Family history of breast cancer and short-term effects of childbirths on breast cancer risk

The long-term protective effect of a pregnancy on breast cancer risk is preceded by a short-term adverse effect, possibly reflecting a promoting effect of pregnancy hormones. In the present study, we explore whether a family history of breast cancer modifies time-related effects of pregnancies, with special emphasis on the transient increase in risk of breast cancer shortly after birth. Our study cohort comprises 1,067,289 Norwegian women aged 20-74 years. The mean follow-up time was 18 years. Incidence rate ratios were estimated by Poisson regression analyses of person-years at risk. Of the 7,377 women diagnosed with breast cancer during follow-up, a total of 828 (11%) had a mother or a sister with breast cancer diagnosis. Women with a family history of breast cancer had a 2-3-fold higher risk of breast cancer than did women without any affected family member, highest for those with a relative diagnosed before they were 50 years. Similar to women without a familial excess risk, increasing parity was associated with an overall protective effect among women with a familial predisposition, regardless of age at diagnosis of the relative. Whereas women with no familial excess risk experienced a transient increase in risk mainly after late age births, women with a family history of breast cancer experienced an adverse effect of pregnancies also at younger ages. The present results give further support to the hypothesis that the adverse effect of a term birth can be explained by a promoting effect of pregnancy hormones.     

Family history and breast cancer tumour characteristics in screened women

Women with a family history of breast cancer have an increased risk of the disease. However, since they tend to experience greater surveillance for the disease, their breast cancers may be detected at an earlier stage, thus making it difficult to assess reliably whether tumour characteristics vary by family history. Information on 9,731 Million Women Study participants with screen-detected breast cancer, diagnosed in 1996-2003, and 37,983 matched controls, who also attended routine screening but were not diagnosed with breast cancer, was used to estimate adjusted relative risks (RRs) of screen-detected breast cancer in women with a family history of the disease. Women with a family history of breast cancer had an increased risk of screen-detected breast cancer (RR 1.57; 95% CI:1.47-1.68) compared with those without such a family history. The RRs were 1.58 (1.46-1.71) and 1.55 (1.34-1.80) for invasive and in situ breast cancer; 1.63 (1.49-1.79) and 1.55 (1.32-1.83) for node-negative and node-positive disease; and 1.56 (1.42-1.70), 1.75 (1.39-2.21) and 1.71 (1.28-2.29) for ductal, lobular and tubular cancers. There was no significant difference in the RR of screen-detected breast cancer associated with a family history of the disease according to invasiveness, size, nodal status, malignancy grade or morphological type of the breast cancer.     

Family history and bilateral primary breast cancer

Summary The prevalence of a family history of breast cancer was established in 54 women with bilateral primary breast cancer and 208 women with unilateral disease. Women with bilateral disease had significantly greater prevalence of family history than women with unilateral breast cancer (P<0.01). Compared with the unilateral cancers, a significantly greater proportion of bilateral cancers had first degree affected relatives (P<0.05). Moreover the affected relatives of probands with bilateral disease showed a significantly higher prevalence of bilateral breast cancer compared with the relatives of women with unilateral disease (P = 0.04). The findings suggested that bilateral disease was a characteristic of familial breast cancer.     

Family history of breast and ovarian cancer and the risk of breast carcinoma in situ

A family history of breast cancer is an important risk factor for breast carcinoma in situ (BCIS), however, there are no detailed analyses of its variation in effect by number, type, laterality or age at onset of affected relatives nor by association with ovarian cancer. In addition, the role of the breast cancer susceptibility genes, BRCA1 and BRCA2, in the development of BCIS is unclear. Objective. To better define the role of: (1) a family history of breast and ovarian cancer and (2) the cancer susceptibility genes, BRCA1 and BRCA2, in the development of BCIS. Methods. The data are 875 ductal carcinoma in situ (DCIS) and 123 lobular carcinoma in situ (LCIS) cases diagnosed among residents of the state of Connecticut from September 15, 1994 to March 14, 1998 and between the age of 20 and 79 years. Controls (n = 999) are female Connecticut residents collected via random-digit-dial and frequency matched to the cases by 5-year age intervals. Telephone interviews were used to collect information on risk factors and cancer screening history.Logistic regression was used to provide maximum likelihood estimates of the odds ratios (OR) with 95% confidence intervals (95% CI). The probability of being a BRCA1 and/or BRCA2 gene carrier was calculated for each case and control, using family history of breast and ovarian cancer, age/age at diagnosis for relatives, prevalence and penetrance data for BRCA1/BRCA2, and self-report of Jewish heritage. Results. Cases with DCIS or LCIS were significantly more likely to report a first degree family history of breast cancer (OR: 1.6, 95% CI: 1.3, 2.1 and 1.8, 95% CI: 1.2, 2.9, respectively) than were controls. In addition, DCIS cases were 2.4 (95% CI: 0.8, 7.2) times more likely than controls to report both an affected mother and sister. An inverse association was suggested between age at onset and DCIS risk with cases aged 49 years or younger at 2.1 (95% CI: 1.3, 3.4) times the risk of controls (95% CI) versus 1.5 (95% CI: 1.1, 2.0) for cases older than 49 years. An elevated risk of DCIS was associated with a family history of ovarian cancer but did not reach statistical significance (OR: 1.3, 95% CI: 0.7, 2.5). Approximately 3.7% and 1.9% of DCIS cases were predicted to carry a mutation in BRCA1 and BRCA2, respectively. Conclusions. A family history of breast cancer is associated with an increased risk of DCIS and LCIS, particularly among women with multiple relatives affected at early ages. Statistical risk models predict a low prevalence rate of BRCA1 and BRCA2 in DCIS; these estimates await confirmation through laboratory testing.     

Family history of breast or ovarian cancer modifies the risk of secondary leukemia after breast cancer: results from a population-based study

We evaluated the impact of a family history of breast/ovarian cancer on the risk of secondary leukemia following breast cancer. At the Geneva cancer registry, we identified 4,397 patients diagnosed with invasive breast cancer between 1990 and 2004. Patients were followed up for leukemia until the end of 2005. Family history was categorized as positive in patients with >or=1 first- or second-degree relative with breast/ovarian cancer. We compared leukemia rates in patients with positive and negative family histories with those expected in the general population, generating standardized incidence ratios (SIRs). With Cox regression analysis, we calculated adjusted risks of secondary leukemia in patients with familial risks compared to those without it. Breast cancer patients had a significantly increased risk of secondary acute leukemia (SIR 3.2, 95% CI: 1.2-6.9) but not of chronic leukemia (SIR 1.6, 95% CI: 0.6-3.5). Among patients with a positive family history (n = 1.125, 25.6%), the SIRs were 5.7 (95% CI: 1.2-16.6) for acute and 5.2 (95% CI: 1.4-13.3) for chronic leukemia. Among breast cancer patients, family history was independently associated with leukemia [adjusted hazard ratio (HR(adj)) of 3.2, 95% CI: 1.1-9.2, among patient with vs. without family history]. The effect of family history was stronger for chronic leukemia (HR(adj): 11.6, 95% CI 1.3-104.7) than for acute leukemia (HR(adj) 1.6, 95% CI: 0.4-6.6). Breast cancer patients with a family history of breast/ovarian have an increased risk of secondary leukemia, both compared to the general population as well as to breast cancer patients without family histories. This excess risk is largely due to the increased risk of secondary chronic leukemia.     

Family history of breast cancer,age and benign breast disease

A major risk factor for breast cancer is having a first-degree family history of the disease. Benign breast disease (BBD), particularly atypical hyperplasia, is also associated with an increased risk of breast cancer. However, the relationship between family history of breast cancer and BBD is unclear. From 1989 through 1997, 80,995 participants in the Nurses' Health Study II were followed; 16,849 reported a first diagnosis of BBD. Pathology slides were reviewed for 1,465 women who reported having a tissue biopsy, and these were classified as nonproliferative BBD, proliferative BBD without atypia or atypical hyperplasia. Women with a family history of breast cancer were more likely to report a physician diagnosis of BBD [rate ratio (RR) = 1.38, 95% confidence interval (CI) 1.29-1.46]. The magnitude of this association declined with age from RR = 1.96 (95% CI 1.55-2.47) at 25-29 years to RR = 1.20 (95% CI 0.95-1.52) at age 45-50 years. Among women with proliferative disease, those with a family history of breast cancer were almost 3 times as likely to have atypia (prevalence odds ratio = 2.72, 95% CI 1.23-5.89) than those with no family history. In conclusion, women with a family history of breast cancer appear to be at increased risk of being diagnosed with BBD, in particular the high-risk types of BBD associated with a greatly increased risk of breast cancer. This link adds weight to the belief that BBD with atypia is a precursor or marker lesion for breast cancer.     

Tea consumption and breast cancer risk in a cohort of women with family history of breast cancer

Laboratory studies have observed chemopreventive effects of black and green tea on breast cancer development, but few epidemiologic studies have identified such effects. We investigated the association between tea consumption and breast cancer risk using data from 45,744 U.S. and Puerto Rican women participating in the Sister Study. Frequency and serving size of black and green tea consumption were measured at cohort enrollment. Breast cancer diagnoses were reported during follow-up and confirmed by medical record review. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We further investigated potential variation according to estrogen receptor (ER) status, menopausal status and body mass index (BMI). Overall, 81.6 and 56.0% of women drank black or green tea, respectively. A total of 2,809 breast cancer cases were identified in the cohort. The multivariable model suggested an inverse association between black (≥5 vs. 0 cups/week: HR = 0.88, 95% CI 0.78, 1.00, p-trend = 0.08) and green tea (≥5 vs. 0 cups/week: HR = 0.82, 95% CI 0.70, 0.95, p-trend < 0.01) consumption and breast cancer risk. We did not observe differences by ER characteristics, menopausal status or BMI. In conclusion, our study suggests drinking at least five cups of green or black tea per week may be associated with decreased breast cancer risk.     

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.     

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).     

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.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

Family history and survival after colorectal cancer diagnosis

BACKGROUND

A history of colorectal cancer in a first‐degree relative is a recognized risk factor for developing this malignancy. The influence of a family history of colorectal cancer on survival after a diagnosis of colorectal cancer was examined in a large cohort of women.

METHODS

We analyzed data from 1001 women diagnosed with colorectal cancer while participating in a prospective cohort study. Data on family history were obtained before cancer diagnosis. We computed Cox proportional hazards for cancer‐specific and overall mortality according to a family history of colorectal cancer, adjusting for other predictors for survival.

RESULTS

Before diagnosis, 16% of colorectal patients reported a history of colorectal cancer in a first‐degree relative. Patients with a history of colorectal cancer in 1 or more first‐degree relatives experienced an adjusted hazard ratio (HR) for overall mortality of 1.32 (95% confidence interval [CI], 1.01–1.72) and colorectal cancer‐specific mortality of 1.38 (95% CI, 1.02–1.86) when compared with those without a family history. Moreover, patients with 2 or more affected relatives had an HR for overall mortality of 2.07 (95% CI, 1.14–3.76) and cancer‐specific mortality of 2.19 (95% CI, 1.10–4.38). The significant deleterious effect of family history was limited to patients with advanced disease at presentation and cancers originating in the colon.

CONCLUSIONS

Among women with colorectal cancer, a history of colorectal cancer in a first‐degree relative was associated with a significant decrease in survival. Additional study is needed to validate these findings and determine whether specific germline polymorphisms correlate with clinical outcomes. Cancer 2008. © 2008 American Cancer Society.     

Mammographic screening for young women with a family history of breast cancer: knowledge and views of those at risk

Although the effectiveness of mammography for women under the age of 50 years with a family history of breast cancer (FHBC) has not yet been proven, annual screening is being offered to these women to manage breast cancer risk. This study investigates women's awareness and interpretation of their familial risk and knowledge and views about mammographic screening. A total of 2231 women from 21 familial/breast/genetics centres who were assessed as moderate risk (17-30% lifetime risk) or high risk (>30% lifetime risk) completed a questionnaire before their mammographic screening appointment. Most women (70%) believed they were likely, very likely or definitely going to develop breast cancer in their lifetime. Almost all women (97%) understood that the purpose of mammographic screening was to allow the early detection of breast cancer. However, 20% believed that a normal mammogram result meant there was definitely no breast cancer present, and only 4% understood that screening has not been proven to save lives in women under the age of 50 years. Women held positive views on mammography but did not appear to be well informed about the potential disadvantages. These findings suggest that further attention should be paid to improving information provision to women with an FHBC being offered routine screening.     

Towards personalized screening: Cumulative risk of breast cancer screening outcomes in women with and without a first‐degree relative with a history of breast cancer

Several reviews have estimated the balance of benefits and harms of mammographic screening in the general population. The balance may, however, differ between individuals with and without family history. Therefore, our aim is to assess the cumulative risk of screening outcomes; screen‐detected breast cancer, interval cancer, and false‐positive results, in women screenees aged 50–75 and 40–75, with and without a first‐degree relative with a history of breast cancer at the start of screening. Data on screening attendance, recall and breast cancer detection were collected for each woman living in Nijmegen (The Netherlands) since 1975. We used a discrete time survival model to calculate the cumulative probability of each major screening outcome over 19 screening rounds. Women with a family history of breast cancer had a higher risk of all screening outcomes. For women screened from age 50–75, the cumulative risk of screen‐detected breast cancer, interval cancer and false‐positive results were 9.0, 4.4 and 11.1% for women with a family history and 6.3, 2.7 and 7.3% for women without a family history, respectively. The results for women 40–75 followed the same pattern for women screened 50–75 for cancer outcomes, but were almost doubled for false‐positive results. To conclude, women with a first‐degree relative with a history of breast cancer are more likely to experience benefits and harms of screening than women without a family history. To complete the balance and provide risk‐based screening recommendations, the breast cancer mortality reduction and overdiagnosis should be estimated for family history subgroups.     

Family history of cancer and subsequent risk of cancer: A large-scale population-based prospective study in Japan

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population-based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self-administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable-adjusted Cox proportional hazards regression models. During 1,802,581 person-years of follow-up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07–1.15]), esophagus (2.11 [1.00–4.45]), stomach (1.36 [1.19–1.55]), liver (1.69 [1.10–2.61]), pancreas (2.63 [1.45–4.79]), lung (1.51 [1.14–2.00]), uterus (1.93 [1.06–3.51]) and bladder cancers (6.06 [2.49–14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high-risk of those cancers.     

Family history of cancer and risk of gastric cancer in Iran

Introduction: Gastric cancer is one of the major causes of cancer related death in the world. A number of risk factors are now known to be related to the development of the disease. Previous reports indicated that a family history is a serious risk, but there is a little information about this in Iran. The aim of this study was to explore the relation between family history of cancer in first and second degree relatives and the risk of GC in Iran. Methods: The present study was designed as unmatched case control study. Cases were 746 patients with histologically confirmed GC and the 746 controls were randomly selected among the healthy participants in a health survey. Family history was extracted from a standard history form completed by the patient or from records created by a health care provider. Mantel-Heanszel odds ratios were computed for removing the confounding effect of age and sex. Results: Overall, 9.7% of cases versus 5.6% of controls reported a family history of GC. Risk increased over twofold for this group. There was no significant association among family history of other cancers and GC (P>0.05). Conclusion: In conclusion, this study showed that family history of GC, especially in first-degree relatives, increases the risk of development of the disease. Further studies are needed to better understand the roles of genetic and environmental factors and their interaction in gastric cancer development in the Iranian community.     

Interval breast cancer risk associations with breast density,family history and breast tissue aging

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case–control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69–0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts—an increased risk of developing an interval breast cancer.