Lactation and the risk of breast cancer in an Italian population

The relation between breast feeding and breast cancer was investigated in a multicentric case-control study conducted in Italy on 2,167 parous women with histologically confirmed breast cancer, diagnosed within 1 year, and 2,208 parous control women admitted to hospitals in the same catchment areas of cases for acute, non-neoplastic, non-gynecological non-hormone-related diseases. Compared with women who had never tried to lactate, those who had always failed had a multivariate odds ratio (OR; adjusted for parity, education and several other potential confounding factors) of 0.94, and those who had lactated had an OR of 1.17. The multivariate ORs of women who had breast fed 1, 2 and 3 or more children were, respectively, 1.14, 1.18 and 1.32, compared with women who had never lactated. None of these ORs was statistically significant. Compared with women who had never breast fed, the multivariate ORs were 1.19 for women reporting less than 6 months of breast feeding, 1.15 for 6–11 months, 1.34 for 12–17 months, 1.10 for 18–23 months and 0.86 for 24 months or more. No appreciable difference was evident across strata of age, menopausal status, parity and age at first birth, while there was a hint of interaction with education. Our study therefore excluded any appreciable protective role for lactation in breast cancer risk, with the patterns of lactation in this European population, aside from the protective role of parity on breast carcinogenesis. © 1996 Wiley-Liss, Inc.     

Lactation and the risk of breast cancer

Some factors are suggested to have an association with an increased risk of breast cancer, which are called risk factors. Lactation is one of the risk factors that still needs to be studied because of conflicting findings in epidemiological studies and also uncertainty regarding biologic plausibility. Our objective was to study the relationship between lactation and the risk of breast cancer. A pair of unmatched case control studies was held among parous women at Dr. Soetomo Hospital (general hospital) and some private hospitals in the Surabaya municipality. There are 219 (51.9%) cases and 203 (48.1%) controls analyzed in this study. Age, age at menarche, regular menstruation and number of parity between both groups are not statistical different. When we divided the age at menarche (below 13), it was statistically different. The cases consisted of more women with menarche below 13 (p = 0.00038). Other factors showing statistical differences in the risk of breast cancer between case and control are age at first delivery, family history of breast cancer and age at menopause. Women who have lactated (more than 4-month duration of breast feeding) show a "protective effect" against breast cancer, OR 0.57 (95% CI 0.33-0.99). However, there was no clear duration of lactation and the risk of breast cancer. Logistic regression analysis showed that lactation was not any independent factor. Lactation exerts a "protective effect" against breast cancer. However, the duration of lactation did not show an influence in reducing the risk of breast cancer, and logistic regression analysis did not show that lactation was an independent factor in the risk of breast cancer.     

Lactation and breast cancer risk: a case-control study in Connecticut

In this report, we examined the relationship between lactation and breast cancer risk, in a case-control study of breast cancer, conducted in Connecticut between 1994 and 1998. Included were 608 incident breast cancer cases and 609 age frequency matched controls, aged 30-80 years old. Cases and controls were interviewed by trained study interviewers, using a standardized, structured questionnaire, to obtain information on lactation and other major risk factors. Parous women who reported ever lactation had a borderline significantly reduced risk of breast cancer (OR = 0.83, 95% CI, 0.63-1.09). An OR of 0.53 (95% CI, 0.27-1.04) was observed in those having breastfed more than 3 children compared to those who never lactated. Women having breastfed their first child for more than 13 months had an OR of 0.47 (95% CI, 0.23-0.94) compared to those who never breastfed. Lifetime duration of lactation also showed a risk reduction while none of the ORs were statistically significant. Further stratification by menopausal status showed a risk reduction related to lactation for both pre- and postmenopausal women, while the relationship is less consistent for the latter. These results support an inverse association between breastfeeding and breast cancer risk.     

Hepatocellular carcinoma in a rural population at risk.

This study of hepatocellular carcinoma in a homogeneous rural Transkeian population at high risk consisted of: evaluation of liver biopsies of 246 patients with hepatocellular carcinoma using routine histology and immunoperoxidase for HBV stains; collection of reliable data on alcohol consumption, blood HBsAg and ALT status in asymptomatic controls from an adequate population sample; assessment of maize intended for human consumption for contamination by carcinogenic fungi. Tumour histology of rural Blacks did not differ from those described in other studies. Cirrhotic livers were present in 45.1% and iron overload in 68% of cases. Tissue HBsAg was detected in 57% (45% of non-cirrhotic and 59% of cirrhotic livers). Asymptomatic controls showed 9.5% of HBsAg positivity, 3.5% had elevated ALT and 41.3% admitted to alcohol abuse. Maize had insignificant contamination by Aspergillus flavus and very frequent contamination by Fusarium moniloforme. This study suggests a multifactorial aetiology of hepatocellular carcinoma, with viral infection being of the most importance.     

Lung cancer in Africans in a South African city population in transition.

In South Africa, a study has been carried out on a series of African patients with lung cancer, who were admitted in 1994-1999 to King Edward VIII Hospital (2000 beds), and who lived in Durban (population includes approximately 650 000 resident Africans). In the urban context, Africans have recently experienced numerous changes in environmental, socio-economic and dietary factors and in other respects, thereby undergoing considerable westernization of lifestyle, compared with the past and the situation still prevailing among Africans in rural areas. In the period indicated, the mean annual number of patients admitted with lung cancer included 56 men and 9 women, thereby yielding standardized incidence rates of 15.5 and 3.5, respectively, per 100 000. While such data have their limitations, it is noteworthy that in the South African Cancer Registry for 1993-1995 the corresponding rates (pathology based) for African men and women for the whole country, rural and urban, were 11.7 and 2.6, respectively, per 100 000. In comparison, in the Registry the corresponding rates reported for white South African men and women were 22.3 and 12.3 per 100 000. With the ongoing transitional changes prevailing, most particularly concerning rises in smoking among adolescents, there is little chance of controlling further rises in the occurrence of the disease. It is significant that in the US, African Americans have been reported to have the highest rate for lung cancer in the world.     

Adolescence and breast carcinoma risk.

BACKGROUND: Breast carcinoma risk may be modified by early life factors, including physical growth and development, diet, and life-style factors of preadolescence and adolescence, as well as genetic factors. METHODS: The authors tested their hypothesis that adolescent growth and development are related to breast carcinoma incidence by evaluating 65,140 women who participated in the Nurses' Health Study. During 16 years of follow-up, 806 women were diagnosed with breast carcinoma prior to menopause, and another 1485 were diagnosed after menopause. Because adolescent growth was not directly observed in this cohort, the peak height growth velocity for each participant was estimated by using a model from another longitudinal study. Finally, Cox proportional hazards regression models were used to study associations between breast carcinoma incidence and adolescent factors in the Nurses' Health Study. RESULTS: Later menarche (relative risk [RR] = 0.52 for > or =15 vs. < or =11 years) and more body fatness at age 10 years (RR = 0.60 for fattest vs. leanest) were associated with a decreased risk of premenopausal breast carcinoma. The risk of postmenopausal breast carcinoma was lower for girls with later menarche (RR = 0.80), more body fat at age 10 years (RR = 0.72), and shorter adult height (RR = 1.29 for > or =67 vs. < or =62 inches). Higher peak height growth velocity, derived from these 3 variables, was associated with increased risk of both premenopausal (RR = 1.31 for highest vs. lowest quintile) and postmenopausal (RR = 1.40) breast carcinoma. These analyses controlled for birth cohort, other possible risk factors from the adolescent period, and family history. These associations persisted after controlling for age at the birth of a first child, parity, adult adiposity, and age at menopause. Post-hoc analyses suggested that, although childhood body fatness was associated with lower risk, increasing body fatness between ages 10 and 20 years was not protective against either premenopausal or postmenopausal breast carcinoma. CONCLUSIONS: Earlier menarche, extremely lean body mass at age 10 years, and taller adult height were predictive of elevated breast carcinoma risk. The same three factors were also predictive of higher peak growth velocities during adolescence, lending credence to the hypothesis that more rapid adolescent growth may increase the risk of breast carcinoma development.     

Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population

BACKGROUND: Identifying BRCA1 and BRCA2 mutation carriers is increasingly important as new management options show promise in decreasing morbidity and mortality in these women. The authors sought to determine the prevalence of family histories suggestive of a hereditary breast carcinoma syndrome in a cohort of patients with a personal history of breast and/or ovarian carcinoma presenting for mammography. METHODS: The authors reviewed the family histories of all women with a history of breast or ovarian carcinoma presenting for mammography over a 37-week period. Using the Myriad model, the authors evaluated the prevalence of family histories with a > or = 10% risk of a BRCA1 or BRCA2 mutation. RESULTS: During the period of the current study, 14,597 women completed a family history questionnaire. Of these women, 1764 had a personal history of breast or ovarian carcinoma, 86.6% had unilateral breast carcinoma, 4.6% had bilateral breast carcinoma, 8.2% had ovarian carcinoma, and 0.5% had both breast and ovarian carcinoma. Overall, 20.6% met the criteria for a > or = 10% risk of mutation according to the Myriad model. This incidence was higher among Ashkenazi women (47.3%) and among patients with a personal history of ovarian carcinoma (35.9%). CONCLUSIONS: Application of the Myriad model to women with a personal history of breast and ovarian carcinoma suggested that approximately 1 in 5 of these women (20.6%) will have family histories suspicious for a genetic mutation. This risk was higher for Ashkenazi women and for those with a personal history of ovarian carcinoma. This prevalence was considerably higher than the rate reported among women with no personal history of cancer, and has significant implications for their management, as well as for the capacity for risk assessment and testing.     

Risk of thyroid carcinoma in a female population after radiotherapy for breast carcinoma.

BACKGROUND: There is increasing concern regarding the risk of developing a second primary tumor in adjacent organs as a result of scattered radiation among patients who have undergone radiotherapy (RT) for breast carcinoma. Previous studies have focused mainly on the possible increase in the incidence of contralateral breast carcinoma. To the authors' knowledge, the risk of thyroid carcinoma among these women has not been explored to date. METHODS: In this population-based, retrospective cohort study, the authors identified 194,798 women who were diagnosed with invasive breast carcinoma (exclusive of those with distant metastasis) between 1973 and 1993, and ascertained subsequent cases of thyroid carcinoma utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute. Poisson regression was used to calculate the age-standardized incidence ratio (SIR) of thyroid carcinoma and to model the influence of RT on the relative risk (RR) between the RT cohort (48,495 women) and the non-RT cohort (146,303 women). RESULTS: A total of 28 women in the RT cohort and 112 women in the non-RT cohort subsequently developed thyroid carcinoma. The distribution of thyroid carcinoma histologies in both the RT cohort and the non-RT cohort was similar to that in the female general population. Overall, there was no significant increase in the risk of thyroid carcinoma in either the RT cohort or the non-RT cohort compared with the general population; the SIR was 1.1 (95% confidence interval [95% CI], 0.8-1.6) for the RT cohort and 1.2 (95% CI, 1.0-1.4) for the non-RT cohort. When the RT cohort was compared with the non-RT cohort, the RR of thyroid carcinoma was 1.0 (95%CI, 0.7-1.5). CONCLUSIONS: The risk of radiation-associated thyroid carcinoma after initial RT for breast carcinoma was so low as to be undetectable in the current large population-based study. Continued monitoring of these women will be required to document that these findings are maintained with even longer follow-up periods. However, with 10,895 women having been followed for > 10 years at the time of last follow-up in the current study, these findings should be reassuring to women considering RT for their breast carcinoma. Therefore, women who have received RT for breast carcinoma require no special surveillance for their thyroid gland. Furthermore, previous breast radiation need not be a factor in determining the optimal management of thyroid nodules arising in women who received RT for breast carcinoma.     

Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population

The double-strand break (DSB) DNA repair pathway has been implicated in breast cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in the repair of DSB through homologous recombination (HR). Some polymorphisms including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to confer increased BC susceptibility. In order to detect novel mutations that may contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2-negative families were screened for mutations in XRCC3. No mutations were detected in the XRCC3 gene. In addition, using a case–control design we studied the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500 controls to evaluate their possible association with BC susceptibility. The XRCC3 Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44 [95%CI 1.34–4.43]). We did not find an association between E233G polymorphism and BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C, Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed between Thr241Met and 135G>C. The combined genotype Thr/Met–E/G was associated with an increased BC risk among women who (a) have a family history of BC, (b) are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR = 10.5 [95%CI 1.16–94.5]). Our results suggested that the variability of the DNA HR repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be underlined by a mutual interaction between these genes. These findings should be confirmed in other populations.     

Beta-benzene hexachloride in breast adipose tissue and risk of breast carcinoma.

BACKGROUND: Epidemiologic studies have recently related benzene hexachloride (BHC) to breast carcinoma risk. Experimental studies have also shown that beta-BHC is weakly estrogenic, hence supporting the alleged association. By directly comparing beta-BHC levels in breast adipose tissue from incident breast carcinoma cases and controls, this study examined the hypothesis that exposure to beta-BHC increases the risk of breast carcinoma in females. METHODS: A total of 490 Connecticut women (304 cases and 186 controls) were enrolled in the study during the period 1994-1997. Cases were patients ages 40-79 years with histologically confirmed incident primary breast carcinoma. Controls were patients with histologically confirmed incident benign breast disease. Breast adipose tissue was collected and analyzed for BHC isomers. A linear logistic regression model was used to adjust for potential confounders in estimating the association of exposure with disease. RESULTS: No significant differences in breast adipose tissue levels of beta-BHC were observed between the cases and their controls overall, nor by menopausal status or estrogen and progesterone receptor status of the breast carcinoma cases. A nonsignificant reduced risk was observed among all subjects and among pre- and postmenopausal women when the highest quartile was compared with the lowest. Parous women with higher beta-BHC levels, regardless of lactation status, had a nonsignificantly reduced breast carcinoma risk, whereas a nonsignificantly increased risk was observed among nulliparous women with higher beta-BHC levels, based on very few study subjects. CONCLUSIONS: The results of this study do not support the hypothesis that increasing adipose tissue levels of beta-BHC are associated with an increased risk of breast carcinoma in females.     

Risk of subsequent contralateral breast carcinoma in a population of patients with in-situ breast carcinoma

One hundred ninety-one cases of unilateral noninvasive breast carcinoma were studied with regard to the development of subsequent cancers in the contralateral breast. The majority of patients were treated by mastectomy and have been followed for an average of nine years. Their overall survival did not differ significantly from that of age-specific population survival figures for U. S. women. Among all cases, 13 or 6.8% subsequently developed contralateral carcinoma; 3.1% of these contralateral tumors were invasive. The authors found only one histological type, namely lobular carcinoma in-situ for which the development of subsequent contralateral carcinomas was statistically significant. Seven of the 68 women with this type developed second breast cancers (10.3%; 4.4% of these were invasive). These data suggest that the occurrence of clinically apparent subsequent cancers developing in the opposite breast following the diagnosis of in-situ carcinoma is relatively small.     

Sociocultural predictors of breast cancer risk perceptions in African American breast cancer survivors.

Although African American breast cancer survivors are at increased risk for developing breast cancer again, empirical data are not available on breast cancer risk perceptions in these women. This study characterized perceived risk of developing breast cancer in African American breast cancer survivors at risk for having a BRCA1 or BRCA1 (BRCA1/2) mutation and identified factors having significant independent associations with risk perceptions. Participants were 95 African American breast cancer survivors at an increased risk for having a BRCA1/2 mutation. Risk perceptions and sociodemographic, clinical, treatment, and sociocultural factors were collected during a structured telephone interview. Most women reported that they had the same or lower risk of developing breast cancer again compared with other women (53%); however, a substantial minority of women (47%) reported that they had a higher or much higher risk. Factors having significant independent associations with heightened risk perceptions included having a >or=10% prior probability of having a BRCA1/2 mutation [odds ratio (OR), 2.91; 95% confidence interval (95% CI), 1.09-7.72; P = 0.03] and more years of formal education (OR, 2.74; 95% CI, 1.02-7.36; P = 0.05). In addition, women who thought about the past a lot were three times more likely to report heightened risk perceptions compared with those who did not think about the past a lot (OR, 3.72; 95% CI, 1.45-9.57; P = 0.01). These results suggest that it may be important to ensure adequate risk comprehension among African American women as part of genetic counseling for inherited breast-ovarian cancer risk. Discussion of risk perceptions within the context of existing beliefs and values may facilitate this process.     

Incremental impact of breast cancer SNP panel on risk classification in a screening population of white and African American women

Breast cancer risk prediction remains imperfect, particularly among non-white populations. This study examines the impact of including single-nucleotide polymorphism (SNP) alleles in risk prediction for white and African American women undergoing screening mammogram. Using a prospective cohort study, standard risk information and buccal swabs were collected at the time of screening mammography. A 12 SNP panel was performed by deCODE genetics. Five-year and lifetime risks incorporating SNPs were calculated by multiplying estimated Breast Cancer Risk Assessment Tool (BCRAT) risk by the total genetic risk ratio. Concordance between the BCRAT and the combined model (BCRAT + SNPs) in identifying high-risk women was measured using the kappa statistic. SNP data were available for 810 women (39 % African American, 55 % white). The mean BCRAT 5-year risk was 1.71 % for whites and 1.18 % for African Americans. Mean genetic risk ratios were 1.09 in whites and 1.29 in African Americans. Among whites, three SNPs had higher frequencies, and among African Americans, seven SNPs had higher and four had lower high-risk allele frequencies than previously reported. Agreement between the BCRAT and the combined model was relatively low for identifying high-risk women (5-year κ = 0.54, lifetime κ = 0.36). Addition of SNPs had the greatest effect among African Americans, with 12.4 % identified as having high-5-year risk by BCRAT, but 33 % by the combined model. A greater proportion of African Americans were reclassified as having high-5-year risk than whites using the combined model (21 vs. 10 %). The addition of SNPs to the BCRAT reclassifies the high-risk status of some women undergoing screening mammography, particularly African Americans. Further research is needed to determine the clinical validity and utility of the SNP panel for use in breast cancer risk prediction, particularly among African Americans for whom these risk alleles have generally not been validated.     

A polygenic risk score for breast cancer risk in a Taiwanese population

Background

Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population.

Methods

In total, 446 breast cancer patients and 514 healthy controls were recruited for this case–control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC).

Results

Logistic regression results showed that nine individual SNPs were significantly associated with breast cancer risk after multiple testing. Among all SNPs, six variants, namely FGFR2 (rs2981582), HCN1 (rs981782), MAP3K1 (rs889312), TOX3 (rs3803662), ZNF365 (rs10822013), and RAD51B (rs3784099), were selected to create PRS model. A dose–response association was observed between breast cancer risk and the PRS. Women in the highest quartile of PRS had a significantly increased risk compared to women in the lowest quartile (odds ratio 2.26; 95% confidence interval 1.51–3.38). The AUC for a model which contained the PRS in addition to clinical risk factors was 66.52%, whereas that for a model which with established risk factors only was 63.38%.

Conclusions

Our data identified a genetic risk predictor of breast cancer in Taiwanese population and suggest that risk models including PRS and clinical risk factors are useful in discriminating women at high risk of breast cancer from those at low risk.

     

Esophagitis in a population at risk for esophageal carcinoma

A previously unreported high incidence of endoscopically identifiable, diffuse, largely nonulcerative esophagitis, is described in a selected population of Southern African blacks at risk of cancer of the esophagus. This is comparable with findings in similar groups in Iran and China. The incidence of dysplasia and "early" cancer is still undefined in South Africa.     

Mammographic density as a risk factor for breast cancer in a low risk population

Background: Mammographic density is a function of abundance of epithelial and connective tissue in breast. It has been identified as an independent risk factor for breast cancer in studies in western populations. We conducted a case control study to evaluate the role of mammographic density as risk factor for the development of breast cancer in Indian patients. Methods: One hundred and one cases of breast cancer and 123 healthy controls were included in the study. Mammographic density of the breast tissue of all controls and the contralateral breast of breast cancer patients was measured using a six category scale by a qualified radiologist. Results: A low prevalence of dense mammographic patterns (16.3% in controls and 26.7% in cases) was seen in the study population. Premenopausal women with breast density of 50% or more had 3.8 times risk of developing breast cancer than women with breast density of Conclusion: High mammographic density patterns are associated with an increased risk for the development of breast cancer in younger women in a low risk population, whereas no such increase in risk is seen in postmenopausal women.     

Oral contraceptive use and risk of breast carcinoma in situ.

There is some indication that oral contraceptive use may be associated with a small increase in risk of invasive breast cancer; however, oral contraceptive use in relation to breast carcinoma in situ (BCIS) has rarely been studied. We investigated oral contraceptive use in relation to risk of BCIS in a large population-based case-control study. Female residents of Wisconsin, Massachusetts, and New Hampshire aged 20 to 74 years with a new diagnosis of BCIS (n=1,878) were identified from statewide tumor registries in 1997 to 2001. Age-matched female controls (n=8,041) were randomly selected from population lists. Information on oral contraceptive use and other risk factors was collected during structured telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. In multivariate models, ever use of oral contraceptives was associated with a small and marginally significant increase in BCIS overall (OR, 1.11; 95% CI, 0.99-1.25) and for ductal carcinoma in situ (OR, 1.15; 95% CI, 1.01-1.31). No strong associations were detected according to age started, duration, time since first or last use, or oral contraceptive use relative to the first full-term pregnancy. The slightly increased risk of BCIS seemed limited to former users (OR, 1.13; 95% CI, 1.00-1.27) and women without a family history of breast cancer (OR, 1.16; 95% CI, 1.01-1.32 for ever versus never use). Consistent with invasive breast cancer, these results suggest that oral contraceptive use is at most a minor contributor to BCIS risk.     

Alcohol consumption as a risk factor for hepatocellular carcinoma in urban southern African blacks.

Our purpose was to ascertain whether alcohol abuse is a risk factor for the development of hepatocellular carcinoma in urban southern Africa blacks and, if so, to relate alcohol consumption to other possible risk factors such as persistent hepatitis-B-virus infection, smoking, male sex, in this subpopulation. A prospective, hospital-based, case-control format involving 101 patients with hepatocellular carcinoma and 101 controls was used. The mean age of the patients was 53.7 +/- 1.85 years and the male:female ratio 3.2:1. An increased risk was found, but only in urban men over the age of 40 years who habitually drank more than 80 g of ethanol daily. The risk remained after adjusting for chronic hepatitis-B infection, smoking, and sex (odds ratio 4.4, 95% confidence interval 1.3 to 16.6; p = 0.003). Smoking proved not to be a risk factor, either alone or in concert with alcohol consumption. Hepatitis-B infection was confirmed as a major risk in younger men and in women, but in urban men over the age of 40 years alcohol abuse was a greater risk. Current hepatitis-B infection and alcohol abuse were additive risks.