Management of Advanced Breast Cancer

Breast cancer is the most common malignancy affecting women and imposes a substantial economic burden on society. Estrogen is thought to play a major role in both the initiation and promotion of hormone dependent breast cancer, and a number of well recognized risk factors for breast cancer reflect increased cumulative estrogen exposure (e.g. early menarche, late menopause).Metastatic breast cancer is an incurable condition and the goals of treatment are to relieve symptoms, improve health-related quality of life and prolong life. Women with hormone receptor-positive disease are candidates for hormonal treatment. In contrast, chemotherapy is traditionally the treatment of choice in those with hormone receptor-negative disease or symptomatic visceral disease.Anastrozole is a highly selective nonsteroidal type II aromatase inhibitor that suppresses plasma and intratumoral estrogen levels. The results of 2 multicenter, randomized, double-blind trials have shown anastrozole to be at least as effective as tamoxifen in the first-line treatment of postmenopausal women with advanced breast cancer, although survival data are lacking. In the smaller of these trials, the median time to disease progression was significantly prolonged (p = 0.005) in anastrozole, compared with tamoxifen, recipients (11.1 vs 5.6 months), although combined analysis of the 2 trials revealed no significant difference between an-astrozole and tamoxifen in terms of this end-point.Similarly, anastrozole has been shown to be at least as effective as megestrol in the second-line treatment of postmenopausal women with advanced breast cancer in 2 multicenter randomized studies. Combined analysis of the studies revealed a significant survival advantage (p < 0.025) for anastrozole 1 mg/day, compared with megestrol 40mg 4 times daily, recipients (estimated hazard ratio 0.78; 97.5% confidence interval 0.6 to <1).Tolerability is an important consideration in women with advanced breast cancer. The most common adverse events associated with anastrozole therapy were gastrointestinal disturbance, hot flushes, asthenia and pain. Anastrozole is associated with less vaginal bleeding and thromboembolic disease than tamoxifen and less bodyweight gain than megestrol. Anastrozole also appears to be a cost-effective option in the first- and second-line treatment of advanced breast cancer, although data are limited. Conclusion: Current treatment guidelines support the use of anastrozole in the second-line treatment of postmenopausal women with advanced breast cancer. Although current treatment guidelines do not yet reflect this, data from recent, well designed studies demonstrate that anastrozole is likely to be a viable alternative to tamoxifen in the first-line treatment of postmenopausal women with advanced breast cancer.     

Obesity Accelerates Mouse Mammary Tumor Growth in the Absence of Ovarian Hormones

Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.     

Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones

Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.     

Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk

The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.     

Body fat distribution and obesity in pre- and postmenopausal breast cancer

BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight.     

The effects of tamoxifen on the female genital tract

Tamoxifen has both agonistic and antagonistic effects on the female genital tract, depending on the ambient oestradiol concentration and the menopausal status of the patient. In postmenopausal women tamoxifen has an oestrogen agonistic effect on the vaginal epithelium, the uterine myometrium and the endometrium. It may induce benign cystic hyperplasia of the endometrial stroma and cause an increase in poly formation. The risk of endometrial cancer increases 2-3-fold after an exposure of up to 5 years. In asymptomatic tamoxifen users, gynaecological surveillance is not recommended. However, if there is postmenopausal bleeding, then transvaginal ultrasonography and histology of the endometrium are indicated. Tamoxifen can aggravate hot flushes and have a negative effect on sexual function. In premenopausal women, tamoxifen may induce ovarian cysts resulting in high serum-oestradiol levels. Oligomenorrhoea and amenorrhoea will occur in half of the patients. Tamoxifen has an antagonistic effect on the endometrium in premenopausal women and is associated with hot flushes and impaired sexual functioning. Teratogenic effects on the foetus have been described. Despite its gynaecological side effects, the benefits of tamoxifen in breast-cancer treatment outweigh the risks. Patients need to be informed about these side effects. Irregular or postmenopausal blood loss must always be reported to the treating physician.     

Survival impact of tamoxifen use for breast cancer risk reduction: projections from a patient-specific Markov model.

The authors estimate tamoxifen's impact on life expectancy among healthy women. A Markov model compared the effects of 5 years of tamoxifen on survival among 50-year-old postmenopausal women. Scenarios were explored using alternative assumptions with regard to tamoxifen's long-term effects on breast and endometrial cancer. Postmenopausal women without a uterus had substantial life expectancy gains from tamoxifen (1 to 4 months), whereas women with a uterus had such gains only if they were at a very high breast cancer risk. If tamoxifen's impact on endometrial cancer persists after treatment is discontinued, women at high risk for endometrial cancer have life expectancy losses from tamoxifen unless they are at a very high risk for breast cancer. The authors conclude that tamoxifen use among postmenopausal women is associated with substantial life expectancy gains. However, this benefit is modulated in women at increased endometrial cancer risk and depends on assumptions concerning tamoxifen's lingering effects on breast and endometrial cancer.     

Postmenopausal hormone use, screening, and breast cancer: characterization and control of a bias.

Previous investigators have suggested that screening-related biases may explain associations between postmenopausal hormone use and breast cancer. To investigate these biases, we studied postmenopausal women in the Nurses' Health Study from 1988 to 1994. Hormone use is associated with increased subsequent screening. Among women not screened in the previous 2 years, the probability difference, comparing current hormone users with others, for having mammography in the following 2 years is 19.5%; among women previously screened, the difference is 4.9%. These differences persist after control for other factors. If the increase in screening is causal, screening by mammogram could be intermediate in the causal pathway to breast cancer diagnosis. To deal with this problem, we restrict attention to a subset of the cohort in which the effect of postmenopausal hormone use on screening is small (women previously screened). In this subset, the rate ratio comparing breast cancer rates among current postmenopausal hormone users with others is 1.28. In a sensitivity analysis, the bias could not by itself plausibly account for the associations in our data. Our data provide evidence of an association between postmenopausal hormone use and breast cancer that is not solely the product of a detection bias.     

Breast cancer and obesity.

Epidemiological evidence links breast cancer, a typical endocrine-related tumor, with western lifestyle, in particular eating habits. Yet, it's necessary to distinguish premenopausal from postmenopausal breast cancer. Visceral obesity and body weight gain are considered responsible for the increased risk of postmenopausal breast cancer. In fact, the mammary gland is sensitive to the level of circulating estrogens, visceral obesity is usually associated with higher levels of free steroid hormones, and the adipose tissue performs important endocrine function (clearance and aromatisation of androgens, regulation of free testoterone/DHEAS molar ratio). Before menopause, ovarian polycystosis is often seen with android obesity, and breast cancer risk could arise; however, as visceral obesity is generally less frequent, genetic factors are more important than nutritional ones. Furthermore, variations have been recorded in the secretion of insulin and insulin-like growth factors, involved in the genesis of the breast cancer. High body weight and male fat distribution negatively influence prognosis of breast cancer, too; this association is linked with the presence of estrogen and progesterone receptors in tumoral cells. Links between diet quality and breast cancer risk are shown: increased use of saturated fats and animal proteins, and a consequently decreased use of vegetables, legumes and fruit, constituting the so-called Mediterranean diet, are considered responsible for the increased risk of breast cancer. Lower fat and alcohol ingestion, the use of dietary fibre and a higher use of complex carbohydrates could reduce breast cancer risk. Finally, starting from the results of our previous animal researches, we suggest using a tryptophan devoid diet for a few days for premenopausal women with male obesity and alterations to the menstrual cycle.     

Management of Hormone-Responsive Postmenopausal Breast Cancer

Postmenopausal breast cancer is frequently hormone responsive and may be treated with agents that prevent estrogen activity. Tamoxifen is the most widely used of these agents, proving effective in both early and advanced disease. However, the role of tamoxifen has been challenged by the development of newer agents which have demonstrated at least equivalent activity and better tolerability, notably the nonsteroidal third-generation aromatase inhibitor anastrozole, which is currently the only other agent approved for primary adjuvant treatment of early disease and first-line treatment of advanced disease.In postmenopausal women with early breast cancer, anastrozole was associated with a significantly higher rate of disease-free survival (86.9% vs 84.5%) and a lower incidence of contralateral breast cancer than tamoxifen. Furthermore, the incidences of thromboembolic events and endometrial cancer were significantly lower with anastrozole. However, anastrozole was associated with an increase in musculoskeletal events (including fractures) and further evaluation of the clinical significance of this finding is warranted. Pharmacoeconomic analyses based on the results of this trial and conducted from different healthcare perspectives have all found anastrozole to be a cost-effective adjuvant therapy for early postmenopausal breast cancer. Clinical trial data indicate that switching patients who have already received 2 years’ tamoxifen treatment to anastrozole reduces the risk of relapse and death compared with continuing treatment with tamoxifen. Further studies are warranted to determine the optimum sequence of agents and duration of adjuvant therapy.Large well designed trials have also shown first-line anastrozole therapy is at least as effective as tamoxifen in prolonging time to disease progression and overall survival in patients with advanced disease. Current data indicate that the drug is more effective than tamoxifen in patients whose tumors are known to express the estrogen receptor. Pharmacoeconomic analyses conducted from various healthcare perspectives support the use of anastrozole as a cost-effective treatment in this indication.Anastrozole has demonstrated similar efficacy to that of other approved agents, including letrozole and fulvestrant, as second-line therapy for patients who have failed first-line therapy (in most cases with tamoxifen).In conclusion, clinical and pharmacoeconomic data support the role of anastrozole as a primary adjuvant treatment for use across the entire spectrum of breast cancer encompassing early disease through to advanced metastatic disease, and reflect current treatment guidelines. Anastrozole has also proven effective in clinical trials in the neoadjuvant setting, though its use in this setting and in breast cancer prevention remains to be fully elucidated.     

Changes in endocrine therapy: anastrozole and advanced breast cancer in postmenopausal women

Emerging data on endocrine therapies necessitates a re-evaluation of treatment strategies for advanced breast cancer. In this review, we present data from recent studies of the third-generation, nonsteroidal aromatase inhibitor (AI) anastrozole that illustrate its changing role in the treatment of postmenopausal women with advanced breast cancer. These studies demonstrate that anastrozole is now a treatment of choice as first-line therapy for patients presenting with advanced breast cancer and for patients who have progressed to advanced disease after adjuvant therapy with tamoxifen. A further trial has also shown that anastrozole is an effective and well-tolerated alternative to tamoxifen as adjuvant treatment for postmenopausal women with early breast cancer.     

Relation between insulin resistance and breast cancer among Chilean women

PURPOSE: In Chile, diabetes and breast cancer are important public health problems. The association between insulin resistance and breast cancer, however, remains largely unexplored. METHODS: We conducted a case-control study to assess the relationship of insulin resistance (IR) and breast cancer in Chilean premenopausal and postmenopausal women. We compared 170 women, 33 to 86 years old, with incident breast cancer and 170 normal mammography controls, matched by 5-year age interval. Plasmatic insulin and glucose were measured and IR was calculated by the homeostasis model assessment method. Anthropometric measurements and sociodemographic and behavioral data were also collected. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multivariable conditional logistic regression. RESULTS: IR was independently associated with breast cancer in postmenopausal women (OR = 2.70, 95%CI = 1.10-6.63), but not in premenopausal women (OR = 0.84, 95%CI = 0.20-3.52). Obesity was not associated with breast cancer at any age (OR = 0.68, 95%CI = 0.39-1.20). CONCLUSION: In this sample, IR increased the risk of breast cancer among postmenopausal women.     

Pre- and postmenopausal breast cancer

It has been postulated that breast cancer is not a single disease, and that the risk factors occurring in premenopausal women are different from those occurring in postmenopausal women. This case-control study of pre- and postmenopausal breast cancer was designed to investigate a variety of variables including age of menarche, parity, age at first full-term birth, breast feeding patterns, age at menopause, and history of oral contraceptive use. The study compared 60 breast cancer cases and 125 matched controls from the same breast cancer screening population. Cases and controls were matched for race, age, place of birth, marital status, education, and annual family income. More cases than controls used oral contraceptives; the differences were statistically significant. The risk ratio estimates were 2.9 (confidence intervals 1.19-7.15). The mean duration of oral contraceptive use was more than two times longer among premenopausal breast cancer cases than controls and five times longer among postmenopausal cases than the controls. The breast cancer cases had significantly more relatives with a history of other cancers than the control group (risk ratio estimate 2.3, P < 0.03). No association was found between height and breast cancer; however, cases were found to be significantly heavier than controls. No differences were found in reproductive variables between breast cancer patients and their matched controls. In addition, a subdivision of breast cancer cases into pre- and postmenopausal groups did not reveal any clear differences in reproductive variables that would support the hypothesis that different specific risk factors are operating during pre- and postmenopausal periods.     

Multivitamin-multimineral supplement use and mammographic breast density

BACKGROUND: The effect of multivitamin-multimineral supplements on the occurrence of chronic diseases, such as breast cancer, is unclear. Breast density is increasingly used as a biomarker of breast cancer risk. OBJECTIVE: The present study evaluated the association of multivitamin-multimineral supplement use with breast density. DESIGN: Premenopausal (n = 777) and postmenopausal (n = 783) women were recruited at the time of screening mammography. Anthropometric measurements were taken at recruitment. Demographic characteristics, behavioral factors, and health conditions were documented by telephone interview. Diet and multivitamin-multimineral and individual vitamin and mineral supplement use were assessed with a self-administered food-frequency questionnaire. Breast density from screening mammograms was measured using a computer-assisted method. Crude and adjusted means in breast density were evaluated according to multivitamin-multimineral supplement use using generalized linear models. RESULTS: Current multivitamin-multimineral supplement use was reported by 21.7% of women (20.7% and 22.6% of premenopausal and postmenopausal women, respectively). Premenopausal women who were currently using multivitamin-multimineral supplements had higher adjusted mean breast density (45.5%) than past (42.9%) or never (40.2%) users (P for heterogeneity = 0.03, P for trend = 0.009). Of the current users, breast density was not related to duration of multivitamin-multimineral supplement use. In postmenopausal women, multivitamin-multimineral supplement use was not associated with breast density (P for heterogeneity = 0.53, P for trend = 0.40). CONCLUSION: Regular use of multivitamin-multimineral supplements may be associated with higher mean breast density among premenopausal women. The relations of multivitamin-multimineral supplement use to breast density and breast cancer risk need to be clarified.     

Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk

BACKGROUND: Cruciferous vegetables are the primary source of isothiocyanates and other glucosinolate derivatives that are known to induce phase II detoxifying enzymes, including glutathione S-transferases (GSTs). OBJECTIVE: We investigated the independent and combined effects of cruciferous vegetable intake and the GSTP1 Ile(105)Val genetic polymorphism on breast cancer risk. DESIGN: Analyses included 3035 cases and 3037 population controls who were participating in the Shanghai Breast Cancer Study and for whom diet and genetic data were complete (87% of cases and 85% of controls). RESULTS: With the use of multivariate logistic regression, the GSTP1 Val/Val genotype was significantly associated with greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous vegetable intake was not significantly associated with breast cancer risk, although subjects reporting greater turnip (P for trend < 0.001) and Chinese cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous vegetable intake and the Val/Val genotype was seen predominantly among premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). CONCLUSIONS: Cruciferous vegetable intake consistent with high isothiocyanate exposure may reduce breast cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the GSTP1 genotype.     

武汉地区女性乳腺癌危险因素的病例对照研究

目的 探讨武汉地区女性乳腺癌的危险因素及其变化情况。方法 以病例对照研究方法,对经病理确诊的213例乳腺癌患者及430例匹配对照进行危险因素的条件logistic回归分析。结果 单因素分析显示:文化程度、乳腺良性肿瘤、初潮年龄、绝经年龄、肉类摄入量、油炸烧烤食物摄入、豆类食品摄入、水果摄入、哺乳时间。体重指数、10～19岁胸透次数、精神心理因素等28项因素与乳腺癌的危险性有关。联合多因素及分组多因素条件1ogistic回归分析显示:文化程度高、精神创伤、乳腺良性肿瘤史、绝经晚、行经年数和初产前行经年数长、体重指数高、常食油炸烧烤和烟熏腊制食物为乳腺癌的危险因素;初潮晚、哺乳时间长、豆类或水果摄入量高、常饮茶为保护因素。绝经前与绝经后的危险因素种类及效应强度有一定差别。经多因素分析,绝经前主要相关因素为乳腺良性肿瘤、初潮年龄、豆类摄入量;绝经后主要与绝经年龄、体重指数、腰臀比和水果摄入量有关。另外,精神创伤及哺乳时间为绝经前后共同的危险因素和保护因素。结论 武汉地区女性乳腺癌危险因素中,饮食习惯和内源性雌激素暴露等相关因素起着重要作用。     

Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients

Breast cancer is the leading cancer in women of reproductive age; more than a quarter of women diagnosed with breast cancer in the US are premenopausal. A common adjuvant treatment for this patient population is chemotherapy, which has been shown to cause premature menopause and infertility with serious consequences to quality of life. Luteinizing‐hormone‐releasing hormone (LHRH) agonists, which induce temporary ovarian function suppression (OFS), has been shown to be a useful alternative to chemotherapy in the adjuvant setting for estrogen‐receptor‐positive breast cancer patients. LHRH agonists have the potential to preserve fertility after treatment, thus, reducing the negative effects on a patient's reproductive health. However, little is known about the association between a patient's underlying degree of OFS and disease‐free survival (DFS) after receiving LHRH agonists. Specifically, we are interested in whether patients with lower underlying degrees of OFS (i.e. higher estrogen production) after taking LHRH agonists are at a higher risk for late breast cancer events. In this paper, we propose a latent class joint model (LCJM) to analyze a data set from International Breast Cancer Study Group (IBCSG) Trial VIII to investigate the association between OFS and DFS. Analysis of this data set is challenging due to the fact that the main outcome of interest, OFS, is unobservable and the available surrogates for this latent variable involve masked event and cured proportions. We employ a likelihood approach and the EM algorithm to obtain parameter estimates and present results from the IBCSG data analysis. Copyright © 2010 John Wiley & Sons, Ltd.     

Potential exposure to PCBs, DDT, and PBDEs from sport-caught fish consumption in relation to breast cancer risk in Wisconsin

In Wisconsin, consumption of Great Lakes fish is an important source of exposure to polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ethers (PBDEs), and other halogenated hydrocarbons, all of which may act as potential risk factors for breast cancer. We examined the association between sport-caught fish consumption and breast cancer incidence as part of an ongoing population-based case-control study. We identified breast cancer cases 20-69 years of age who were diagnosed in 1998-2000 (n = 1,481) from the Wisconsin Cancer Reporting System. Female controls of similar age were randomly selected from population lists (n = 1,301). Information about all sport-caught (Great Lakes and other lakes) fish consumption and breast cancer risk factors was obtained through telephone interviews. After adjustment for known and suspected risk factors, the relative risk of breast cancer for women who had recently consumed sport-caught fish was similar to women who had never eaten sport-caught fish [relative risk (RR) = 1.00; 95% confidence interval (CI), 0.86-1.17]. Frequency of consumption and location of sport-caught fish were not associated with an increased risk of breast cancer. Recent consumption of Great Lakes fish was not associated with postmenopausal breast cancer (RR = 0.78; 95% CI, 0.57-1.07), whereas risk associated with premenopausal breast cancer was elevated (RR = 1.70; 95% CI, 1.16-2.50). In this study we found no overall association between recent consumption of sport-caught fish and breast cancer, although there may be an increased breast cancer risk for subgroups of women who are young and/or premenopausal.