Validation study of the LAMBDA model for predicting the BRCA1 or BRCA2 mutation carrier status of North American Ashkenazi Jewish women.

LAMBDA is a model that estimates the probability an Ashkenazi Jewish (AJ) woman carries an ancestral BRCA1 or BRCA2 mutation from her personal and family cancer history. LAMBDA is relevant to clinical practice, and its implementation does not require a computer. It was developed principally from Australian and UK data. We conducted a validation study using 1286 North American AJ women tested for the mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2. Most had a personal or family history of breast cancer. We observed 197 carriers. The area under the receiver operator characteristic (ROC) curve (a measure of ranking) was 0.79 [95% confidence interval (CI) = 0.77-0.81], similar to that for the model-generating data (0.78; 95% CI = 0.75-0.82). LAMBDA predicted 232 carriers (18% more than observed; p = 0.002) and was overdispersed (p = 0.009). The Bayesian computer program BRCAPRO gave a similar area under the ROC curve (0.78; 95% CI = 0.76-0.80), but predicted 367 carriers (86% more than observed; p < 0.0001), and was substantially overdispersed (p < 0.0001). Therefore, LAMBDA is comparable to BRCAPRO for ranking AJ women according to their probability of being a BRCA1 or BRCA2 mutation carrier and is more accurate than brcapro which substantially overpredicts carriers in this population.

Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.

BACKGROUND: To the authors' knowledge, there are no long-term cohort studies of lymphedema, despite the substantial morbidity of arm swelling. The goal of this study was to identify prevalence of breast carcinoma-related lymphedema, time of onset, and associated predictive factors. METHODS: A cohort of 923 women consecutively treated with mastectomy and complete axillary dissection at our center between 1976 and 1978 was observed intensively for 20 years. Two hundred sixty-three study subjects (28.5%) who were alive and recurrence free constituted the cohort for the current study. A subset of 52 women (20% of study population) with contralateral mastectomy was analyzed separately. Subjects reported circumferential arm measurements taken using a validated instrument. In addition to providing analysis of clinical and treatment variables, this study is the first to the authors' knowledge to analyze possible etiologic factors in the posttreatment years, such as occupation, general physical activity, and sports/leisure activities. Univariate and multivariate analytic methods were used. RESULTS: At 20 years after treatment, 49% (128 of 263) reported the sensation of lymphedema. Arm swelling measurements were severe (> or = 2.0 in [5.08 cm]; patients reported measurement in inches) for 13% (33 of 263 women). Seventy-seven percent (98 of 128) noted onset within 3 years after the operation; the remaining percentage developed arm swelling at a rate of almost 1% per year. Of the 15 potential predictive factors analyzed, only 2 were statistically significantly associated with lymphedema: arm infection/injury and weight gain since operation (P < 0.001 and P = 0.02, respectively). CONCLUSIONS: This defined cohort, treated by axillary dissection 20 years ago, documents the high prevalence of lymphedema and its time course. Two significantly associated factors, both potentially controllable, are identified. The current study provides further support for treatments that limit lymph node dissection. The authors are prospectively evaluating patients undergoing sentinel lymph node biopsy.

Carcinoma of the male breast: analysis of prognosis compared with matched female patients.

BACKGROUND: Considerable debate exists concerning the prognosis of breast cancer in male patients compared with that in female patients. Some studies have observed worse prognosis for men; others suggested the higher mortality rates were primarily due to delayed diagnosis. METHODS: Survival time from diagnosis with invasive disease to death resulting from breast cancer of 58 men treated between 1973 and 1989 was compared with survival of 174 women treated between 1976 and 1978 who were matched by stage of disease and age at diagnosis. All patients were treated by mastectomy and axillary dissection. RESULTS: Tumors were < or = 2 cm in 70% of cases and 55% were free of axillary metastases. The histology of the tumors differed significantly by gender (p < 0.05). Significantly more men had estrogen receptor-positive tumors (87%) than did women (55%, p < 0.001). Survival at 10 years was similar for male and female patients. Multivariate analysis controlling for tumor size, number of positive axillary lymph nodes, age at diagnosis, histology, and receptor status indicated no significant difference in survival of male compared with female patients. CONCLUSIONS: These data conflict with the conventional wisdom that breast cancer in men carries a worse prognosis than the disease in women. Although histology of the tumor and receptor status differed by gender, these factors did not have an impact on survival in these paired patients. Our data indicate that breast carcinoma in males is not biologically more aggressive than in females.

p53 haplotype determination in breast cancer.

Inheritance of certain germ line haplotypes consisting of three biallelic polymorphisms of p53 has been proposed as a risk factor for breast cancer and colorectal cancer [A. Själander et al., Carcinogenesis (Lond.), 17: 1313-1316, 1996, and Carcinogenesis (Lond.), 16: 1461-1464, 1995]. In their studies, pairwise haplotypes of these three polymorphisms were estimated. Extended haplotypes were further projected from the pairwise combinations. To overcome the necessity to estimate pairwise and extended haplotype frequencies, a PCR method has been developed to determine the absolute extended p53 haplotypes in diploid genomes. The method requires allele-specific PCR, confirmed by restriction analysis, and successive amplicon analysis. It has been applied to a nested case-control study of breast cancer (284 subjects; 99 cases and 185 controls; 182 Caucasians, 56 Hispanics, and 46 African-Americans). Evidence is presented that minor variants of the intron 3, codon 72, and intron 6 polymorphisms were moderately elevated in Caucasian breast cancer cases (intron 3, P = 0.03 for genotype and P = 0.01 for allelic frequency; codon 72, P = 0.07 for genotype and P = 0.054 for allelic frequency; and intron 6, P = 0.02 for genotype and P = 0.02 for allele frequency). Accordingly, analysis of haplotype distributions suggested an association of minor p53 haplotypes with breast cancer risk in Caucasians (P = 0.07). The relative allelic frequencies in breast cancer cases compared with controls also differed by age and menopausal status; the 1-2-1 haplotype was overrepresented in postmenopausal cases (P = 0.02) and cases older than 50 years (P = 0.02), whereas the other minor haplotypes (1-1-2 and rare variants) were overrepresented in premenopausal cases (P = 0.003) and cases 50 years of age and younger (P = 0.02). Genotype distributions at each locus and for all control groups were consistent with Hardy-Weinberg equilibria. Differences in haplotype distribution were associated with ethnicity (Caucasians versus African-Americans and Caucasians versus Hispanics, P < 0.001). The new haplotyping method may be useful in the study of gene-environment interactions.

The timing of breast cancer surgery during the menstrual cycle.

A number of recent studies have suggested that survival among premenopausal women after primary treatment of breast cancer may be affected by the estimated hormonal milieu at the time of surgery, especially in those with axillary lymph node metastases. The concept has created considerable controversy and has resulted in the publication of many negative reports. However, several biological mechanisms have been suggested for the observed survival advantage. These include cyclical patterns of immune function, as well as cell division and cell death, that correlate with hormonal fluctuations of the menstrual cycle. Comparisons among studies of timing have been complicated by differences in menstrual cycle divisions, variability in the sources of study populations, limited availability of menstrual history data, and changes over the past 2 decades in primary and adjuvant breast cancer therapy. Several recent publications have been enhanced by the availability of serum collected at the time of surgery that enables accurate measurement of the hormonal milieu. In these studies, the likelihood of misclassification by menstrual cycle phase is reduced, and dependence on recalled menstrual history is eliminated. High progesterone levels have been associated with improved survival. These findings have encouraged some to suggest that perioperative administration of progesterone or tamoxifen (Nolvadex) may provide a preventive avenue comparable to scheduling surgery during the luteal phase. Further multidisciplinary studies are needed, however, to clarify the influence of the naturally occurring or medically induced hormonal milieu at the time of breast cancer surgery on survival in premenopausal women.

Pregnancy influences breast cancer stage at diagnosis in women 30 years of age and younger.

BACKGROUND: To evaluate the purported decreased survival of pregnancy-associated (PA) breast cancer, a previously described homogeneous cohort of women of childbearing age with primary operable cancer was studied. The current analysis was designed to (a) identify those patients among the cohort known to have PA cancer and (b) compare clinical factors, pathologic characteristics, stage at diagnosis, and survival statistics for PA and non-PA cancer subgroups. METHODS: All patients < or =30 years of age who underwent definitive operation between 1950 and 1989 at the Memorial Sloan-Kettering Cancer Center (MSKCC) for primary operable (stages 0-IIIA) breast adenocarcinoma were analyzed. RESULTS: Twenty-two of the 227 young women with primary operable breast cancer had PA cancer. Disease-related survival was decreased (p = 0.004) in these 22 women compared with the remaining 205 patients with non-PA cancer. PA cancer patients were found to have larger tumors (p < 0.005), and a greater proportion had advanced staged (IIB or IIIA) cancers (p < 0.02). Among patients diagnosed with early invasive cancers (stages I or IIA), no difference (p = NS) in survival was observed comparing PA and non-PA subgroups (73% vs. 74% 10-year survival). Patients with stage IIIA cancer had shorter disease-free and overall survival when associated with pregnancy (0% vs. 35% 10-year survival). CONCLUSIONS: Women 30 years of age or younger with PA breast cancer have decreased survival compared with patients with non-PA cancer from the same cohort. Women with PA cancer have larger, more advanced cancers at the time of definitive surgery. Women with early staged PA cancers appear to have survival similar to that for women with early staged non-PA cancer.

Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy.

OBJECTIVE: The purpose of this study was to evaluate the regional pancreatectomy as surgical therapy for ductal adenocarcinoma of the pancreas and to evaluate potential prognostic factors. SUMMARY BACKGROUND DATA: Regional pancreatectomy was developed as a more adequate surgical procedure for pancreatic cancer in an attempt to improve the cure rate for this highly lethal disease. Few studies have evaluated large numbers of patients treated with this technique, and in recent years the emphasis has been on more limited surgery for pancreatic cancer. METHODS: Fifty-six patients with ductal adenocarcinoma of the pancreatic head were treated by regional subtotal or total pancreatectomy. Clinical and pathologic parameters were reviewed and potential prognostic factors were compared statistically. The three patients who died within 30 days of the operation were excluded from the survival analysis. RESULTS: Primary tumor size was the strongest determinant of prognosis. The mean tumor size was 3.9 cm (range, 1-7 cm). Eighty-five percent of patients had peripancreatic soft tissue invasion microscopically, and 58% had regional lymph node metastasis. Kaplan-Meier survival curves indicated a 33% 5-year survival for patients with tumor 2.5 cm or less in diameter (n=12) and 12% for patients with larger tumors (n=39). No patient with a tumor larger than 5 cm survived more than 5 years. Mean tumor size was not significantly associated with lymph node metastases, but 5 of 12 patients (42%) with primary tumor < or =2.5 cm had lymph node metastases. Twenty-four percent of patients with negative lymph nodes and 14% with positive lymph nodes survived 5 years. The difference was not statistically significant (p=0.3), but this is likely related to sample size. The 30- day operative mortality was 5.3%. The most common complications were infection, gastrointestinal bleeding, and gastric stasis. CONCLUSIONS: After regional pancreatectomy, tumor size is the strongest predictor of prognosis. A multi- institutional randomized prospective trial of regional pancreatectomy versus pancreaticoduodenectomy is warranted in previously untreated, noninfected cases.

Improved survival in young women with breast cancer.

BACKGROUND: Young age has been hypothesized to be an adverse prognostic factor for women with breast cancer. This association, based on historical data, may not reflect recent advances in breast cancer management. METHODS: A retrospective study was conducted of all women age 30 or younger who underwent definitive operation at our institution for primary operable breast carcinoma during one of two consecutive 20-year periods (1950-1969 or 1970-1989). All cancers were restaged according to current staging criteria. Actuarial survival and recurrence-free survival rates from the two patient eras were compared with each other and with published statistics for older breast cancer patients. RESULTS: Eligibility criteria were met by 81 women from the 1950-1969 era and 146 women from the 1970-1989 era. Histologic diagnoses, tumor sizes, incidence of axillary nodal metastases, number of positive nodes, and American Joint Committee on Cancer stage at presentation were similarly distributed in the two eras. Despite these similarities, improved survival (p = 0.009) was observed in the later era. Local recurrences were also more common (p < 0.05) in the later era in association with less extensive resections. These local recurrences had an adverse impact on recurrence-free survival in the later era, but no concomitant decrease in overall survival was observed. Node-positive patients who received chemotherapy demonstrated a trend toward improved survival (p = 0.06) compared with node-positive patients who did not. Survival for patients in the later era was similar to that for older women as reported in other published series. CONCLUSIONS: The stage of presentation of breast cancer in women 30 years or younger appears unchanged from prior decades, but survival has improved in association with the use of less extensive surgical resections and the introduction of cytotoxic chemotherapy. With current treatment, primary operable breast cancer in young women appears to have a similar prognosis to breast cancer in older women.

Condom use relative to knowledge of sexually transmitted disease prevention, method of birth control, and past or present infection.

The purpose of this study was to assess knowledge regarding STD spread and prevention, and to assess motivational and behavioral factors that influence the use of condoms to prevent STD acquisition among inner-city women at high risk for STD infection. In addition, the effect of past and/or current STD infection on a woman's knowledge of the mechanism of STD acquisition and subsequent use of a condom to prevent STD infection was explored. We utilized three inner-city clinics offering family planning or gynecologic care located in Brooklyn, New York. Our study linked clinical findings regarding current infection with chlamydia or Trichomonas vaginalis. One thousand four hundred and four sexually active black and Hispanic women participated in the study. A past history of STD (37%) or current infection (29%) was recorded for 54% of the study population (12% were positive for both past and current infection). On average, only 60% of women who reported prior treatment for STD infection reported receiving any information regarding prevention of re-infection during the course of treatment. Depending on the specific STD, from 6.8% to 42.9% of women reporting prior treatment for an STD did not know the disease they were being treated for was sexually transmitted. Condom use for disease prevention was more frequently reported by women who had previously been treated for an STD (OR = 1.62, 95% CI 1.23-2.13). However, condom use for contraception was a stronger predictor of use for STD prevention. Women who relied on condoms for contraception were almost 10 times more likely to also report condom use for STD prevention relative to women who did not use condoms for contraceptive purposes (OR = 9.71, 95% CI 7.0-13.5). In addition, condom use was associated with the perceived attitude of their sexual partner toward such use. Condom use to prevent STD acquisition was more than twice as frequently reported when a favorable attitude was perceived by a male sexual partner (OR = 2.30, 95% CI 1.54-3.43). Our findings suggest that prevention of unplanned pregnancy was a stronger motivator for condom use than disease prevention among the women comprising our study group. The findings also indicate the need for more extensive information regarding STD prevention among women at high risk for STD acquisition.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: A study was conducted among 1404 sexually active black and Hispanic women in three clinics offering family planning or gynecologic care in Brooklyn, New York, to assess levels of knowledge regarding the spread and prevention of sexually transmitted diseases (STD), as well as the motivational and behavioral factors which influence condom use to prevent STD acquisition among inner-city women at high risk for STD infection. The study also explored the effect of past and/or current STD infection upon a woman's knowledge of the mechanism of STD acquisition and subsequent use of a condom to prevent STD infection. The study linked clinical findings regarding current infection with chlamydia or Trichomonas vaginalis. A past history of STD (37%) or current infection (29%) was recorded for 54% of the study population. Overall, only 60% of women who reported prior treatment for STD infection reported receiving any information on preventing reinfection during the course of treatment. Depending upon the specific STD, 6.8-42.9% of the women reporting prior treatment for STD infection did not know the disease for which they were being treated was transmitted sexually. Further, condom use was more frequently reported by women who been previously treated for a STD. Women who relied upon condoms for contraception were almost ten times more likely to also report condom use for STD prevention relative to women who did not use condoms for contraception. Condom use to prevent against STDs also was more than twice as frequently reported when a favorable attitude was perceived by a male sex partner.

Method of tumor detection influences disease-free survival of women with breast carcinoma.

BACKGROUND: Screening mammography provides the primary means of reducing breast cancer mortality. Clinical breast examination (CBE) and breast self-examination (BSE) may be complementary screening modalities enabling palpation of interval cancers and detection of tumors not visualized by mammography; however, their combined contribution to improving prognosis has not been evaluated adequately. METHODS: Disease-free survival was assessed in relation to method of tumor detection among 729 consecutive patients treated by mastectomy and axillary dissection for primary breast carcinoma between 1976 and 1978. RESULTS: Disease-free survival at 10 years was significantly higher after detection by mammography (77% of 30 patients) or CBE (78% of 101 patients) compared to self-detection (64%). The hazard ratio of recurrence associated with clinical examination or mammography in contrast to self-detection was significantly reduced to 0.55 (95% CI, 0.37-0.81; P = 0.001). In addition, annual CBE, compared to less frequent clinical palpation, reduced the risk of recurrence controlling for detection modality (P = .03). In multivariate analyses, the method of detection and frequency of clinical breast examination remained statistically significant prognostic factors after controlling for number of screening mammograms, history of prior breast surgery, family history of breast cancer, and age at diagnosis. Differences in self-examination frequency were not associated with prognosis. CONCLUSIONS: Among patients diagnosed before widespread mammography screening, tumor detection by CBE was associated with a significant reduction in recurrence compared with detection by self-palpation. Improvement in the frequency and quality of CBE and BSE may enhance the contribution of these modalities to early detection, complementing the role of screening mammography in reducing breast cancer mortality rates.

Menstrual timing of treatment for breast cancer.

Although the hormone dependency of breast cancer has been recognized for nearly a century, the influence on disease progression of cyclical hormonal levels among premenopausal women has not been extensively researched. The findings of recent studies, assessing the effect on prognosis of the hormonal milieu at the time of surgery, have been conflicting. However, several reports have noted improved survival among patients with positive, axillary lymph nodes surgically treated in the later phase of the menstrual cycle when progesterone levels are elevated. Biologic support for the influence of menstrual timing is provided by cyclical patterns of cell division and cell death observed in normal breast tissue as well as potential tumor cell dissemination during surgery among patients with positive axillary nodes. Immune parameters, which also respond to cycling endogenous hormones, may influence the metastatic potential of circulating tumor cells. Comparisons among studies of menstrual timing of surgery have been complicated by differences in cycle divisions, extent of primary surgery, frequency of adjuvant therapy, duration of follow-up, and analytic procedures. Although several clinicians are now scheduling breast surgery of premenopausal women in relation to day of the menstrual cycle, a majority of surgeons have deferred consideration of menstrual timing until additional research is available. While waiting 5-10 years for the results of prospective studies, additional retrospective analyses, using carefully collected data, may provide clinical guidance. With increasing concern for issues related to women's health, multidisciplinary studies will be required to adequately characterize the influence of the menstrual cycle and other aspects of women's reproductive physiology on breast cancer and other medical conditions.

Is breast size a predictor of breast cancer risk or the laterality of the tumor?

The relationship of breast size both to breast cancer risk and to the laterality of the tumor was studied among 261 women diagnosed with breast cancer and 291 control subjects who were enrolled in the United States' Breast Cancer Detection and Demonstration Project from 1973 to 1980. Standardized measures of breast area were obtained by applying planimetry to bilateral screening mammograms taken four years before breast cancer was diagnosed in case subjects. The left breast was larger in 53 percent of women with breast cancer and in 60 percent of women in the control group; the difference in breast area by laterality was significant only among controls (P = 0.01). To assess breast cancer risk, breast area was categorized by quartiles, with the lowest quartile being the referent group. Risk was increased minimally among women with the largest breast area (odds ratios = 0.9, 0.9, 1.2); however, the point estimates were not statistically significant and there was no evidence of a linear trend. Left-sided diseased was diagnosed in 51 percent of women in the case group. Although the mean area of the breast with the malignancy did not differ significantly from the opposite breast, cancer developed in the larger breast of 57 percent of women with left- and 46 percent of women with right-sided disease. Breast size was associated with cancer of the left breast but not the right. However, these size differences were small since the area of the larger breast was less than 10 percent greater than the smaller breast among half of the case subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between HIV infection and cervical neoplasia: implications for clinical care of women at risk for both conditions.

OBJECTIVE: Both AIDS and cervical neoplasia (CN) can result from sexual transmission of HIV infection and may affect similar groups of women. Available data on the association between AIDS and CN have practical implications for gynecological care. We review these data to provide an estimate of the magnitude of the association between CN and HIV infection. DESIGN: Twenty-one studies were reviewed, including reports and abstracts published from January 1986 to July 1990. Of these, five included a comparison group and had sufficient data for inclusion in the analysis. RESULTS: All five controlled studies reported a significant association between HIV infection and CN. One included women with both intraepithelial and invasive lesions; the other four considered women with intraepithelial lesions only. The summary odds ratio indicated that the odds of HIV-infected women having CN are 4.9 (95% confidence interval, 3.0-8.2) times that of HIV-negative women. CONCLUSIONS: Research is needed to clarify etiological relationships and the role of human papillomavirus in the causal pathway of the observed association. Meanwhile, available data are sufficient to encourage regular Papanicolaou's smear screening of HIV-infected women, and HIV testing and counseling of women with CN considered at risk for HIV infection.

Obesity at diagnosis of breast carcinoma influences duration of disease-free survival.

OBJECTIVE: To study disease-free survival at 10 years in relation to obesity at the time of diagnosis. DESIGN: A prospective study of consecutively treated patients with primary breast cancer. SETTING: Memorial Sloan-Kettering Cancer Center, New York. PATIENTS: Nine hundred twenty-three women treated by mastectomy and axillary dissection. MAIN RESULTS: Women who were obese (25% or more over optimal weight for height) at the time of primary breast cancer treatment were at significantly greater risk for recurrence (42%) compared with nonobese patients (32%) 10 years after diagnosis (P less than 0.01). In multivariate analyses, obesity remained a statistically significant prognostic factor after controlling for measured tumor size, number of positive axillary lymph nodes, age at diagnosis, and adjuvant chemotherapy with a hazard ratio of 1.29 (95% CI, 1.0 to 1.67). When analyses were restricted to the 557 patients free of lymph node metastases, the hazard ratio of recurrence associated with obesity was 1.59 (CI, 1.06 to 2.39); 32% of obese patients developed recurrent disease compared with 19% of nonobese women. CONCLUSIONS: Obesity at the time of diagnosis is a significant prognostic factor that may limit the reduction in breast cancer mortality attainable through detection at an early stage of disease. Because obesity and the risk for breast cancer increase with age, interventions that encourage weight control may influence breast cancer survival rates.

Timing of breast cancer excision during the menstrual cycle influences duration of disease-free survival.

OBJECTIVE: To study disease-free survival at 10 years in relation to timing of breast tumor excision during the menstrual cycle. DESIGN: A prospective study of consecutively treated patients with primary breast cancer. SETTING: Memorial Sloan-Kettering Cancer Center, New York. PATIENTS: Two hundred and eighty-three premenopausal patients treated by mastectomy and axillary dissection. MAIN RESULTS: When the tumor was excised during the follicular phase, approximated by setting the putative day of ovulation on day 14 after the onset of last menses, a higher recurrence risk (43%) was observed compared with excision later in the menstrual cycle (29%, P = 0.02). The rate peaked among patients treated between days 7 and 14 and was lowest between days 20 and 30. Multivariate analysis using the Cox regression model to control for tumor size, nodal status, estrogen receptor status, adjuvant chemotherapy, and family history indicated that the hazard rate of breast cancer recurrence after excision during the follicular phase was 1.53 (95% Cl, 1.02 to 2.29). Stratification by nodal status indicated that the effect of phase was statistically significant only among patients with positive nodes (hazard ratio, 2.10; Cl, 1.19 to 3.70). CONCLUSIONS: Our results support the hypothesis that the risk for recurrence may be affected by the hormonal milieu of the menstrual cycle; these findings must be confirmed, however, by a prospective study in which cycle phase at time of tumor excision is biochemically documented.

Evaluation of glare in normal and pseudophakic subjects.

It has been difficult to document the subjective complaint of glare. Devices to quantify this problem include the Miller-Nadler glare tester (MNGT) and the brightness acuity tester (BAT). We used these devices to evaluate a group of pseudophakic subjects (15 eyes with posterior-chamber intraocular lenses) and a group of normal subjects (32 low myopic eyes). A subject's ability to discern contrast with a background glare source is measured as a percentage with the MNGT. The number of lines lost on the Snellen chart as a light is brightened progressively over the line of vision is the BAT score. A Wilcoxon signed-ranks test showed no significant change without correction (SC) to with correction (CC) with the BAT but was significant at P less than .001 with the MNGT. The BAT scores for the normal group CC (mean, 0.59) compared with the intraocular lens group CC (mean, 3.0) with the Mann-Whitney U test showed a statistically significant difference (P less than .001). There also was a difference with the MNGT between normal group CC (mean, 5.1%) and pseudophakic group CC (mean, 8.9%) at P less than .001). These results suggest that pseudophakic subjects have marked visual dysfunction secondary to glare. The BAT, however, showed a more easily quantifiable change unaffected by spectacle correction.

The relationship between body mass and breast cancer among women enrolled in the Cancer and Steroid Hormone Study.

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.

Atypical carcinoid tumor of the larynx. A critical review of the literature.

To better characterize the clinical and pathological features of the laryngeal atypical carcinoid (LAC), 127 of the published cases were analyzed. The LAC had a predilection for males (3 m:1 f), with a peak incidence in the 6th and 7th decades of life. Seventy-eight percent of patients with a relevant clinical history were smokers. Most tumors presented in the supraglottic larynx (96%) and the mean size of the measured primary lesions was 1.6 cm. The tumors were frequently argyrophil (97% of those so stained), rarely argentaffin (2 cases), and on immunohistochemistry were often reactive when stained for keratins (96%), chromogranin A (94%), and calcitonin (80%). Surgical resection was the principal modality of treatment. Of the 127 cases, metastasis to neck nodes were found in 43%, to skin or subcutaneous sites in 22%, and to distant sites in 44%. Of the 119 patients with follow-up, 49% died with tumor. The cumulative proportion surviving was 48% at 5 years and 30% at 10 years, and there were significantly worse survival rates among patients with tumors larger than 1 cm, and for patients developing tumor involvement of skin and subcutaneous tissues. Adjuvant radiation did not affect survival rates.