Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study

Narod, Steven A.; J, Brunet; Ghadirian, Parviz; Robson, Mark E.; Heimdal, Ketil; Neuhausen, Susan L.; Stoppa‐Lyonnet, Dominique; Lerman, Caryn; Pasini, Barbara; Rios, Patricia; Weber, Barbara; Lynch, Henry T.

doi:10.1016/s0140-6736(00)03258-x

Cited by 500 publications

(263 citation statements)

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“…33 Currently, nonsurgical chemoprevention options available for BRCA carriers are based on interrupting the estrogen-signalling pathway and implicate an important role of sex hormones in the etiology of the disease. Although the majority of BRCA1 (but not BRCA2) tumours are estrogen receptor negative, oophorectomy [34][35][36] and tamoxifen 37 have been shown to reduce the risk of breast cancer among carriers of either mutation. Based on this observation, alternative dietary and lifestyle strategies that minimize exposure to estrogen or alter the 2-OHE/16a-OHE ratio may also impact overall risk.…”

Section: Discussionmentioning

confidence: 99%

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Nkondjock

Ghadirian

Kotsopoulos

et al. 2005

Intl Journal of Cancer

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Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high-risk women who carry BRCA mutations. We performed a matched case-control analysis on 1,690 women with a BRCA1 or BRCA2 mutation from 40 centers in 4 countries. Average lifetime coffee consumption was estimated via a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for potential confounders, the ORs for breast cancer in BRCA carriers who habitually drank 0, 1-3, 4-5 and 6 or more cups of coffee were 1.00, 0.90 (95% CI 0.72-1.12), 0.75 (95% CI 0.47-1.19) and 0.31 (95% CI 0.13-0.71; p-trend 5 0.02). The effect was limited to the consumption of caffeinated coffee. These results suggest that among women with BRCA gene mutation, coffee consumption is unlikely to be harmful and that high levels of consumption may in fact be related to reduced breast cancer risk. ' 2005 Wiley-Liss, Inc.Key words: BRCA1; BRCA2; breast cancer; coffee; case-control study Coffee is among the most widely consumed beverages in the world and is a major source of dietary caffeine. Over the last 2 decades, coffee and caffeine have been studied with regard to their potential role in breast cancer etiology. A number of animal studies have reported caffeine to both stimulate and to suppress breast tumors, depending upon the species and the phase of administration. 1 Coffee consumption (or caffeine intake) has been directly associated with plasma estradiol, estrone and sex hormone-binding globulin levels, and inversely associated with testosterone. 2,3 Coffee consumption also induces cell differentiation 4 and may inhibit mitosis. 5 These effects suggest that coffee consumption may affect breast cancer risk, but epidemiologic evidence supporting the association between coffee consumption and breast cancer risk is scant. A decrease in breast cancer risk in women with high levels of coffee consumption has been reported in several studies, 6,7 but other investigators have detected no relationship between coffee consumption and breast cancer risk. 1,8 It has been estimated that the risk of developing breast cancer among women with a mutation in BRCA1 or BRCA2 is as high as 80% by the age of 70. 9 Whether or not coffee affects BRCArelated breast cancer risk is currently unknown. To address this issue, we examined the association between coffee consumption and the risk of breast cancer among women with BRCA1 and BRCA2 gene mutations from 40 participating centers in 4 countries. Material and methods Study population and designThe study population has been described elsewhere. 10 Briefly, eligible study subjects included women who were currently alive and were known to be carriers of deleterious mutations of the BRCA1 or BRCA2 gene. These women were identified from 40 participating clinical cancer geneti...

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Section: Discussionmentioning

confidence: 99%

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Nkondjock

Ghadirian

Kotsopoulos

et al. 2005

Intl Journal of Cancer

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“…36,37 A protective effect of tamoxifen in the 50% range against contralateral breast carcinoma has been observed in both BRCA1 carriers and BRCA2 carriers, although a question remains about the ability of tamoxifen to reduce the risk of hormone receptor-negative tumors that often are associated with BRCA1. 5,38 Thirty-six point six percent of the current cohort consisted of women who had their risk reduced before their initial screen. Eleven of 41 women had undergone a previous BSO, and 6 of 41 women were taking tamoxifen: two of those women had their risk reduced by both methods.…”

Section: Discussionmentioning

confidence: 99%

Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinoma

Hartman

Daniel

Kurian

et al. 2004

Cancer

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Surface tension and viscosity are the important properties of liquid binders affecting wet granulation processes. They could be used to control solids flow pattern and relative motion of particles for controlling wetting, granule growth, consolidation, and breakage. This study aims to investigate experimentally the impacts of the two properties with a conical high shear granulator. The results show significant effects of viscosity and surface tension on solids flow pattern and relative motion of particles. The relative importance of the two parameters, the surface tension and the viscosity, are found to vary with the axial and radial positions in the granulator. For example, the viscosity force decreases with an increase in the bed height in the axial direction (vertical plane). The viscosity force between particles coated with PEG4000 solution is in mN order, whereas that between particles coated with ethanol and water is in μN order. © 2009 American Institute of Chemical Engineers AIChE J, 2009

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“…Moreover, it is becoming clear that prophylactic oophorectomy not only reduces the incidence of ovarian cancer in mutation carriers but also that of breast cancer . Finally, it has been shown that both oophorectomy and adjuvant TAM treatment reduce the risk of contralateral breast cancer in mutation carriers (Narod et al, 2000;Metcalfe et al, 2004). This raises the possibility that the initial stages of tumour formation in BRCA1 and BRCA2 mutation carriers are hormone dependent, in which case early endocrine therapy might be an effective prevention strategy.…”

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Effects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations

Bramley¹,

Clarke²,

Howell

et al. 2006

Br J Cancer

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There is considerable interest in whether anti-oestrogens can be used to prevent breast cancer in women bearing mutations in the BRCA1 and BRCA2 genes. The effects of oestradiol (E 2 ), tamoxifen (TAM) and fulvestrant (FUL) on proliferation and steroid receptor expression were assessed in normal breast epithelium taken from women at varying risks of breast cancer and implanted into athymic nude mice, which were treated with E 2 in the presence and absence of TAM or FUL. Tissue samples were taken at various time points thereafter for assessment of proliferative activity and expression of oestrogen and progesterone receptors (ERa and PgR) by immunohistochemistry. Oestradiol increased proliferation in the breast epithelium from women carrying mutations in the BRCA1/2 genes, those otherwise at increased risk and those at population risk of breast cancer. This increase was reduced by both TAM and FUL in all risk groups. In the absence of E 2 , PgR expression was reduced in all risk groups but significantly more so in the BRCAmutated groups. Subsequent E 2 treatment caused a rapid, complete induction of PgR expression in the population-risk group but not in the high-risk or BRCA-mutated groups in which PgR induction was significantly delayed. These data suggest that the mechanisms by which E 2 induces breast epithelial PgR expression are impaired in BRCA1/2 mutation carriers, whereas those regulating proliferation remain intact. We conclude that early anti-oestrogen treatment should prevent breast cancer in very high-risk women. British Journal of Cancer (2006) Approximately 5% of all cases of breast cancer are associated with inherited predisposition syndromes and about half of these are attributable to mutations in the BRCA1 and BRCA2 genes (Hopper, 2001). Carriers of mutations in the BRCA1 and BRCA2 genes have up to a 90% lifetime risk of developing breast cancer (Rebbeck, 2002) and effective preventative strategies are required for these women.A number of trials have now shown that endocrine agents such as tamoxifen (TAM) or raloxifene can prevent breast cancer in women at increased risk of the disease (Cuzick et al, 2003). The question arises as to whether agents such as these can be used for prevention specifically in women bearing BRCA1 or BRCA2 mutations. The prevalence of mutations in the total cohort in the NSABP P1 trial was unknown (Fisher et al, 1998) and therefore no conclusion regarding the effectiveness of TAM in mutation carriers can be made from this study. It has been suggested that endocrine agents such as TAM will not be effective in preventing breast cancer in BRCA1 mutation carriers because the majority of tumours (up to 80%) arising in these women are oestrogen receptor a (ERa) negative, have a high mitotic rate and are of high histological grade (Lakhani, 1999;Lakhani et al, 2002). All these features are associated with resistance to endocrine therapy and it is clear from the overview that TAM and raloxifene reduce the incidence of ERa-positive but not -negative tumours (Cuzick et al, 2003). ...

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Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study

Cited by 500 publications

References 31 publications

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinoma

Effects of oestrogens and anti-oestrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations

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