Risk Of Breast Carcinoma Research Articles

Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma.

BackgroundLeptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in LEP and LEPR have implications for susceptibility to and prognosis in breast carcinoma.MethodsWe used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the LEP and LEPR genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses.ResultsA significantly increased risk of breast carcinoma was associated with heterozygous LEP (-2548) GA (OR = 1.45; P = 0.04) and homozygous LEP (-2548) AA (OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous LEPR 223QR genotype (OR = 1.68; P = 0.007) or homozygous LEPR 223RR genotype (OR = 2.26; P = 0.001) and breast carcinoma.Moreover, the presence of the LEP (-2548) A allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the LEPR 223R allele showed a significant association with decreased overall survival.ConclusionOur results indicated that the polymorphisms in LEP and LEPR genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis.

High risk of contralateral breast carcinoma in women with hereditary/familial non‐BRCA1/BRCA2 breast carcinoma

The objectives of the current study were to estimate the risk of developing contralateral breast carcinoma (CBC) among women with hereditary/familial non-BRCA1/BRCA2 breast carcinoma and to determine the factors that may predict their risk of CBC. The study sample consisted of all families (n = 217 families) that were referred between 1994-2001 to the Clinic of Cancer Genetics at the University Hospital of Umeå for suspected hereditary breast carcinoma. The study included all women in the 217 families who had carcinoma of the breast as their first primary invasive malignancy diagnosed between 1970-2001 in northern Sweden. Exclusion criteria were an estimated lifetime risk < 20%, BRCA1/BRCA2 mutation, noninvasive carcinoma (ductal or lobular carcinoma in situ), and bilateral breast carcinoma. In the final analysis, 204 women were included from 120 families. The cumulative probability of developing CBC among women who had hereditary/familial non-BRCA1/BRCA2 breast carcinoma after 20 years was 27.3% (95% confidence interval, 15.0-37.8) compared with the expected risk (4.9%) among women in northern Sweden who had primary breast carcinoma. A significantly increased risk of CBC was associated with age younger than 50 years at the time of diagnosis of the first primary breast carcinoma (P = 0.006). Adjuvant hormone therapy reduced the risk of CBC (P = 0.036). Women with hereditary/familial non-BRCA1/BRCA2 breast carcinoma had a high risk of developing CBC. This risk was attenuated further among women who were younger at the time of onset, who had a cumulative probability of developing CBC of nearly 40% after 15 years, which is similar to the estimated risk among BRCA1/BRCA2 mutation carriers. The results of this study emphasized the importance of genetic counseling for these women.

Genetic Variation in IL-8 Associated with Increased Risk and Poor Prognosis of Breast Carcinoma

Interleukin-8 (IL-8), a potent chemoattractant, has been demonstrated to contribute to human cancer progression through its potential functions as a mitogenic, angiogenic, and motogenic factor. We designed a broad study to investigate whether genetic variation in IL-8 has implications for susceptibility to and prognosis in breast carcinoma. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 308 unrelated Tunisian patients with breast carcinoma and 236 healthy control subjects. Associations of the clinicopathologic parameters and the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. A significantly increased risk of breast carcinoma was associated with heterozygous IL-8 (−251) TA (OR = 1.58, p = 0.02) and homozygous IL-8 (−251) AA (OR = 1.76, p = 0.01) variants. A significant association between the IL-8 (−251) AA homozygous genotype and the aggressive phenotype of breast carcinoma as defined by the high histological grade, auxiliary’s lymph node metastasis, and large tumor size was found. The IL-8 (−251) A allele manifested a significant association with decreased overall survival and disease-free survival for breast carcinoma patients. The polymorphism in the promoter region of the IL-8 gene may not only represent a marker for the increased risk of breast carcinoma but also predict the clinical outcome.

Evaluation of breast involvement in relation to Cowden syndrome: a radiological and clinicopathological study of patients with PTEN germ-line mutations

We describe the clinical, radiological, and pathological findings of the diverse benign and malignant breast neoplasms found in association with Cowden syndrome. Patients with Cowden syndrome had a substantially increased risk of breast carcinoma. We find that 33% of the patients in our study population with Cowden disease have developed breast carcinoma to date. An association between Cowden disease and multiple tubular adenomas or breast hamartomas was found in two patients, suggesting a genetic origin. PTEN germ-line mutations were found in all four patients presenting with relevant benign or malignant breast pathology. We also assess the value of specific diagnostic tools used in the surveillance management. Screening mammography was useful in the diagnosis of small, high-grade carcinomas.

Is BRCA1/BRCA2‐related breast carcinogenesis estrogen dependent?

Estrogen is a well known promoting factor of sporadic breast carcinoma. With regard to hereditary breast carcinoma, such as in BRCA1/BRCA2 syndromes, to date, the effects of estrogens on risk modification are not clear. Several studies have shown that prophylactic oophorectomy may decrease the risk of breast carcinoma in BRCA1/BRCA2 mutation carriers. Moreover, adjuvant tamoxifen therapy for primary breast carcinoma appears to diminish the risk of a second breast malignancy in BRCA1 mutation carriers. Conversely, exogenous estrogens, such as oral contraceptives, may increase the risk of breast carcinoma in familial breast cancer, as suggested by clinical studies. Paradoxically, the majority of BRCA1-related breast carcinomas are negative for ER. There is some biologic evidence of interactions between estrogens and BRCA proteins. BRCA1 expression could be induced by estradiol in experimental models, whereas recent studies indicate that BRCA1 modifies the regulatory effects of the estrogen receptor (ER) alpha (ERalpha). Prospective studies will be required to estimate the potential benefits of estrogen suppression therapies for the prevention and adjuvant treatment of BRCA1/BRCA2-related breast carcinomas.

Polymorphisms in CYP1A1 and breast carcinoma risk in a population‐based case–control study of Chinese women

Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. The authors evaluated common polymorphisms in the CYP1A1 gene in relation to breast carcinoma risk in a large population-based case-control study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3 and CYP1A1*4 alleles were not detected in the study population, analyses were performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls. The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure.

Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy

Studies of patients with ductal carcinoma in situ (DCIS) "treated" by diagnostic biopsy alone have been rare, but provide important opportunities to gain insights into the natural history of these lesions. During a review of 1877 breast biopsy specimens in a nested case-control study of benign breast disease and breast carcinoma risk, the authors identified 13 biopsy specimens with DCIS that were originally diagnosed as benign. Because each of these women was initially given a benign diagnosis, they received no treatment beyond the diagnostic biopsy. When compared with women with nonproliferative lesions, the odds ratio (OR) for the development of invasive breast carcinoma among those with retrospectively identified DCIS (n = 6) was 13.5 (95% confidence interval [CI], 3.7-49.7). The OR for the development of any subsequent invasive or in situ breast carcinoma event (n = 10) was 20.1 (95% CI, 6.1-66. 5). A retrospective review of these DCIS biopsy specimens revealed that the nuclear grade was low in four lesions, intermediate in six, and high in three. None showed comedo-type necrosis. Invasive carcinomas developed among women with DCIS of all nuclear grades. All 10 breast carcinoma events (100%) were in the ipsilateral breast. These results provided further evidence that patients with DCIS who received no treatment beyond a diagnostic biopsy were at substantially increased risk for developing ipsilateral invasive breast carcinoma, and that the increased risk in this setting was seen in DCIS of low, intermediate, and high nuclear grades.

Reproducibility of cytologic atypia in repeat nipple duct lavage

It is believed that atypical cells identified by nipple duct lavage (NDL) indicate an increased risk for breast carcinoma similar to atypical ductal hyperplasia diagnosed by tissue biopsy, but many basic performance characteristics of NDL currently are undefined. NDL was performed in 108 patients unselected for breast carcinoma risk and then was repeated after 2-14 months (median, 8 months) if the initial lavage was classified as atypical. Breast magnetic resonance images (MRIs) were obtained from a subset of patients who had atypical lavage results. Marked atypia was diagnosed in 22% of 36 breasts with an incident carcinoma compared with 7% of 172 unaffected breasts (P = 0.01). After excluding breasts with an incident carcinoma, there were 32 patients (30%) with either mild or marked atypia. The lavage was repeated in 23 of these women, and the second lavage was classified as atypical in 48%. Neither marked atypia on the initial lavage nor a 5-year Gail risk > or = 1.7% predicted atypia on repeat lavage, but there was a trend for improved reproducibility when the atypia initially was diagnosed in a fluid-producing duct. MRIs were abnormal in 13% of 24 breasts with an atypical lavage, and ductal carcinoma in situ was diagnosed subsequently in 1 breast. Atypia frequently is diagnosed by NDL, but the reproducibility of repeat lavage is low. Lavage atypia may be physiologic or artifactual rather than pathologic in many instances. Marked atypia occasionally may represent mammographically occult ductal carcinoma in situ.

Breast carcinoma chemoprevention in the community setting

The United States Preventive Services Task Force recommends that women who are at both high risk for breast carcinoma and low risk for adverse events should receive counseling regarding tamoxifen for chemoprevention. Estimates of the risks and benefits of tamoxifen based on results from clinical trials may not reflect the real-world experience. The authors determined the prevalence of women in a community-based cohort who would meet the definition of high risk for breast carcinoma and calculated the number of women needed to screen to determine one for whom the benefits of tamoxifen would outweigh the risks. Baseline incidence also was examined for adverse health events in this community-based cohort compared with participants in the Breast Cancer Prevention Trial. The study participants were women ages 40-70 years (n = 6048 women) who were members of the CLUE II cohort, which started in 1989, and who responded to questionnaire surveys in 1996 and 2000. Eighteen percent of all women had a 5-year risk of invasive breast carcinoma > or = 1.66%. The number of women needed to screen to find 1 woman for whom the benefits outweighed the risks of tamoxifen ranged from 26 women ages 40-49 years to 142 women ages 60-70 years. For women who had undergone a hysterectomy, the numbers needed to screen were lower. Baseline incidence rates of fracture and thromboembolic disease were higher in the community-based cohort compared with the rates observed among prevention trial participants; thus, fewer women had to be treated with tamoxifen to prevent one fracture. However, fewer women in the community also had to be treated to observe harm with a thromboembolic event. Clinicians who counsel women about tamoxifen should take into consideration community-level risks and benefits.

Breast carcinoma in men

We read with interest the recent article by Giordano et al.1 Utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for breast carcinoma cases diagnosed among men between 1973–1998 (August 2000 submission), they reported a 26% increase in the overall incidence rate of male breast carcinoma, based on 5-year increments and including in situ tumors. The explanation for this increase was unclear, meriting further investigation. Using the more recent SEER database for breast carcinoma cases diagnosed through 2001 (November 2003 submission), we added 3 years of observation and compared stage-specific trends among male and female breast carcinoma cases. Overall breast carcinoma rates were found to have increased 29% for men and 58% for women, based on 5-year increments and including in situ tumors. During the last three decades there were temporal increases for in situ and invasive localized breast carcinomas with decreases for invasive regional and distant tumors among both men and women. Rates of in situ tumors increased the most rapidly: 123% and 555% among men and women, respectively. Invasive localized disease rates were found to have increased a more modest 37% and 78% among men and women, respectively. Conversely, the disease rates of invasive regional and distant breast carcinoma declined for men and women during the 1980s and 1990s. For example, the distant disease rate was found to have decreased 41% among men from 0.09 per 100,000 man-years during 1975–1980 to 0.053 per 100,000 man-years during 1997–2001. The rapid rise in early-stage female breast carcinomas diagnosed during the 1980s undoubtedly resulted from increases in screened-derived “occult” in situ and invasive localized tumors.2 Advances in screening mammography could not account for the dramatic increases noted in early-stage breast carcinoma among men, given that men are not routinely screened for breast carcinoma. However, a heightened awareness of male breast carcinoma might result in the earlier detection of “symptomatic” in situ and invasive localized tumors because of the easier detection of small lesions in men with a small breast volume.3 Male breast carcinoma is a rare disease and the absolute numbers for breast carcinoma cases among men were low for certain stages of disease. Therefore, we must interpret stage-specific male breast carcinoma rates with caution. Nonetheless, temporal trends for male breast carcinoma have remained essentially stable for decades whereas those for female breast carcinoma have increased worldwide.4, 5 Additional surveillance is certainly warranted to determine whether the recent report by Giordano et al.1 foreshadows a change in the risk of male breast carcinoma or simply reflects earlier detection over time. William F. Anderson M.D.*, Susan S. Devesa Ph.D. , * Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

Risk of subsequent invasive breast carcinoma after in situ breast carcinoma in a population covered by national mammographic screening

Sweden was the first country to establish a nationwide breast cancer screening service. We used the Swedish Family-Cancer Database to evaluate the risk of invasive carcinoma after in situ carcinoma of the breast. Risk estimates for contralateral and ipsilateral invasive malignancies following age and histology specific in situ breast carcinomas were calculated using Poisson's regression analysis. The agreement between concordant and discordant morphologies of invasive and in situ breast cancer was measured using the kappa statistic. Women with in situ breast cancer showed a relative risk of 2.03 for contralateral and 3.94 for ipsilateral invasive breast cancer. The risk was higher for in situ carcinomas diagnosed before the age of 50 years and after lobular in situ breast cancers. A comparison of the risks during the past decades suggested that the risk of ipsilateral breast cancer has increased in Sweden but that of contralateral breast cancer has remained unchanged. In situ and the subsequent invasive breast cancers did not seem to share their morphologies.

Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: Results of a prospective study

We report on a prospective study to assess the association of postmenopausal serum levels of sex hormones with subsequent risk of breast carcinoma in situ. We conducted a case-control study nested within the cohort of the New York University Women's Health Study, a large prospective study documenting a positive association of circulating levels of estrogens and androgens with invasive breast cancer. The study included 69 cases of incident in situ carcinoma and 134 individually matched controls. No statistically significant trend of increasing risk with increasing level of any of the hormones was observed. Odds ratios (95% CIs) for the highest tertile relative to the lowest were 1.10 (0.51-2.39) for estradiol, 0.95 (0.41-2.19) for estrone, 1.63 (0.69-3.88) for testosterone, 0.99 (0.44-2.24) for androstenedione, 0.99 (0.45-2.20) for dehydroepiandrosterone sulfate and 0.81 (0.38-1.74) for sex hormone-binding globulin. Adjusting for potential confounders did not materially affect the results, nor did limiting the analysis to the 59 cases of ductal carcinoma in situ, the lesion thought to be the direct precursor of most invasive breast cancers. Our results are at variance with the positive associations observed in this same cohort with risk of invasive breast cancer. Possible explanations for our results include lack of power, an effect of sex hormones limited to the progression from in situ to invasive tumors, overrepresentation of indolent tumors or an effect of sex hormones on the induction of only a subset of in situ tumors, those that would develop into invasive tumors.

XRCC1 and glutathione-S-transferase gene polymorphisms and susceptibility to radiotherapy-related malignancies in survivors of Hodgkin disease.

One of the most serious late effects of treatment for childhood cancer is the occurrence of subsequent malignancy. Survivors of Hodgkin disease (HD), in particular, have been shown to be at high risk of subsequent malignancy, the occurrence of which has been associated strongly with exposure to radiotherapy. In the current study, the authors investigated the association between polymorphisms in 3 genes--glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and XRCC1, with roles in protection from a variety of DNA-damaging agents-and the risk of subsequent malignancy in 650 survivors of HD enrolled in the Childhood Cancer Survivor Study who had received radiotherapy. Individuals lacking GSTM1 but not GSTT1 were at increased risk of any subsequent malignancy (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0-2.3), and for subsequent cancer within the radiation field (OR, 1.4; 95% CI, 0.9-2.1). A nonsignificant increased risk of thyroid carcinoma was observed in individuals lacking either GSTM1 (OR, 2.9; 95% CI, 0.8-10.9) or GSTT1 (OR, 3.7; 95% CI, 0.6-23.5). Individuals having the genotype of the arginine/glutamine polymorphism at codon 399 in the XRCC1 gene (R399) showed a nonsignificant increased risk of breast carcinoma compared with those without (OR, 1.4; 95% CI, 0.7-2.7), and a nonsignificant decreased risk against a subsequent thyroid carcinoma (OR, 0.6; 95% CI, 0.2-1.6). No differences in genotype frequencies were observed between survivors with basal cell carcinoma when compared with survivors without a subsequent cancer. These data illustrated the potential value of incorporating the collection of genomic DNA in longitudinal cohort studies of populations with well defined, potentially carcinogenic exposures. Evaluation of additional genetic polymorphisms in this cohort may help define genes that influence individual sensitivity to radiotherapy.

Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women.

Genes encoding enzymes involved in estrogen metabolism are held to be candidate genes for associations with breast disease. In these candidate genes, no critical combination of single-nucleotide polymorphisms (SNPs) for assessing breast carcinoma risk has been reported to date. In a large case-control study, the authors investigated 10 estrogen-metabolizing SNPs in 396 patients with breast carcinoma, 154 patients with fibroadenoma, and 1936 healthy control patients without breast carcinoma in their personal history. The following 10 SNPs were analyzed using sequencing-on-chip technology via a solid-phase polymerase chain reaction assay performed on oligonucleotide microarrays: catechol-O-methyltransferase Val158Met G-->A, 17-beta-hydroxysteroid dehydrogenase type 1 vIV A-->C, cytochrome P-450 (CYP) family 17 A2 allele T-->C, CYP1A1-1 MspI restriction fragment length polymorphism (RFLP) T-->C, CYP1A1-2 Ile462Val A-->G, CYP19-1 Trp39Arg T-->C, CYP19-2 Arg264Cys C-->T, CYP19-3 Cys1558Thr C-->T, steroid-5-alpha reductase type 2 Val89Leu G-->C, and vitamin D receptor BsmI RFLP. A total of 21,350 genotypes were evaluated. Associations and two-way interaction models were calculated using stepwise logistic regression. In a multiple model, CYP1A1-1 (P = 0.004) and CYP1A1-2 (P = 0.03) were found to be associated with significantly decreased and increased risks of breast carcinoma, respectively. When two-way interactions involving investigated SNPs were ascertained, no significant interactions among polymorphisms were noted. Comparison of patients with fibroadenoma with control patients revealed significantly increased and decreased risks of fibroadenoma when the mutant alleles of CYP17 (P = 0.02) and CYP1A1-1 (P = 0.04), respectively, were present. The authors obtained the first SNP data indicating that CYP17 and CYP1A1-1 play a role in the pathogenesis of fibroadenoma. Although the authors were not able to develop interaction models involving SNPs, they did provide evidence that CYP1A1 is a low-penetrance susceptibility gene with respect to breast carcinoma in a large series of Caucasian women.

Familial risk and clustering of nasopharyngeal carcinoma in Guangdong, China.

Previous studies have suggested that genetic susceptibility may play an important role in the etiology of nasopharyngeal cancer (NPC). However, to date, few large-scale studies have been conducted on familial risk and clustering of NPC in a high-risk area of China. In the current study, 2252 patients with NPC who were treated at the Cancer Center of Sun Yat-Sen University in Guangdong Province, China, were identified as probands. Family histories of NPC and other malignancies were observed in first-degree relatives (FDRs) and second-degree relatives, and other information was obtained through interviews. One thousand nine hundred and three Cantonese families were selected for further investigation. To assess familial aggregation, the authors used standardized incidence ratios (SIRs) to measure the risk of NPC for FDRs and compared the observed number of cases with the number predicted by population-based frequencies in the Cantonese population of Hong Kong. The current analysis indicated that families with > or = 3 relatives who had NPC were distributed predominantly among a high-risk subgroup of the Cantonese population in Guangdong Province and that the frequency of these families was 0.68%. An SIR of 2.09 (95% confidence interval [CI], 1.80-2.40) was observed among 13,833 FDRs in the high-risk subgroup, and a significantly elevated risk for NPC was observed in FDRs of probands with early age of onset (age < 40 years; SIR, 9.01 [95% CI, 6.10-13.30]). Furthermore, decreased risks of hepatic, lung, esophageal, gastric, and breast carcinoma, as well as malignancy of all sites, were observed among FDRs of probands with NPC when Hong Kong and Shanghai populations were used as reference groups. NPC tends to aggregate in Cantonese families in Guangdong Province, and the malignancies in these families appear to be site specific, with no excess of any other malignancy.

Lobular neoplasia on core-needle biopsy--clinical significance.

Approximately 25% of all cases of atypical ductal hyperplasia (ADH) diagnosed on core biopsy of the breast are associated with ductal carcinoma in situ (DCIS) or invasive malignancy at the same site. As a result, surgical excision has become the standard of care for patients with ADH. In contrast, because data on the relation between breast malignancy and lobular neoplasia (LN) detected on core biopsy are limited, clinical management of patients with LN remains controversial. The goal of the current study was to determine the incidence of breast carcinoma at sites of core biopsy exhibiting LN compared with sites of core biopsy exhibiting ADH. The results of 2053 core biopsies were reviewed to identify cases of LN and cases of ADH. Follow-up findings on excisional biopsy were categorized as malignancy (DCIS or invasive malignancy) or no malignancy and were compared between the LN group and the ADH group. Mammograms and medical records were reviewed for patients with atypical findings on core biopsy. One hundred six (5.2%) of 2053 biopsy samples exhibited atypia on core biopsy. Among these 106 samples, ADH was found in 49 (46%), LN was found in 45 (42%), and both ADH and LN were found in 12 (12%). Malignant disease was detected on follow-up excisional biopsy in 22% of patients with ADH (9 of 41), 14% of patients with LN (3 of 21), and 33% of patients with both ADH and LN (4 of 12) on core biopsy. In the LN group, two cases of malignant disease were associated with lobular carcinoma in situ, and the third case was associated with atypical lobular hyperplasia. Mammographic and clinical features were unable to distinguish patients with malignant findings on excisional biopsy from patients without malignant findings. Malignant disease was found in a substantial percentage of excisional biopsy samples (14%) following the detection of LN on core biopsy. Thus, like patients with ADH, patients with LN on core biopsy could be considered candidates for surgical excision, which would allow full assessment of breast carcinoma risk and thereby facilitate the planning of prevention strategies.

Reproductive factors and risk of breast carcinoma in a study of white and African-American women.

Few studies have investigated the association between reproductive factors and the risk of breast carcinoma among African-American women. The authors assessed whether the number of full-term pregnancies, age at first full-term pregnancy, and total duration of breastfeeding were associated with similar relative risk estimates in white and African-American women in a large multicenter, population-based case-control study of breast carcinoma. Case patients were 4567 women (2950 white women and 1617 African-American women) ages 35-64 years with newly diagnosed invasive breast carcinoma between 1994 and 1998. Control patients were 4668 women (3012 white women and 1656 African-American women) who were identified by random-digit dialing and were frequency matched to case patients according to study center, race, and age. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. For white women, the reduction in risk of breast carcinoma per full-term pregnancy was 13% among younger women (ages 35-49 years) and 10% among older women (ages 50-64 years). The corresponding risk reductions for African-American women were 10% and 6%, respectively. Risk decreased significantly with increasing number of full-term pregnancies for both races and both age categories. Duration of lactation was inversely associated with breast carcinoma risk among younger parous white (trend P = 0.0001) and African-American (trend P = 0.01) women. African-American women tended to have more children compared with white women, but parity rates were lower in younger women than in older women in both racial groups. However, breastfeeding was substantially more common in young white women than in young African-American women. Overall, parity and lactation had similar effects on breast carcinoma risk in white and African-American women. If younger African-American women now are giving birth to fewer children than in the past, without a substantial increase in breastfeeding, breast carcinoma rates may continue to increase at a more rapid rate among these women compared with white women.

Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma.

Aurora-A/BTAK/STK15, involved in regulating centrosomes and chromosome segregation, is overexpressed in human breast carcinoma and other cancers. The Phe31-->Ile polymorphism in Aurora A alters the kinase function, with the Ile31 variant being preferentially amplified and associated with degree of aneuploidy in human tumors. We have previously shown that the Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal cancer. This case-control study examined the contribution of this polymorphism to susceptibility to development and progression of breast cancer. Aurora A genotypes were determined in 520 patients with breast carcinoma, 191 patients with benign breast diseases (BBD) and 520 controls. It was found that the Aurora A Ile/Ile genotype was significantly associated with increased risk of breast carcinoma occurrence [odds ratio (OR) 1.66; 95% confidence interval (95% CI) 1.29-2.12] compared with the Phe/Phe or Phe/Ile genotype. The increased risk for BBD and breast carcinoma related to the Ile/Ile genotype was more pronounced in younger subjects. Moreover, we found that patients carrying the Ile/Ile genotype tended to have ER-carcinomas (OR 2.56; 95% CI 1.24-5.26). No significant association was observed between the polymorphism and metastasis and disease stage of the cancer. These findings suggest that the Phe31Ile polymorphism in Aurora A may be a genetic modifier for developing breast carcinoma.

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

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

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

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