Tsukuba Medical Center Hospital between January, 1990 and March, 1997. Two controls were individually matched to the cases by age and residence. A self-administered questionnaire was used to obtain information on the family history of breast cancer, reproductive history, education, body size and lifestyle factors. Conditional logistic regression analysis was used to estimate oddsratios (ORs)and 95% confidence intervals (95% CI). RESULTS: After adjustment for potential confounders, heavy weight and higher body mass index were associated with an increased risk of breast cancer among postmenopausal women (OR = 1.76, 95% CI = 0.69, 4.48; OR = 1.57, 95% CI=0.61, 3.99, respectively). Current or ex-smokers were found to be at an increased risk for breast cancer (OR = 3.33; 95% CI = 1.63, 6.80). Women who take hot baths had a decreased risk for breast cancer (OR = 0.67; 95% CI = 0.43, 1.06). Recreational physical activity was associated with a reduced risk of breast cancer (PTrend = 0.005).OR for breast cancer among physically active women was 0.36 (95% CI = 0.19, 0.70), as compared with inactive women. Taller women had an increased risk of breast cancer relative to shorter women (OR = 1.49; 95% CI = 0.83, 2.70). No significant association between alcohol consumption and breast cancer risk was detected. CONCLUSION: Our results suggest that several potentially modifiable lifestyle factors may be useful for the prevention of breast cancer.     

Physical activity and breast cancer risk in women aged 20-54 years

BACKGROUND/METHODS: Although several studies have suggested that physical activity is associated with a decreased risk of breast cancer, such a decrease has not been found consistently, perhaps because physical activity was assessed in different ways and for restricted periods. Few studies have assessed the risk of breast cancer in relation to lifetime physical activity. We used data from a population-based, case-control study, including 918 case subjects (aged 20-54 years) and 918 age-matched population control subjects, to examine associations between breast cancer risk and physical activity at ages 10-12 years and 13-15 years, lifetime recreational activity, and title of longest held job. RESULTS: Women who were more active than their peers at ages 10-12 years had a lower risk of breast cancer (odds ratio [OR] = 0.68; 95% confidence interval [CI] = 0.49-0.94). Women who had ever engaged in recreational physical activity had a reduced risk of breast cancer compared with inactive women (OR = 0.70; 95% CI = 0.56-0.88). Neither very early recreational activity (before age 20 years) nor recent activity (last 5 years) was associated with a greater reduction in risk than recreational activity in the intermediate period. Furthermore, women who started recreational activities after age 20 years and women who started earlier and continued their activities throughout adult life experienced a similar reduction in risk. Lean women, i.e., women with a body mass index (weight in kg/[height in m](2)) less than 21. 8 kg/m(2), appeared to have a lower risk associated with recreational physical activity than women with a body mass index greater than 24.5 kg/m(2) (OR = 0.57 [95% CI = 0.40-0.82] and OR = 0. 92 [95% CI = 0.65-1.29], respectively). CONCLUSIONS: Our findings support the hypothesis that recreational physical activity is associated with a decreased risk of breast cancer. Physical activity in early or recent life does not appear to be associated with additional beneficial effects.     

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.     

Risk Factor Analysis for Breast Cancer in Premenopausal and Postmenopausal Women of Punjab,India

Objective: Amritsar, the second largest town of agrarian state of Punjab, India reports high number of breast cancer cases every year. The present study investigated the etiology of breast cancer using various obesity indices and other epidemiological factors among breast cancer patients residing in and around Amritsar city. Methods: In this case control study, risk factors for breast cancer were analyzed in 542 female subjects: 271 females with breast cancer patients and 271 unrelated healthy females matched for age as control females. Results: Bivariate analysis for risk factors in cases and controls showed a lower risk (OR=0.65, 95% CI 0.43-0.99, p=0.04) in obese cases with BMI≥25kg/m2 as compared to subjects with normal BMI. Risk factor analysis showed that parameter which provided risk for cancer in postmenopausal women was obesity and in premenopausal women was parity. Postmenopausal women with BMI (overweight: OR=0.39, 95% CI 0.17-0.92, p=0.03; obese: OR= 0.26, 95% CI 0.13-0.52, p=0.00), WC (OR=0.17, 95% CI 0.05-0.52, p=0.00) and WHtR (p=0.02) had highr risk. Premenopausal women with 3 or less than 3 children had a higher risk (OR=5.54, 95 % CI 2.75-11.19, p=0.00) than postmenopausal women when compared to women with more than 3 children. Binary logistic regression analysis revealed that low parity (≤3) substantially increased the risk for breast cancer (OR=4.80, 95% CI 2.34-9.85, p=0.00) in premenopausal women. Conclusion: Obesity, parity associated breast cancer risk and reduced breastfeeding cumulatively predispose the premenopausal women of this region to higher risk of breast cancer.     

Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger

Differences in incidence, prognosis, and treatment response suggest gene expression patterns may discern breast cancer subtypes with unique risk factor profiles; however, previous results were based predominantly on older women. In this study, we examined similar relationships in women ≤ 56 years, classified by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 for 890 breast cancer cases and 3,432 frequency-matched population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) for tumor subtypes were calculated using multivariate polytomous regression models. A total of 455 (51.1%) tumors were considered luminal A, 72 (8.1%) luminal B, 117 (13.1%) non-luminal HER-2/neu+, and 246 (27.6%) triple negative. Triple negative tumors were associated with breast feeding duration (per 6 months: OR = 0.76, 95% CI 0.64-0.90). Among premenopausal women, increasing body size was more strongly associated with luminal B (OR = 1.73, 95% CI 1.07-2.77) and triple negative tumors (OR = 1.67, 95% CI 1.22-2.28). A history of benign breast disease was associated only with increased risk of luminal A tumors (OR = 1.89, 95% CI 1.43-2.50). A family history of breast cancer was a risk factor for luminal A tumors (OR = 1.93, 95% CI 1.38-2.70) regardless of age, and triple negative tumors with higher risks for women <45 (OR = 5.02, 95% CI 2.82-8.92; P for age interaction = 0.005). We found that little-to-no breastfeeding and high BMI were associated with increased risk of triple negative breast cancer. That some risk factors differ by molecular subtypes suggests etiologic heterogeneity in breast carcinogenesis among young women.     

The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's breast cancer patients.

BACKGROUND: The 1995 Calman-Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in National Health Service cancer care. Its main recommendation was to concentrate care into the hands of site-specialist multidisciplinary teams. This study aimed to determine whether these teams improved processes and outcomes of care for breast cancer patients. PATIENTS AND METHODS: All patients diagnosed and treated with breast cancer in the Yorkshire region of the UK from 1995 to 2000 were identified within the Northern and Yorkshire Cancer Registry and Information Service database. Changes in the use of breast-conserving surgery, adjuvant radiotherapy following breast-conserving surgery and 5-year survival were assessed among these patients in relation to their managing breast cancer team's degree of adherence to the manual of cancer service standards (which outlines the specification of the 'ideal' breast cancer team) and the extent of site specialisation of each team's surgeons. RESULTS: Variation was observed in the extent to which the breast cancer teams in Yorkshire had conformed to the Calman-Hine recommendations. Increases in adherence to the recommendations in the manual of cancer service standards were associated with a reduction in the use of breast-conserving surgery [odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.70-0.98, P < 0.01]. Increases in both surgical specialisation (OR = 1.23, 95% CI = 1.00-1.55, P = 0.06) and adherence to the manual of cancer service standards (OR = 1.22, 95% CI = 0.97-1.52, P = 0.05) were associated with the increased use of radiotherapy following breast-conserving surgery. There was a trend towards improved 5-year survival (hazard ratio = 0.93, 95% CI = 0.86-1.01, P = 0.10) in relation to increasing surgical site specialisation. All these effects were present after adjustment for the casemix factors of age, stage of disease, socio-economic background and year of diagnosis. CONCLUSIONS: The extent of implementation of the Calman-Hine report has been variable and, on the basis of limited clinical and organisational information available, its recommendations appear to be associated with improvements in processes and outcomes of care for breast cancer patients.     

Maternal breast cancer risk after the death of a child

The possible association between a severe traumatic life event (death of a child) and breast cancer risk was examined in a case-control study nested within a nation-wide cohort in Sweden. Our study population included 27,571 women with breast cancer and 141,798 control women born between 1925-1976. After adjustment for age, parity, age at first birth and education, the overall risk estimate for breast cancer among all women that had experienced the death of a child was 1.05 (95% confidence interval [CI] = 0.96-1.15). Among uniparous women the corresponding odds ratio (OR) was 1.27 (95% CI = 0.98-1.64). When stratifying for child's age at death a significant risk increase was detected among women that had lost their only child when the child was between 1-4 years of age (OR = 2.65; 95% CI = 1.06-6.60). These findings do not support an overall increase in breast cancer risk after the death of a child, a severe traumatic life event. Based on a small number of subjects, our finding of an increased risk in a subgroup of uniparous women losing their only child could be due to chance.     

One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.     

Role of physical activity in modulating breast cancer risk as defined by APC and RASSF1A promoter hypermethylation in nonmalignant breast tissue.

Physical activity reduces breast cancer risk. Promoter hypermethylation of the tumor suppressor genes APC and RASSF1A, which is potentially reversible, is associated with breast cancer risk. We conducted a cross-sectional study in 45 women without breast cancer to determine the association of physical activity with promoter hypermethylation of APC and RASSF1A in breast tissue. We used quantitative methylation-specific PCR to test the methylation status of APC and RASSF1A, and questionnaires to assess study covariates and physical activity (measured in metabolic equivalent hours per week). In univariate analyses, the study covariate, benign breast biopsy number, was positively associated with promoter hypermethylation of APC (P = 0.01) but not RASSF1A. Mulitvariate logistic regression indicated that, although not significant, physical activities for a lifetime [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.22-1.45; P = 0.24], previous 5 years (OR, 0.62; 95% CI, 0.34-1.12; P = 0.11), and previous year (OR, 0.72; 95% CI, 0.43-1.22; P = 0.22) were inversely related to promoter hypermethylation of APC but not RASSF1A for all physical activity measures. Univariate logistic regression indicated that physical activities for a lifetime, previous 5 years, and previous year were inversely associated with benign breast biopsy number, and these results were approaching significance for lifetime physical activity (OR, 0.41; 95% CI, 0.16-1.01; P = 0.05) and significant for physical activity in the previous 5 years (OR, 0.57; 95% CI, 0.34-0.94; P = 0.03). The study provides indirect evidence supporting the hypothesis that physical activity is inversely associated with promoter hypermethylation of tumor suppressor genes, such as APC, in nonmalignant breast tissue.     

Case-control study of anthropometric measures and breast cancer risk

A population-based case-control study of 1,233 incident breast cancer cases and 1,241 controls was conducted in Alberta between 1995 and 1997 to examine the influence of anthropometric factors on the risk of breast cancer using several newly derived variables. Data on current height, weight and waist and hip circumference were collected by interviewers using standardized methods. Respondents recalled their body weight at each decade from age 20 to the referent year. Several variables were estimated, and unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations for any of the estimated variables with breast cancer risk for premenopausal women (462 cases, 475 controls) were found. The results for postmenopausal women (771 cases, 762 controls) in the highest vs. lowest quartiles were, for waist circumference, OR = 1.30 (95% CI 0.97-1.73); waist-hip ratio, OR = 1.43 (95% CI 1.07-1.93); weight gain since age 20, OR = 1.35 (05% CI 1.01-1.81); difference between maximum and minimum weights over adult lifetime, OR = 1.56 (95% CI 1.16-2.08); and the reference weight minus the minimum weight since age 20, OR = 1.47 (95% CI 1.10-1.97). Statistically significant trends in risk were observed for these variables. Effect modification with hormone replacement therapy use was found for most variables assessed for postmenopausal women, with much stronger associations found among never-users compared to ever-users. We found strong evidence that waist-hip ratio and weight gained over lifetime, as assessed by different variables, are postmenopausal breast cancer risk factors. These effects were independent of dietary intake and lifetime total physical activity.     

Risk factors for breast cancer in nulliparous women

The relation between hormonal and lifestyle factors and breast cancer risk in nulliparae was investigated using data from two case-control studies conducted in Italy between 1983 and 1994. The study included 1041 nulliparae with histologically confirmed incident breast cancer and 1002 nulliparous controls admitted to hospital for a wide range of acute, non-neoplastic, nonhormone-related diseases. In premenopausal nulliparae, there was an inverse relation with age at menarche [odds ratios (OR) 0.45; 95% confidence intervals (CI) 0.24-0.86 for > or = 15 years vs < 12], while no association emerged in postmenopausal. Breast cancer risk increased with age at menopause, the OR being 1.91 (95% CI 1.26-2.90) for nulliparae reporting age at menopause > or = 53 years compared with < 45. Abortion was not related to breast cancer risk, the OR being 0.92 for any spontaneous, 0.97 for any induced and 0.77 for > or = 2 total abortions compared to none. The OR was 1.75 (95% CI 1.03-2.97) for women reporting their first abortion at age > or = 30 years compared with < 30. Oral contraceptives and hormone replacement therapy in menopause were moderately related to risk. The OR was 2.71 (95% CI 1.85-3.95) in nulliparae with a family history of breast cancer and 1.60 (95% CI 1.20-2.14) in those with a history of benign breast disease. Compared with nulliparae reporting a low physical activity, the OR was 0.79 (95% CI 0.54-1.16) for those reporting intermediate/high activity. Breast cancer risk increased with total energy intake, the OR being 1.65 (95% CI 0.99-2.75) in the highest tertile; beta-carotene was inversely related to risk (OR 0.60, 95% CI 0.38-0.95) for the highest tertile. Thus, most risk factors for breast cancer in nulliparae were similar to those in women generally.