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Family History of Breast Cancer and Breast Cancer Risk in Japan.

We studied 132 families with a family history of breast cancer (familial aggregation cases, FA cases) to assess the breast cancer risk presented by such a family history. For comparison with these FA cases, we randomly selected 132 control families of sporadic cases (SP controls) by adjusting for the age of the proband at surgery. Information on family history was collected for all first-degree female relatives and maternal and paternal grandmothers. Japanese women with a first-degree relative affected by breast cancer were found to have an increased risk of the disease. The odds ratio (OR) for women with a family history of breast cancer was 1.99 (95% confidence interval [ CI ], 1.48-2.66). The OR for FA-case doughters of women with breast cancer was 1.54 (95% CI, 0.91-2.63). A higher risk was not observed if a woman's mother had breast cancer. If the proband had a sister with breast cancer, a slightly increased risk of other cancers of the proband was observed (OR, 1.85 [ 0.87-3.92]). These results suggest that a family history of breast cancer in Japanese women may affect their risk of developing cancer of the breast and other organs.

Journal Article↗

Contamination of breast milk obtained by manual expression and breast pumps in mothers of very low birthweight infants.

The objective of this study was to compare the rates of bacterial contamination of expressed breast milk (EBM) obtained by manual expression and breast pumps in mothers of very low birthweight (VLBW) infants (<1501 g). This was a randomized, controlled study carried out on 28 mothers of such babies and 92 specimens of EBM were collected: 41 specimens from 13 mothers assigned to the manual group and 51 specimens from 15 mothers in the breast-pump group. EBM was cultured quantitatively by the Miles and Misra method. Breast milk expressed by breast pumps (86.3% or 44/51 specimens) had a significantly higher rate of bacterial contamination than milk expressed by the manual method (61.0% or 25/41 specimens) (P= 0.005). When breast milk was expressed in the hospital, there was no significant difference in contamination rates between the two methods. When breast milk was expressed at home, the rates of bacterial contamination by staphylococci (P= 0.003) and Gram-negative bacilli (P= 0.002) were significantly higher in the breast-pump group than the manual group. In conclusion, the rate of bacterial contamination of EBM of mothers of VLBW infants was high, especially when EBM was obtained by the breast pump or when expression was carried out at home.

Adult↗

Bigger is not always better: body image dissatisfaction in breast reduction and breast augmentation patients.

This study investigated body image dissatisfaction in breast reduction and breast augmentation patients. Thirty breast reduction and 30 breast augmentation patients completed two body image measures preoperatively. Breast reduction patients reported greater dissatisfaction with their overall body image as compared with breast augmentation patients, part of which can be understood as a function of their increased body weight. When asked specifically about their breasts, reduction patients displayed increased body image dysphoria and maladaptive behavioral change, including embarrassment about their breasts in public areas and social settings and avoidance of physical activity. Results are discussed in the context of ideal body weight cutoffs by third-party payers for reimbursement for breast reduction. Recommendations for reimbursement criteria that de-emphasize the role of body weight are made.

Adult↗

Enhancing patient outcomes in aesthetic and reconstructive breast surgery using triple antibiotic breast irrigation: six-year prospective clinical study.

BACKGROUND: Capsular contracture remains one of the most commonly reported complications in aesthetic and reconstructive breast patients. Previous in vitro studies from the authors' laboratory have recommended a new triple antibiotic povidone-iodine irrigation (2000) and subsequently a triple antibiotic non-povidone-iodine-containing irrigant (2001) to optimize broad-spectrum coverage of various bacteria implicated in capsular contracture; however, the clinical efficacy of these in vitro studies remains unproven. The purpose of this study was to determine the clinical efficacy for the previously reported triple antibiotic breast irrigation. The cost-effectiveness of universal application of irrigation solutions in breast prosthesis surgery was analyzed as well. METHODS: Patients undergoing aesthetic and reconstructive breast implant procedures were treated with a standardized operative technique, including the use of triple antibiotic breast irrigation by a single surgeon. Capsular contracture was assessed using a simplified Baker scale and graded by two independent caregivers to maximize objectivity and consistency. Additional complications were also recorded, including reoperation. Patient charges for antibiotic irrigation and reoperation for contracture were determined and compared. RESULTS: A total of 335 patients operated on since 1997 were evaluated prospectively. They ranged in age from 18 to 86 years, and the mean follow-up was 14 months (range, 6 to 75 months). The rate of grade III/IV capsular contracture in the study groups was 1.8 percent for patients undergoing primary breast augmentation. Patients undergoing augmentation-mastopexy had a grade III/IV contracture rate of 0 percent. Breast reconstruction patients had a 9.5 percent rate of grade III/IV contracture. CONCLUSIONS: Triple antibiotic breast irrigation is clinically associated with a low incidence of capsular contracture compared with other published reports, and its clinical efficacy supports previously published in vitro studies. Application of triple antibiotic irrigation is recommended for all aesthetic and reconstructive breast procedures and is cost effective.

Journal Article↗

Contamination in expressed breast milk following breast cleansing.

The purpose of this study was to determine if preexpression breast cleansing reduced the bacterial count in expressed breast milk. The study involved the collection of 178 breast milk samples (89 matched samples); 38 matched samples were from mothers of term infants and 51 matched samples were from mothers of preterm infants. One half of the samples were collected following breast cleansing with Phisoderm and tap water. The other half were collected following breast cleansing with tap water only. Hand and equipment washing with Phisoderm and tap water preceded all sample collections. Storage containers were sterile. Samples were cultured for pathogenic and nonpathogenic bacteria and examined at 24 and 48 hours. Data were analyzed by Wilcoxon Matched-Pairs sign test and Chi square. Breast cleansing with Phisoderm and water was not more effective than water alone at reducing nonpathogenic bacteria or eliminating pathogenic bacteria. Mothers of preterm infants had higher levels of both nonpathogenic and pathogenic bacteria than mothers of full-term infants. The most common form of bacterial contamination was coagulase-negative Staphylococcus epidermidis. This particular bacteria is found in higher levels in the stools of breast fed infants than formula fed infants and it also the most common contaminant found in the blood of preterm infants who develop sepsis. The findings of this study reveal that chemical interventions may not be effective at rendering breast milk free from pathogenic bacteria. More research is needed to determine the optimal cleansing protocol to achieve bacterial decontamination of breast milk or to determine the clinically acceptable level of contamination based on the effects on infants.

Chi-Square Distribution↗

Differential regulation of breast tumor cell proliferation by stromal fibroblasts of various breast tissue sources.

A stromal fibroblast-mediated paracrine regulation of epithelial tumor cell proliferation and differentiation plays an important role in the development and progression of breast tumors. We have studied the paracrine growth regulation of various phenotypically different breast cancer cell lines using conditioned serum-free media (C-SFM) from primary breast fibroblasts. Fibroblast cultures were established from malignant primary tumors and adjacent normal breast tissue, benign fibroadenomas, cosmetic reduction mammoplasties and breast skin tissues. All fibroblast-conditioned media were shown to stimulate the proliferation of breast cancer cell lines. However, the C-SFM-induced MCF-7 proliferative response was shown to be significantly higher than the proliferative response observed with any of the other cell lines tested. More importantly, the MCF-7 proliferative response obtained with malignant tumor tissue fibroblast C-SFM was shown to be significantly higher than the response to C-SFM from paired (and unpaired) normal adjacent breast tissue fibroblasts. The MCF-7 proliferative response to fibroblast C-SFM from normal tissue (adjacent to the tumor) was further shown to be comparable to the MCF-7 response using benign or reduction mammoplastic tissue fibroblast C-SFM. In addition, we show that IGFs are only partly responsible for the observed proliferative effect of the C-SFMs, while EGF, TGF alpha and basic-FGF are shown not to be involved. We conclude that stromal fibroblasts can differentially regulate breast cancer cell proliferation. Both the fibroblast's tissue source as well as the target tumor cell's phenotype will determine the extent of the proliferative response.

Breast↗

A comparison of serum and breast duct fluid-immunoassayable prolactin and growth hormone with bioassayable lactogenic hormones in healthy women and patients with cystic breast disease.

Serum and breast fluid obtained by nipple aspiration were collected from 46 healthy premenopausal women, and 36 patients with cystic breast disease and cyclical mastalgia of similar age. Serum prolactin and growth hormone levels determined by radioimmunoassay were similar in the two groups, but the patients showed a significant elevation in bioactive lactogenic hormones (prolactin plus growth hormone) as determined by the Nb2 rat lymphoma cell bioassay (P less than 0.001). The radioimmunoassayable prolactin levels in breast fluid were extremely variable; there was a trend towards higher concentrations in the cystic breast disease patients, but this just failed to achieve statistical significance (P = 0.06). Immunoreactive growth hormone was rarely detected in nipple aspirates obtained from either the patient or control groups. The mean breast fluid bioactive lactogenic hormone level was significantly higher in the cystic breast disease patients than in the normal controls (P less than 0.001); also ten of 46 (22%) controls, but only two of 36 (6%) patients had no detectable bioactivity. It is concluded that lactogenic hormone bioactivity, when assessed by the Nb2 cell assay, is indicative of an endocrine abnormality which is associated with benign breast disease, and is reflected in breast duct fluid, but is not identified by the conventional radioimmunoassays.

Adult↗

Thermography in the follow-up of breast cancer patients after breast-conserving treatment by tumorectomy and radiation therapy.

It is often suggested in the literature that thermography is able to diagnose a recurrence in the breast after breast-conserving therapy by a rise in breast temperature much earlier than other diagnostic tools, but no thermographic values are presented. The thermographic data of a prospective study of 309 women after breast-conserving therapy were evaluated. Seventeen of these women had an intramammary recurrence. A total of 2432 individual measured values were evaluated from 292 patients without evidence of a recurrence and 146 measured values from 17 patients with intramammary recurrence. The thermographic behavior of the breast after breast-conserving therapy is not uniform. However, the breast temperatures of the patients with intramammary recurrences were not significantly different from those without recurrences. This means that thermography is of no value in the care after breast-conserving therapy.

Body Temperature↗

Incidence and mortality from breast cancer in the Mama Program for Breast Screening in Finland, 1973-1986.

BACKGROUND: A cohort of women enrolled in the Mama breast self-examination-(BSE) containing breast screening program in Finland from 1973 through 1975 (with BSE used for screening and mammography for diagnosis) was studied. METHODS: Twenty-eight thousand seven hundred eighty-five women who returned calendars recording their practice of BSE over a 2-year period have been followed by linkage with the records of the Finnish Cancer Registry through 1986. The incidence of and mortality from breast cancer was compared with that expected in the Finnish population based on a model incorporating Finnish national data for breast cancer incidence and case fatality. RESULTS: Breast cancer incidence was higher than expected (a rate ratio of 1.19 over all ages). The stage distribution of cases was not different from that expected from Finnish cancer registry data for 1980, but the breast cancer mortality was lower than expected (a rate ratio of 0.75). The latter difference occurred mainly in Years 3-6 of the follow-up period. The effect seemed similar in women under and over the age of 50 years. The cohort was of higher educational status than the Finnish population, and the mortality from all causes was lower than the general Finnish population, an effect seen in previous studies of compliers with breast screening. CONCLUSIONS: The reduction in mortality from breast cancer in the study cohort is consistent with an effect of the BSE-containing Mama program, though selection bias, inherent in any observational study of screening, provided an alternative explanation for the findings.

Adult↗

Reducing the cost of diagnosis of breast carcinoma: impact of ultrasound and imaging-guided biopsies on a clinical breast practice.

BACKGROUND: The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen-detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas. METHOD: Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies. RESULTS: The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm. CONCLUSIONS: Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.

Biopsy, Needle↗

Prognostic value of morphometry in patients with normal breast tissue or usual ductal hyperplasia of the breast.

Women with usual ductal hyperplasia have a relative risk of 1.6-1.9 of subsequent breast cancer development. This slightly increased risk is generally not considered sufficiently high to justify (chemo)preventive therapy. It is therefore important to identify high-risk ductal hyperplastic lesions that would benefit from such a treatment. Nuclear morphometric features have been shown in previous work to be useful for objectively describing morphologic features associated with high risk in (pre)invasive breast lesions. The aim of this study was to evaluate whether such morphometric features can also predict subsequent invasive cancer development in patients with the common pattern of usual ductal hyperplasia or a normal breast biopsy. The present case-control study included 423 women with normal breast biopsies (n = 89) or biopsies containing usual ductal hyperplasia (n = 334). Of these 423 women, 132 developed invasive breast cancer during follow-up (mean 16.7 +/- 7.0 years). On the original hematoxylin and eosin-stained sections, nuclear morphometry was performed with a digitizing video overlay system, and mitotic and apoptotic indices were assessed. Patients with mean nuclear feature values for area, perimeter, diameter or longest axis above the 75th percentile had 1.6-1.7 times the breast cancer risk of women with mean nuclear feature values below this value. Pairwise combinations of these features yielded slightly higher cancer risks for the fourth quartile patients, with the highest risk (1.9) for patients with SD of nuclear area and perimeter values above the 75th percentile. The number of apoptotic or mitotic cells had no prognostic value for patients with apparently normal tissue or usual ductal hyperplasia. Our results give a first indication that normal breast tissue or usual ductal hyperplasia harbor nuclear morphologic changes that, when assessed by morphometry, may be used to predict breast cancer development. It is worthwhile studying this further in independent groups of patients with long-term follow-up.

Adolescent↗

Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals.

Two potential breast cancer susceptibility genes, encoding the BRCA1-interacting proteins ZNF350 (or ZBRK1) and BRIP1 (or BACH1), have been identified in yeast two-hybrid screens. We sequenced these genes in probands from 21 families with potentially inherited breast/ovarian cancer, all of which were negative for BRCA1/BRCA2 mutations. Families had at least one case of male breast cancer, two cases of ovarian cancer, or three or more cases of breast and ovarian cancer. In addition, 58 early-onset (before age 35) breast cancer cases and 30 reference individuals were analyzed. Of 17 variants detected in ZBRK1, a missense mutation Val524Ile was identified in the proband of one high-risk family, but no other family members were available for testing. Of 25 variants identified in BRIP1, in addition to four common silent or missense mutations, we identified Gln540Leu, a non-conservative amino acid change, in a single familial proband with inflammatory breast cancer, but this mutation was not present in her three relatives with breast cancer. Haplotype analysis suggests that all ZBRK1 SNPs fall within a single block with two SNPs capturing 92% of the haplotype diversity, while the BRIP1 SNPs fall in two blocks, with five SNPs capturing 89% of the haplotype diversity. Based on sequencing of ZBRK1 and BRIP1 in 21 BRCA1/2-negative probands from inherited breast/ovarian cancer families, it appears unlikely that mutations in these genes account for a significant fraction of inherited breast cancer. Further analysis in unselected cases will be required to know whether the identified variants play a role in genetic predisposition to breast cancer in the general population. Hum Mutat 22:121-128, 2003. Published 2003 Wiley-Liss, Inc.

BRCA1 Protein↗

Combined breast ductal lavage and ductal endoscopy for the evaluation of the high-risk breast: a feasibility study.

BACKGROUND AND OBJECTIVES: Evaluation of the ductal epithelium of the breast at increased risk for breast cancer is needed to define the carcinogenic pathway, for risk assessment, and to improve selection of women for chemoprevention therapy. We studied the feasibility of combining breast ductal endoscopy with ductal lavage in the high-risk contralateral breast of women with ipsilateral breast cancer for the evaluation of high-risk ducts and acquisition of ductal epithelial cells for analysis. METHODS: Breast ducts were studied by ductal lavage and ductal endoscopy, and epithelial cell content studied cytologically and quantitatively. RESULTS: Twenty-five subjects and 44 ducts, including 22 (50.0%) which did not produce nipple aspirate fluid (NAF), were studied. Cellular atypia was present in five subjects. Ductal endoscopy was performed on 1 or more ducts in 24 subjects. Structural changes were noted in 63.6% of the ducts, most commonly fibrous stranding or bridging. Ductal sampling with endoscopic brush and coil sampling devices provided additional cellular samples of relatively pure ductal epithelial content (> or = 91% purity) in 8/11 subjects. CONCLUSIONS: Breast ductal endoscopy combined with ductal lavage represents a feasible approach for characterizing the ducts and ductal epithelium of the high-risk breast, especially in a research setting.

Adult↗

Cultural barriers to mammography, clinical breast exam, and breast self-exam among Chinese-American women 60 and older.

BACKGROUND: This study examined screening utilization at least once and regular adherence to mammography, clinical breast exam, and breast self-exam among older Chinese-American women. METHOD: One hundred women were recruited from senior centers in two metropolitan cities. Participants completed a questionnaire that included sections on demographics, health history, health insurance coverage, breast cancer screening, common and cultural barriers to screening, and acculturation. RESULTS: Logistic regression models found insurance coverage for mammography and acculturation to be significant predictors of having had a mammogram at least once. Low perceived need/lack of physician recommendation and recency of physical examination were significant predictors of having had a mammogram in the past year. Acculturation and modesty were significant predictors of having had a clinical breast exam at least once, while recency of physical examination was a significant predictor of having had a clinical breast exam in the past year. Reliance on medial professionals for screening and forgetting were significant predictors of having performed breast self-exam at least once, and forgetting was a significant predictor of regular performance of breast self-exam. CONCLUSIONS: These findings suggest that both common and cultural barriers play a role in breast cancer screening among older Chinese-American women, with cultural factors being more influential in the initiation of cancer screening behavior.

Acculturation↗

Prevalence of aneuploidy, overexpressed ER, and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer.

Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available. We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR). The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p < 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p < 0.001). A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development.

Adult↗

Breast compliance: a new method for evaluation of cosmetic outcome after conservative treatment of early breast cancer.

As a measure of cosmetic outcome, the compliance of normal and irradiated breasts has been quantified using a new method of Breast Compliance Evaluation (BCE). A total of 151 women were studied, of whom 100 were normal controls and 51 had previous breast irradiation as part of breast-conserving treatment. Compliance was taken as the difference between the anterior breast surface length from infra-mammary fold to the nipple when the patient was in erect and supine positions. Irradiated cases were rated as having satisfactory outcome (good or excellent cosmetic result) or unsatisfactory (fair or poor cosmetic result). Mean compliance of normal cases was 1.8 cm. In the irradiated women with satisfactory cosmetic results, mean compliance was 1.45 compared with only 0.77 cm in those with unsatisfactory outcome. The difference between the compliance of both breasts was 0.1 cm for the controls, 0.3 cm in the satisfactory group and 2 cm in the unsatisfactory group. A difference in compliance greater than 1 cm was usually associated with an unsatisfactory cosmetic outcome. Factors determining cosmetic outcome included volume of excised lump and breast size. The cosmetic result was not affected by tumour site, clinical or pathological tumour size, or the total number of axillary nodes excised. This simple, painless, and easily reproducible measurement may be a useful objective indicator of cosmetic result after conservative treatment of early breast cancer.

Adult↗

A breast pre-cancer test? Preliminary results based on a breast temperature rhythm abnormality during the menstrual cycle.

This study documents the menstrual thermal cycle of 16 breasts considered at normal risk for breast (8 women) and 15 breasts considered at high risk for breast cancer (i.e. ipsilateral N = 7 or contralateral N = 8 to a previously [locally] excised carcinoma). The surface thermometry studies were carried out for 1 1/2 hours each evening for one menstrual cycle using a special automated instrumentation, the 'Chronobra', with the subject at home. The surface temperatures were adjusted to remove the fluctuations in arterial blood temperature during the menstrual cycle, so that they are thought to represent a breast-specific menstrual rhythm. Across subjects, the cycles were synchronised by the day of the progesterone peak obtained by radioimmunoassay of saliva collected daily. Following ovulation, the normal risk breasts exhibited a steady rise of temperature for 14 days to a well defined peak. In contrast the 'high-risk' breasts exhibited a continuous hyperthermia with smaller peaks. Linear discrimination analysis by multiple regression achieved a complete separation of the individual normal and 'high-risk' data sets. The method shows promise for the development of a non-invasive screening test for breast pre-cancer in premenopausal women.

Adult↗