Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.     

Dietary Phytoestrogen, Serum Enterolactone and Risk of Prostate Cancer: The Cancer Prostate Sweden Study (Sweden)

Objective

Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer.

Methods

In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer.

Results

High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57–0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15–0.55), 0.63 (95% CI: 0.35–1.14) and 0.74 (95% CI: 0.41–1.32).

Conclusions

Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.     

Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women

Background

It is known that use of hormone replacement therapy (HRT) by postmenopausal women increases the risk of breast cancer.

Method

In this study, oestrogen receptor (ER)-α expression is examined using standard immunoperoxidase technique.

Results

Normal breast samples of 11 Australian postmenopausal women have been included in the ER-α study; the result showed a strong correlation (r ² = 0.80) between ER-α expression in normal breast epithelial cells and body mass index (BMI) in normal women who currently use HRT.

Conclusion

This finding confirms that the possibility of increased risk of breast cancer associated with increased ER-α expression in normal breast epithelial cells, in turn associated with high BMI and the use of HRT.     

Lack of prospective associations between plasma and urinary phytoestrogens and risk of prostate or colorectal cancer in the European Prospective into Cancer-Norfolk study

Dietary phytoestrogens are suggested to reduce the risk of prostate and colorectal cancer, but the results of epidemiologic studies have not yielded consistent support for this proposed effect, possibly due to inadequate databases of phytoestrogen levels in foods. Biomarkers of phytoestrogen intakes may provide a clearer insight into the relationship between phytoestrogen exposure and the risk of prostate or colorectal cancer risks. From the European Prospective into Cancer-Norfolk cohort (ages 45-75), serum and urine samples were analyzed for seven phytoestrogens [daidzein, enterodiol, enterolactone, genistein, glycitein, O-desmethylangolensin (O-DMA), and equol] among 193 cases of prostate cancer and 828 controls, and 221 cases of colorectal cancer with 889 controls. Summary variables of total lignans (enterodiol and enterolactone) and total isoflavones (daidzein, genistein, O-DMA, equol, and glycitein) were created and analyzed in conjunction with individual phytoestrogens. Logistic regression analyses revealed that there was no significant association between prostate cancer risk and total serum isoflavones [odds ratio (OR), 1.01; 95% confidence interval (CI), 0.93-1.10] or total serum lignans (OR, 0.94; 95% CI, 0.86-1.04) or between colorectal cancer risk and total serum isoflavones (OR, 1.01; 95% CI, 0.94-1.08) or total serum lignans (OR, 1.03; 95% CI, 0.94-1.12). Similarly, null associations were observed for individual serum phytoestrogens and for all urinary phytoestrogen biomarkers. In conclusion, we have found no evidence to support an inverse association between phytoestrogen exposure and prostate or colorectal cancer risk.     

Associations of change in television viewing time with biomarkers of postmenopausal breast cancer risk: the Australian Diabetes,Obesity and Lifestyle Study

Purpose

Sedentary behavior has been previously shown, in a cross-sectional study, to have deleterious associations with biomarkers of postmenopausal breast cancer risk. We examined the associations of change in sedentary behavior [daily television (TV) viewing time, h/day] over a 5-year period with putative markers of postmenopausal breast cancer risk.

Methods

The analytic cohort consisted of 1,001 postmenopausal women from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study (1999–2005). Multivariate linear regression models were used to examine associations of change in TV viewing time with biomarkers of the following risk mechanisms: adiposity (body mass index [BMI], waist circumference); metabolic dysfunction (fasting plasma glucose, 2-h plasma glucose, fasting insulin, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]); and inflammation (high-sensitivity C-reactive protein (hs-CRP)). All analyses were adjusted for age, baseline TV viewing, and potential confounders.

Results

Hourly increments of change in TV viewing time were positively associated with BMI (β = 0.50, 95 % CI 0.20, 0.81; p = 0.001), waist circumference (β = 1.18, 95 % CI 0.49, 1.87; p = 0.001), fasting insulin (β = 38.13 %, 95 % CI 37.08, 39.20; p = 0.01) and HOMA-IR (β = 37.93 %, 95 % CI 36.92, 38.98; p = 0.03) in fully adjusted models. Significant associations with BMI, waist circumference, fasting insulin and HOMA-IR were also present in analyses using categories of change in TV viewing time (reduced, same, increased).

Conclusions

The findings suggest that increasing habitual sedentary behavior over time could increase breast cancer risk among postmenopausal women. Further investigation into the role of sedentary behavior in breast cancer etiology is warranted.     

A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

Introduction

Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).

Methods

The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls).

Results

We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed.

Conclusion

Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.     

p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy

Introduction

Shc adapter proteins are secondary messenger proteins involved in various cellular pathways, including those mediating receptor tyrosine kinase signaling and apoptosis in response to stress. We have previously reported that high levels of tyrosine-phosphorylated Shc (PY-Shc) and low levels of its inhibitory p66 Shc isoform are strongly prognostic for identifying both early node-negative and more advanced, node-positive, primary breast cancers with high risk for recurrence. Because aberrant activation of tyrosine kinases upstream of Shc signaling proteins has been implicated in resistance to tamoxifen – the most widely prescribed drug for treatment of estrogen receptor-positive breast cancer – we hypothesized that Shc isoforms may identify patients at increased risk of relapsing despite tamoxifen treatment.

Methods

Immunohistochemical analyses of PY-Shc and p66 Shc were performed on archival primary breast cancer tumors from a population-based cohort (60 patients, 9 relapses) and, for validation, an independent external cohort (31 patients, 13 relapses) in which all patients received tamoxifen as a sole systemic adjuvant prior to relapse.

Results

By univariate and multivariate analyses, the Shc proteins were very strong and independent predictors of treatment failure in both the population-based cohort (interquartile hazard ratio = 8.3, 95% confidence interval [CI] 1.8 to 38, P = 0.007) and the validating cohort (interquartile relative risk = 12.1, 95% CI 1.7 to 86, P = 0.013).

Conclusion

These results suggest that the levels of PY-Shc and p66 Shc proteins in primary tumors identify patients at high risk for relapsing despite treatment with tamoxifen and therefore with further validation may be useful in guiding clinicians to select alternative adjuvant treatment strategies.     

Urinary phytoestrogen excretion and prostate cancer risk: a nested case�Ccontrol study in the Multiethnic Cohort

Background:

Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries.

Methods:

This case–control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status.

Results:

The median excretion of daidzein was 0.173 nmol mg⁻¹ creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31–0.98, P_trend=0.03) and seemed to apply to localized (P_trend=0.08) as well as advanced or high-grade cancer (P_trend=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk.

Conclusion:

Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.     

Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Introduction

Increasing parity and age at first full-term pregnancy are established risk factors for breast cancer in the general population. However, their effects among BRCA1 and BRCA2 mutation carriers is still under debate. We used retrospective data on BRCA1 and BRCA2 mutation carriers from the UK to assess the effects of parity-related variables on breast cancer risk.

Methods

The data set included 457 mutation carriers who developed breast cancer (cases) and 332 healthy mutation carriers (controls), ascertained through families seen in genetic clinics. Hazard ratios were estimated by using a weighted cohort approach.

Results

Parous BRCA1 and BRCA2 mutation carriers were at a significantly lower risk of developing breast cancer (hazard ratio 0.54, 95% confidence interval 0.37 to 0.81; p = 0.002). The protective effect was observed only among carriers who were older than 40 years. Increasing age at first live birth was associated with an increased breast cancer risk among BRCA2 mutation carriers (p trend = 0.002) but not BRCA1 carriers. However, the analysis by age at first live birth was based on small numbers.

Conclusion

The results suggest that the relative risks of breast cancer associated with parity among BRCA1 and BRCA2 mutation carriers may be similar to those in the general population and that reproductive history may be used to improve risk prediction in carriers.     

Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer

Introduction

We have previously reported that tumour-specific expression of the rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR), in the mevalonate pathway is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up.

Methods

The expression of HMG-CoAR was assessed by immunohistochemistry on tissue microarrays with tumour specimens from 498 consecutive cases of breast cancer with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the rate of recurrence-free survival (RFS) and breast cancer specific survival (BCSS).

Results

In line with our previous findings, tumour-specific HMG-CoAR expression was associated with low grade (p < 0.001), small size (p = 0.007), oestrogen receptor (ER) positive (p = 0.01), low Ki-67 (p = 0.02) tumours. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS, even when adjusted for established prognostic factors (relative risk [RR] = 0.60, 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In ER-negative tumours, however, there was a trend, that was not significantly significant, towards a shorter RFS in HMG-CoAR expressing tumours.

Conclusions

HMG-CoAR expression is an independent predictor of a prolonged RFS in primary breast cancer. This may, however, not be true for ER-negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status.     

Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk

Purpose

To investigate the association between intake of flaxseed—the richest source of dietary lignans (a class of phytoestrogens)—and breast cancer risk.

Methods

A food frequency questionnaire was used to measure the consumption of flaxseed and flax bread by 2,999 women with breast cancer and 3,370 healthy control women who participated in the Ontario Women’s Diet and Health Study (2002–2003). Logistic regression was used to investigate associations between consumption of flaxseed and flax bread and breast cancer risk. Confounding by established and suspected breast cancer risk factors, as well as dietary factors, was assessed.

Results

Flaxseed or flax bread was consumed at least weekly by 21 % of control women. None of the 19 variables assessed were identified as confounders of the associations between flaxseed or flax bread and breast cancer risk. Consumption of flaxseed was associated with a significant reduction in breast cancer risk (odds ratio (OR) = 0.82, 95 % confidence interval (CI) 0.69–0.97), as was consumption of flax bread (OR = 0.77, 95 % CI 0.67–0.89).

Conclusions

This Canadian study is, to our knowledge, the first to report on the association between flaxseed alone and breast cancer risk and has found that flaxseed intake is associated with a reduction in breast cancer risk. As dietary intake of flaxseed is modifiable, this finding may be of public health importance with respect to breast cancer prevention.     

Association between allergies, asthma, and breast cancer risk among women in Ontario, Canada

Purpose

To investigate the association between allergies, asthma, and breast cancer risk in a large, population-based case–control study.

Methods

Breast cancer cases (n = 3,101) were identified using the Ontario Cancer Registry and population controls (n = 3,471) through random digit dialing. Self-reported histories of allergies, hay fever, and asthma were collected by questionnaire. Logistic regression was used to assess associations between breast cancer risk and history of allergy/hay fever and asthma, with 16 possible confounders examined. Analyses were stratified by menopausal status.

Results

A history of allergies or hay fever was associated with a small reduction in breast cancer risk [age-adjusted odds ratio (AOR) = 0.86, 95 % confidence interval (CI) 0.77–0.96] and did not differ by menopausal status. Asthma was not associated with breast cancer risk overall; however, among premenopausal women, asthma was associated with a reduced risk of breast cancer (AOR = 0.72, 95 % CI 0.54–0.97).

Conclusions

A history of allergies may be associated with a modest reduction in breast cancer risk. Asthma does not appear to be associated with breast cancer risk overall; however, asthma may be associated with reduced breast cancer risk among premenopausal women.     

Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk

Introduction

The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use.

Methods

We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project.

Results

No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power.

Conclusion

These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer.     

Plasma matrix metalloproteinase 1, 3, and 7 levels and breast cancer risk in the Nurses’ Health Study

Purpose

Matrix metalloproteinases (MMPs), in particular MMP1, 3, and 7, are believed to be critical to breast cancer invasion and metastasis and also may have important functions earlier in breast carcinogenesis. However, the relationship between circulating levels of MMP1, 3, and 7 and breast cancer risk is uncertain.

Methods

We examined associations between plasma MMP1, 3, and 7 and breast cancer risk in a prospective case–control study nested within the Nurses’ Health Study. Blood samples were collected from 801 cases who developed breast cancer between 1992 and 2000 and 801 matched controls, and MMP levels were measured via immunofluorescence assay.

Results

No overall association was observed between any of these MMPs and breast cancer risk [top vs. bottom quintile; MMP1: odds ratio (OR) 0.9; 95 % confidence interval (CI) 0.7, 1.3; p-trend = 0.51; MMP3: OR 1.1; 95 % CI 0.8, 1.5; p-trend = 0.88; MMP7: OR = 1.2; 95 % CI 0.8, 1.7; p-trend = 0.18]. Further, findings did not significantly vary by time since blood draw, body mass index, or postmenopausal hormone use, or by breast cancer subtypes.

Conclusions

Circulating MMP1, 3, and 7 levels do not appear to be predictive of overall breast cancer risk.     

A case report of pseudoprogression followed by complete remission after proton-beam irradiation for a low-grade glioma in a teenager: the value of dynamic contrast-enhanced MRI

Background

There are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies.

Methods

We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.

Results

Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.

Conclusions

These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.     

Germline DNA copy number variation in familial and early-onset breast cancer

Introduction

Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease."

Methods

Using whole-genome comparative genomic hybridization on microarrays, we screened a cohort of women fulfilling criteria for hereditary breast cancer who did not carry BRCA1/BRCA2 mutations.

Results

The median numbers of total and rare CNVs per genome were not different between controls and patients. A total of 26 rare germline CNVs were identified in 68 cancer patients, however, a proportion that was significantly different (P = 0.0311) from the control group (23 rare CNVs in 100 individuals). Several of the genes affected by CNV in patients and controls had already been implicated in cancer.

Conclusions

This study is the first to explore the contribution of germline CNVs to BRCA1/2-negative familial and early-onset breast cancer. The data suggest that rare CNVs may contribute to cancer predisposition in this small cohort of patients, and this trend needs to be confirmed in larger population samples.     

BRCA2 mutation carriers,reproductive factors and breast cancer risk

Background

Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear.

Methods

In a case–control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis.

Results

An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years.

Conclusion

The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.     

Tubal ligation in relation to menopausal symptoms and breast cancer risk

Background:

Local inflammation after tubal ligation may affect ovarian function and breast cancer risk.

Methods:

We analysed tubal ligation, menopausal characteristics, and breast cancer risk in the Sister Study cohort (N=50 884 women).

Results:

Tubal ligation was associated with hot flashes (hazard ratio (HR) 1.09; 95% confidence interval (CI): 1.06–1.12) but not menopausal age (HR 0.99; 95% CI: 0.96–1.02). Tubal ligation did not have an impact on breast cancer overall (HR 0.95; 95% CI: 0.85–1.06), but had a suggested inverse relation with oestrogen receptor+/progesterone receptor+ invasive tumours (HR 0.84; 95% CI: 0.70–1.01), possibly because of subsequent hysterectomy/bilateral oophorectomy.

Conclusion:

Tubal ligation does not influence overall breast cancer risk.     

Breast cancer in association with thyroid disorders

Background

The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid disease.

Methods

Clinical and ultrasound evaluation of thyroid gland, determination of serum thyroid hormone and antibody levels, and fine-needle aspiration of thyroid gland were performed in 150 breast cancer patients and 100 control individuals.

Results

The mean values for anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than in control individuals (P = 0.030). The incidences of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than in control individuals (38% versus 17%, P = 0.001; 26% versus 9%, P = 0.001, respectively).

Conclusion

Our results indicate an increased prevalence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients.     

Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

Background

Several anthropometric measures have been found to be associated with the risk of breast cancer. Current weight, body mass index, and adult weight gain appear to be predictors of postmenopausal breast cancer. These factors have been associated with a reduced risk of premenopausal breast cancer. We asked whether there is an association between changes in body weight and the risk of breast cancer in women who carry a mutation in either breast cancer susceptibility gene, BRCA1 or BRCA2.

Methods

A matched case–control study was conducted in 1,073 pairs of women carrying a deleterious mutation in either BRCA1 (n = 797 pairs) or BRCA2 (n = 276 pairs). Women diagnosed with breast cancer were matched to control subjects by year of birth, mutation, country of residence, and history of ovarian cancer. Information about weight was derived from a questionnaire routinely administered to women who were carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between weight gain or loss and the risk of breast cancer, stratified by age at diagnosis or menopausal status.

Results

A loss of at least 10 pounds in the period from age 18 to 30 years was associated with a decreased risk of breast cancer between age 30 and 49 (odds ratio (OR) = 0.47; 95% confidence interval (CI) 0.28–0.79); weight gain during the same interval did not influence the overall risk. Among the subgroup of BRCA1 mutation carriers who had at least two children, weight gain of more than 10 pounds between age 18 and 30 was associated with an increased risk of breast cancer diagnosed between age 30 and 40 (OR = 1.44, 95% CI 1.01–2.04). Change in body weight later in life (at age 30 to 40) did not influence the risk of either premenopausal or postmenopausal breast cancer.

Conclusion

The results from this study suggest that weight loss in early adult life (age 18 to 30) protects against early-onset BRCA-associated breast cancers. Weight gain should also be avoided, particularly among BRCA1 mutation carriers who elect to have at least two pregnancies.