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PubMed1989

Influence of exogenous estrogens, proliferative breast disease, and other variables on breast cancer risk.

The authors reevaluated 10,366 consecutive breast biopsy specimens of benign lesions performed between 1950 and 1968. Follow-up information was obtained on 3303 women with a median duration of follow-up of 17 years. This sample contained 84% of the patients originally selected for follow-up. The relative risk (RR) of developing breast cancer was 0.98 for women who took exogenous estrogens as compared to 1.8 for women who did not. Exogenous estrogens lowered the observed breast cancer risk in women with atypical hyperplasia (RR = 3.0 versus 4.5), proliferative disease without atypia (RR = 0.92 versus 1.9), and in women without proliferative disease (RR = 0.69 versus 0.91). Women who took estrogens before 1956 were at 2.3 times the risk of other estrogen users, presumably due to a dose effect. There was no significant association between breast cancer risk and birth control pills, cigarette smoking, or alcohol consumption. Exogenous estrogens are not associated with increased breast cancer risk in women with benign breast disease. A previous history of benign breast disease does not contraindicate replacement estrogen therapy.

Adult↗
PubMed2001

Intracystic epidermal growth factor level is predictive of breast-cancer risk in women with gross cystic disease of the breast.

Women affected by gross cystic disease of the breast have an increased risk of breast cancer. We report here the incidence of breast cancer by cyst type and intracystic epidermal growth factor (EGF) concentration. Our retrospective study included 504 women who had at least 1 cyst aspiration between 1985 and 1993. Cyst fluids were processed for electrolyte concentration (n = 378), EGF concentration (n = 347) or both (n = 337). Age-standardized incidence ratios (SIRs) were estimated using the population of the Genoa Cancer Registry. A multivariate Poisson regression model was used to estimate relative risks (RRs) when the study groups were compared directly. By June 1999, 19 invasive breast cancers had developed in the cohort of women. The age SIR of breast cancer calculated for the whole cohort was 3.32 (95% confidence interval 2.00-5.18). The ratio was not affected by age and was only moderately increased in women with a positive family history of breast cancer and type I cysts (i.e., those with a Na+/K+ ratio <3). However, it was significantly increased in women with high EGF concentrations. Direct comparisons confirmed that age, cyst type and family history only moderately increased the RR, whereas EGF concentration was a strong predictor of risk. Our results confirm that women affected by palpable cysts have an increased risk of developing breast cancer and suggest that the risk is higher in women with high intracystic EGF concentrations.

Adult↗
PubMed2003

Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers.

BACKGROUND: BRCA1 and BRCA2 alterations are associated with an increased risk of developing breast carcinoma. The authors hypothesized that the progression of breast neoplasia may differ between patients with hereditary disease and patients with nonhereditary disease and that this difference in progression may be visualized by studying the prevalence of precursor lesions and neoplastic lesions. METHODS: The authors developed two case cohorts of high-risk patients with a strong family history of breast carcinoma who underwent prophylactic mastectomy. The first cohort was comprised of women who underwent therapeutic mastectomy and contralateral prophylactic mastectomy, and the second cohort was comprised of women who underwent bilateral prophylactic mastectomy. Patients without a family history of breast carcinoma who underwent unilateral or bilateral prophylactic mastectomy were selected as a control group. DNA from peripheral blood leukocytes was screened for BRCA1 and BRCA2 mutations. The available pathologic materials were reviewed independently by two pathologists, and all neoplastic and precursor lesions were identified and classified. Proliferation activity was assessed using MIB-1 immunohistochemistry on all available lesions from the unilateral mastectomy cohort. RESULTS: The 28 women from the unilateral cohort with deleterious BRCA1/2 mutations had a lower prevalence of proliferative fibrocystic changes (PFC) (7%) compared with their matched control group (25%) (P = 0.075) and with patients who had a family history but no BRCA1/2 mutation (22-33%). None of the 11 deleterious mutation carriers from the bilateral cohort (0%) had PFC compared with 36% of women in the matched control group (P = 0.03). There was no major difference in the prevalence of other precursor lesions (including in situ carcinoma) in either cohort. Invasive carcinomas from the deleterious mutation carriers in the unilateral cohort were of higher grade compared with the control group (P = 0.003) and patients without a mutation (P < 0.0001) but were of similar grade compared with carriers of unclassified variant BRCA1/2 alterations (P = 0.20). Neoplastic lesions from the deleterious mutation carriers in the unilateral cohort had higher MIB-1 proliferation indices compared with other patients with and without a family history of breast carcinoma. CONCLUSIONS: The current data suggest that the progression rate of breast neoplasia is accelerated in women who carry BRCA1/2 deleterious mutations compared with other patients who have breast carcinoma with or without a family history. This increased progression rate should be taken into account when considering the surveillance of asymptomatic women.

Adenocarcinoma↗
PubMed2006

Extra-tumoral breast tissue in breast cancer patients: variations with steroid contraceptive use.

The association between oral contraceptive (OC) use and benign breast changes in extra-tumoral breast tissue was studied histologically in 1,503 breast cancer patients from The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. The occurrence of ductal hyperplasia, ductal atypia, sclerosing adenosis, cysts, apocrine metaplasia, apocrine hyperplasia, apocrine atypia, adenosis, lobular atypia, duct ectasia, calcifications, inflammatory reaction, lactational metaplasia and a high epithelial-stromal ratio was graded semi-quantitatively. Prevalence odds ratio (POR) for each histologic variable was calculated by logistic regression analyses. Patients who had ever used OC had lower occurrence of ductal hyperplasia than never users (POR 0.72 (95% CI 0.52-0.99)). Current use and more than 8 years of use was also associated with a lower prevalence of ductal hyperplasia (POR 0.40 (0.20-0.81) and POR 0.33 (0.17-0.64), respectively). Age > 35 years at first use was associated with increased prevalence of ductal carcinoma in situ (POR 2.15 (1.05-4.40)), but not of atypical ductal hyperplasia. Our results show that the effects of OC use on ductal hyperplasia in non-neoplastic breast tissue of breast cancer patients are similar to what others have found in patients with benign breast disease only. The increased prevalence of extra-tumoral ductal carcinoma in situ in breast cancer patients who started OC use at high age may possibly be explained by a longer preinvasive phase in these patients.

Adult↗
PubMed1982

The comparative epidemiology of benign breast lumps and breast cancer in Western Australia.

Totals of 313 patients with breast cancer and 1,283 patients biopsied for benign breast lumps were found in Western Australia in 1978 through review of all histopathological, hospital and cancer registry records. The incidence of breast cancer rose to 146.9 per 100,000 at age 45-54 years and thereafter increased little. The biopsy rate for benign breast lumps rose more sharply to 420.2 per 100,000 at age 45-54 years and then fell. This pattern was mainly due to benign mammary dysplasia (BMD); fibroadenoma showed an earlier peak biopsy rate (30-34 years) and other (mainly non-neoplastic) benign lumps were biopsied at a relatively constant rate throughout adult life. Rates of breast cancer, BMD and fibroadenoma showed similar relationships to the other descriptive variables studied. The rates of each were higher in single than married women, in residents of the Perth area than residents of other parts of the State and in women employed in professional and related occupations than other employed women. They were lower in migrants from Europe (excluding Great Britain) than native-born Australians and in women of low socio-economic status than women of high status. Not all these differences were statistically significant. Rates of other breast lumps did not generally vary in these ways and were conversely related to country of birth, area of residence and socio-economic status. The parallels in descriptive epidemiology between breast cancer, BMD and fibroadenoma suggest that they may share aetiological factors.

Adolescent↗
PubMed1989

In situ oestrone synthesis in normal breast and breast tumour tissues: effect of treatment with 4-hydroxyandrostenedione.

An isotopic infusion technique has been used in an attempt to determine the contribution that local, in situ, oestrone synthesis makes to the oestrogen content of breast tumours. 3H-Androstenedione and 14C-oestrone were infused into women with advanced breast cancer for 12 hr before operation. At surgery, normal breast and breast tumour biopsy samples were obtained and 3H-androstenedione, 3H-oestrone derived from 3H-androstenedione and 14C-oestrone were isolated and measured. DNA polymerase alpha activity, a marker of cellular proliferation, was also measured to examine whether local synthesis of oestrone exerted a biological effect. The study was repeated after patients had been treated with the aromatase inhibitor, 4-hydroxyandrostenedione, before undergoing further surgery for removal of their tumours. In 4/6 tumours examined, in situ synthesis of 3H-oestrone from 3H-androstenedione accounted for the major part (84.3 +/- 9.0%) of the 3H-oestrone detected, while no significant in situ synthesis occurred in 2 other tumours. Although treatment with 4-hydroxyandrostenedione did not significantly alter the uptake of 3H-androstenedione or 14C-oestrone into breast tissues, in situ formation of 3H-oestrone was only detected in one tumour sample after treatment. DNA polymerase alpha activity decreased in 4/6 tumours after treatment with 4-hydroxyandrostenedione. Overall, however, there was no significant correlation between the level of 3H-oestrone formed in situ and DNA polymerase alpha activity (r = 0.38, NS). It is concluded that in some, but not all, breast tumours in situ formation of oestrone can make an important contribution to the oestrogen content of breast tumours.

Aged↗
PubMed1995

Long-term impact of previous breast biopsy on breast cancer screening modalities.

Approximately 80% of breast biopsies are performed for what proves to be a benign process. The patients who undergo these procedures should continue screening with breast physical examination and mammography. The long-term impact of breast biopsy on these screening modalities has not been well studied. We performed a prospective, follow-up evaluation in 63 patients who underwent needle localization biopsy with benign histology at our institution between 6 and 7 years ago. This evaluation consisted of a directed history, breast physical examination, and follow-up mammogram. Two patients (3%) had undergone mastectomy for an interval breast cancer; 17 others (28%) had undergone subsequent biopsies. No patient had changes on physical examination of the biopsy site. All mammograms were evaluated as normal or as having benign abnormalities. Excisional breast biopsy does not generally produce long-term changes affecting the interpretation of breast physical examination or mammography.

Aged↗
PubMed2006

Proteomic analysis in human breast cancer: identification of a characteristic protein expression profile of malignant breast epithelium.

Gene expression analysis has become a promising tool in predicting the clinical course of malignant disease and the response to antineoplastic therapy. Surprisingly, only little is known about the protein expression pattern of human tumors. Recent advances in proteomic analysis allow proteins of interest to be identified by their expression and/or modification pattern in 2-DE rather than using the traditional approach of translating gene expression data. To identify a proteomic pattern that is characteristic for malignant breast epithelium, we performed differential 2-DE analysis in sets of microdissected malignant breast epithelia and corresponding adjacent normal breast epithelia from five patients with invasive breast carcinoma. Thirty-two protein spots were found to be selectively regulated in malignant epithelium, and were subjected to MALDI-TOF and/or immunoblotting for protein identification. Thirteen of the identified proteins had previously not been associated with breast cancer. The validity of these findings was confirmed by literature review and immunohistochemistry for identified proteins in an independent cohort of 50 breast cancer specimens. We here describe, for the first time, a proteomic analysis of matched normal and malignant epithelia from invasive breast carcinomas. This strategy leads to a better understanding of oncogenesis at an operational level and helps to characterize the malignant phenotype of individual tumors, and thereby to identify novel targets for antineoplastic therapy.

Adult↗
PubMed1992

The role of breast self-examination in early breast cancer detection (results of the 5-years USSR/WHO randomized study in Leningrad).

A randomized population-based study has been carried out since 1985 in Leningrad in order to evaluate the efficacy of breast self-examination (BSE) in early breast cancer detection. The population under study covers 120,310 women aged 40-64 years with no history of breast cancer. About half of these women were exposed to BSE training (60,221) and 60,098 women constituted the control group. BSE teaching was carried out on a person-to-person basis and each patient received the BSE calendar. BSE education sessions resulted in a higher frequency of visits to specialists with complaints about "pathology" of the breast, a higher rate of referral to a specialized institution for an examination, and a higher number of excision biopsies due to a benign lesion (RR = 1.5; 95% C.I. = 1.1 - 1.9) as compared with the control group. As a result of examination, 190 breast cancer patients in the BSE group and 192 patients in the control group were detected. Comparisons of patients from both groups with regard to the size of primary tumor and the incidence of metastatic lesion in the regional lymph nodes showed no differences. The study is ongoing and all cases of breast cancer in the BSE group will be registered up to 1994 and followed-up to 1999; information will then be available on the impact of BSE upon breast cancer mortality.

Adult↗
PubMed1987

Breast self-examination practices and attitudes of women with and without a history of breast cancer.

Breast self-examination (BSE) practices and attitudes of three groups of women were compared using a mailed survey. Subjects were 59 women with previous breast cancer, 33 women with previously treated benign breast lump(s), and 80 general-population women with no history of breast disease. Groups were compared on frequency, proficiency, and knowledge of BSE. Determinants of practice were examined using attitudinal variables from the Health Belief Model. Results indicated that the breast cancer group had significantly higher rates of BSE frequency, proficiency, and knowledge than did the general-population group. The breast cancer group perceived cancer to be significantly less threatening than did the other two groups, although the general-population group reported significantly less susceptibility to breast cancer. Within-group analyses revealed that barriers to BSE practice accounted for the greatest amount of variance in BSE frequency in all three groups. These results are discussed.

Attitude to Health↗
PubMed1982

The contralateral breast at reconstructive surgery after breast cancer operation--a histopathological study.

The present study concerns 73 patients with known unilateral breast carcinoma. Thirty of the patients had a primary invasive carcinoma removed and at a later operation contralateral subcutaneous mastectomy with implantation of a prosthesis. This was performed with or without ipsilateral breast reconstruction. Forty-three of the cases had an in situ carcinoma found by local excision, whereafter bilateral subcutaneous mastectomy was performed in 38 cases. Five cases had already had an ipsilateral mastectomy and contralateral subcutaneous mastectomy was performed. The histological examination of the subcutaneous mastectomy specimens was extensive with breasts cut into 3-5 mm slices, which were embedded and cut in large sections and cut in large sections allowing us to map all lesions. 42.5 per cent of the contralateral breasts contained invasive or in situ carcinoma. In about 70 per cent of the cases other histological lesions, considered more or less precancerous, were found in the contralateral breast. Our results speak in favor of an active approach to the contralateral breast at reconstruction, especially in cases with a long life expectancy after the first carcinoma. It is psychologically comforting to the patient to know that most of the breast gland, which could be the future origin of a new carcinoma, has been removed.

Breast↗
PubMed2002

Breast MRI for monitoring response of primary breast cancer to neo-adjuvant chemotherapy.

The objective of the present study was to monitor response to preoperative chemotherapy with breast MRI in patients with large breast cancer. Fifty-eight women in whom core biopsy had confirmed the presence of breast carcinoma underwent breast MRI prior to beginning chemotherapy and before surgical excision. In 24 cases patients underwent one or two additional examinations during chemotherapy to monitor their progress. Breast MRI included both T2-weighted spin-echo sequences and T1-weighted gradient-echo sequences before and 1, 2, 3, and 8 min after bolus injection of gadolinium-DTPA. Tumor size and the dynamic contrast medium uptake patterns of the respective carcinomas were evaluated and compared with the final histology findings. Based on their MR tomographic findings (change in tumor size and intensity of contrast media uptake), patients were assigned to groups with non-response (NR), partial response (PR), and complete response (CR). Based on MR tomographic findings, there were 12 patients in the NR group, 34 in the PR group, and 12 in the CR group. In NR group contrast medium uptake tended to increase or show no more than minimal decrease. Diagnostic accuracy for assigning patients to the NR group was 83.3% and to the PR group 82.4%. In patients whose tumors showed only slight response to chemotherapy, breast MRI proved very reliable in determining the size of the lesions. In patients whose tumors displayed significant response and in the CR group, the size of the residual tumor was underestimated in 8 of 12 cases. In 66.7% of patients in the CR group histology revealed residual tumor masses in areas up to 5 cm in diameter. During chemotherapy, intensity of contrast medium uptake decreased in 88.2% of patients with PR and in all patients with CR. Reliable determination of response was possible within 6 weeks following the initiation of chemotherapy. Breast MRI is suitable as a monitoring method. The determination of residual tumor size is unreliable in carcinomas exhibiting significant response to chemotherapy which may lead to false-negative results. The method may be employed for monitoring response to chemotherapy after 6 weeks.

Adult↗
PubMed2004

Increased expression of ADAM family members in human breast cancer and breast cancer cell lines.

PURPOSE: ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane-bound cell surface glycoproteins, which have numerous functions in cell growth, differentiation, and motility. We wished to investigate the expression of ADAM 9, 10, 12, 15, and in human breast cancer. METHODS: Expression of ADAMs was determined in breast cancer specimens and the corresponding non-neoplastic breast tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM antibodies on cell proliferation were assessed by measuring DNA-synthesis. RESULTS: Breast cancer tissue samples showed increased mRNA expression of ADAM 9, 12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7 and MDA-MB453 cell lines, with the highest expression levels being observed for ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be stimulated by the administration of anti-ADAM 12 antibody. CONCLUSION: The results of this study suggest that ADAMs are differentially expressed in human breast cancer and are capable of modulating tumour cell growth.

ADAM Proteins↗
PubMedDate not supplied

Effect of breast surgery on serum levels of insulin-like growth factors (IGF-I, IGF-II, and IGF binding protein-3) in women with benign and malignant breast lesions.

BACKGROUND: There is evidence that insulin-like growth factors play a role in the development of breast cancer. Antiestrogens reduce circulating levels of IGF-I, but the influence of other breast cancer treatments, including surgery, is unknown and is investigated in this study. METHODS: Circulating serum concentrations of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured before and after breast surgery in 31 patients with breast cancer and 12 controls with benign breast lesions. Serum albumin was measured as a marker of the nonspecific metabolic effect of surgery. RESULTS: Serum IGF-I, IGF-II, IGFBP-3, and albumin fell 24 hours after surgery for breast cancer but largely normalized again over the next 7 days. The fall in IGF-I and IGFBP-3 was not significant when the change in serum albumin was used as a covariate, suggesting a nonspecific effect of surgery. However, the reduction in IGF-II remained significant when adjusted for albumin and was greater after lumpectomy of malignant tumors (-8 +/- 2%) compared with benign disease (2 +/- 2%, P = .001). The fall in IGF-II was significantly related to the size of the removed tumor. CONCLUSIONS: Breast cancer may directly influence the serum concentration of IGF-II, possibly by direct tumor production.

Adult↗
PubMed2006

Human breast duct anatomy, the 'sick lobe' hypothesis and intraductal approaches to breast cancer.

INTRODUCTION: Information about central and peripheral duct anatomy is a requirement for developing intraductal approaches to human breast cancer, but remains sparse. This study looks at the acquisition and digital modelling of data describing breast duct branching from thick ('subgross') sections using data structures from the neurosciences, and at high-throughput imaging of duct anatomy in the nipple. METHODS: The branching of a large breast duct system was modelled using data extracted from cleared and stained 2 mm 'subgross' sections of an autopsy breast using a public-domain neuron modelling program (CVAPP), and episcopic fluorescence image capture (EFIC) was used to collect a stack of 1100 autofluorescence images of ducts in a mastectomy nipple. RESULTS: The duct skeleton was captured in 440 line segments with some pruning of terminal ducts. Extracting this data manually in a usable form was, however, laborious and error prone, emphasising the need for improved morphological informatics. EFIC captured anatomical detail and subsequent 3D reconstruction was consistent with the distinction between 'type A' and 'type B' nipple ducts proposed by Going and Moffat (J Pathol 203: 538-544, 2004). CONCLUSIONS: Whole-lobe duct modelling and EFIC reveal central and peripheral duct anatomy in human breast. Such knowledge is required for understanding normal breast development, the growth of cancer precursors, and for developing the intraductal approach to breast cancer.

Breast Neoplasms↗
PubMed2006

Do breast cancer risk factors modify the association between hormone therapy and mammographic breast density? (United States).

OBJECTIVE: To evaluate whether the association between hormone therapy (HT) and breast density differs by levels of breast cancer risk factors. METHODS: We evaluated 80,867 screening mammograms from 39,296 postmenopausal women from Washington State. We estimated odds ratios and 95% confidence intervals for dense breasts (Breast Imaging Reporting and Data System categories 3 "heterogeneously dense" and 4 "extremely dense") compared to fatty breasts (categories 1 "almost entirely fat" and 2 "scattered fibroglandular") among HT users compared to never users. We separately examined former HT use and current HT use by type (estrogen plus progestin therapy (EPT) and estrogen-only therapy (ET)). We stratified the associations by age, BMI, race, family history, and reproductive and menopausal factors. RESULTS: Current EPT users had a 98% (1.87-2.09) greater odds of having dense breasts and current ET users had a 71% (1.56-1.87) greater odds compared to never users. Current HT users were more likely to have dense breasts if they were older, had more children, or younger at first birth compared to never users; these associations were stronger among EPT users than ET users. CONCLUSIONS: HT, particularly EPT, may reduce protective effects of older age, parity, and younger age at first birth on mammographic density.

Adult↗
PubMed2006

Role of ultrasonography in detecting mammographically occult breast carcinoma in women with dense breasts.

PURPOSE: The purpose of this study was to assess the usefulness of routine ultrasonography in women with negative mammography and dense breasts [Breast Imaging Reporting and Data System (BIRADS D3-4)]. MATERIALS AND METHODS: We applied a protocol involving routine ultrasonography in a consecutive series of subjects with negative mammography and dense breasts. After evaluation by internal and external reviewers of cancers detected by ultrasonography performed to confirm negative mammography, we determined the additional cancer detection rate of ultrasonography and the cost of the protocol. RESULTS: Out of 17,883 total mammographies, 167 cancers were diagnosed (detection rate: 0.93%). Out of 257 suspicious mammographies, 138 cancers were detected. Out of 17,626 negative mammographies, 6,449 (36.5%) were classified as "dense breast" and underwent ultrasonography: 29 cancers were detected (detection rate: 0.44%, or 17.3% of total cancers). Out of 25 cancer cases reviewed, negative mammography and asymptomatic status was confirmed in 15 (detection rate 0.23%, or 8.9% of total cancers). The cancer detection rate was 0.11%, 0.22%, 0.32% and 0.14% for age groups <40, 40-49, 50-59 and >59, respectively. The cost per additional carcinoma detected by ultrasonography alone was euro 25,847.85 whereas that per examined woman was euro 21.68. CONCLUSIONS: The study confirms the possibility that ultrasonography can detect mammographically occult breast carcinoma in dense breasts. The evidence is insufficient to recommend this policy in routine screening practice but suggests that, at least in current clinical practice, adding ultrasonography in dense breasts may be useful despite the substantial costs.

Adult↗
PubMed1983

Interactions between benign breast disease and other risk factors for breast cancer.

A population-based incident case-control study of breast cancer in Northern Alberta, Canada, provided an opportunity to evaluate interactions between the occurrence of benign breast disease (BBD) and other potential risk factors. Overall there was a 2-fold excess risk of breast cancer among women with BBD. This excess persisted regardless of the number of years from first biopsy for BBD to diagnosis of breast cancer, suggesting a permanent alternation in risk with BBD. Significant variations of the BBD--breast cancer association were noted with several factors. The excess risk of breast cancer among women with BBD was enhanced by having a later age at menarche, a later age at first birth, or lower parity. The usual protective effect of late age at menarche was seen only among women without BBD, and was supplanted by a 4-fold elevated risk among women with BBD. The deleterious effects of later age at first birth and nulliparity were greater among women with BBD. These patterns generally support the notion that hormonal factors mediate the relation between BBD and the development of breast cancer.

Adult↗