Virginia L. Ernster

Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women

Abstract ▪Purpose:To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong...

Consensus Conference on the Classification of Ductal Carcinoma of the Breast, April 22–25, 1999

Ductal carcinoma in situ (DCIS/intraductal carcinoma/noninvasive ductal carcinoma) is a proliferation of malignant cells confined within the basement membrane of the ducts of the breast. Until the late 1970s, DCIS was detected infrequently, usually presenting as a mass or as nipple discharge. As screening mammography became almost universally accepted, the mammographic finding of calcifications leading to the diagnosis of DCIS has become commonplace. When initially described two generations ago, DCIS was considered an initial step in an inexorable progression to invasive breast carcinoma. Within the past generation, it has been documented that only a minority of patients develop invasive breast carcinoma after the excision of DCIS, so treatment options have expanded. Mastectomy had been the initial treatment for the majority of patients with DCIS, but as this additional information has become available, many physicians currently treat women with DCIS by local excision and radiation therapy or local excision alone as an alternative to mastectomy.

Performance of Screening Mammography among Women with and without a First-Degree Relative with Breast Cancer

Many guidelines recommend that women at high risk for breast cancer undergo regular screening mammography at a younger age than those at average risk (1). However, few studies have evaluated the performance of screening mammography among younger women at increased risk for breast cancer. One group reported that the positive predictive value of mammography was two- to threefold higher (2) but the sensitivity was slightly lower (3) in women who had at least one first-degree relative with a history of breast cancer compared with those who did not. No randomized, controlled trials or subgroup analyses of data from existing randomized, controlled trials of screening mammography have evaluated the efficacy of the test in women with a family history of breast cancer. Understanding whether a family history of breast cancer influences the test performance characteristics of mammography may be important in developing screening strategies. This may be especially true for younger women, in whom the positive predictive value of mammography is low and the likelihood of associated diagnostic procedures to evaluate an abnormal result is high (2, 4, 5). We pooled data from seven mammography registries in order to provide a more stable estimate of the accuracy of screening mammography among women with a first-degree family history of breast cancer. We also compared the accuracy of the test in these women and in women of similar age without a family history. In this study, we report the rate of cancer, cancer yield per breast biopsy, and positive predictive value and sensitivity of mammography according to family history and decade of age. Methods Participants and Data Sources Our study sample included women 30 to 69 years of age who underwent screening mammography from April 1985 to November 1997. Data were pooled from seven mammography registries that participate in the National Cancer Institute Breast Cancer Surveillance Consortium (BCSC) (6). The seven registries, which are funded by the National Cancer Institute or the Department of Defense, are the San Francisco Mammography Registry (SFMR), San Francisco, California; Group Health Cooperative (GHC), Seattle, Washington; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, Washington; New Mexico Mammography Project (NMMP), Albuquerque, New Mexico; Vermont Mammography Registry (VMR), Burlington, Vermont; Colorado Mammography Advocacy Project (CMAP), Denver, Colorado; and New Hampshire Mammography Network (NHMN), Hanover, New Hampshire. The SFMR provided data from April 1985 to December 1993, the GHC provided data from January 1986 to December 1993, the FHCRC provided data from December 1987 to December 1996, the NMMP provided data from June 1992 to December 1995, the VMR provided data from January 1994 to December 1996, the CMAP provided data from August 1994 to December 1996, and the NHMN provided data from May 1996 to November 1997. One mammographic examination per woman was included in the pooled analysis. If a woman had more than one mammographic examination in a mammography registry, results from her earliest dated examination were included and results from any subsequent screening examinations were excluded. We excluded women with a previous diagnosis of breast cancer and those with a palpable breast mass by history or on physical examination. Women whose ZIP codes were outside the catchment areas of their regional Surveillance, Epidemiology, and End Results (SEER) program or state tumor registry were also excluded to minimize incomplete follow-up information. The University of California, San Francisco, Committee on Human Research approved the study. Measurements We obtained a self-reported risk profile for breast cancer for each woman, as well as a mammographic assessment of two standard screening views per breast. The risk profile for breast cancer included questions about family history of breast cancer in a first-degree relative. Women were considered to have a family history of breast cancer if they reported having at least one first-degree relative (mother, sister, or daughter) with breast cancer. Results of initial screening examinations were classified as normal or abnormal. In mammography registries that used the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) (7) or terminology consistent with BI-RADS to assign mammographic assessment categories (SFMR, FHCRC, NMMP, VMR, NHMN, and CMAP), findings considered negative (category 1) or benign (category 2) were classified as normal. Examinations reported with any of the following BI-RADS assessments were categorized as abnormal: 1) probably benign (category 3); 2) incomplete, needs additional imaging evaluation (category 0), 3) suspicious (category 4), and 4) highly suggestive of malignancy (category 5). Before using BI-RADS, GHC used three mammographic assessment codes: negative, indeterminate, and positive. Negative and indeterminate assessments (for which follow-up in 1 year was recommended) were classified as normal; indeterminate assessments (for which 6-month follow-up examinations, additional imaging, or biopsy was recommended) and all positive assessments were classified as abnormal. Follow-up Breast biopsies performed to evaluate an abnormal mammography result were identified by contacting the womans personal physician, performing data linkage with a pathology database, or performing data linkage with a radiology database, depending on the study site. Breast biopsies included excisional and core biopsies. Women who had screening examinations were linked by computer to a pathology database (VMR, NHMN), to SEER (GHC, SFMR, NMMP, FHCRC), or to a state tumor registry (VMR, NHMN, CMAP) that collects population-based cancer data. To maintain participant confidentiality, procedures for linkage were performed according to protocols for human subjects research. Women were linked by using their full names, birth dates, addresses, ZIP codes, and Social Security numbers, when available, by using a probability-matching software program (Automatch, Vality Technology, Inc., Boston, Massachusetts) (VMR, NHMN, SFMR) or a comparable software program developed for linkage by a mammography registry (GHC, FHCRC, NMMP, CMAP). To allow adequate time for breast cancer to be reported to a tumor registry after a normal mammography result, we included only women who were screened through November 1997. Women were considered to have breast cancer if reports from a breast pathology database, SEER program, or state tumor registry showed any invasive carcinoma or ductal carcinoma in situ. Women with lobular carcinoma in situ only were excluded. Results for all cases of breast cancer and results for invasive cancer are presented separately. Definitions If breast cancer was diagnosed within 12 months of a normal mammography result, the examination was considered to be a false negative. If breast cancer was not diagnosed within 12 months of a normal mammography result, the examination was considered to be a true negative. If breast cancer was diagnosed within 12 months of an abnormal mammography result, the examination was considered to be a true positive. If breast cancer was not diagnosed within 12 months of an abnormal mammography result, the examination was considered to be a false positive. The diagnosis date was the date reported by a SEER program, the date reported by a state tumor registry, or the biopsy date recorded in a pathology database. Statistical Analysis The positive predictive value of screening mammography was calculated as the percentage of women with abnormal screening examinations who received a diagnosis of breast cancer within 12 months of the screening examination. Since the positive predictive value of mammography is influenced by the criteria used to define an examination as abnormal, we also reported the number of cases of breast cancer detected per 1000 screening examinations (normal and abnormal combined) when breast cancer was diagnosed within 1 year of the screening examination. The cancer yield per breast biopsy was calculated as the percentage of women who had a breast biopsy and received a diagnosis of breast cancer within 12 months of the screening examination. The sensitivity of mammography was calculated as the number of true-positive examinations divided by the number of true-positive examinations plus the number of false-negative examinations. The specificity of mammography was calculated as the number of true-negative examinations divided by the number of false-positive examinations plus the number of true-negative examinations. The chi-square test and the Fisher exact test were used for comparison of proportions. The chi-square test for trend and the chi-square test for homogeneity were used to compare proportions stratified by age. All Pvalues were two sided. Role of the Funding Sources The funding sources had no role in the collection, analysis, or interpretation of the data or in the decision to submit the paper for publication. Results A total of 389 533 screening examinations were performed among seven mammography registries. Of these, 50 834 (13.0%) were performed in women with a family history of breast cancer. Five registries record self-reported previous use of mammography. In data from these registries, previous use was similar among women with a family history of breast cancer (81.7% [28 574 of 34 973]) and among those without (80.2% [170 505 of 212 729]). Abnormal Mammography Results Among women without a family history of breast cancer, the overall frequency of abnormal examination results was 10.8% (95% CI, 10.7% to 11.0%). The frequency of abnormal results ranged from 8.8% to 11.3% across age groups and was lowest for women 30 to 39 years of age (Table 1). The frequency of abnormal examination results was higher among women with a family history of breast cancer than among those without (12.7% vs. 10.8%; P<0.001 [chi-square test]); these differe

Facial wrinkling in men and women, by smoking status.

OBJECTIVES This study examined the association of smoking status and pack-years of smoking with facial wrinkling in men and women. METHODS We conducted a cross-sectional study of 299 never smokers, 551 former smokers and 286 current smokers, aged 30 through 69 years, drawn from a health maintenance organization. Smoking status, pack-years of smoking, and potential confounding variables were assessed by questionnaire. Facial wrinkle category, a dichotomous variable, and facial wrinkle score, a computed continuous variable, were assessed by blinded standardized visual assessment. Wrinkling was so uncommon among 30- through 39-year-old subjects that analyses were restricted to subjects aged 40 and over (227 never smokers, 456 former smokers, and 228 current smokers). RESULTS With age, average sun exposure, and body mass index controlled, the estimated relative risk of moderate/severe wrinkling for current smokers compared to never smokers was 2.3 (95% confidence interval [CI] = 1.2, 4.2) among men and 3.1 (95% CI = 1.6, 5.9) among women. Pack-years was positively associated with facial wrinkle score in women aged 40 through 69 years and in men aged 40 through 59 years. In both groups, the increased risk of wrinkling was equivalent to about 1.4 years of aging. CONCLUSIONS Our results support earlier findings that risk of facial wrinkling is greater in cigarette smokers than in never smokers.

Women and tobacco: moving from policy to action.

A gender perspective contributes to a better understanding of the epidemiological trends, social marketing strategies, economic policies, and international actions relating to women and the tobacco epidemic. Evidence is provided in this article for the negative impact of tobacco use by women and of passive smoking on the health of women and children. Use of tobacco by women is increasing and this is related to the tobacco industrys aggressive advertising, sponsorship and promotion strategies. Policy directions are proposed in this article. At all levels, a multi-pronged strategy--including changes in legislation and fiscal policies, improvements in gender-sensitive health services, and cessation programmes--should be considered. Much more gender-specific research on tobacco use is needed, particularly in developing countries. Womens empowerment and leadership should be at the centre of all tobacco control efforts and are essential for the success of national programmes and the recently introduced Framework Convention on Tobacco Control.

Benefits and risks of menopausal estrogen and/or progestin hormone use,

Current evidence is reviewed here on risks and benefits of estrogen and progestin use by peri- and postmenopausal women in relation to the following conditions: endometrial cancer, breast cancer, osteoporosis, and coronary artery disease (CAD). On balance, estrogen therapy appears to be beneficial for menopausal women, as it probably reduces the risks of CAD and osteoporosis, two of the major causes of mortality and morbidity. Although unopposed estrogen therapy increases the risk of endometrial cancer, that cancer is relatively rare and is not fatal in the vast majority of cases associated with estrogen use. Definitive conclusions about the relation of menopausal estrogens to breast cancer cannot be drawn due to inconsistent evidence to date. Although evidence from randomized controlled trials is lacking, biochemical and clinical evidence suggest that progestin supplementation is associated with a reduction in endometrial cancer risk in women taking menopausal estrogens. Progestin supplementation also may augment the beneficial effects of estrogens in providing protection against osteoporosis, although this effect is not yet well established. There is little direct evidence bearing on the relation of menopausal progestins to breast cancer. Although studies of CAD per se are lacking at present, progestins probably unfavorably alter lipoprotein profiles, thereby increasing a users risk of CAD. Given the relatively high incidence and mortality of CAD in postmenopausal women, any negative effects on CAD risk could potentially counterbalance beneficial effects on other causes. We conclude that estrogen replacement therapy is of potential benefit to postmenopausal women, but that the question of progestin supplementation requires further study, particularly for CAD risk.

Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players

BACKGROUND The use of smokeless tobacco (ST), which has increased in popularity over the past 2 decades, results in considerable systemic exposure to nicotine. Nicotine might contribute to atherosclerosis by an effect on cardiovascular risk factors. METHODS The effects of ST use on cardiovascular risk factors and cotinine and nicotine levels were studied in 1061 professional baseball players during spring training in 1988 and 1989. RESULTS Of the study participants 477 (45%) were users. ST use was more common among Whites (55%) than among Blacks (29%) or Hispanics (21%), and users reported heavier consumption of alcohol (p less than .001) and had higher mean serum caffeine levels (p less than .001) than nonusers. ST users did not differ from nonusers in adjusted levels of systolic and diastolic blood pressure, pulse, and total or HDL-cholesterol. Among ST users, participants using snuff had higher mean serum cotinine levels than those who used chewing tobacco (p less than .001). There was no association between serum cotinine levels and adjusted levels of any cardiovascular risk factor studied. However, higher diastolic blood pressures were associated with higher mean serum nicotine levels (p = .02). CONCLUSIONS Smokeless tobacco use has at most a modest effect on cardiovascular risk factors in young physically fit men.

Factors associated with obtaining nipple aspirate fluid: Analysis of 1428 women and literature review

SummaryStudies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid.New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed.

The epidemiology of lung cancer in women

Female lung cancer mortality rates have increased dramatically since 1950, and in 1987 lung cancer surpassed breast cancer as the leading cause of cancer death among US women. The epidemic in women, as in men, is attributable to cigarette smoking. Smoking prevalence in women peaked in the 1960s and 1970s and has since been declining, although fully 23.5% of adult women were current smokers in 1991. As a reflection of declines in smoking prevalence, lung cancer incidence and mortality rates are declining slightly in women under 45 years old, and it is predicted that overall age-adjusted rates may begin to turn around early in the next century. Survival for the disease is poor; the relative 5-year survival rate for women diagnosed between 1981 and 1987 was only 16% for whites and 13% for African-Americans. This article describes trends in female lung cancer rates by race and age, provides staging and survival statistics, and briefly reviews the evidence on smoking and other risk factors (environmental tobacco smoke, radon, pollution, family history, previous lung disease, and diet) for lung cancer in women.

Smokeless tobacco cessation intervention for college athletes: results after 1 year.

OBJECTIVES The purpose of this study was to determine the efficacy of a college-based smokeless tobacco cessation intervention targeting college athletes. METHODS Sixteen colleges were matched for prevalence of smokeless tobacco use in their combined baseball and football teams and randomly assigned within college pairs to the intervention or the control group. One-year prevalence of cessation among smokeless tobacco users was determined by self-report of abstinence for the previous 30 days. Differences between groups were analyzed in a weighted version of the Fisher 1-sided permutation test for paired samples after adjustment for significant predictors of quitting other than the intervention (i.e., smokeless tobacco uses per week and most frequently used brand). RESULTS Cessation prevalences were 35% in the intervention colleges and 16% in the control colleges when subjects with unknown quit status were defined as nonquitters. After adjustment for other significant predictors of quitting, the difference of 19% increased to 21%. The intervention effect increased with level of smokeless tobacco use. CONCLUSIONS This intervention was effective in promoting smokeless tobacco cessation, especially among those who were more frequent users.