Does folate intake decrease risk of postmenopausal breast cancer among women with a family history?

BACKGROUND: Several recent studies suggest that adequate dietary folate may attenuate the risk of breast cancer associated with intake of alcohol. We examined whether the putative benefit extends to women with a family history (FH) of breast cancer using a cohort of 33,552 postmenopausal women aged 55-69 years in 1986. METHOD: Folate and alcohol intake was estimated from a food frequency questionnaire completed at baseline. Folate was categorized as upper 50th, 31st-50th, 11th-30th, and <10th percentiles. Alcohol use was initially classified into three levels; never drinkers, less than the median and greater than the median. Subsequent models collapsed levels of intake to any versus none. Occurrence of breast cancer was determined through linkage to the Iowa SEER registry. Multivariate-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated through Cox proportional hazards regression, stratified on FH using non-drinkers with high folate and no FH as the referent group. RESULTS: Through 14 years, 1823 incident cases were identified, 308 among FH+ women. Among FH- women, low folate was not a risk factor among non-drinkers (RR = 0.96, CI = 0.73-1.26), but was among drinkers (RR = 1.40, CI = 1.05-1.86). Drinkers with high folate were not at elevated risk (RR = 1.03, CI = 0.89-1.19). Among FH+ women, low folate was a risk factor among drinkers (RR = 2.21, CI = 1.43-3.41) and non-drinkers (RR = 2.39, CI = 1.36-4.20). Further, drinkers with high folate remained at increased risk (RR = 1.67, CI= 1.30-2.14). However, FH+ women with high folate who did not drink alcohol had no elevated risk. CONCLUSION: These results suggest that folate may attenuate the risks of postmenopausal breast cancer associated with family history, but only if alcohol use is avoided or minimized.     

Family history and risk of breast cancer: nurses’ health study

Family history of cancer remains underused in general clinical practice. We assess age at diagnosis and the role of family history in risk of breast cancer. Prospective follow-up of nurses' health study participants from 1980 to 2006. Updated assessment of family history in mother and sister including age at diagnosis. We used youngest age at diagnosis for family member when classifying risk. We confirmed 4327 incident invasive breast cancers confirmed. Breast cancer incidence models fitted to women with and without family history to assess variation in the risk for established risk factors. Compared to women with no family history those whose mother was diagnosed before age 50 had an adjusted relative risk of 1.69 (95% CI 1.39-2.05) and those with mother diagnosed at 50 or older had a relative risk of 1.37 (1.22-1.53). Sister history was associated with increased relative risk; 1.66 (1.38-1.99) for those with sister history before age 50 and 1.52 (1.29-1.77) for those with sister diagnosed at age 50 or older. Women with either mother or sister diagnosed before age 50 had a relative risk of 1.70 (1.48-1.95) significantly higher than those with diagnosis at age 50 or older (RR = 1.30; (1.27-1.54), P = 0.016). The magnitude of risk associated with established reproductive and lifestyle risk factors did not differ significantly between women with and those without family history with the exception of risk after bilateral oophorectomy in which setting women with family history had greater reduction in risk of subsequent breast cancer. Women with a family member diagnosed with breast cancer before age 50 had increased risk of breast cancer compared to women with family members diagnosed at older ages. Consistent findings for risk factors regardless of family history adds to robust evidence for risk identification and risk stratification in clinical settings where prevention strategies will apply equally to women with and without family history.     

Does family history influence survival in breast cancer cases?

A few studies have suggested a relatively better prognosis for breast cancer (BC) cases reporting a positive family history (FH). We aimed at comparing the survival of patients according to FH in a large hospital-based series of 1,278 BC cases. Information on FH for BC was obtained at diagnosis by interview. All cases reporting a first- or second-degree FH for breast carcinoma were compared with cases without FH. Overall survival was estimated using a product-limit method. Hazard ratios (HRs) and the corresponding 95% confidence intervals (95% CIs), adjusted for confounding factors, were computed using proportional hazard models. Overall, 240 (18.8%) cases reporting, at diagnosis, a positive FH (156 with at least 1 first-degree relative and 84 with at least 1 second-degree relative) were compared with 1,038 patients without FH for BC. No significant differences were found in terms of distribution of age at diagnosis, tumor stage, nodal involvement, receptor status and histology. Cumulative survival rates at 5 years for cases without FH and with first-degree and second-degree FH for BC were 79.8 (95% CI 77.0-83.0), 78.6 (95% CI 70.0-88.0) and 80.2 (95% CI 68.0-92.0), respectively (log-rank test, chi(2) (2) = 0.02, p = 1.0). After adjustment for age, pathologic size and nodal involvement, the HR among cases of invasive cancer with a first-degree FH of BC was 0.91 (95% CI 0.55-1.48); however, the HR for cases with second-degree FH was 1.18 (95% CI 0.62-2.25) compared to cases without FH. Our study, based on a large series of consecutive invasive BC cases, did not find any significant survival differences associated with a positive FH for breast carcinoma, suggesting the existence of a large heterogeneity among BC cases with FH.     

Screening younger women with a family history of breast cancer – does early detection improve outcome?

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P<0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P<0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P<0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.     

Mammographic density as a marker of breast cancer risk?

Mammographic density is a strong, independent risk factor for breast cancer. Women with high mammographic density have a fourfold increased risk for breast cancer compared with women with low density. Because age and obesity are the strongest predictors of mammographic density, it is important to adjust for them in risk analyses. In randomized trials, tamoxifen decreased risk for breast cancer and also decreased mammographic density. Combined estrogen plus progestin therapy increased mammographic density. Density is a strong risk factor in low-risk groups (Asian women) and high-risk groups (BRCA mutation carriers). Several risk assessment tools now incorporate mammographic density, including an updated Gail model, though these models require additional validation before they should be used widely. Improvements in density measurements may allow risk assessment to occur routinely with mammography and improve targeting of breast cancer prevention efforts.     

Family history of cancer and risk of breast cancer in the Black Women’s Health Study

Introduction  

Relatively little research has been conducted on familial breast cancer in African American women.     

Reproductive history and breast cancer survival: Findings from the African breast cancer—Disparities in outcomes cohort and implications of Africa's fertility transition on breast cancer prognosis

Reproductive characteristics are known risk factors for breast cancer but, other than recent birth, their role as prognostic factors is less clear, and has not been studied in Sub-Saharan Africa (SSA). In this setting, we examined whether reproductive factors independently influence breast cancer survival in a subset of the African Breast Cancer—Disparities in Outcomes cohort study. In 1485 women with incident breast cancer recruited between 2014 and 2017, we examined birth cohort changes in reproductive factors, and used Cox models to examine whether reproductive characteristics were associated with all-cause mortality after adjusting for confounders (age, stage, treatment, HIV, and social factors). Four years after diagnosis, 822 (56%) women had died. Median parity was 4 (IQR = 2, 6) and 209 (28%) of premenopausal women had had a recent birth (<3 years prior to cancer diagnosis). Each pregnancy was associated with a 5% increase (95% CI: 2%, 8%) in mortality rates, which held among postmenopausal women (5%, [1%-9%]). Pre-menopausal women with a recent birth had 52% (20%, 92%) higher mortality rates. Fertility trends by birth cohort showed declining parity, increasing age at first birth and declining age at last birth, however the impact of these population-level changes on future average survival was predicted to be very small (<3% absolute gain).     

Accuracy of self-reported family history of cancer in a large case–control study of ovarian cancer

OBJECTIVE: To evaluate the reliability of self-reported family history of cancer in first-degree female relatives and to examine possible determinants of accurate reporting. METHODS: Women with ovarian cancer and controls were recruited between 1995 and 1999 and interviewed. The study comprised 579 cases and 1,564 controls with 6,265 first-degree female relatives. Self-reported familial cancer diagnoses were validated from registry data. Sensitivity, specificity, and kappa were calculated, and possible determinants were examined by logistic regression. RESULTS: The sensitivity of self-reporting ranged from 0.78 to 0.90 for all cancers but was lower for self-reporting of most site-specific cancers, ranging from 0.29 to 0.94. The specificity of self-reporting ranged from 0.91 to 0.99 for cancer in general and from 0.99 to 1.00 for site-specific cancers. Type of relative, age at interview, and length of education influenced the sensitivity and specificity significantly. The odds ratio for ovarian cancer was higher when based on registry data than on self-reported data and was significant (OR = 2.58 vs. 1.56). CONCLUSIONS: Cancer diagnoses in first-degree relatives are not always accurately reported by patients with ovarian cancer or by controls. The results indicate that studies of associations with family cancer history should validate self-reported family cancer diagnoses as carefully as possible.     

The incidence of breast cancer from screening women according to predicted family history risk: Does annual clinical examination add to mammography?

In breast cancer, mutations of predisposition genes such as BRCA-1/2 and other genes as yet uncharacterised are manifest in up to 10% of cases. Although the prior probability of the presence of a breast cancer predisposing gene can be calculated for individual women, there is no published evidence to justify predicted risk as a selection criteria for screening. This study aims to define which patient groups with a significant family history should be screened, and whether clinical examination is necessary in addition to mammography. The Claus model was used to predict breast cancer risk in women with a family history. Women were divided into two groups according to their predicted risk: group I consisted of women at standard risk (lifetime risk less than 1:6) and group II with moderate/high risk (lifetime risk greater than or equal to 1:6). Women were cancer-free at the point of entry, and screening consisted of annual clinical examination and mammography from the age of 35 years. This study consisted of 1500 women in group I and 1078 in group II. The period of observation was 5902.0 and 4327.8 women years, respectively. A total of 31 cancers were detected, 12 in group I and 19 in group II. The median age at diagnosis in group II was 45 years (range 26-66 years) compared with 54.5 years (range 38-63 years) in group I (P=0.03). The relative risk of developing breast cancer in group II was 2.6 (95% confidence interval (CI) 1.2-5.8). When compared with breast cancer incidence in the normal population, the standardised incidence ratio in group II was significantly higher at 2.8 (95% CI: 1.7-4.2). The standardised incidence ratio of women in group I was similar to that of the general population (1.1 (95% CI: 0.6-1.8)). A total of 26/31 (84%) cancers detected were palpable, of which 14 (54%) were not visible on mammography. Approximately one-third of all palpable cancers were detected at routine follow-up. Mammography correctly identified 17/31 cancers (55%), but 29% of these were not palpable. Family history screening programmes are effective and women should be selected for screening according to predicted risk. The younger age of diagnosis in group II justifies screening from an earlier age using both annual clinical examination and mammography.     

History of benign breast disease and risk of breast cancer among women in China: a case–control study

Background  Data from the Shanghai Breast Cancer Study were analyzed to evaluate the relationship between benign breast disease (BBD) and breast cancer among Chinese women with a self-report of physician-diagnosed BBD. Methods  Study participants consisted of 3,452 breast cancer cases and 3,474 population controls recruited by the Shanghai Breast Cancer Study. In-person interviews were conducted to collect information on demographics and suspected risk factors for breast cancer, including a detailed history of BBD. Unconditional logistic regression was used to derive adjusted odds ratios (OR_adj) and 95% confidence intervals (CI) for the association between self-reported BBD and breast cancer. Results  Women with breast cancer were significantly more likely to have a self-reported history of BBD including lobular proliferation (OR_adj = 1.6; 95% CI 1.4–1.8), fibroadenoma (OR_adj = 1.9; 95% CI 1.6–2.3), and other BBD (OR_adj = 1.6; 95% CI 1.3–2.1). Breast cancer risk was lower for surgically treated fibroadenoma as compared to non-surgically treated and higher for other BBDs that were surgically treated versus non-surgically treated. Conclusions  Our results suggest that personal history of BBD is associated with an increased risk of future breast cancer among women in China. Surgical intervention for fibroadenoma may reduce the risk.     

Does a family history of cancer increase the risk for postmenopausal endometrial carcinoma? A prospective cohort study and a nested case-control family study of older women.

BACKGROUND: As part of the hereditary nonpolyposis colon carcinoma (HNPCC) constellation of neoplasia caused by defects in mismatch repair genes, some endometrial carcinomas are known to have a genetic contribution to etiology. However, most endometrial carcinomas occur in postmenopausal women, presumably without the HNPCC defect. Consequently, the genetic contribution to these cases is unclear. The objective of this study was to determine whether family history of cancer is a risk factor for endometrial carcinoma in older women. METHODS: The authors analyzed incident endometrial carcinoma data, as well as data on family history of various cancers in first-degree relatives, from a cohort of 24,848 postmenopausal Iowa women ages 55-69 years who were cancer free at baseline in 1986. Because a positive family history is dependent on many factors, including the age of the patient, the number of relatives, and the distribution of other risk factors in relatives, the authors also conducted a nested case-control study on family members of 95 patients with endometrial carcinoma diagnosed during 1988-1989 and 91 cancer free controls who were chosen randomly from subjects matched for age (+/-1 year). RESULTS: During 10 years of follow-up of the cohort, 322 incident endometrial carcinoma cases occurred. Women who reported a positive family history of cancer overall or at any specific site (e.g., the endometrium, colon, or breast) were not at increased risk for endometrial carcinoma. Adjustment for potential confounders, such as age, obesity, parity, oral contraceptive use, and estrogen replacement therapy, did not alter these results. Analysis of the family members of the cases and controls produced little evidence to suggest that this lack of association between family history and endometrial carcinoma could be explained by unequal distribution of known risk factors among relatives. Case family members were slightly older than control family members, but no significant differences were found in body mass index (kg/m2), age at menarche, age at menopause, or number of pregnancies. Relation to a case or control was not associated with increased risk of endometrial, ovarian, breast, or colon carcinoma for family members. Controlling for a variety of potential confounders did not alter the results. CONCLUSIONS: No evidence was found that genetics contribute to the risk of postmenopausal endometrial carcinoma for women with no personal cancer history.     

Family history of malignancies and risk of breast cancer: prospective data from the Shanghai women’s health study

A population-based cohort study was conducted in Shanghai, China, to investigate the relationship between family cancer history in first-degree relatives and risk of breast cancer. A total of 570 newly diagnosed breast cancer patients were identified from the cohort of 73,222 women during the follow-up period. Breast cancer risk was elevated (RR = 1.74, 95% CI: 1.10–2.73) for those with a family history of breast cancer and the risk was stronger for women who were younger than 55 years (RR = 2.07, 95% CI: 1.17–3.64). In addition, a significantly increased risk was observed for women with a family history of leukemia (RR = 2.06; 95% CI: 1.02–4.15) and among younger women, those who reported having a family history of any cancer (RR = 1.41, 95% CI: 1.10–1.82), lung cancer (RR = 1.72, 95% CI: 1.12–2.65), and esophageal cancer (RR = 2.99, 95% CI: 1.62–5.51). This cohort study suggests that, as previously observed in high risk populations, family history plays an important role in breast cancer also in a low risk population. The link between breast cancer risk and family history of cancers of the lung and esophagus, as well as leukemia, warrants further investigation.     

“This is a kind of betrayal”: a qualitative study of disability after breast cancer

Objective

We proposed to document the effect of arm morbidity and disability in 40 Canadian women who were 12–24 months post breast cancer surgery.

Methods

We completed 40 qualitative interviews as one component of a multidisciplinary national longitudinal study of arm morbidity after breast cancer (n = 745) involving four research sites (Fredericton/Saint John, Montreal, Winnipeg, Surrey). During semi-structured interviews, participants who had reported arm morbidity and disability in earlier surveys were asked to discuss the effects of these conditions on everyday life.

Results

The interviewees reported making major adjustments to paid and unpaid work, which often involved the assistance of family members, thus demonstrating the effect of disability. Interview data resulted in the creation of a model that addresses arm morbidity and disability, and that holds implications for health care professionals.

Conclusions

Based on the interview findings, we conclude that a robust measure of disability after breast cancer should be developed. In the absence of a validated measure of the effect of disability, evaluating qualitative responses to questions about everyday activities could provide the impetus for provision of physical therapy and emotional support.     

Early-onset colorectal cancer patients without family history are “at very low risk” for lynch syndrome

Introduction

Several studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS.

Methods

Early-onset CRC patients (≤ 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H.

Results

117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features “No Amsterdam Criteria” and ”left sided CRC” to exclude MSI-H, accuracy was 89.7% (84.2-95.2).

Conclusions

Early-onset CRC patients, with left sided CRC and without family history are “at very low risk” for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients.     

Issues related to family history of cancer at the end of life: a palliative care providers’ survey

Addressing the concerns of end-of-life patients or their relatives about their family history of cancer could benefit patients and family members. Little is known about how palliative care providers respond to these concerns. The purpose of this pilot study was to assess palliative care providers’ knowledge about familial and hereditary cancers and explore their exposure to patients’ and relatives’ concerns about their family history of cancer, and their self-perceived ability to deal with such concerns. A cross-sectional survey was conducted in the Quebec City (Canada) catchment area among palliative care professionals. Fifty-eight palliative care professionals working in hospice, home care and hospital-based palliative care units completed the questionnaire. All physicians and 63% of nurses occasionally addressed concerns of patients and relatives about their family history of cancer, but they reported a low confidence level in responding to such concerns. They also showed knowledge gaps in defining features of a significant family history of cancer, and most (78%) would welcome specific training on the matter. Our findings highlight the relevance of offering education and training opportunities about familial cancers and associated risks to palliative care providers. The needs and concerns of end-of-life patients and their families need to be explored to ensure palliative care providers can adequately assist patients and their relatives about their family history of cancer. Ethical implications should be considered.     

Spontaneous “healing” of breast cancer

BACKGROUND: Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma. OBJECTIVE: To clarify the clinicopathological characteristics of breast cancer with healing. PATIENTS AND METHODS: At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing. RESULTS: (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen. CONCLUSION: The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.