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Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer.

BACKGROUND: Although the conservation management of breast cancer has become a routine method of treatment in most centers, there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control. PURPOSE: Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer. We attempted to define low-risk groups of women for breast and distant site relapse (i.e., recurrence outside the breast) who might be spared breast irradiation or adjuvant systemic therapy. METHODS: Eight hundred thirty-seven patients were randomly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer. RESULTS: Breast irradiation reduced relapse in the breast from 25.7% in the controls to 5.5% in the irradiated patients. There was no difference in survival between the two groups (median follow-up, 43 months). A low-risk group (less than 5% chance of relapse in the breast without irradiation) could not be defined. Tumor size (greater than 2 cm), age (less than 40 years), and poor nuclear grade were important predictors for breast relapse. Age (less than 50 years) and poor nuclear grade were important predictors for mortality. The presence of ductal carcinoma in situ did not predict breast relapse. CONCLUSIONS: Breast irradiation significantly reduces breast relapse, but it does not influence survival. Important predictors of breast relapse are age, tumor size, and nuclear grade, but not the presence of ductal carcinoma in situ. Age and, in particular, nuclear grade predict survival. IMPLICATIONS: Further follow-up may define an acceptable low-risk group for breast relapse. Until then, we recommend that all patients receive breast irradiation. Systemic adjuvant therapy should be considered for patients with poor nuclear grade tumors.

Age Factors↗

Comparison of age at first full-term pregnancy between women with breast cancer and women with benign breast diseases.

Benign breast diseases have a broadly similar risk profile to that of breast cancer, possibly reflecting a similar underlying endocrine milieu. We have hypothesized that a crucial distinction between breast cancer and benign breast diseases is that mammary gland terminal differentiation has not been successfully accomplished among women who tend to develop breast cancer. From October 2001 to December 2002, information concerning breast cancer risk factors and sociodemographic characteristics was collected from 174 women with breast cancer and 116 women with benign breast diseases, all 30 years old or older, who were histologically diagnosed at a major prevention center in Athens, Greece. Among the examined breast cancer risk factors, only age at first full-term pregnancy was significantly associated with the odds of having breast cancer rather than benign breast disease, and the association was evident among premenopausal [odds ratio (OR) per 5 years = 1.76, 95% confidence interval (CI) 1.10-2.93] and postmenopausal (OR = 2.10, 95% CI 1.16-3.71) women, as well as among all women (OR = 1.93, 95% CI 1.34-2.70). There was no evidence that any of the remaining breast cancer risk factors could discriminate between breast cancer and benign breast diseases. We conclude that early age at first pregnancy may convey substantial protection against breast cancer risk among women with benign breast diseases, probably operating through induction of terminal differentiation of mammary gland cells. The finding is accentuated by the fact that women with benign breast diseases are already at a relatively high risk for breast cancer.

Adult↗

Efficacy of Breast Conservation Therapy in Early Stage Bilateral Breast Cancer.

The purpose of this study was to evaluate the outcome of patients with bilateral breast cancer as compared to unilateral breast cancer treated with breast conservation therapy. Sixty patients with bilateral breast cancer (BBC) and 1,080 unilateral breast cancer (UBC) patients treated with breast conservation therapy from 1977 to 1994 were analyzed for outcome. Of the 60 bilateral patients, 44 were metachronous bilateral breast cancer patients (MBBC) and 16 were synchronous bilateral breast cancer patients (SBBC). The majority of patients received lumpectomy, axillary node dissection, and localized radiation therapy. Median tumor size was 1.4 cm for BBC and 1.5 cm for UBC patients. Median total dose to the tumor bed was 60 Gy for both unilateral and bilateral patients. Of the 44 MBBC patients, 14 received breast conservation for both the first and second lesions, while 30 received breast conservation for only the second metachronous lesion. Thus 58 lesions in 44 patients were treated with breast conservation therapy. Of the SBBC patients, 13 of 16 patients received breast-conserving therapy for both breasts, while 3 received a mastectomy for the second synchronous primary. Median follow-up was 50 months for SBBC patients, 45 months for MBBC patients, and 52 months for UBC patients. Local control and survival were analyzed in patients with SBBC, MBBC, and UBC. The interval to development of local recurrence and survival were calculated from the time of development of the second breast lesion in patients with MBBC. No differences were found for survival and failure-free survival in patients with SBBC, MBBC, or UBC. Five-year overall survival by lifetable analysis was 76% for SBBC, 78% for MBBC, and 87% for UBC patients (p = 0.32 by log-rank analysis). The 5-year failure-free survival was 79% for SBBC, 73% for MBBC, and 85% for UBC patients (p = 0.28 by log-rank analysis). No significant differences were seen for median age, tumor size, pathologic node status, tamoxifen use, chemotherapy use, or median total radiation dose for SBBC, MBBC, or UBC patients. A significant difference was found in the incidence of family history of breast cancer in patients with unilateral versus bilateral breast cancer (p = 0.028 by chi-square analysis). However, there was no difference in outcome of patients by family history of breast cancer. The local control was identical in both BBC and UBC patients, with a local failure rate of 3%. Therefore, breast conservation therapy in local-regional, early stage breast cancer is a rational and efficacious treatment modality for patients with SBBC, MBBC, and UBC.

Journal Article↗

Fatty acid composition of the subcutaneous adipose tissue and risk of proliferative benign breast disease and breast cancer.

BACKGROUND: Studies in animals and geographic correlations across populations suggest that fatty acid intake may have a positive relationship with breast cancer risk, but analytic epidemiologic studies of fat intake have been less supportive. Adipose tissue analysis provides a more objective assessment of intakes of fatty acids that are not endogenously synthesized than do the questionnaire survey methods used in many epidemiologic studies. PURPOSE: This case-control study of postmenopausal women was designed to examine the relationship between fatty acid composition of subcutaneous adipose tissue and risk of breast cancer and proliferative benign breast disease. In addition, we examined specific hypotheses that breast cancer risk is negatively associated with long-chain N-3 fatty acid intake, positively associated with trans fatty acid intake, and positively associated with increased intake of polyunsaturated fat together with low intake of antioxidants. METHODS: Aspirates of subcutaneous fat from the buttocks were obtained from 380 women with newly diagnosed stage I or II breast cancer and 176 with proliferative benign breast disease. A total of 397 women who were evaluated for breast abnormalities at the same institutions but did not require breast biopsy or whose biopsy revealed nonproliferative benign breast disease served as the control group. We examined associations between saturated, monounsaturated, polyunsaturated, trans, or long-chain N-3 fatty acids and breast cancer, atypical hyperplasia, or proliferative benign breast disease without atypia. RESULTS: We observed no consistent patterns of association between breast cancer risk and any of the categories of fatty acids or the individual constituent fatty acids in the adipose tissue. Saturated fatty acids were inversely associated with risk of proliferative benign breast disease without atypia but not with atypical hyperplasia or breast cancer. This association was not observed, however, when total fat intake was taken into account. Women with high levels of polyunsaturated fatty acids in adipose tissue and low serum or dietary levels of antioxidants were not observed to be at higher risk of breast cancer. CONCLUSIONS: Using an objective measure of intake, we observed no major associations between polyunsaturated fatty acids, including long-chain N-3 fatty acids and trans fatty acids, and risk of breast cancer or proliferative benign breast disease. IMPLICATIONS: These data do not support the hypothesis that intake of specific fatty acids, particularly polyunsaturated and trans fatty acids, is an important risk factor for malignant or benign breast disease.

Adipose Tissue↗

Cyclin D1 protein overexpression and gene amplification in benign breast tissue and breast cancer risk.

Cyclin D1 amplification and/or protein overexpression have been observed not only in breast cancer but also in the putative early stages of breast neoplasia. In a case-control study nested within a cohort of 4888 women, we investigated whether the occurrence of cyclin D1 gene amplification and/or protein overexpression in benign breast tissue might identify women at increased risk of subsequent breast cancer development. Cases were 92 women with a histological diagnosis of benign breast disease who subsequently developed breast cancer. Five controls (women with benign breast disease who had not developed breast cancer by the date of diagnosis of the corresponding case) were selected randomly for each case from those non-cases available within strata defined by screening centre, National Breast Screening Study (NBSS) study arm, year of birth and age at diagnosis of benign breast disease. Paraffin blocks of benign tissue were suitable for immunostaining for 71 cases and 293 controls. Sufficient DNA for analysis was obtained from a total of 356 subjects (69 cases, 287 controls). The benign breast tissues and breast cancers were immunostained for cyclin D1 and also analysed for the presence of cyclin D1 gene amplification by differential polymerase chain reaction (PCR). Fifteen cases and 60 controls showed evidence of cyclin D1 immunostaining, and 12 cases and 29 controls showed cyclin DL gene amplification. There was essentially no association between cyclin D1 protein overexpression in benign breast tissue and risk of subsequent breast cancer (adjusted odds ratio (OR) 1.06; 95% confidence interval (CI) 0.56-2.02). After adjustment for potential confounding, there was a statistically non-significant 40% increase in risk of breast cancer in association with cyclin D1 gene amplification (adjusted OR 1.41; 95% CI 0.62-3.22). As multiple genetic changes are required to develop breast cancer, it may not be until the cascade of molecular alterations leading to breast cancer development is understood that identification of biomarkers of breast cancer risk will be possible.

Adult↗

Coronary calcium scoring with MDCT: the radiation dose to the breast and the effectiveness of bismuth breast shield.

OBJECTIVE: The purpose of our study was to determine the breast radiation dose during coronary calcium scoring with multidetector computerized tomography (MDCT). We also evaluated the degree of dose reduction by using a bismuth breast shield when performing coronary calcium scoring with MDCT. MATERIALS AND METHODS: The dose reduction achievable by shielding the adult (35 years or older) female breasts was studied in 25 women who underwent coronary calcium scoring with MDCT. All examinations were performed with a 16-MDCT scanner. To compare the shielded versus unshielded breast dose, the examinations were performed with (right breast) and without (left breast) breast shielding in all patients. With this technique the superficial breast doses were calculated. To determine the average glandular breast radiation dose, we imaged an anthropomorphic dosimetric phantom into which calibrated dosimeters were placed to measure the dose to the breast. The phantom was imaged using the same protocol. Radiation doses to the breasts with and without the breast shielding were measured and compared using the Student's t-test. RESULTS: The mean radiation doses with and without the breast shield were 5.71+/-1.1 mGy versus 9.08+/-1.5 mGy, respectively. The breast shield provided a 37.12% decrease in radiation dose to the breast with shielding. The difference between the dose received by the breasts with and without bismuth shielding was significant, with a p-value of less than 0.001. CONCLUSION: The high radiation during MDCT greatly exceeds the recommended doses and should not be underestimated. Bismuth in plane shielding for coronary calcium scoring with MDCT decreased the radiation dose to the breast. We recommend routine use of breast shields in female patients undergoing calcium scoring with MDCT.

Adult↗

Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group.

BACKGROUND: Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients. PURPOSE: We present an update of results from a randomized clinical trial designed to examine the efficacy of breast irradiation following conservation surgery in the treatment of women with axillary lymph node-negative breast cancer. The patients were enrolled from April 1984 through February 1989. Initial results were published in 1992 after a median follow-up time of 43 months. It was reported that recurrence of cancer in the breast occurred in 5.5% of the patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two treatment groups. Now that the median patient follow-up has reached 7.6 years, the trial end points have been re-examined and an attempt has again been made to identify a group of patients at low risk for recurrence of cancer in the breast. METHODS: Eight hundred thirty-seven patients with node-negative breast cancer were randomly assigned to receive either radiation therapy (n = 416) or no radiation therapy (n = 421) following lumpectomy and axillary lymph node dissection. The cumulative local recurrence rate as a first event, distant recurrence (i.e., occurrence of metastasis) rate, and overall mortality rate for the treatment groups were described by the Kaplan-Meier method and compared with the use of the logrank test. The Cox proportional hazards model was used to adjust the observed treatment effect for the influence of various prognostic factors (patient age, tumor size, estrogen receptor level, and tumor histology) at study entry on the outcomes of local breast recurrence, distant recurrence, and overall mortality. All P values resulted from the use of two-tailed statistical tests. RESULTS: One hundred forty eight (35%) of the nonirradiated patients and 47 (11%) of the irradiated patients developed recurrent cancer in the breast (relative risk for patients in the former versus the latter group = 4.0; 95% confidence interval = 2.83-5.65; P < .0001). Ninety-nine (24%) of the patients in the former group have died compared with 87 (21%) in the latter group. Age (< 50 years), tumor size (> 2 cm), and tumor nuclear grade (poor) continued to be important predictors for local breast relapse. On the basis of these factors, we were unable to identify a subgroup of patients with a very low risk for local breast cancer recurrence. Tumor nuclear grade, as previously reported, and tumor size were important predictors for mortality. CONCLUSIONS: Breast irradiation was shown to reduce cancer recurrence in the breast, but there was no statistically significant reduction in mortality. A subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy was not identified.

Adult↗

Breast cancer found at the time of breast reduction.

In a recent study involving 27,500 women who had breast reduction surgery in Ontario, Canada, 17 women who were diagnosed as having breast cancer at the time of their breast reduction surgery were identified. The aims of this study were to (1) describe a population-based series of patients who had breast cancer diagnosed at the time of breast reduction, (2) describe the treatment of these cancers, and (3) compare their survival rate with survival in patients in the general population who had breast cancer. Information about these women, their treatment, and outcome was extracted from hospital records, pathology reports, and reports from regional cancer centers. The chance of finding an invasive breast cancer at the time of breast reduction was 0.06 percent, which is lower than what has been reported previously. Sixty-seven percent of these women were treated with total mastectomy. In the remaining 33 percent, who were treated with partial mastectomy, the entire tumor was removed at the time of breast reduction. Fifty percent of the women were treated with radiation, and 25 percent were treated with chemotherapy or hormonal therapy. Compared with women in the general population of Ontario who have breast cancer, women whose breast cancer is discovered during breast reduction surgery are more likely to be treated with complete mastectomy and less likely to be treated with radiotherapy or chemotherapy. Seventy-one percent of the breast reduction group were axillary node-negative at diagnosis, compared with 58 percent in the general population of women with breast cancer. Survival from breast cancer in women diagnosed at the time of breast reduction (88 percent, 5-year survival) was better than survival from breast cancer in the general population (77 percent). These findings suggest that cancers found in women at the time of breast reduction are less advanced, possibly because they are diagnosed at an earlier stage.

Breast Neoplasms↗

A prospective study of the development of breast cancer in 16,692 women with benign breast disease.

The authors studied the relation between benign breast disease and subsequent breast cancer in 16,692 women with biopsy-diagnosed benign breast disease who had participated in the Breast Cancer Detection Demonstration Project throughout the United States. Women were classified into one of five benign breast disease categories: atypical hyperplasia, proliferative disease without atypia, nonproliferative disease, fibroadenoma, and other benign breast disease. A total of 485 incident cases of breast cancer were identified in the women from August 1973 to February 1986 after a median follow-up period of 8.3 years from the diagnosis of benign breast disease. Age-adjusted incidence rates were calculated for benign breast disease types stratified by family history and calcification status. Relative risk (RR) estimates of breast cancer for women in the five benign breast disease categories, compared with the screened women who did not develop recognizable breast disease (normal subjects), were computed using the proportional hazards model. Results indicated that risk was associated with the degree of epithelial atypia. Over all age groups, women with nonproliferative disease, proliferative disease without atypia, and atypical hyperplasia displayed progressively increasing risks of 1.5, 1.9, and 3.0, respectively, compared with normal subjects, with 95% confidence intervals (CI) exceeding unity. Particularly high risk was seen among women under age 46 years with atypical hyperplasia (RR = 5.7, 95% CI 3.0-10.6). Women with fibroadenoma as the only indication of their benign breast disease had a relative risk of 1.7, with a lower 95% confidence limit of 1.0. No increased risk was seen for women with other benign breast disease. Positive family history (RR = 1.8) and calcification (RR = 1.2) significantly increased a woman's risk proportionately over the risk associated with each benign breast disease subtype. The authors conclude that the risk of developing breast cancer varies by category of benign breast disease and is directly related to the degree of epithelial atypia.

Adenofibroma↗

The effect of benign breast biopsy on subsequent breast cancer detection practices.

PURPOSE/OBJECTIVES: To determine the effect of benign breast biopsy results on the frequency of subsequent breast self-examination (BSE), mammograms, and clinical examinations. DESIGN: Retrospective, descriptive design. SETTING: Two surgical oncology practices of an academic health science center in the southeastern United States and one surgical oncology practice and three family practices in another southern U.S. city. SAMPLE: A nonprobability sample consisting of 238 women with benign breast biopsies and a comparison group of 243 women with no histories of breast disease. METHODS: Questionnaires based on American Cancer Society (ACS) breast cancer detection guidelines were designed and mailed to all women who had benign breast biopsies within the past three years at the academic health science center. Similar questionnaires were mailed to women randomly selected from three family practices who had no histories of breast disease. Chi-square, Kruskal-Wallis one-way analysis of variance, and Wilcoxon matched pairs signed-ranks test were used in the data analysis. MAIN RESEARCH VARIABLES: Frequency of breast cancer detection practices including BSE, mammography, and clinical breast examinations. FINDINGS: In the group that had undergone biopsies, breast abnormalities were found by mammogram (38.8%), BSE (28.3%), clinical examination (16.9%), and accidental discovery (8.7%). The percentage of women performing monthly BSE increased from 47.4% to 67.3% postbiopsy (p < 0.0001). The frequency of mammography and clinical breast examinations also significantly increased postbiopsy (p < 0.0001). Similarly, the postbiopsy rate of BSE, mammography, and clinical breast examinations was higher than the rates for the control group. Women whose breast abnormalities were found by mammography became significantly more fearful of mammography (p < 0.05). CONCLUSIONS: Benign breast biopsies are associated with increased breast cancer detection practices. IMPLICATIONS FOR NURSING PRACTICE: All women need to follow ACS guidelines for breast cancer detection. Women who have undergone breast biopsy may be unduly afraid about the results of future detection practices and may need support and encouragement.

Adult↗

Stage of breast cancer at diagnosis among women with cosmetic breast implants.

Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found.

Adult↗

Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Several studies have reported that the risk of breast cancer decreases with increasing duration of breast-feeding. Whether breast-feeding is associated with a reduced risk of hereditary breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations is currently unknown. METHODS: We conducted a case-control study of women with deleterious mutations in either the BRCA1 or the BRCA2 gene. Study participants, drawn from an international cohort, were matched on the basis of BRCA mutation (BRCA1 [n = 685] or BRCA2 [n = 280]), year of birth (+/-2 years), and country of residence. The study involved 965 case subjects diagnosed with breast cancer and 965 control subjects who had no history of breast or ovarian cancer. Information on pregnancies and breast-feeding practices was derived from a questionnaire administered to the women during the course of genetic counseling. Conditional logistic regression analyses were used to estimate odds ratios (ORs) for the risk of breast cancer. All statistical tests were two-sided. RESULTS: Among women with BRCA1 mutations, the mean total duration of breast-feeding was statistically significantly shorter for case subjects than for control subjects (6.0 versus 8.7 months, respectively; mean difference = 2.7 months, 95% confidence interval [CI] = 1.4 to 4.0; P<.001). The total duration of breast-feeding was associated with a reduced risk of breast cancer (for each month of breast-feeding, OR = 0.98, 95% CI = 0.97 to 0.99; P(trend)<.001). Women with BRCA1 mutations who breast-fed for more than 1 year were less likely to have breast cancer than those who never breast-fed (OR = 0.55, 95% CI = 0.38 to 0.80; P =.001), although no such association was seen for BRCA2 (OR = 0.95, 95% CI = 0.56 to 1.59; P =.83). CONCLUSIONS: Women with deleterious BRCA1 mutations who breast-fed for a cumulative total of more than 1 year had a statistically significantly reduced risk of breast cancer.

Adult↗

Breast cancer stage at diagnosis and survival among patients with prior breast implants.

Longstanding concern exists regarding the potential for women with breast implants to experience delayed detection of breast cancer. Furthermore, survival among cosmetic breast implant patients who subsequently develop breast cancer is a concern. Since 1976, this institution has monitored cancer incidence in a cohort of 3182 women who underwent cosmetic breast augmentation between 1959 and 1981. The distributions of stage at diagnosis and survival of the 37 women who subsequently developed in situ or invasive breast cancer were compared with the observed population distributions. The distribution of stage at diagnosis for cosmetic breast implant patients who subsequently developed breast cancer was virtually identical to that of all breast cancer patients in Los Angeles County who were of the same age and race, and were diagnosed during the same time period. Furthermore, the 5-year survival rate of the 37 patients did not differ from that which would be expected based on rates established by the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. These results suggest that cosmetic breast implant patients are not at increased risk of delayed detection of breast cancer, nor do they suffer a poorer prognosis when breast cancer does occur. Although the number of breast cancer patients in this study is small, the results are highly consistent with the existing epidemiologic evidence related to breast cancer detection and survival among breast implant patients. Although breast implant patients should continue appropriate breast cancer screening behavior, there seems to be no cause for alarm.

Adult↗

MR imaging screening of the contralateral breast in patients with newly diagnosed breast cancer: preliminary results.

PURPOSE: To investigate the role of screening magnetic resonance (MR) imaging in the detection of synchronous contralateral breast cancer in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: Between January 1999 and July 2001, 182 patients with newly diagnosed breast cancer (after either core or excisional biopsy with positive or close margins of resection) underwent bilateral contrast material-enhanced MR imaging at 1.5 T with a dedicated bilateral breast multicoil array. The contralateral breast was imaged for cancer screening. Family history of breast cancer, index cancer histology, breast density, and age at diagnosis of first breast cancer were assessed as potential risk factors for synchronous contralateral breast cancer. RESULTS: Fifteen patients (8.2%) had a suspicious enhancing lesion depicted in the contralateral breast. Seven patients (3.8%) had malignant results: ductal carcinoma in situ (DCIS) in four, invasive ductal carcinoma with DCIS in two, and invasive ductal carcinoma in one. Eight patients (4.4%) had benign results: fibrocystic changes in four, atypical ductal hyperplasia in two, atypical lobular hyperplasia and focal lobular carcinoma in situ in one, and ductal hyperplasia in one. Six patients with negative MR findings underwent prophylactic mastectomy; no malignancy was found. No significant differences were noted among patients with true-positive (n = 7), false-positive (n = 8), or negative (n = 167) MR findings with regard to family history of breast cancer (P <.27), index cancer histology (P <.19), breast density (P <.34), or age at diagnosis of first breast cancer (P <.10). CONCLUSION: The preliminary results demonstrate the feasibility of using MR imaging of the breast in a screening role, specifically to evaluate the contralateral breast in patients with newly diagnosed breast cancer to detect mammographically and clinically occult synchronous breast cancer.

Adult↗

Malignant breast epithelium selects for insulin-like growth factor II expression in breast stroma: evidence for paracrine function.

Paracrine interactions between stromal and epithelial cells are important influences on the growth and malignant behavior of breast cancers. Insulin-like growth factors I and II (IGF-I and II) are expressed by fibroblasts in benign and malignant breast lesions, and both are strong mitogens for a number of breast cancer epithelial cell lines in vitro. We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin. IGF-I expression was easily detected in all fibroblasts derived from normal breast tissue. In general, lesser amounts of IGF-I mRNA were detected in fibroblasts derived from breast tumors or skin. In contrast, IGF-II expression was detected at very low levels in only 3 of 8 normal breast fibroblasts, but was present in 6 of 8 tumor fibroblasts. IGF-II mRNA was expressed in all skin fibroblasts tested. IGF-II-negative stromal fibroblasts from normal breast, which were plated at low density and allowed to grow to confluence in the presence of MCF-7 breast tumor epithelial cells, demonstrated a marked increase in IGF-II mRNA expression. IGF-II in situ hybridization studies confirmed that IGF-II expression is seen at high levels in stroma of many invasive breast cancers but not normal breast. We conclude that paracrine influences, mediated by soluble factors released by breast tumor epithelium, are able to specifically increase expression of IGF-II in breast stroma, most likely by a process of clonal selection.

Breast↗

Pregnancy and lactation after breast-conserving therapy for early stage breast cancer.

BACKGROUND: To identify patients treated with breast conservation therapy for early-stage breast cancer who subsequently experienced full-term pregnancies, and to identify: (1) The proportion of women who experienced lactation in the treated breast; and (2) treatment, disease, and/or host factors that may be related to the presence or absence of lactation and the ability to breast-feed successfully. METHODS: The records of 890 patients treated at the radiation therapy facilities of the Department of Therapeutic Radiology, Yale University, New Haven, CT, for early-stage (Stage I or II) breast cancer were reviewed to identify patients who had become pregnant subsequent to completing breast conservation therapy. Data were collected from the patients' departmental records, and interviews were conducted by phone and/or questionnaire. RESULTS: Thirteen patients were identified, and 11 patients who experienced 13 pregnancies were interviewed. All patients reported little or no swelling of the treated breast during pregnancy. After delivery, lactation from the treated breast was present in four instances, absent in six, and pharmacologically suppressed in three. One patient successfully breast-fed from the treated breast for 4 months. In the majority of cases, breast-feeding from the untreated breast was successful. The interval from the time of treatment to the time of delivery did not appear to affect adversely lactation from the treated breast; one patient reported lactation from the treated breast 75 months after completion of treatment. Circumareolar incision was associated with the absence of lactation in three patients (four pregnancies). Thus, lactation from the treated breast may be less likely to occur in the case of centrally located lesions. CONCLUSION: Successful breast-feeding from the untreated, as well as the treated breast, is possible after conservative surgery and radiation. Implications for patients of child-bearing age undergoing conservative surgery and radiation therapy are discussed.

Adult↗

The risk of a contralateral breast cancer among women diagnosed with ductal and lobular breast carcinoma in situ: data from the Connecticut Tumor Registry.

BACKGROUND: Women diagnosed with breast carcinoma in situ are at increased risk for developing a contralateral breast cancer. The magnitude of this risk and the relationship between this risk and age, time since diagnosis, histologic subtype, and treatment for the first breast cancer is continuing to be defined. METHODS: The risk of developing a contralateral breast cancer is examined among 4198 women diagnosed with breast carcinoma in situ and reported to the Connecticut Tumor Registry (CTR) between January 1, 1975 and March 14, 1998 using Kaplan-Meier estimation. A Cox proportional hazards model is used to assess the effect of surgical treatment, radiation therapy, age at diagnosis, race, histology, marital status, anatomic location within the breast, and time since diagnosis upon this risk. RESULTS: The cumulative 5- and 10-year probabilities of being diagnosed with a contralateral breast cancer among women initially diagnosed with a ductal breast carcinoma in situ (DCIS) were 4.3% (95% confidence interval, 3.6-5.0%) and 6.8% (95% confidence interval, 5.5-8.2%), respectively. These risks are 3.35 times greater than those for women without a history of breast cancer but are similar to those for women diagnosed with non-metastatic invasive ductal carcinomas of the breast. The cumulative 5- and 10-year probabilities of being diagnosed with a contralateral breast cancer among women initially diagnosed with a lobular breast carcinoma in situ (LCIS) were 11.9% (95% confidence interval, 9.5-14.3%) and 13.9% (95% confidence interval, 11.0-16.8%), respectively. CONCLUSIONS: Women diagnosed with LCIS were 2.6 (95% confidence interval, 2.0-3.4%) times more likely than women with DCIS to be diagnosed with a contralateral breast cancer within the first six months of the first breast primary. The risk of developing a contralateral breast cancer more than 6 months after the initial breast cancer was independent of surgical or radiation therapy, time since diagnosis, age at diagnosis, histology, race, marital status, or anatomic location of the cancer within the breast.

Adult↗

Comparisons of interval breast cancers with other breast cancers detected through mass screening and in outpatient clinics in Japan.

In a nation-wide collaborative study on mass screening for breast cancer, we collected 152 cases of interval breast cancer diagnosed at 35 hospitals or clinics distributed throughout Japan. The definition of interval breast cancer used in the present study is "breast cancer cases which were diagnosed as having 'no malignant findings' in a previous screening for breast cancer but subsequently diagnosed as 'breast cancer' at a hospital or medical clinic within two years of the previous screening." The clinical stages and prognoses of these interval cancer were analyzed and compared with those of other breast cancers detected through mass screening and in outpatient clinics. In the clinical staging of interval breast cancer, Tis (non infiltrating cancer) accounted for only 2.1%, compared to 8.0% in cases detected through mass screening. At stage I 43.4% were interval breast cancers compared to 32.9% breast cancers detected through mass screening and 25.4% diagnosed in outpatient clinics. The stage differences between interval breast cancers and breast cancers detected through mass screening were not statistically significant. Five-year survival rates were 85.6% for interval breast cancers, 91.7% for breast cancers detected through mass screening and 84.7% for breast cancers diagnosed in outpatient clinics. Ten-year survival rates were 75.9, 80.5 and 78.1%, respectively, suggesting the interval breast cancer cases to show a similar prognosis to that of breast cancer cases diagnosed in outpatient clinics. The differences in five- and 10-year survival rates among the three groups were not statistically significant. From the present study we were not able to confirm the general belief of interval cancer being more aggressive in nature and showing a poorer prognosis than cancer detected through periodic screening. The reasons for this are discussed.

Adult↗