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Inherited BRCA1 mutations confer elevated cancer risk. Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of cancer risk. A cohort of 2,825 BRCA1 mutation carriers was used to evaluate the association of haplotypes at ATM, BRCC36, BRCC45 (BRE), BRIP1 (BACH1/FANCJ), CTIP, ABRA1 (FAM175A), MERIT40, MRE11A, NBS1, PALB2 (FANCN), RAD50, RAD51, RAP80, and TOPBP1, and was associated with time to breast and ovarian cancer diagnosis. Statistically significant false discovery rate (FDR) adjusted P values for overall association of haplotypes (P(FDR)) with breast cancer were identified at ATM (P(FDR) = 0.029), BRCC45 (P(FDR) = 0.019), BRIP1 (P(FDR) = 0.008), CTIP (P(FDR) = 0.017), MERIT40 (P(FDR) = 0.019), NBS1 (P(FDR) = 0.003), RAD50 (P(FDR) = 0.014), and TOPBP1 (P(FDR) = 0.011). Haplotypes at ABRA1 (P(FDR) = 0.007), BRCC45 (P(FDR) = 0.016 and P(FDR) = 0.005 in two haplotype blocks), and RAP80 (P(FDR) < 0.001) were associated with ovarian cancer risk. Overall, the data suggest that genomic variation at multiple loci that encode proteins that interact biologically with BRCA1 are associated with modified breast cancer and ovarian cancer risk in women who carry BRCA1 mutations., (©2011 AACR.)

Germline mutations in two major susceptibility genes, BRCA1 and BRCA2, account for nearly 20% of familial breast cancers. A majority of the remaining genetic factors involved in heritable breast cancer susceptibility are, however, unknown. Recently, a new BRCA1-interacting protein, receptor associated protein 80 (RAP80), was identified. RAP80 plays an important role in BRCA1-mediated DNA damage responses (DDRs) by recruiting BRCA1 to DNA double-strand breaks (DSBs). A comprehensive screening of DNA from affected index cases of 112 BRCA1/BRCA2 mutation-negative Finnish breast cancer families revealed altogether 10 alterations in RAP80, one of which, c.241-243delGAA, resulted in a single glutamic acid deletion at residue 81 in a highly conserved region of ubiquitin interaction motif 1. The resultant delE81 protein product displayed significantly reduced ubiquitin binding and DSB localization. Expression of the RAP80 delE81 allele impaired both BRCA1 and ABRA1 DSB recruitment, thus compromising BRCA1-mediated DDR signaling. Compared with wild-type RAP80, expression of the delE81 allele was associated with a significant increase in cytogenetically detectable chromosomal aberrations, particularly chromatid breaks. Although evidently quite rare, these results suggest that critical constitutional mutations in RAP80 abrogate DDR function and may be involved in genetic predisposition to cancer.

The object of this study was to examine whether MUC-1 can be detected in the axillary lymphatic drainage of patients who have undergone conservative surgery for breast cancer and to assess the correlations between the presence of MUC-1 and prognostic factors in breast cancer. Sixty-eight women with invasive ductal carcinoma of the breast underwent wide local excision and axillary lymph node dissection. Axillary drains were inserted in all these cases, and the presence of MUC-1 and beta-actin was evaluated by RT-PCR in the lymphatic fluid collected after the operation. Prognostic factors included tumour size and grade, vascular and lymphatic invasion, clearance margins of the resected specimens and status of the axillary lymph nodes. RT-PCR assays for MUC-1 in the axillary fluid were positive in 17 patients (25%). The presence of MUC-1 was associated with increased tumour size and showed a positive correlation with axillary lymph node metastases and incomplete resection of the tumour. RT-PCR can disclose cancer cells in the axillary fluid after conservative surgery for breast cancer. The presence of MUC-1 in the axillary drainage may be associated with poor prognostic features, and its detection may have implications for therapy as it suggests that re-excision should be considered.

Background: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer., Objective: To evaluate the presence and prognostic value of MUC1 and Met-hepatocyte growth factor/scatter factor in the axillary drainage of these patients., Methods: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-HGF/SF and beta-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status., Results: RT-PCR assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.0 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05)., Conclusion: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.

Background: The diverse biological effects of hepatocyte growth factor/scatter factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on epithelial cells. Met signaling has a role in normal cellular activities, and may be associated with the development and progression of malignant processes. In this study we examined whether Met can be detected in the axillary drainage from patients who underwent conservative operations for breast cancer, and its prognostic significance., Methods: Thirty-one consecutive patients with invasive ductal carcinoma of the breast suitable for breast-conserving treatment were studied. The output of the drain that had been placed in the axilla during the operation was collected, and the presence of Met and beta-actin were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were compared with the pathological features of the tumor and the axillary lymph nodes, and with the estrogen receptor and progesterone receptor status., Results: RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of the patients. Positive assays were correlated with increasing tumor size and grade, with capillary and lymphatic invasion, and with lymph node metastasis (P < 0.02, for all comparisons). All 12 patients with axillary lymph node metastases had positive assays for Met, compared with 57.9% of patients without lymph node metastases. All five patients with tumor involvement in the margins of the resection had positive assays for Met in their lymphatic fluid, compared with 18 of 26 positive assays (69.2%) for patients without involved margins (P < 0.04). Finally, Met showed negative correlations with positivity for estrogen receptor and progesterone receptor (P < 0.02)., Conclusion: Met can be detected in the axillary fluids of patients with breast cancer and its expression in the axillary drainage may have potential as a prognostic factor. This finding might be relevant to therapeutic considerations, because a positive assay for Met in histologically node-negative patients might point to the need to search for node microinvasion or involvement of the excision margins with tumor.

Objective: To identify from the literature and clinical experience a rational approach to management of fibroadenomas of the breast., Method: Recent literature on detection, diagnosis, and natural history of fibroadenomas was reviewed. Experience with over 4,000 women evaluated in the breast clinic at the Tel-Aviv Medical Center contributed to the management strategies suggested by review of the literature., Results: Fibroadenomas of the breast are common, accounting for 50% of all breast biopsies performed. Physical examination, sonography, and fine needle aspiration are effective in distinguishing fibroadenomas from breast cancer. Transformation from fibroadenoma to cancer is rare; regression or resolution is frequent, supporting conservative approaches to follow-up and management., Conclusion: Age-based algorithms that allow for conservative management and that limit excision to patients whose fibroadenomas fail to regress are presented.

Objective: To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts., Design and Participants: Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens., Main Outcome Measure: Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors., Results: After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio = 1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer-specific mortality., Conclusions: Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women.

The relationship between social ties, stage of disease, and survival was analyzed in a population-based sample of 525 black and 486 white women with newly diagnosed breast cancer. There were significant differences between the two race groups in reported social ties. Using logistic regression to adjust for the effects of age, race, study area, education, and the presence of symptoms, there was little or no evidence for an association between individual network measures of social ties and stage of disease. However, a summary measure of social networks was found to be associated modestly with late stage disease, attributable in part to significantly more advanced disease among black, but not white, women reporting few friends and relatives [relative risk (RR) = 1.8; 95% confidence interval (CI) = 1.1-3.0]. With adjustments for differences in stage of disease and other covariates, and with the use of Cox proportional hazards modeling to estimate hazard ratios, the absence of close ties and perceived sources of emotional support were associated significantly with an increased breast cancer death rate. White women in the lowest quartile of reported close friends and relatives had twice the breast cancer death rate of white women in the highest quartile (RR = 2.1; 95% CI = 1.1-4.4). Notably, both black and white women reporting few sources of emotional support had a higher death rate from their disease during the 5-year period of follow-up (RR = 1.8; 95% CI = 1.3-2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Numerous studies have reported differences in cancer staging at diagnosis and in survival between Black and White patients with breast cancer. Utilizing data obtained from the National Cancer Institute's (NCI's) Black/White Cancer Survival Study for the period 1985-1986, a new study is presented here that systematically examines multiple explanatory factors (e.g., lack of mammograms) associated with these cancer-staging differences., Purpose: We evaluated within a single study the relationship of selected demographic, lifestyle, antecedent medical experiences, and health care access factors to cancer staging at diagnosis in Black and White breast cancer patients., Methods: Data utilized in this population-based cohort study of 1222 eligible women (649 Black and 573 White) newly diagnosed for the period 1985-1986 with histologically confirmed primary breast cancer were obtained from the NCI's Black/White Cancer Survival Study. Sources of data included abstracts of hospital medical records, central review of histology slides by a study consultant pathologist, and patient interviews obtained from three metropolitan areas: Atlanta, New Orleans, and San Francisco-Oakland. Within each area, 70% of all Black incident cases were randomly selected, and a sample of White cases, frequency matched by age groups (20-49 years, 50-64 years, and 65-79 years), was selected for comparison. Stage of breast cancer at diagnosis was classified according to the international tumor-lymph node-metastases (TNM) system. Statistical models utilized in this study included the log-linear and polychotomous logistic regression with multiple predictor variables., Results: Factors associated with cancer staging were differentially expressed in Blacks and Whites. Indicators of access to health care, a lack of mammograms, and an increased body mass index significantly (P < .02) contributed to stage differences in Blacks, whereas income was marginally associated (P = .06) with stage for Whites only. Nuclear grade, having a breast examination by a physician, and a history of patient delay explained approximately 50% of the excess risk for stage III-IV cancer versus stage I-IIN0 cancer among Blacks compared with Whites (odds ratio reduction from 2.19 to 1.68)., Conclusion: These findings suggest that no single factor or group of factors can explain more than half of the race-stage differences noted in this study with respect to Black and White breast cancer patients.

We used data from a study of racial differences in cancer patient survival to examine the association between estrogen receptor status and the intake of nutrients and food groups among 689 black and white women, ages 20-79, with breast cancer newly diagnosed in 1985 and 1986. We reviewed medical records and collected interview data, including a 34-item food frequency questionnaire. Consistent with published reports, we found positive estrogen receptor status to be positively associated with age and inversely associated with parity and oral contraceptive use. Whites were more likely than blacks to have estrogen receptor-positive tumors. We examined eight nutrients and six food groups in multivariate analyses for association with estrogen receptor status. After adjusting for age, race, usual body mass index, and parity, a high percentage of calories from fat was associated with estrogen receptor-positive cancer, and a high percentage of calories from carbohydrates was associated with estrogen receptor-negative breast cancer. These findings indicate that women with breast cancer who are on diets with a high percentage of calories from fat may be more likely to develop estrogen receptor-positive cancers.

Background: The National Cancer Institute Black/White Cancer Survival Study began patient accrual in 1985 and was designed to investigate factors that might contribute to the observed racial differences in survival for cancer of the breast, uterine corpus, colon, and bladder., Methods: To determine whether there were racial differences in treatment in a clinically homogeneous set of patients, 305 (25%) of the 1222 women in this study with Stage II node-positive (N+) breast cancer were evaluated., Results: Patient characteristics for blacks and whites were similar for age, metropolitan area of residence, tumor size, extent of nodal involvement, and steroid receptors. Differences in histologic findings, tumor grade, and nuclear atypia were observed. Blacks had a higher frequency of comorbid conditions, especially hypertension (P < 0.00001). Fewer blacks underwent breast-conserving surgery (P = 0.004). In a multivariate analysis, race was no longer a significant factor in the selection of primary treatment, but education and metropolitan area of residence remained significant. Blacks and whites received similar postoperative systemic therapy, with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and tamoxifen, the most common cytotoxic and endocrine therapies used., Conclusions: The National Cancer Institute consensus statement concerning adjuvant therapy for breast cancer was published in the middle of the 2-year period that study cases were accrued, and treatment plans in this study generally agreed with consensus guidelines. Should survival differences in black and white patients with Stage II N+ disease in this study be found, they are unlikely to be attributable to differences in initial or postoperative treatment.

This experimental study attempts to determine if an in-home educational intervention conducted by lay health workers (LHWs) can increase adherence among low-income, inner-city black women to schedules for screening for breast cancer and cervical cancer, as well as increase the women's knowledge and change their attitudes regarding these cancers. This paper is a description of the purposes, hypotheses, design, subject recruitment, intervention, and evaluation of the study conducted by Morehouse School of Medicine. Subjects were recruited from a variety of sources, including patients seen in a community health center, women referred by the National Black Women's Health Project (NBWHP), residents of public and senior citizen housing projects, and persons identified in various community settings. Fewer than half of those asked to participate agreed to do so. The 321 women who were recruited were demographically diverse. Overall, about half of these volunteer subjects self-reported at least one Papanicolaou (Pap) smear and one breast examination within a year before enrollment in the study. There was little variation by source of recruitment in compliance with screening recommendations, except that referrals from NBWHP were more likely (P less than 0.01) to have had a Pap test and breast self-examination, while residents of public housing projects were somewhat less likely to have done so. About 35 percent of participants ages 35 and older had a mammogram within an appropriate interval. Participants were randomly assigned to intervention and control groups. Women in the intervention group were visited in their homes by LHWs on three occasions; the LHWs provided education on cancer and reproductive health. The groups were comparable in their baseline sociodemographic status and previous screening history.

Background: Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail., Methods: We conducted a case-control study in a cohort of 82,700 women given a diagnosis of breast cancer from 1973 to 1985 in five areas of the United States. Detailed information about therapy was obtained for 90 patients with leukemia and 264 matched controls. The dose of radiation to the active marrow was estimated from individual radiotherapy records (mean dose, 7.5 Gy)., Results: The risk of acute nonlymphocytic leukemia was significantly increased after regional radiotherapy alone (relative risk, 2.4), alkylating agents alone (relative risk, 10.0), and combined radiation and drug therapy (relative risk, 17.4). Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide. Melphalan was 10 times more leukemogenic than cyclophosphamide (relative risk, 31.4 vs. 3.1). There was little increase in the risk associated with total cyclophosphamide doses of less than 20,000 mg., Conclusions: Although leukemia occurs in few patients with breast cancer, significantly elevated risks were linked to treatments with regional radiation and alkylating agents. Melphalan is a more potent leukemogen than cyclophosphamide or radiotherapy. Low risks were associated with the levels of cyclophosphamide in common use today. Systemic drug therapy combined with radiotherapy that delivers high doses to the marrow appears to enhance the risk of leukemia.

Background: Studies in the United States have reported that Black women have higher fatality rates than White women following a diagnosis of breast cancer and are more likely to be diagnosed with late-stage cancers., Purpose: To evaluate reasons for these racial differences, we explored the difference between Black and White women in the length of time from symptom recognition to initial medical consultation. We also evaluated the extent to which other factors related to the length of this interval might contribute to any observed racial difference., Methods: As part of a collaborative study of differences in the survival rates of Black patients and White patients with cancer, we interviewed a sample of 410 Black women and 325 White women from Atlanta, New Orleans, and San Francisco/Oakland who were newly diagnosed in 1985 or 1986 with invasive breast cancer. Retrospective data were collected on symptoms, dates of symptom recognition and initial medical consultation, and several other factors which may affect the interval between symptom recognition and medical consultation. Data were analyzed as if from a follow-up study, using product limit procedures and proportional hazards regression., Results: At diagnosis, Black women with breast cancer were two times more likely to have stage IV breast cancer and one and one-half times more likely to have stage III breast cancer than White women with breast cancer and were only approximately one-half as likely to have stage I breast cancer. Similarly, Black women were almost twice as likely as White women to have tumors that were larger than 5 cm or tumors that had extensions to the chest wall or skin at presentation. However, the average rate at which Black women with breast cancer obtained an initial medical consultation lagged behind that for White women by only a slight but statistically significant difference (15%). The median time between symptom recognition and medical consultation was slightly longer for Black women (16 days) than for White women (14 days) (P = .06). Adjustment for other characteristics predictive of the length of this interval had little effect on racial differences. The racial differences tended to vary somewhat by age and metropolitan area, suggesting that the results may not apply equally to all demographic subgroups and regions in the United States., Conclusion: This small difference in the time from symptom recognition to medical consultation is unlikely to account for the large racial differences in survival rates and in stage of disease at the time of diagnosis.

Background: The incidence of breast cancer has been increasing over time in the United States., Methods: To determine the role of screening in this increase, trends in the incidence of in situ and invasive carcinoma of the breast were evaluated using records of the metropolitan Atlanta SEER program between 1979 and 1986. From a sample of records, evidence of symptoms and mammographic screening prior to diagnosis was recorded., Results: The average annual age-adjusted incidence of invasive disease rose 29 percent among Whites and 41 percent among Blacks. Incidence increased in all age groups. A trend towards earlier detection of invasive disease was found. Asymptomatic tumors accounted for only 40 percent of the increased incidence among whites and 25 percent of the increased incidence among blacks, with mammography as the principal contributing procedure., Conclusions: These data suggest that increased detection accounts for some but not all of the rising incidence of breast cancer in the United States.

We examined the relationship between body mass [weight (kg)/height (m)2] and breast cancer using data from the Cancer and Steroid Hormone Study. The study compared 4323 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4358 women randomly selected from the general population of the same geographic areas. Among naturally menopausal women, risk of breast cancer increased with increasing body mass index (BMI); those severely overweight (BMI greater than or equal to 32.30) had nearly 3-fold higher risk of breast cancer compared with women in the leanest category (BMI less than 20.00). This positive association appeared stronger with increasing years since menopause and in women who had ever used estrogen replacement therapy. A positive association between body mass and breast cancer risk also was observed among premenopausal women; however, risk estimates were substantially lower. Substantial weight gain from adolescence to adulthood was a more important risk factor than lifelong obesity. Prevalence of obesity increases with age; our results suggest that interventions that prevent this trend could have an important effect on breast cancer risk, especially during the menopausal years.

The effects of nutritional status on differences in the survival of black and white women with breast cancer were studied in a cohort of 1,960 Georgia women diagnosed during 1975-1979. After data were adjusted for stage of disease, socioeconomic status, and other prognostic factors, poorer survival rates were shown in black women. Within each stage classification, lower levels of serum albumin and hemoglobin and higher relative body weight were more common among blacks and were independently associated with poorer survival. Among women with stage 3 disease, adjustment for these variables substantially reduced the excess mortality rate among blacks, suggesting that racial differences in survival may be partly explained by differences in nutritional status or extent of disease within stage.

In May 1988, the National Cancer Institute issued a clinical alert calling for the routine use of systemic adjuvant therapy for all node-negative breast cancers. Subsequent review of the data that the National Cancer Institute used as a basis for its endorsement revealed several limitations, including failure to consider cost-benefit ratios and failure to exclude late toxicities. The authors conclude that the issuance of the release was premature and that it does not attempt to balance the slight lengthening of disease-free survival against the overall population costs. It is suggested that physicians individually assess the potential merits of such a treatment regimen in each of their patients with node-negative breast cancer.

The histopathological and biochemical characteristics of cells and multicellular structure of benign and malignant breast changes have highly significant implications as to the risk of acquiring and dying of breast cancer. Consequently, every breast biopsy merits highly specific histopathological characterization as well as assay for hormone receptors. Certain aspects of a woman's personal and family history may be associated with increased or decreased risk. Clinical application of these variables to the prediction of future outcome requires an understanding of the definitions of risk. These definitions must then be applied appropriately when assessing risk. The definition of risk used must be explicitly stated and consistently used. Provided is a review of the definitions of risk and the risk of acquiring breast cancer according to age, family history, and histopathological characteristics of benign breast biopsies. The highly variable relative risk of dying from breast cancer when diagnosed is also reviewed.

The Breast Cancer Demonstration and Detection Project in Louisville (BCDDP-L) screened 10,128 women for cancer. From this screening, another project evolved wherein those patients diagnosed as having chronic cystic mastopathy (CCM) were followed over a 10-year period to evaluate any association between CCM and breast cancer. In all, 1396 breast biopsies were performed, with 165 cancers being diagnosed either on initial screening or during subsequent years. Three of these are excluded, since histopathologic slides could not be obtained for central review. Of this group, cancer was associated with CCM in 116 specimens and without CCM in 46 specimens. One subset of 355 patients with biopsy-proven CCM but no breast cancer was followed for 6 to 12 years, for a total of 2443.5 woman-years of observation. Within this subset, a total of only four cancers occurred (4 cancers/2443.5 woman-years for 0.00164 cancers/woman-years). This incidence is not significantly different from the expected value. However, an estimate is provided as to the power of the test that could be obtained from a larger sample size derived from other BCDDPs. This group of 355 women was sorted into subsets by establishing a matrix matching ten histopathologic subdivisions of CCM against six subdivisions of Wolfe's xeromammographic (XM) patterns. The numbers of cancers in each cell of this matrix is reported. The results found no concentration of these four cancers in this matrix.

A population-based case-control study was conducted to examine whether tumor estrogen receptor status differentiated risk factor patterns for breast cancer. From December 1980 to December 1982, 458 women with newly diagnosed breast cancer and 568 control women, aged 20-54 years, from the Atlanta, Georgia, metropolitan area were interviewed. On the basis of tumor estrogen receptor results, cases were classified as receptor-positive or receptor-negative. Intercase analysis showed that age was positively and significantly associated with estrogen receptor-positive breast cancer (p = 0.001); the relative risk for an estrogen receptor-positive as opposed to an estrogen receptor-negative tumor was elevated threefold among women aged 50-54 years compared with those aged less than 35 years. In the case-control analysis, race was the only individual factor that demonstrated a significant difference in the risk for estrogen receptor-positive versus estrogen receptor-negative cancer (p less than 0.05), with blacks being at a 25% excess risk for estrogen receptor-negative cancer compared with whites. Although a history of benign breast disease was a risk factor for both positive and negative tumors, the association was stronger for the estrogen receptor-positive tumors. Postmenopausal women were at a lower risk for both cancer subtypes compared with premenopausal women. Compared with non-users, women who had ever taken oral contraceptives had a 16% decrease in the risk for receptor-positive cancer and a 22% increase in the risk for receptor-negative cancer. These results are consistent with the notion that certain exposure variables may relate to hormonal status, possibly by augmentation or suppression of estrogen receptor activity.

A population-based study was utilized to calculate breast cancer incidence rates in White and Black women, ages 30 to 54, according to tumor estrogen receptor status. Both racial groups had higher incidence curves for estrogen receptor negative breast cancer between ages 30 and 49. There was an excess of receptor negative cancer in young Black women, an observation that may help explain the racial disparity in breast cancer survival.

The relationship between breast self-examination (BSE) and survival was evaluated in 2093 women with breast cancer newly diagnosed between June 1975 and February 1979. In this population self-examiners were younger, more educated, and more likely to be white, premenopausal, and married than nonexaminers. Self-examiners also tended to seek medical care more rapidly and to have earlier stages of disease at diagnosis. Five years after diagnosis, the cumulative observed survival rates from breast cancer were 76.7% among self-examiners and 60.9% among nonexaminers (P less than 0.0001). In a multivariate analysis known sociodemographic and treatment confounders accounted for 25% of the excess of breast cancer deaths among nonexaminers. Approximately half of the remaining survival differential was attributable to the more limited disease among selfexaminers. The residual association between BSE and survival may be related to uncontrolled effects of stage or other unrecognized confounders.

The purpose of this study is to report the time elapsing between the moment a breast cancer reaches threshold size that would permit detection and the size at actual detection defined as sojourn time (STt) using data from the Breast Cancer Detection and Demonstration Project (Louisville data and reported composite data from 27 centers) by dividing prevalence rates by incidence rates. The number of cellular generations (n) required to produce cancers of different volumes was calculated at threshold (nt), at detection (nd), and the difference between the two (nd - nt). By dividing the difference (nd - nt) into STt, the average actual or net tumor volume doubling time (DTact) in this interval have been estimated. The STt value for carcinoma in situ was 557 and for cancer it was 538. At ages 35-39, STt ranged from 365-456 days, by ages 70-74, 942-1383 days. The average DTact similarly varied with age, carcinoma in situ, cancer with negative axillary nodes, and cancer with positive axillary nodes over a range of 28-732 days (95% confidence). The estimated DTact in the predetectable period was manyfold less than the DTact measured for mammographically visible cancers, in keeping with the predictions of decelerating growth. Models of the cytokinetic and clinical behavior of breast cancer are discussed.

The hypothesis that white women with breast cancer survive longer than black women with this disease was evaluated in a retrospective analysis of a population-based prospective follow-up study. All female residents of metropolitan Atlanta with a first diagnosis of primary breast cancer between 1 January 1978 and 31 December 1982 were eligible for inclusion. The study population of 2322 white and 536 black women was followed through the end of calendar year 1983 to determine vital status. Univariate, multivariate and excess death rate analyses were performed to evaluate race as a prognostic factor. Overall, the cumulative percentage of survivors at 3 years was 83% among whites, compared with 71% among blacks. The racial difference in survival was greatest among women with advanced disease, and a higher proportion of black women with advanced disease did not receive surgery. Even when the type of surgery and stage of disease were controlled, race was a significant prognostic factor.

The aim of this study is to provide a long-term follow-up of patients with tubular carcinoma and to investigate whether the separation of the mixed type of tubular carcinoma, tubular component more than 75%, from invasive ductal carcinoma with a major tubular component (ductal carcinoma MTC), tubular component 50 to 75%, is supported by long term follow-up. For this study 388 consecutive breast carcinomas were selected from the files of the Department of Pathology, Bispebjerg Hospital, Denmark for the years: 1956-59. Twenty tubular carcinomas were found and 16 ductal carcinomas MTC were also identified. For each patient with tubular carcinoma and ductal carcinoma MTC, two controls with ductal carcinoma NOS were selected. The patients in these four groups were followed until 1 April 1982. None of the patients were lost to follow-up. Among the 20 patients with tubular carcinoma, 10 died within this period compared to 37 of the 40 controls. Of the 16 patients with ductal carcinoma MTC, 15 died compared to 29 of the 32 controls. The difference in Kaplan-Meier survival curves between the tubular carcinomas and their controls is highly significant. There is no significant difference between ductal carcinomas MTC and their controls. These findings are not changed significantly when 5, 10, and 20 year survival rates are corrected for expected survival. This study demonstrates long-term survival for patients with tubular carcinoma as compared to ductal carcinoma NOS. There is no difference in long-term survival between ductal carcinoma MTC, tubular component between 50 and 75%, and ductal carcinoma NOS. It therefore seems appropriate to set 75% tubular component as a reasonable cut-off point for the mixed type of tubular carcinoma.

Objective: To identify from the literature and clinical experience a rational approach to management of fibroadenomas of the breast.Method: Recent literature on detection, diagnosis, and natural history of fibroadenomas was reviewed. Experience with over 4,000 women evaluated in the breast clinic at the Tel-Aviv Medical Center contributed to the management strategies suggested by review of the literature.Results: Fibroadenomas of the breast are common, accounting for 50% of all breast biopsies performed. Physical examination, sonography, and fine needle aspiration are effective in distinguishing fibroadenomas from breast cancer. Transformation from fibroadenoma to cancer is rare; regression or resolution is frequent, supporting conservative approaches to follow-up and management.Conclusion: Age-based algorithms that allow for conservative management and that limit excision to patients whose fibroadenomas fail to regress are presented. [ABSTRACT FROM AUTHOR]