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PubMedDate not supplied

Mammographically detected, clinically occult ductal carcinoma in situ treated with breast-conserving surgery and definitive breast irradiation.

PURPOSE: Ductal carcinoma in situ (DCIS) is increasingly detected as a nonpalpable lesion on mammographic screening performed for the early detection of breast cancer. Because of the growing incidence of mammographically detected DCIS, the present study was undertaken to determine the outcome of treatment of nonpalpable, mammographically detected intraductal carcinoma of the breast using breast-conserving surgery and definitive breast irradiation. MATERIALS AND METHODS: An analysis was performed of 110 women who presented with unilateral, nonpalpable, mammographically detected intraductal carcinoma of the breast and who were treated with breast-conserving surgery and definitive breast irradiation at 10 institutions in Europe and the United States. In all patients, complete gross excision of the primary tumor was performed, and breast irradiation was delivered with definitive intent. When performed, pathologic axillary lymph node staging was node negative (n=29). The median follow-up time was 9.3 years. RESULTS: The 10-year actuarial overall survival rate was 93%, and the 10-year actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 15 local recurrences in the treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at 10 years. The histology of the local recurrence was intraductal carcinoma in 9 cases and invasive ductal carcinoma (with or without associated intraductal carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean, 5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage treatment, 14 of the 15 patients with local recurrence were alive without evidence of disease at the time of last follow-up examination. The crude incidence of local recurrence was 7% (3/42) when the final pathology margin of tumor excision was negative, 29% (5/17) when the margin was close or positive, and 14% (7/51) when the margin was unknown. There was no difference in the rate of local recurrence based on pathologic characteristics of the primary tumor. DISCUSSION: Results from the present study demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases at 10 years following the treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Local recurrences within the treated breast were detected early and were treated with salvage for cure. These results support the initial treatment of nonpalpable, mammographically detected DCIS of the breast using breast-conserving surgery and definitive breast irradiation. Improvements in patient selection have the potential to reduce the risk of local recurrence.

Adult↗
PubMed1998

The presence of proliferative breast disease with atypia does not significantly influence outcome in early-stage invasive breast cancer treated with conservative surgery and radiation.

PURPOSE: To evaluate the influence of the benign background breast-tissue change of atypical hyperplasia (AH) on outcome in patients with early-stage invasive breast cancer treated with conservative surgery and radiation. MATERIALS AND METHODS: Four hundred and sixty women with Stage I--II breast cancer treated with conservative surgery and radiation from 1982-1994 had pathologic assessment of their background adjacent benign breast tissue. The median follow-up was 5.6 years (range 0.1-15). The median age was 55 years (range 24-88). Of these, 23% had positive axillary nodes; 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (17%) tamoxifen. Of the total, 24% received adjuvant tamoxifen alone. The patients were divided into 2 groups: 131 patients with atypical hyperplasia (ductal, 99 patients; lobular, 20 pts; and type not specified, 12 pts), and 329 patients with no proliferative changes or proliferative changes without atypia. RESULT: A statistically significant difference was observed between the 2 groups for method of detection, primary tumor size, presence of lobular carcinoma in situ (LCIS), pathologic nodal status, region(s) treated with radiation, and type of adjuvant therapy. Patients with atypical hyperplasia (AH) had smaller primary tumors (T1 80% vs. 70%) more often detected solely by mammography (51% vs. 36%) with negative axillary nodes (87% vs. 73%) and radiation treatment to the breast only (93% vs. 78%). LCIS was observed in 9% of the patients with AH and 3% of those without AH. Patients with AH more often received tamoxifen alone (32% vs. 21%), rather than chemotherapy (15% vs. 29%). There were no statistically significant differences between the 2 groups for race, age, menopausal status, family history, histology, histologic subtype DCIS when present, the presence or absence of an extensive intraductal component, final margin status, estrogen or progesterone receptor status, use of re-excision, or total radiation dose to the primary. The 5- and 10-year actuarial ipsilateral breast tumor recurrence rates were 2% and 12% for patients with AH and 4% and 8% for those without AH (p=0.44). Younger women or those with a positive family history of breast cancer with AH did not have an increased rate of breast failure when compared to similar patients without AH. There were no significant differences in the 5- and 10-year actuarial rates of distant metastases (AH 5- and 10-year 7% and 7%, no AH 5- and 10-year 8% and 16%,p=0.31), regional node recurrence (AH 1% and 1%, no AH 1% and 1%,p=0.71), contralateral breast cancer (AH 3% and 3%, no AH 3% and 8%,p=0.71), overall survival (AH 95% and 86%, no AH 95% and 89%, p=0.79), or cause-specific survival (AH 98% and 95%, no AH 96% and 91%,p=0.27). Subset analysis for ipsilateral breast tumor recurrence, distant metastases, overall, and cause-specific survival for T1 vs. T2 tumors and path node-negative vs. path node-positive patients revealed no significant differences between the 2 groups. CONCLUSION: AH was not associated with an increased risk of ipsilateral breast tumor recurrence or contralateral breast cancer in this study of patients with invasive breast cancer treated with conservative surgery and radiation. Therefore, the presence of proliferative changes with atypia in background benign breast tissue should not be a contraindication to breast-conservation therapy.

Adult↗
PubMed1996

Dose to contralateral breast: a comparison of four primary breast irradiation techniques.

PURPOSE: Contralateral breast dose from primary breast irradiation has been implicated in the risk of second breast malignancies. It has been previously shown that the use of half-beam blocking can increase the opposite breast dose by a factor of five. This study evaluates four different breast treatment techniques to compare the radiation dose to the contralateral breast. METHODS AND MATERIALS: Dose measurements were made using thermoluminescent dosimeters (TLD) capsules, which were placed in the Rando phantom in the following locations in the contralateral breast: seven along the central axis plane, on at 5 cm superior to, and one 5 cm inferior to the central axis plane. One TLD capsule was placed in the midcenter of the treated breast. The following radiation techniques were used: (a) half-beam with a custom block (HB+CB), (b) half-beam using asymmetric collimator jaw (HB/AJ), (c) half-beam using asymmetric collimator jaw with custom block (H/AJ+CB), and (d) isocentric technique with nondivergent posterior borders [Joint Center for Radiation Therapy (JCRT) techique]. For each technique, isodose distributions for the Rando phantom were optimized using (a) 15 degree medial and lateral compensating wedges, and (b) a single 30 degree lateral compensating wedge. The phantom was treated with 6 MV photons. Each technique was repeated six times, and the TLD readings were averaged. RESULTS: The custom cerrobend half-beam block technique gives the highest contralateral breast dose, regardless of wedge. The remaining techniques give results in a similar range, with the asymmetric jaw with no medial wedge technique giving the lowest total dose (p = not significant). The use of a medial wedge increases the opposite breast dose for all techniques. The asymmetric half-beam technique gives significantly less dose than the cerrobend half-beam technique, due to decreased transmission through the asymmetric collimators. The asymmetric jaw vs JCRT technique results in similar contralateral breast dose. CONCLUSIONS: As expected, dose to the contralateral breast increases with the use of a medial wedge. Cerrobend half-beam blocking gives the highest opposite breast dose. The lowest contralateral breast dose is with the asymmetric jaw with no medial wedge and no block. The asymmetric jaw technique with block yields equivalent contralateral breast doses to the JCRT technique.

Breast↗
PubMed2003

Prospective comparison of breast pain in patients participating in a randomized trial of breast-conserving surgery and tamoxifen with or without radiotherapy.

PURPOSE: To determine whether breast pain affects quality of life (QOL) after breast-conserving surgery and tamoxifen (TAM) with or without adjuvant breast radiotherapy (RT). METHODS AND MATERIALS: A randomized clinical trial was carried out at the Princess Margaret Hospital between 1992 and 2000 to evaluate the need for breast RT in addition to TAM in women >or=50 years treated with breast-conserving surgery for T1-T2N0 breast cancer. A companion study to assess breast pain was carried out during the last 2 years of the randomized clinical trial. The short-form McGill Pain Questionnaire (SF-MPQ), the European Organization for Research and Treatment of Cancer (EORTC) QOL (QLQ-C30) and EORTC breast cancer module (QLQ-BR23) questionnaires were completed by patients within 1 week of randomization in the randomized clinical trial (baseline) and at 3, 6, and 12 months. RESULTS: Eighty-six patients participated in the breast pain study; 41 received RT plus TAM and 45 received TAM alone. The median age was 70 years (range 51-80). The baseline pain and QOL scores were similar for the two groups. No significant difference was found between the two groups for each scale of the QLQ-C30 and QLQ-BR23 questionnaires at 3, 6, or 12 months (p >0.100), except that at 12 months, the score for role function (QLQ-C30) was higher in the RT plus TAM group than in the RT-only group (p = 0.02). At 3 months, the difference between the mean scores for the SF-MPQ was 0.553 (p = 0.47). At 12 months, the pain scores had decreased in both groups; the difference was 0.199 (p = 0.71). The number of breast operations or surgical complications did not correlate with breast pain in either group. Acute RT toxicity scores did not correlate with breast pain or QOL scores at 12 months. CONCLUSION: These results suggest that breast RT does not significantly contribute to breast pain or adversely impact the QOL up to 12 months after treatment in postmenopausal patients with node-negative breast cancer who take TAM.

Aged↗
PubMed2005

Mammographic breast density as an intermediate phenotype for breast cancer.

The amount of radiologically dense breast-tissue appearing on a mammogram varies between women because of differences in the composition of breast tissue, and is referred to here as mammographic density. This review presents evidence that mammographic density is a strong risk factor for breast cancer, and that risk of breast cancer is four to five times greater in women with density in more than 75% of the breast than in women with little or no density in the breast. Density in more than 50% of the breast could account for about a third of breast cancers. The epidemiology of mammographic density is consistent with its being a marker of susceptibility to breast cancer. Twin studies have shown that the proportion of the breast occupied by density, at a given age, is highly heritable, and inherited factors explain 63% of the variance. Mammographic breast density has the characteristics of a quantitative trait and might be determined by genes that are easier to identify than those for breast cancer itself. The genes that determine breast density might also be associated with risk of breast cancer, and their identification is also likely to provide insights into the biology of the breast and identify potential targets for preventive strategies.

Age Factors↗
PubMed2001

The effect of age and density of the breast on the sensitivity of breast cancer diagnostic by mammography and ultasonography.

PURPOSE: We studied which, age of the patient or density of the breast accounts for the sensitivity of mammography and ultrasonography (US). Furthermore we studied whether the overall impression on the density of the breast or the density in tumour area accounts for the sensitivity of mammography and ultrasonography. MATERIALS AND METHODS: The material consisted of 572 consecutive histologically and 5 cytologically verified breast cancer cases. Mammography and US examinations were performed immediately before breast cancer operations and information on the findings were received from the original patient files and classified as malignant or benign. The density of breast parenchyma to fatty, mixed or dense in total breast and separately in tumour area was defined by a radiologist group from the original mammograms by comparing to model mammograms. The sensitivity (Se) of mammography and US was compared in 3 age groups (26-49, 50-59 and 60-92) and in the different density classes. RESULTS: Sensitivity of mammography increased by age (density-adjusted OR = 0.2, 95%, CI 0.1-0.5) in age group 26-49 compared to age group 60-92) and with fattiness of the breast (age-adjusted OR= 0.4, 95%, CI 0.1-1.0 for dense breast parenchyma in tumour area compared to fatty breast). Sensitivity of US was inversely related to age (density-adjusted OR = 2.3, 95%, CI 1.0-5.2 in age group 26-49 compared to age group 60-92) and directly related with fattiness of breast (age-adjusted OR = 0.5, 95%, CI 0.2-0.9 by dense breast parenchyma in tumour area compared to fatty breast). Density in the tumour area compared to total breast density was related only mariginally better sensitivity both of mammography (0.4 vs. 0.6) and of US (0.5 vs. 0.6). CONCLUSION: Sensitivity of both mammography and sensitivity of US are independently related both to the age of the patient and to the density of the breast. The effect of age is inverse and that of density parallel between mammography and US on sensitivity. The effect of overall breast density was close to the effect of density at the site of the tumour on the sensitivity of both mammography and US.

Adult↗
PubMed1996

Breast self-care practices in women with primary relatives with breast cancer.

Breast cancer is a major threat to the health of women; two-thirds of women diagnosed with breast cancer are likely to die from the disease. In North America one woman in nine will experience breast cancer at some point in her lifetime. In the United Kingdom, the figure is somewhat lower, one in 12, and increasing. Increasing age and a family history of breast cancer are considered major risk factors. With no known primary prevention, early detection measures remain the main hope of decreasing mortality. Despite controversy surrounding the effectiveness of breast self-examination in reducing mortality, breast self-examination or breast self-'awareness' are advocated by health departments and voluntary cancer organizations. In this paper, breast self-care practices of women with a family history of breast cancer are reported. A descriptive study using in-depth semi-structured interviews as the prime data collection procedure was conducted with 55 women who had mothers, sister(s) or mothers and another primary relative with breast cancer. All interviews were tape recorded, transcribed and analysed using latent content analysis and constant comparison techniques. The findings revealed that women constructed their own personal meanings about the benefits and limitations of breast self-examination and their use of this self-care behaviour within their daily lives. Women used breast self-examination as a means of gaining control over their feelings of the threat of breast cancer. Women's earlier involvement with their relative during the cancer experience and their own processing of their personal risk for breast cancer influenced their breast self-care practices.

Adult↗
PubMed1998

Exposure to breast milk in infancy and adult breast cancer risk.

BACKGROUND: There is considerable interest in the possibility of an infectious etiology for human breast cancer. Although studies have shown that certain strains of mice transmit mammary tumor virus via breast milk, few epidemiologic studies have addressed this topic in humans. METHODS: We evaluated the relationship between having been breast-fed as an infant and breast cancer risk among 8299 women who participated in a population-based, case-control study of breast cancer in women aged 50 years or more. Case women were identified through cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin); control women were identified through statewide driver's license lists (age <65 years) or Medicare lists (ages 65-79 years). Information on epidemiologic risk factors was obtained through telephone interview. We used multiple logistic regression to assess having been breast-fed and maternal history of breast cancer in relation to breast cancer occurrence both in premenopausal women (205 case women; 220 control women) and in postmenopausal women (3803 case women; 4071 control women). RESULTS: We found no evidence that having been breast-fed increased breast cancer risk in either premenopausal women (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.41-1.04) or postmenopausal women (OR = 0.95; 95% CI = 0.85-1.07). In addition, breast cancer risk was not increased by having been breast-fed by a mother who later developed breast cancer. CONCLUSION: Our results do not support the hypothesis that a transmissible agent in breast milk increases breast cancer risk. Because premenopausal women were not well represented in our study population, our findings with regard to this group may not be generalizable and should be viewed with caution.

Breast Feeding↗
PubMedDate not supplied

Breast MRI screening in patients with increased familial and/or genetic risk for breast cancer: a preliminary experience.

AIMS AND BACKGROUND: Breast cancer is the most common cancer affecting women, and it is associated with or due to a genetic predisposition in 5%-10% of the cases. Owing to the higher risk of developing breast cancer and the early onset of the disease in women proved or suspected to be carriers of a breast cancer susceptibility gene, a dedicated screening should be offered as a less invasive approach with the otherwise suggested prophylactic mastectomy. This should be optimized in order to overcome the limitations of conventional breast imaging with the application of new technologies such as breast magnetic resonance imaging. METHODS: A diagnostic protocol for routine control in patients at high risk of developing breast cancer has been prepared. Within a 7-month period, 23 patients suspected or proved to carry a breast cancer susceptibility gene underwent breast magnetic resonance imaging. RESULTS: Four breast cancers were identified with breast magnetic resonance imaging. In these cases, mammography was negative because of the density of the parenchyma or for its fibroglandular pattern. Ultrasound was negative in 2 cases, not specific for malignancy in 1 case, and considered as only possibly malignant but with biopsy recommendation on the basis of magnetic resonance findings in the last one. Clinical analysis was positive for a mass in 2 cases. CONCLUSIONS: The accuracy of breast magnetic resonance imaging is known to be higher than that of conventional imaging in the study of breast parenchyma. High spatial resolution, no breast density influence and multiplanarity can give more detailed information about the smaller lesions and the right extension of the disease. Preliminary studies where breast magnetic resonance imaging is performed in addition to mammography within this group of patients are encouraging. We also believe that the application of breast magnetic resonance imaging can be very useful in the detection of cancer as early as possible with the aim to obtain the highest chance of survival after treatment.

Adult↗
PubMed2001

Investigation of an interaction of alcohol intake and family history on breast cancer risk in the Minnesota Breast Cancer Family Study.

BACKGROUND: One explanation for the variability in results in studies of alcohol consumption and breast cancer could be the presence of effect modifiers, such as genetic susceptibility. The authors examined the interaction of alcohol and family history of breast cancer on breast cancer risk in a population-based family study of 426 multigenerational breast cancer families. The authors evaluated whether alcohol use was a stronger risk factor for breast cancer among sisters, daughters, nieces, and granddaughters of breast cancer probands than among women who married into these families. METHODS: Analyses were performed on surrogate and self-reported data combined and on self-reported data alone. To evaluate the interaction of alcohol and breast cancer risk among women with a family history of breast cancer, the authors performed analyses on all 426 families and on a subset of 132 families that had 3 or more breast and/or ovarian cancers in their family. RESULTS: A total of 9032 blood relatives and marry-ins and 558 breast cancer cases were available for analysis. In the entire 426 families, there was a suggestion of an interaction of relationship to the proband and frequency of alcohol consumption on breast cancer risk (P(interaction) = 0.14) for surrogate and self-reported information combined. Among first-degree relatives of the proband, daily drinkers had a significantly increased risk of breast cancer compared with never drinkers (RR = 2.45 [1.20, 5.02]), but this increase was less evident among second-degree relatives who reported daily alcohol intake (RR = 1.27 [0.73, 2.22]) and was not evident in marry-ins who reported daily use of alcohol (RR = 0.90 [0.42, 1.90]). The findings based on the subset of 132 high-risk families with 3 or more breast and/or ovarian cancers were similar to findings based on all 426 families (P(interaction) = 0.07). An interaction of family history with alcohol use was also suggested when the analyses were restricted to self-respondents, although the interaction test P-value was no longer of borderline significance. CONCLUSION: An increased risk of breast cancer due to an increased frequency of alcohol consumption may be limited to women with a family history of breast cancer.

Adult↗
PubMed1988

Breast cancer family history as a risk factor for early onset breast cancer.

Since full breast cancer screening is not generally recommended for young women, it is important to identify individuals who are at higher risk for early onset breast cancer. We investigated the relationship between age of onset of breast cancer in 328 probands (consecutively ascertained patients from our oncology clinic) and breast cancer incidence and age of onset in their female relatives. We found that a family history of early onset breast cancer was associated with higher risk of early onset breast cancer. A family history of early onset breast cancer occurred more frequently among young (less than 40) breast cancer probands than among older (greater than or equal to 40) breast cancer probands (p less than 0.001; OR = 23). This relationship was particularly evident when the analysis was restricted to the hereditary breast cancer probands (p less than 0.001; OR = 44). We also observed a positive family history of breast cancer (any age) more frequently in young breast cancer probands than in older breast cancer probands (p less than 0.001; OR = 2.8). These observations have important pragmatic implications for surveillance. We recommend intense surveillance for breast cancer, initiated earlier, for women with close relatives diagnosed with early onset breast cancer.

Adult↗
PubMed1990

Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy.

The identification of factors associated with breast recurrence following conservative surgery (CS) and radiation therapy (RT) is of potential use in refining patient selection criteria and treatment technique. In an attempt to define such factors we examined the relationship between various clinical, pathologic and treatment characteristics and the likelihood of breast recurrence in 783 patients with clinical stage I or II breast cancer treated between July 1968 and December 1982. Treatment consisted of complete gross excision of the primary tumor and RT to a total dose of at least 60 Gy to the primary site. During this period, pre-treatment mammograms and detailed histologic assessment of the margins of resection were not routinely performed. Median follow-up for surviving patients was 80 months. Thirteen patients (1.6%) were lost to follow-up. Ninety-one patients (12%) have developed a breast recurrence, corresponding to 5- and 10-year actuarial rates of 10 and 18%, respectively. The major feature associated with breast recurrence was the presence of an "extensive intraductal component" (EIC+). An EIC+ tumor was seen in 28% of evaluable cases with infiltrating ductal carcinoma and accounted for 60% of breast recurrences. Forty-three of 166 patients (26%) with EIC+ tumors developed a breast recurrence compared with 29 of 418 patients (7%) without an EIC (EIC-) (p = 0.0001). The 5-year actuarial rates of breast relapse were 24 and 6%, respectively (p = 0.0001). Very young age (defined as 34 years of age or younger) was also a significant factor associated with the risk of breast recurrence. Very young patients comprised 8% of the patient population and accounted for 16% of breast recurrences. Fifteen of 61 very young patients (25%) developed a breast recurrence compared with 76 of 722 older patients (11%) (p = 0.001). The corresponding 5-year actuarial rates of breast recurrence were 21 and 9% (p = 0.005). None of the other clinical or pathological factors examined by univariate analysis were significantly correlated with recurrence in the breast. A multivariate model of site of first failure (polychotomous logistic regression) also showed that EIC+ tumors and very young age were the main factors associated with a high relative risk of breast recurrence. We conclude that EIC+ tumors and very young age are associated with a high risk of breast recurrence for patients treated with limited excision prior to RT.

Actuarial Analysis↗
PubMed2006

An exploration of the relationship between postnatal distress and maternal role attainment, breast feeding problems and breast feeding cessation in Australia.

OBJECTIVES: To explore the relationships between maternal distress, breast feeding cessation, breast feeding problems and breast feeding maternal role attainment. DESIGN: Longitudinal cohort study. SETTING: Three urban hospitals within Sydney, Australia. PARTICIPANTS: 449 women were invited to participate in the study, with an 81% response rate. MEASUREMENT: Self-report questionnaires were used to collect the data in pregnancy (28-36 weeks) and 2 weeks and 3 months after birth. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure postnatal distress, and the Maternal Role Attainment subscale (MRA) of the Maternal Breast Feeding Evaluation Scale (MBFES) was used to measure breast feeding maternal role attainment. FINDINGS: Women with high MRA were less likely to stop breast feeding (even when they had breast feeding problems) than women with low MRA. Antenatal EPDS and anxiety scores were not related to breast feeding cessation or breast feeding problems when analysed alone. As hypothesised, the relationship between breast feeding cessation and postnatal distress (EPDS scores) varied according to MRA level. Women who were categorised as high MRA and no longer breast feeding had higher EPDS scores and were more likely to be categorised as distressed (36%) than women who had low MRA (<12%) or women who had high MRA and continued to breast feed (7%). IMPLICATIONS: There is a complex relationship between maternal identity, stopping breast feeding earlier than desired, and psychological distress. Women with strong beliefs about the importance of breast feeding to their maternal role may benefit from psychological assessment and support should they decide to stop breast feeding earlier.

Adult↗
PubMed1999

An analysis of movement and discomfort of the female breast during exercise and the effects of breast support in three cases.

Breast pain is common during exercise, occurring in up to 56% of subjects in some surveys. This pain is mainly associated with the movement of breast tissue. In an attempt to analyse this movement and the resulting pain, the movement of the female breast tissue was quantified in four conditions of breast support ("sports bra", "fashion bra", "crop top" and bare breasted) during four different activities (running, jogging, aerobics march and walking). These activities represented general patterns of exercise for adult females in Australian society. All three subjects were healthy, active, young women of varying breast size (12B, 14B & 14C) that were typical of young women. Two of the subjects had noted breast pain whilst exercising. The results showed that wearing external support for the breast tissue reduced absolute vertical movement and maximum downward deceleration force on the breast. Support also reduced perceived pain. When compared to other forms of breast support a "sports bra" (brassiere designed for breast support whilst exercising) provided superior support for the breast in relation to the amplitude of movement, deceleration forces on the breast, and perceived pain. The data indicates that adult females should wear appropriate breast support to reduce perceived breast discomfort or pain. Of the three garments examined in this study, the fitted sports bra provided superior support and pain reduction.

Adult↗
PubMed2001

Detection of VIP receptors in MNU-induced breast cancer in rats: implications for breast cancer targeting.

Vasoactive intestinal peptide (VIP) is a 28 amino acid neuropeptide with a wide range of biological activities. Receptors for VIP (VIP-R) are overexpressed in breast cancer, where they may have diagnostic and therapeutic implications. Although N-methyl nitrosourea (MNU)-induced breast cancer in rats is used extensively as a model to study mammary carcinogenesis, there is no information about the expression of VIP-R in this model. Therefore, the purpose of this study was to investigate the presence of VIP-R in MNU-induced breast cancer in rats so that this model can be used to perform studies involving VIP-R. Breast cancer was induced in 36-day-old virgin female Sprague-Dawley rats, by a single intravenous injection of MNU (50 mg/kg body weight). The breast tumors were detected 100-150 days after injection. The normal and cancerous rat breast tissue were excised and 20 micro sections were incubated with 40 nM fluorescein-labeled VIP (Fluo-VIP(TM)), in the presence and absence of 1000-fold excess unlabeled VIP, pituitary adenylate cyclase activating polypeptide (PACAP) or secretin. The sections were visualized under a fluorescence microscope and photographed. Fluo-VIP(TM) stained rat breast cancer tissue homogeneously and to a much greater extent than normal rat breast tissue (p < 0.05). This staining was specific as indicated by displacement of Fluo-VIP(TM) by excess unlabeled VIP and PACAP. Displacement of Fluo-VIP(TM) by secretin indicated the probable presence of VIP receptors of type VPAC1 (VIP receptor subtype 1) in the rat breast. These data suggest that, as in human breast cancer, VIP-R, predominantly of type VPAC1, are overexpressed in MNU-induced rat breast cancer tissue as compared to the normal rat breast tissue. Thus, MNU-induced rat breast cancer model can be used as a tool to study the functional role of VIP-R in human mammary carcinogenesis and VIP-R mediated active breast cancer targeting. This could have implications in the diagnosis, prognosis and therapy of human breast cancer.

Alkylating Agents↗
PubMed2003

Expression of estrogen receptor beta isoforms in normal breast epithelial cells and breast cancer: regulation by methylation.

Two novel estrogen receptor beta (ERbeta) mRNA isoforms that diverge in their 5'-untranslated regions, ERbeta mRNA (0K-1) and ERbeta mRNA (0N-1), have recently been identified. This indicates that transcription of the human ERbeta gene occurs from at least two different promoters, named promoter 0K and promoter 0N. The aim of this study was to investigate the expression of ERbeta isoforms in primary cultures of normal breast epithelial cells, a panel of breast cancer cell lines and in normal breast and breast cancer tissues; and to examine whether methylation of the two ERbeta promoters is involved in regulation of ERbeta gene expression. Using quantitative real-time PCR techniques, we found that ERbeta mRNA levels were significantly lower in breast cancer cell lines than in primary cultures of normal breast epithelial cells. Bisulfite genomic sequencing analysis revealed that two promoters of the ERbeta gene exhibit distinct methylation patterns. Promoter 0N was unmethylated in normal breast epithelial cells, but extensively methylated in breast cancer cell lines. In contrast, promoter 0K was unmethylated in both normal and malignant breast epithelial cells. We demonstrated a significant correlation between promoter 0N hypermethylation and loss of ERbeta mRNA expression in breast cancer cell lines. Treatment of breast cancer cells with demethylating agent effectively reactivated the expression of ERbeta mRNA. The observations from the cell lines were also reflected in primary breast cancer tumors. Thus, expression of ERbeta mRNA in breast tumors was found to be inversely associated with the degree of methylation of promoter 0N. Our results suggest that a decreased level of ERbeta mRNA may be associated with breast tumorigenesis, and that DNA methylation is an important mechanism for ERbeta gene silencing in breast cancer.

Breast Neoplasms↗
PubMed1994

Familial clustering of breast and prostate cancers and risk of postmenopausal breast cancer.

BACKGROUND: Previous studies have suggested that cancers of the breast and prostate cluster in families and that the presence of both diseases in a family may be associated with increased risk of breast cancer. PURPOSE: Our purpose was to evaluate whether 1) prostate cancer aggregates in families with postmenopausal breast cancer, 2) families with cancers of the breast and prostate are the same ones as families with cancers of the breast and ovary, and 3) a family history of prostate cancer is associated with increased risk of postmenopausal breast cancer. METHODS: We analyzed data from a large prospective cohort study of Iowa women that were (at baseline) aged 55-69 years in 1986. At the third follow-up survey in 1992, self-reported data on family history of breast, ovarian, and prostate cancers in parents and siblings were provided by 30,883 women. Additional information was collected to ascertain whether the age-of-onset of breast cancer in mothers or sisters was before or after the age of 45 years. Cancer occurrence was documented using the State Health Registry of Iowa. RESULTS: History of prostate cancer in their father or a brother was reported by 3384 (11.0%) of the women, and a total of 4090 women (13.2%) reported breast cancer in their mother or a sister. A positive family history of both cancers was reported by 556 women, significantly (two-sided P < .001) greater than the 457 women expected if the family histories were independent. The aggregation of breast, prostate, and ovarian cancers was reported by 22 participants, greater than the 2.7 expected (two-sided P < .0001). During 6 years of follow-up, 578 breast cancers were identified in the cohort at risk. Compared with women without a family history of either cancer, women with a family history of breast cancer had a relative risk (RR) of 1.37 (95% confidence interval [CI] = 1.06-1.79) if the affected relative had onset after the age of 45 years, and an RR of 1.71 (95% CI = 1.13-2.61) if the affected relative had onset at or before the age of 45. A family history of prostate cancer in the absence of a family history of breast cancer was associated with an RR of 1.19 (95% CI = .90-1.56). However, a family history of both breast and prostate cancers was associated with RRs of 2.06 (95% CI = 1.23-3.45) and 2.35 (95% CI = .97-5.67) for breast cancer onset in relatives of greater than 45 and less than or equal to 45 years, respectively. CONCLUSIONS: These observations are concordant with recent reports that suggest a shared familial risk (inherited or environmental) for these hormone-dependent malignancies.

Aged↗
PubMed1999

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

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