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[Breast-conserving treatment for early invasive lobular breast cancer: 15 years results].

BACKGROUND: Infiltrating lobular cancer is biologically different from invasive ductal cancer and there is disagreement regarding appropriate local management of this disease. PURPOSE: To examine treatment outcomes after breast-saving surgery for patients with invasive lobular breast cancer. MATERIAL AND METHODS: Between 1983 and 1987, 77 women with early, stage I-II invasive lobular breast cancer were treated with complete gross excision of the tumour and axillary dissection. Fifty-eight of these patients were treated with 50 Gy ipsilateral breast irradiation, and 19 did not receive radiotherapy. During 176 month median follow-up local-regional recurrences, distant metastases, contralateral breast cancers, breast cancer deaths and deaths caused by other disease were scored. The probability of survival was estimated by Kaplan-Meier method. In uni- and multivariate analysis the Cox-model was used. Relative risk (RR) and associated confidence intervals (CI) were calculated from the regression coefficients. Statistical differences in proportions and means were assessed by log rank and Fisher exact-tests. RESULTS: In the saved breast, the actual rate of local recurrence at 15 years was 13% for irradiated and 53% for non-irradiated patients (RR: 0.1; 95% CI: 0.03-0.31; p: < 0.0001). The incidence of total breast cancer relapses (local-regional recurrences and distant metastases) was also higher for non-irradiated than for irradiated patients (74% vs. 40%; p: 0.0168). In multivariate analysis irradiation (no vs. yes) showed a significant effect on local tumour control (RR: 0.08: 95% CI: 0.02-0.28; p: 0.0001), but menopausal (pre vs. post), T-(T1 vs. T2) and N-(N0 vs. N1) status did not. The breast cancer specific survival at 15 years was 74% without and 62% with local recurrence (RR: 1.45; 95% CI: 0.53-3.96; p: 0.4697). The majority of local recurrences (9 of 14) were curable by salvage surgery. For all patients the rate of contralateral breast cancer was 6.5%. CONCLUSION: Results of long-term follow-up confirmed that breast-conserving surgery and radiotherapy is a reasonable treatment for patients with early invasive lobular breast cancer. The majority of local recurrences are curable by salvage surgery.

Adult↗

Mutation analysis of the breast cancer gene BRCA1 among breast cancer Jordanian females.

OBJECTIVE: To screen mutations of the tumor suppressor breast cancer susceptibility gene 1 (BRCA1) within 3 exons among Jordanian breast cancer females. METHODS: A total of 135 Jordanian breast cancer females were genetically analyzed by denaturing gradient electrophoresis (DGGE) for mutation detection in 3 BRCA1 exons (2, 11 and 20) between 2000-2002 in Al-Basheer Hospital, Amman, Jordan. RESULTS: Of the studied patients 50 had a family history of breast cancer, 28 had a family history of cancer other than breast cancer, and 57 had no family history of any cancer. Five germline mutations were detected among breast cancer females with a family history of breast cancers (one in exon 2 and 4 mutations in exon 11). Another germline mutation (within exon 11) was detected among breast cancer females with family history of cancer other than breast cancer, and no mutation was detected among breast cancer females with no family history of any cancer or among normal control females. CONCLUSION: Screening mutations within exon 2, exon 11 and exon 20 showed that most screened mutations were within BRCA1 exon 11 among breast cancer Jordanian families with a family history of breast cancer.

Adult↗

[Breast cancer in adipose breasts].

The authors have studied breast cancer in fatty breasts in an attempt to prove their observations that Wolfe's classification "N1" on mammography was not necessarily "normal". Two groups of women, the first called group "A" consisting of 384 women with cancer of the breast, and group "B", the control group of 400 women who had no abnormality in the breast, were studied and correlated for epidemiological, thermographic, mammographic, and anatomo-pathological parameters. The following epidemiological factors were studied: age, marital status, profession, age at menarche and at menopause, menstrual behaviour, age at the first pregnancy that went to term, parity (live and still births), type of delivery, length of breast feeding, number of abortions, use of hormones, and family history of cancer of the breast. In the thermographic studies: the topography of the heat pattern, the primary pathological signs and the thermic state were studied. In mammography: the mammographic appearance after Wolfe and the presence of microcalcifications was studied. In group "A" the following histological group parameters were studied: which breast, in which quadrant the nodule was situated, the type of breast the contour and size of the tumour, the number of axillary nodes removed, the histological type of the cancer, the histological grade of the malignancy, vascular invasion, details about the skin and the areola, calcifications, lymphocytic infiltration of the stroma, multicentricity, the co-existence of cystic disease of the breast and invasion of the axillary nodes. All these above-mentioned parameters were correlated with: the age, the existence of previous pregnancies at term, the macroscopic type of the breast and the mammographic type according to Wolfe. The breasts were divided into three macroscopic types: fatty, fibrous and intermediate. The correlation of the mammographic type according to Wolfe showed that types N1 and P1 corresponded to fatty and partially intermediate types. In group "A" the macroscopically fatty as compared with the other type of breasts showed a more extensive degree of infiltrations: vascular (76.5%), skin (90.3%), areolae (88.9%) and lymphocytic (80.1%), as well as a higher percentage of axillary metastases (57.7%).

Adipose Tissue↗

Detection of a breast tissue-associated antigen by antiserum to Raji cell-bound circulating immune complexes of human breast cancer.

Rabbits tolerant to human immunoglobulin G were used to raise antisera against the Raji cell-bound circulating immune complexes from human breast cancer sera. After solid-phase adsorption treatment with glutaraldehyde-cross-linked normal human plasma, acetone-extracted normal liver tissue powder, and glutaraldehyde-fixed Raji cells, one antiserum reacted specifically with breast tissue extracts but not with extracts of other tissues, as examined by a counterimmunoelectrophoresis technique. Immunological reactivity of the treated antiserum was removed by incubation with normal, primary, or metastatic breast tumor tissue extracts. Incubation with normal human serum or extracts derived from tissues other than the breast showed no neutralizing effect on the antibodies. This specific antiserum reagent was used in a modification of the Raji cell radioimmunoassay. Raji cells were incubated with sera from cancer patients or normal controls and then reacted with 125I-labeled F(ab')2 fraction of the treated antiserum reagent. The amount of 125I-F(ab')2 bound was then determined. Although all sera exhibited elevated circulating immune complexes by the conventional Raji cell radioimmunoassay, 14 of 18 breast carcinoma sera demonstrated a significant uptake when compared with the normal population group as opposed to five (three lung and two colon) of 29 other cancer sera examined (p less than 0.001). An immunologically reactive breast tissue-associated antigen, purified from malignant breast tumor or normal breast tissue extracts with the use of antiserum reagent, exhibited an apparent molecular weight of 85,000 by sodium dodecyl sulfate; polyacrylamide gel electrophoresis and a pI value of 4.9 +/- 0.2. These results demonstrated that a breast tissue-associated antigen rather than a breast tumor-associated neoantigen, was involved in circulating immune complexes of breast cancer patients as detected by Raji cell immunoassay. It also implied the occurrence of disease-related autoimmunity in human breast cancer.

Antigen-Antibody Complex↗

The status of cyclooxygenase-2 expression in ductal carcinoma in situ lesions and invasive breast cancer correlates to cyclooxygenase-2 expression in normal breast tissue.

OBJECTIVES: There is a paucity of data on cyclooxygenase (COX)-2 expression in normal breast tissue and on the changes in COX-2 expression from normal tissue via ductal carcinoma in situ (DCIS) lesions to invasive cancer. The aim of this study, therefore, was to investigate COX-2 protein expression in normal breast tissue, DCIS, and invasive breast cancer in samples from the same patients. METHODS: In 39 patients, we investigated and compared COX-2 expression in paired samples of invasive cancer and normal adjacent breast epithelium by immunohistochemistry with a monoclonal COX-2 antibody. Furthermore, in 29 of these cases, we also analyzed a concomitant DCIS lesion. RESULTS: Patients without COX-2 expression in normal breast tissue also do not express COX-2 in invasive breast cancer and in DCIS lesions, respectively. Conversely, COX-2 expression in normal breast tissue was an indicator for COX-2 expression in the paired breast tumors. There was no significant correlation between COX-2 expression and pathologic tumor stage, nodal status, hormone receptor status, tumor size, grading, and lymphovascular space involvement. CONCLUSIONS: This is the largest study to date investigating COX-2 in paired samples of breast tumors and normal adjacent breast tissue. Our data are consistent with the hypothesis that COX-2 overexpression is an early event in breast carcinogenesis.

Adult↗

Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease.

BACKGROUND: Although childbearing is known to protect against breast cancer, whether or not breastfeeding contributes to this protective effect is unclear. METHODS: Individual data from 47 epidemiological studies in 30 countries that included information on breastfeeding patterns and other aspects of childbearing were collected, checked, and analysed centrally, for 50302 women with invasive breast cancer and 96973 controls. Estimates of the relative risk for breast cancer associated with breastfeeding in parous women were obtained after stratification by fine divisions of age, parity, and women's ages when their first child was born, as well as by study and menopausal status. FINDINGS: Women with breast cancer had, on average, fewer births than did controls (2.2 vs 2.6). Furthermore, fewer parous women with cancer than parous controls had ever breastfed (71% vs 79%), and their average lifetime duration of breastfeeding was shorter (9.8 vs 15.6 months). The relative risk of breast cancer decreased by 4.3% (95% CI 2.9-5.8; p<0.0001) for every 12 months of breastfeeding in addition to a decrease of 7.0% (5.0-9.0; p<0.0001) for each birth. The size of the decline in the relative risk of breast cancer associated with breastfeeding did not differ significantly for women in developed and developing countries, and did not vary significantly by age, menopausal status, ethnic origin, the number of births a woman had, her age when her first child was born, or any of nine other personal characteristics examined. It is estimated that the cumulative incidence of breast cancer in developed countries would be reduced by more than half, from 6.3 to 2.7 per 100 women by age 70, if women had the average number of births and lifetime duration of breastfeeding that had been prevalent in developing countries until recently. Breastfeeding could account for almost two-thirds of this estimated reduction in breast cancer incidence. INTERPRETATION: The longer women breast feed the more they are protected against breast cancer. The lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries.

Adult↗

The expanding role of pathologists in the diagnosis and management of breast cancer: Worldwide Excellence in Breast Pathology Program.

Pathology is the study of human illness and it involves the morphologic and biologic recognition of abnormalities that are associated with a disease. Breast pathology represents an excellent example of this discipline. By providing diagnostic information and by characterizing the biologic behavior of a breast lesion, a pathologist plays a critical role in a patient's life. Any mistake in this exercise is associated with serious consequences. In addition, there are many unresolved issues in breast pathology, which contribute to our limited understanding of the biology of breast cancer, variability in diagnostic criteria, and significant diversity in breast cancer management and therapy. Furthermore, breast pathology has remained an underrecognized discipline, and its importance in diagnosis and disease management is not fully realized. In order to better serve our patients, particularly medically underserved women and those living in countries with limited resources, we must place emphasis on effectively using the talent and expertise of pathologists around the globe. For example, to provide a cost-effective way to diagnose breast cancer, particularly at advanced stages, pathologists can sample lesions by fine-needle aspiration biopsy (FNAB), stain the resulting smears, and provide an immediate bedside diagnosis. This is a valid contribution; however, this exercise requires the availability of a pathologist with experience in breast cytopathology. Alternatively the pathologist may seek consultations from more experienced pathologists. Developing strategies to better recognize the importance of high-quality breast pathology services and to train qualified and innovative breast pathologists is an ambitious task. The proposed Worldwide Excellence in Breast Pathology Program may provide such an opportunity.

Breast↗

Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts.

BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.

Adult↗

Women with breast cancer: histologic findings in the contralateral breast.

PURPOSE: To investigate contralateral breast biopsy histologic findings in women with breast cancer. MATERIALS AND METHODS: Histologic findings in 237 patients with breast cancer who underwent contralateral breast biopsy for clinically or mammographically detected abnormalities were retrospectively reviewed. Malignant findings were categorized by histologic type. Benign findings were categorized by risk of breast cancer. Comparison was made with mammographically guided breast biopsy results in 1,294 patients without breast cancer. RESULTS: Of the 237 patients, 168 (70.9%) had either malignancy or high-risk histologic findings. One hundred thirty-nine patients (58.6%) had malignant findings; 98 (41.4%) had benign findings. Of the 98 with benign findings, 29 (30%) had high-risk histologic findings. Thirty (33%) of the 91 patients with invasive cancer had invasive lobular carcinoma. Forty-seven (45.6%) of the 103 patients with malignant lesions at mammographically guided biopsies had ductal carcinoma in situ alone. CONCLUSION: Compared with biopsy in women without breast cancer, contralateral biopsy in women with breast cancer was more likely to show malignancy, invasive lobular carcinoma, or ductal carcinoma in situ alone (P < .001) or to show high-risk histologic benign findings (P < .001). Mammographic and clinical findings in the contralateral breast should be regarded as more suspicious than those in patients without known breast cancer.

Adult↗

Immunohistochemical study of beta- and kappa-casein in the human breast and breast carcinomas, using monoclonal antibodies.

The immunohistochemical analysis of human beta- and kappa-caseins in the human breast, benign breast disease, and breast carcinomas is reported. The monoclonal antibodies LICR-LON-32.2 and LICR-LON-14.1 which react with human beta- and kappa-casein, respectively (Earl, H. M., and McIlhinney, R. A. J. Mol. Immunol., 22: 981-991, 1985) were used for these studies. Human beta- and kappa-caseins were detected in lactating human breast tissue, lactational foci in the resting breast, and heterogeneously in the 16th-week pregnant breast, but not in normal breast tissue. In benign breast disease occasional epithelial cells were demonstrated to synthesize beta- and kappa-caseins, but this finding did not appear to correlate with the hormonal status or previous obstetric histories of the patients. However, similar studies in 45 breast carcinomas with a wide range of estrogen receptor content, demonstrated no detectable beta- or kappa-casein. These results demonstrate that the caseins, which are biochemical markers of mammary gland differentiated function, and have been previously put forward as markers of breast cancer, were not synthesized in the 45 human breast carcinomas studied here, even in tumors with high levels of estrogen receptor protein.

Antibodies, Monoclonal↗

Benign and malignant breast disease: initial study results of serum and breast fluid analyses of endogenous estrogens.

Design, methods, and study population of a long-term multidisciplinary investigation of benign and malignant breast disease were reported. This initial report focused on the relation of menstrual, reproductive, and other factors to serum and breast fluid estrogen measures [estradiol (E2), estrone (E1), percent free estrogen, and sex hormone binding globulin] among control women. After adjustment for the factors found to be related to the various estrogen measures, estrogen levels in women with benign and malignant disease were compared to those of controls. Findings were as follows: a) little evidence of any relation of most breast cancer risk factors with the various serum estrogen parameters studied; b) differences in breast fluid estrogen levels that may be relevant to the protective effect of parity on breast cancer risk; c) markedly higher levels of E2 and E1 in breast fluid than in serum and no evidence of a correlation of serum with breast fluid measures; d) no support for the hypothesis that breast cancer patients have higher serum percent free E2 than controls or women with benign breast disease; and e) higher breast fluid E2 and E1 levels in women with biopsied benign breast disease than in controls.

Adult↗

Relationships of barriers and facilitators to breast self-examination, mammography, and clinical breast examination in a worksite population.

The American Cancer Society recommends a regimen for breast cancer screening that includes mammograms, clinical breast examination, and breast self-examination. Compliance with breast cancer screening guidelines has been linked to a number of barriers and facilitators. These barriers and facilitators seem to lie within the cognitive framework and generalized beliefs of women, and in the situational contexts in which they lead their lives. A comprehensive study was designed to investigate variables related to breast cancer screening behaviors (breast self-examination, mammography, and clinical breast examination) of working women > or = 35 years of age at their worksite environments. A factor analysis identified similar sets of composite variables related to each of the screening modalities, and a discriminant analysis was performed for each screening technique to identify those variables that were most significant in predicting compliance with screening guidelines. The variables discomfort, perceived efficacy, and desire for control over health were significant for all three screening behaviors. Perceived importance was identified as a fourth variable for mammography and clinical breast examination, and lack of knowledge was a fourth variable for breast self-examination. Effective breast cancer screening programs involve all three screening techniques. In the design of education and intervention programs at worksites, it is critical to emphasize the commonalities of the variables that emerged in this study as important for each screening technique. Health-care professionals who implement such intervention programs need to explore and bring into the open these common barriers and facilitators to maximize working women's compliance with breast screening guidelines.

Adult↗

The Outcome of Patients with Breast Cancer Who Underwent Breast Conserving Treatment with or without Immediate Volume Replacement with Autogenous Tissue.

BACKGROUND: Breast conserving treatment (BCT) is accepted as an appropriate therapy for most patients with stage I and stage II breast cancer. However, BCT is associated with a relatively high incidence of local recurrence, and aesthetically unacceptable results occur in some patients. A novel method of immediate volume replacement using autogenous tissue has been developed to strike a balance between adequate excision and cosmesis. We determined the oncological outcome inpatients with breast cancer treated with wide excision, immediate volume replacement with autogenous tissue, and axillary dissection followed by radiotherapy. METHODS: One hundred fifty-three patients with TIS, stage I, II, or III breast cancer underwent wide excision and axillary dissection. The surgical margin ofexcised breast tissue was examined histologically during surgery. If involved, the breast tissue adjacent to the primary site was excised. When the margin of re-excision was positive, patients underwent modified radical mastectomy with or without breast reconstruction. After wide excision, immediate volume replacementwith autogenous tissue was perform-ed, unless the deformity was corrected by undermining and conization of the residual breast tissue. Postoperatively, all patients received breast irradiation. RESULTS: Eighteen patients underwent modified radical mastectomy. The surgical margin was negative in 132 of the 135 patients who underwent BCT. The crude local recurrence rate was 0.7% (1/135). Estimated overall and disease-free 5-year survival rates were 96% and 94%, respectively. CONCLUSION: Wide excision with tumor-free margins and axillary dissection followed by breast irradiation provides adequate local control in many patients with breast cancer. Immediate breast volume replacement with autogenous tissue mayavoid some unpleasant cosmetic results associated with extensive local resection. Our technique eliminates the need for mastectomy in selected patients.

Journal Article↗

The association between breast surgeons' attitudes toward breast reconstruction and their reconstruction-related information-giving behaviors: a nationwide survey in Japan.

BACKGROUND: Breast reconstruction after breast cancer surgery has come to be regarded as an achievable treatment option to improve patients' quality of life. Although it has been pointed out that surgeons' information-giving behaviors affect women's decision to undergo breast reconstruction surgery, little is known about the factors that influence these behaviors. This study investigated Japanese surgeons' reconstruction-related information giving to patients and the factors that affect these behaviors. METHODS: A nationwide postal survey of 1313 board-certified Japanese breast surgeons was conducted. In the questionnaire, surgeons were asked about their reconstruction-related information-giving behaviors and their attitudes toward six hypothetical critical statements regarding breast reconstruction. RESULTS: Among 635 responding surgeons, 199 (31.3 percent) answered that they did not give reconstruction-related information at all when explaining breast cancer treatment options, and 291 (45.8 percent) stated that they selectively choose patients with whom they provide information based on patients' backgrounds such as age and marital status. Results from the multiple logistic regression analysis indicated that respondents who agreed to the statements "Breast reconstruction may delay the detection of local recurrence," "The aesthetic results of reconstructed breasts are not worth the cost and effort involved," "Breast reconstruction is a luxury," and "Surgeons should pursue breast conserving surgery rather than breast reconstruction" showed significantly decreased likelihood to give reconstruction-related information to patients. CONCLUSION: Surgeons need to be aware of the adverse effect that their own attitudes and values with regard to breast reconstruction may have on a patient's ability to choose treatment options.

Adult↗

The influence of risk factors on breast carcinoma screening of Medicare-insured older women. National Cancer Institute Breast Cancer Screening Consortium.

BACKGROUND: It is not certain whether older women with additional breast carcinoma risk factors are adequately screened or whether they are more likely to undergo screening than other older women. This study was conducted to determine whether selected risk factors influence the breast carcinoma screening rates of Medicare-insured older women (i.e., age 65 years or older). METHODS: Self-reported rates of screening mammography and clinical breast examination in the previous year were compared for women with benign breast disease, women with a family history of breast carcinoma, and women lacking these risks, using samples of non-Hispanic white, Medicare-insured women surveyed at the 5 National Cancer Institute Breast Cancer Screening Consortium sites in 1991 (n = 5376, mean age = 69.7 years) and 1994 (n = 5086, mean age = 69.7 years). RESULTS: In 1993, rates of screening mammography reported in the previous year at the 5 Consortium sites had a range of 46-61% for women with a family history of breast carcinoma, 49-66% for women with benign breast disease, and 31-43% for women lacking these risks. Women with a positive family history or a personal history of benign breast disease were also more likely to report having had a clinical breast examination in the previous year and having received a physician's mammography recommendation. A substantial proportion of older women with a positive family history remain inadequately screened, however. Between 25% and 35% of women in this group had not had a screening mammogram in the previous 2 years, while at some Consortium sites more than 20% reported never having had a mammogram in their lives. CONCLUSIONS: Older women with additional risk factors are more likely to undergo screening mammography. This is due partly to more frequent physician recommendations for screening and partly to more frequent provision of clinical breast examinations. However, a substantial proportion of high risk older women remain inadequately screened, despite widespread clinical consensus that these women should be regularly screened. Interventions that target older women with risk factors and their physicians appear warranted. Understanding the mechanisms by which risk factors influence screening is an important area for future research.

Aged↗

Magnetic resonance imaging of breast cancer: clinical indications and breast MRI reporting system.

Magnetic resonance imaging (MRI) is well suited to the investigation of breast cancer by virtue of its noninvasive nature and its multiplanar imaging abilities. MRI investigations showed high sensitivity but modest specificity for breast cancer detection and diagnosis. Most early studies tested the ability of MRI to evaluate and diagnose findings in the breast discovered by other imaging tests or by breast physical examination (1-4). When it was discovered that MRI identified small breast cancers undetected by mammography or breast ultrasound, MRI was used to estimate breast cancer extent in known cancer cases for surgical planning (5,6). These investigations led to the use of MRI in a multitude of breast imaging applications, raising further questions about the use of MRI in everyday practice: What are the indications for breast MRI in general practice? What is its role in light of other imaging tests? What are its benefits and limitations in each setting? How do I report these studies? The purpose of this article is to review the clinical background regarding indications for the use of MRI and relevant cases in which MRI can impact patient management in breast disease, and to describe new developments in reporting breast MRI studies. J. Magn. Reson. Imaging 2000;12:975-983.

Breast↗

Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease.

BACKGROUND: Biopsy-proven benign breast disease (BBD) is a risk factor for developing breast carcinoma; however, to the authors' knowledge, little is known regarding factors related to progression to carcinoma. A cohort study was conducted to examine the role of cyclooxygenase (COX) polymorphisms and nonsteroidal anti-inflammatory drugs (NSAIDs) in the progression of BBD to breast carcinoma. METHODS: Among participants in an ongoing cohort study, 1467 women underwent a breast biopsy for BBD. Of these women, 91 subsequently developed breast carcinoma. Medication data were collected in 1989 and in 1996. COX genotypes were determined using DNA extracted from blood specimens collected in 1989. RESULTS: A decrease in breast carcinoma risk was observed among women who reported using aspirin in 1989 (odds ratio [OR] of .46; 95% confidence interval [95% CI], .22-.98) and in 1996 (OR of .47, 95% CI, .18-1.21). Furthermore, a higher frequency, dose, and longer duration of aspirin use were associated with a decrease in the odds of developing breast carcinoma. Overall, no association was observed between COX genotypes and the subsequent development of breast carcinoma. However, among women not using NSAIDs, one COX-2 polymorphism (rs2143416) was found to be significantly associated with the development of breast carcinoma. CONCLUSIONS: Findings from the current study suggest that inflammation through COX-2 pathways may play a role in the progression of BBD to breast carcinoma and that aspirin may help to lower the risk of progression to breast carcinoma among women with BBD.

Adult↗

Establishing a molecular continuum in breast cancer DNA microarrays and benign breast disease.

Although the risk of breast cancer for women in the United States is approximately 1 in 9, identification of risk factors and translation of that knowledge into strategies for prevention have been inhibited by poor understanding of disease pathogenesis. A few benign breast proliferations are associated with higher risks of breast cancer, but definition of a preneoplastic morphologic continuum is lacking. If progression from a premalignant state to malignancy is accompanied by genetic changes, then identification in benign breast disease lesions (BBD) of alterations similar to those found in breast cancer should strengthen the perception of BBD as a premalignant condition. Current testing for hereditary breast cancer susceptibility presumes that only women with invasive breast or ovarian cancer are gene carriers. Therefore, neither in situ breast cancer nor atypical hyperplasias are considered clinically as evidence of a breast-ovarian syndrome, nor are these diagnoses used to predict carrier status within at-risk families. This reflects lack of evidence that breast cancer develops along a recognized morphologic continuum from precursor lesions. New mutation screening procedures such as DNA microarrays can provide sensitivity, specificity, and high throughput that circumvent limitations imposed on the scope of molecular marker analyses applied to archival resources. We have studied a BRCA1-mutant individual with loss of the wild type BRCA1 allele in benign breast proliferations. Both her benign and malignant lesions showed molecularly identical TP53 mutations, indicating that significant genetic alterations can occur in BBD and supporting the clonal evolution from BBD to malignancy.

BRCA1 Protein↗