Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers.

BACKGROUND: Although mammographic screening is useful for detecting early breast cancer, some tumors are detected in the interval between screening examinations. This study attempted to characterize fully the tumors detected in the two different manners. METHODS: Our study utilized a case-control design and involved a cohort of women undergoing mammographic screening within the defined population of a health maintenance organization (the Group Health Cooperative of Puget Sound). Women were classified as having "interval" or "interval-detected" cancers (n = 150) if their diagnosis was made within 24 months after a negative-screening mammogram or one that indicated a benign condition. Cancers were classified as "screen detected" (n = 279) if the diagnosis occurred after a positive assessment by screening mammography. Tumors from women in each group were evaluated for clinical presentation, histology, proliferative characteristics, and expression of hormone receptors, p53 tumor suppressor protein, and c-erbB-2 protein. RESULTS: Interval-detected cancers occurred more in younger women and were of larger tumor size than screen-detected cancers. In unconditional logistic regression models adjusted for age and tumor size, tumors with lobular (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 0.9-4.2) or mucinous (OR = 5.5; 95% CI = 1.5-19.4) histology, high proliferation (by either mitotic count [OR = 2.9; 95% CI = 1.5-5.7] or Ki-67 antigen expression [OR = 2.3; 95% CI = 1.3-4.1]), high histologic grade (OR = 2.1; 95% CI = 1.2-4.0), high nuclear grade (OR = 2.0; 95% CI = 1.0-3.7), or negative estrogen receptor status (OR = 1.8; 95% CI = 1.0-3.1) were more likely to surface in the interval between screening examinations. Tumors with tubular histology (OR = 0.2; 95% CI = 0.0-0.8) or with a high percentage of in situ components (50%) (OR = 0.5; 95% CI = 0.2-1.2) were associated with an increased likelihood of screen detection. CONCLUSIONS: Our data from a large group of women in a defined population indicate that screening mammography may miss tumors of lobular or mucinous histology and some rapidly proliferating, high-grade tumors.

Variation in mammographic breast density by race.

PURPOSE: Because of the observed racial differences in risk of developing breast cancer, the authors conducted a study to determine the variation in breast density, a strong predictor of breast cancer risk, by race and age. METHODS: Study subjects were women enrolled in Group Health Cooperative of Puget Sound, Seattle, WA, aged 20-79 years, who had a screening mammogram between 6/1/96 and 8/1/97. Women with increased breast density (BI-RADS "heterogeneously dense" and "extremely dense") (n = 14,178) were compared to those with fatty breasts (BI-RADS "almost entirely fat" and "scattered fibroglandular tissue") (n = 14,323). Logistic regression was used with adjustment for age, parity, age at first birth, menopausal status, current use of hormone replacement therapy, and body mass index. RESULTS: The odds ratio (OR) for having dense breasts versus fatty breasts, comparing Asian to White women, increased from 1.2 [95% confidence interval (CI) 0.9-1.6] for women age <45 to 1.6 (95% CI 1.3-2.2) for women over 65. Conversely, the OR for Black compared to White women was highest for the women age 65 and younger (OR 1.7 (1.2-2.3), 1.3(1.0-1.7), and 1.7 (1.2-2.3) for women age <45, 46-55, and 56-65, respectively), whereas Black women over 65 had similar density as Whites. Hispanic women had similar density compared to Whites for all ages. CONCLUSIONS: These racial differences in breast density generally do not conform to differences in race and age-specific breast cancer incidence rates.

Effect of cervical carcinoma in situ and its management on pregnancy outcome.

OBJECTIVE: To assess the effect of cervical carcinoma in situ (CIS) and its management on subsequent pregnancy outcome. METHODS: We used a population-based retrospective cohort design that included record linkage between cancer data and birth records. The Cancer Surveillance System records of women with CIS (n = 1851, 312 diagnosed during pregnancy) diagnosed between 1984 and 1992, were linked to birth certificates of their first subsequent deliveries after CIS diagnosis. The comparison group (n = 9201) was a random sample of women without CIS who gave birth during the same years. The outcome measures were preterm and low birth weight infants subsequent to CIS diagnosis and treatment. Treatments included no therapy, dilation and curettage or endocervical curettage, cryosurgery or laser vaporization, and conization. RESULTS: Women with CIS who were not treated with conization had a small increased risk of preterm delivery (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.0, 2.0) and no increased risk of low birth weight infant (OR 1.0, 95% CI 0.7, 1.6), compared with women without CIS, after adjusting for maternal smoking, race, parity, marital status, and history of induced pregnancy termination. Women with CIS who had conization were more likely to deliver premature infants (OR 1.6, 95% CI 1.2, 2.0) than women without CIS, after adjusting for the same confounding factors. The apparently increased risk of low birth weight (OR 1.8, 95% CI 1.4, 2.4) seemed to be a reflection of premature delivery. CONCLUSION: The risk of prematurity increased after conization for CIS and did not increase when women with CIS had other procedures.

Amniotic fluid interleukin-6 and preterm delivery: a review.

OBJECTIVE: To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection. DATA SOURCES: We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords "labor/infant," "premature," "cytokines/interleukin-6," and "AF." We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles. METHODS OF STUDY SELECTION: The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery. TABULATION, INTEGRATION, AND RESULTS: There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33-70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered. CONCLUSION: Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.

Reproductive and hormonal factors associated with mammographic breast density by age (United States).

OBJECTIVES: We determined the association of certain reproductive and hormonal factors with breast density over decades of life. METHODS: Subjects were women age 20-79 years who had a screening mammogram between 1 June 1996 and 1 August 1997, in Seattle, Washington. Women with increased breast density (upper two categories of BI-RADS terminology) (n = 14,432) were compared to those with fatty breasts (lower two categories (n = 14,552). Unconditional logistic regression was used with adjustment for age at mammogram, parity, age at first birth, menopausal status, current use of hormone replacement therapy (HRT), and body mass index. RESULTS: The association of nulliparity with density was evident for women at all ages (odds ratio (OR) and 95% confidence interval (CI) = 1.5 (1.3-1.7) and 1.6 (1.4-1.9) for women age < or = 45 and > 65, respectively). Older age at first birth was more strongly associated with density among women > 55 than among younger women. The association of current use of HRT with density, but not of former use, increased with age when compared to never users (OR = 1.4 (1.2-1.7) and 2.2 (2.0-2.5) for women age 46-55 and > 65, respectively). CONCLUSIONS: Results suggest that pregnancy at an early age has a permanent beneficial association with density, while HRT has a transitory adverse association.