Charles R. Key

Prognostic factors for thyroid carcinoma

A number of prognostic factors for thyroid carcinoma have been identified, including sociodemographic characteristics, such as age and gender, and tumor characteristics, such as histology and stage. The relative importance of these factors as independent predictors of survival for patients with papillary, follicular, anaplastic, and medullary thyroid carcinoma has been extensively studied but remains uncertain.

Human Papillomavirus Genotype Distributions: Implications for Vaccination and Cancer Screening in the United States

Background Limited data are available describing human papillomavirus (HPV) genotype distributions in cervical cancer in the United States. Such studies are needed to predict how HPV vaccination and HPV-based screening will influence cervical cancer prevention. Methods We used the New Mexico Surveillance, Epidemiology, and End Results Registry to ascertain cases of in situ (n = 1213) and invasive (n = 808) cervical cancer diagnosed during 1985–1999 and 1980–1999, respectively, in the state of New Mexico. HPV genotyping was performed using two polymerase chain reaction–based methods on paraffin-embedded tissues from in situ and invasive cancers and on cervical Papanicolaou test specimen from control subjects (ie, women aged 18–40 years attending clinics for routine cervical screening [n = 4007]). Relative risks for cervical cancer were estimated, and factors associated with age at cancer diagnosis and the prevalence of HPV genotypes in cancers were examined. Results The most common HPV genotypes detected in invasive cancers were HPV type 16 (HPV16, 53.2%), HPV18 (13.1%), and HPV45 (6.1%) and those in in situ cancers were HPV16 (56.3%), HPV31 (12.6%), and HPV33 (8.0%). Invasive cancer case subjects who were positive for HPV16 or 18 were diagnosed at younger ages than those who were positive for other carcinogenic HPV genotypes (mean age at diagnosis: 48.1 [95% confidence interval {CI} = 46.6 to 49.6 years], 45.9 [95% CI = 42.9 to 49.0 years], and 52.3 years [95% CI = 50.0 to 54.6 years], respectively). The proportion of HPV16-positive in situ and invasive cancers, but not of HPV18-positive cancers, declined with more recent calendar year of diagnosis, whereas the proportion positive for carcinogenic HPV genotypes other than HPV18 increased. Conclusions HPV16 and 18 caused the majority of invasive cervical cancer in this population sample of US women, but the proportion attributable to HPV16 declined over the last 20 years. The age at diagnosis of HPV16- and HPV18-related cancers was 5 years earlier than that of cancers caused by carcinogenic HPV genotypes other than HPV16 and 18, suggesting that the age at initiation of cervical screening could be delayed in HPV-vaccinated populations.

Stage at Diagnosis of Cancer Varies With the Age of the Patient

The stage of a cancer at diagnosis is multiply determined, theoretically depending on such disparate factors as tumor biology, patient education, and physician behaviors. Data from all Hispanic and non‐Hispanic white residents of New Mexico diagnosed with a malignancy from 1969 through 1982 were analyzed to determine the relationship between the age of the patient and the stage of cancer at the time of diagnosis. Three general patterns were apparent. For cancers of the bladder, breast, cervix, ovary, thyroid, and uterus, and for melanoma, there were significant linear trends for the cancers to be diagnosed at more advanced stages in older patients. For cancers of the lung, pancreas, rectum, and stomach, there were significant linear trends for cancers to be diagnosed at an earlier stage in older patients. For cancers of the colon, kidney, liver, and prostate, there were no significant linear trends in stage at diagnosis versus age of the patient.

Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study

A forensic autopsy series of 519 women more than 14 years old was studied for prevalence of benign, atypical, and occult malignant breast lesions. The women included Anglos (non‐Hispanic whites), Hispanics, and American Indians from New Mexico and Eastern Arizona. These three ethnic/racial groups are at markedly different risk for the development of breast cancer (Anglo 89 of 100,000) women per year, Hispanic 45.5, and American Indian 24.9. There were striking ethnic/racial and age‐related differences in both the prevalence and magnitude of all forms of nonproliferative and proliferative fibrocystic disease. The various subsets of fibrocystic disease were highly associated with each other. Such lesions as apocrine metaplasia, sclerosing adenosis, and lobular microcalcification showed as much difference according to ethnic/racial background and age as the more common cystic change and duct epithelial hyperplasia. Atypical lobular and ductal hyperplasia, carcinoma fit situ, and occult invasive carcinoma were uncommon and also occurred in ethnic/racial groups in a pattern that parallels the cancer risk in those groups.

Discrepancy between Consensus Recommendations and Actual Community Use of Adjuvant Chemotherapy in Women with Breast Cancer

Context National Institutes of Health consensus guidelines recommend adjuvant chemotherapy for premenopausal or postmenopausal women with node-positive tumors or node-negative breast tumors greater than 1 cm, regardless of hormone receptor status. The actual (and age-specific) use of chemotherapy in women with breast cancer is unknown. Contribution Using data from the New Mexico Tumor Registry, these investigators show that chemotherapy is used much less frequently than recommended and that frequency decreases sharply with advancing age. Implications Since only a minority of postmenopausal women receive adequate treatment for breast cancer, many unnecessary deaths could probably be prevented by following the National Institutes of Health guidelines. The Editors Although the efficacy of chemotherapy in prolonging survival for women with breast cancer has been well documented (1-12), limited population-based information is available on the actual use of chemotherapy. Some hospital-based surveys of breast cancer have examined the use of chemotherapy (13-15), but the completeness of information has been questioned because chemotherapy is frequently administered in outpatient settings. The evolution of recommendations about the use of adjuvant chemotherapy in women with early breast cancer is illustrated by the National Institutes of Health (NIH) consensus development conferences (1, 3, 12). In 1985, the consensus conference recommended chemotherapy for premenopausal women with lymph nodepositive cancer (1). By 1990, the consensus conference recommended chemotherapy for both premenopausal and postmenopausal women with lymph nodepositive cancer and for women with cancer confined to the breast but with poor prognostic features, such as large size or negative hormone receptor status (3). The 2000 consensus conference extended the recommendation of chemotherapy to premenopausal and postmenopausal women with node-positive tumors or with node-negative tumors greater than 1 cm in size, regardless of hormone receptor status (12). Because limited information is available from clinical trials of chemotherapy in women 70 years of age and older, none of the consensus conferences made specific recommendations for that age group, other than to invoke individual decisions based on clinical circumstances and patient preferences. We recently reported on chemotherapy use in women age 65 years and older by using the Surveillance, Epidemiology, and End Results (SEER) tumor registry data linked to Medicare data (16, 17). As expected, chemotherapy use sharply decreased in women older than 70 years of age, and women with higher-stage, larger, or estrogen receptornegative tumors were more likely to receive chemotherapy (16, 17). We review the use of chemotherapy in women residing in New Mexico who were 20 years of age or older and received a diagnosis of breast cancer between 1991 and 1997. We hypothesized that chemotherapy use would not vary by age in women younger than 65 years of age who have tumor characteristics for which chemotherapy is generally recommended. Furthermore, we hypothesized that use of chemotherapy would vary by age with highest use in younger women (<45 years of age) among women who had tumors with characteristics for which no clear consensus recommendations had been made. Methods Data Source The New Mexico Tumor Registry is a statewide, population-based tumor registry that was established in 1966; it is one of the seven original members of the SEER registry (18). New Mexico residents who are given a diagnosis and treated at facilities outside the state are identified through data exchange with surrounding state registries in Colorado, Arizona, Utah, and Texas; in addition, information is obtained from the New Mexico Bureau of Vital Records and Health Statistics and from pathology laboratories and hospitals that operate close to New Mexico borders (19). Patients We examined data on 5101 patients age 20 years or older with a diagnosis of stage I, stage II, or stage IIIA breast cancer (using the American Joint Committee on Cancer staging system) from 1991 through 1997 (19, 20). We restricted our analyses to these stages because chemotherapy is considered the primary treatment for higher cancer stages rather than an adjuvant treatment. The Institutional Review Boards of the University of Texas Medical Branch and the University of New Mexico approved this study. Chemotherapy Information on chemotherapy was coded as follows (20): 0 = none (n = 4093); 1 = chemotherapy, not otherwise specified (n = 158); 2 = chemotherapy, single agent (n = 34); 3 = chemotherapy, multiple agents or combination regimen (n = 1504); 4 to 6 = not used for coding; 7 = patient or patients guardian declined chemotherapy (n = 81); 8 = chemotherapy recommended but actual administration unknown (n = 77); and 9 = unknown (n = 0). For our analyses, we recoded 1, 2, 3, and 8 as having received chemotherapy; 0 and 7 were recoded as having not received chemotherapy. The pattern of the results did not change if we recoded category 8 as not receiving chemotherapy or if we excluded the 77 cases in category 8 from the analysis. Hormone Therapy Information on hormone therapy was coded as follows (20): 0 = none (n = 3435); 1 = hormones, not otherwise specified, including antihormones (n = 1568); 2 = endocrine surgery or endocrine radiation (n = 5); 3 = combination of 1 and 2 (n = 0); 4 to 6 = not used for coding; 7 = patient or patients guardian declined hormone therapy (n = 26); 8 = hormone therapy recommended but actual administration unknown (n = 65); and 9 = unknown (n = 2). For our analyses, we recoded 1, 2, 3, 8, and 9 as having received hormone therapy; 0 and 7 were recoded as not having received hormone therapy. The pattern of the results did not change if we recoded 8 and 9 as not having received hormone therapy or if we excluded the 67 cases in categories 8 and 9 from the analysis. Statistical Analysis Our analytical strategy had three components. First, we examined the overall and age-specific rate (percentage) of chemotherapy use. The percentage of women receiving chemotherapy was a ratio of the number of women who received chemotherapy to the total number of women with a diagnosis of breast cancer. We used the MantelHaenszel chi-square test for trend to obtain the change in use of chemotherapy with age (21). Second, we used multivariable logistic regression analysis to generate the odds ratio of receiving chemotherapy in women with breast cancer and to determine the effect of age (Table 1) on chemotherapy use. In this model, we adjusted for race (white, black, or others), tumor stage (stage I, stage II, or stage IIIA), node status, hormone receptor status (Table 2), whether the patient had received surgery and radiation therapy (categorized as breast-conserving surgery without radiation, breast-conserving surgery with radiation, or mastectomy), and adjuvant hormone therapy use (yes or no). Table 1. Use of Chemotherapy in Women with Breast Cancer from 1991 through 1997 in New Mexico, by Patient Age and Tumor Stage Table 2. Use of Adjuvant Chemotherapy in Women with Stage I, Stage II, or Stage IIIA Breast Cancer from 1991 through 1997 in New Mexico by Age, Lymph Node Status, and Hormone Receptor Status In addition to odds ratios, we generated the probabilities of receiving chemotherapy from the parameters of the logistic regression for women with different ages by holding other factors constant. We used the method described by Hosmer and Lemeshow. Finally, we performed sensitivity analyses to assess the potential effects of unmeasured confounders on the associations observed between age and chemotherapy use (23). The method developed by Greenland (23) for dichotomous exposure and confounding variable was expanded to accommodate the eight-level exposure variable for age groups. The prevalence of the unmeasured confounding variable was dichotomized at different age cut-points (ages younger than the cut-point had one prevalence rate and ages greater than or equal to the cut-point had another). Over the different prevalence levels, the odds ratio between the unmeasured confounder and chemotherapy ranged from 1.5 to 10.0. We then generated multivariable logistic regression models (which included this unmeasured confounding variable) to determine the effect of unmeasured factors on the result. All computer programming and analyses were done by using SAS software (SAS Institute, Inc., Cary, North Carolina) (21). Role of the Funding Source The National Cancer Institute of the National Institutes of Health and the Sealy and Smith Foundation funded this project but had no role in the collection, analysis, and interpretation of the data or in the decision to submit the paper for publication. Results Among 5101 women with stage I, stage II, or stage IIIA breast cancer diagnosed from 1991 through 1997 in New Mexico, age at diagnosis ranged from 20 to 98 years; the mean age was 61 years. Table 1 presents the percentage of women receiving chemotherapy by tumor stage and patient age. Overall, 29% of women received chemotherapy, and the rate of chemotherapy use for stage I, stage II, and stage IIIA was 11%, 47%, and 68%, respectively. Across all tumor stages, the use of chemotherapy decreased substantially with increasing age (P < 0.001 for trend). Overall, 66% of women younger than 45 years of age received chemotherapy compared with 44% of women between 50 and 54 years of age, 31% of women between 55 and 59 years of age, and 18% of women between 60 and 64 years of age. Only 12% of women between 65 and 69 years of age and 3% of those older than 75 years of age received chemotherapy. Table 2 presents the use of chemotherapy by patient age, lymph node status, and hormone receptor status in women with stage I, stage II, or stage IIIA breast cancer. As expected, chemotherapy was used more often in women with node-positive tumors and women with estrogen receptornegative

Uranium mining and lung cancer in Navajo men.

We performed a population-based case-control study to examine the association between uranium mining and lung cancer in Navajo men, a predominantly nonsmoking population. The 32 cases included all those occurring among Navajo men between 1969 and 1982, as ascertained by the New Mexico Tumor Registry. For each case in a Navajo man, two controls with nonrespiratory cancer were selected. Of the 32 Navajo patients, 72 per cent had been employed as uranium miners, whereas no controls had documented experience in this industry. The lower 95 per cent confidence limit for the relative risk of lung cancer associated with uranium mining was 14.4. Information on cigarette smoking was available for 21 of the 23 affected uranium miners; eight were nonsmokers and median consumption by the remainder was one to three cigarettes daily. These results demonstrate that in a rural nonsmoking population most of the lung cancer may be attributable to one hazardous occupation.

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Pagets disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.

Metastases from occult thyroid carcinoma. An autopsy study from Hiroshima and Nagasaki, Japan

In an autopsy series in Hiroshima and Nagasaki, Japan, cervical lymph node dissections were performed in 128 autopsy cases in which occult papillary thyroid carcinoma had been found, and metastatic carcinoma was demonstrated in 20 cases (16%). These 20 cases with metastatic carcinoma, and an additional 25 occult papillary thyroid carcinomas previously known to have metastases, were compared with the 108 cases which had lymph node dissections negative for metastatic thyroid carcinoma. Significantly increased lymph node metastases occurred in association with the following changes in the the thyroid gland: multiple tumor foci, larger tumor size, greater tumor invasiveness, more than 50% papillary differentiation, and tumor psammoma bodies. Metastases were significantly more frequent in men than in women. In 5 of the 25 additional cases, only the cervical lymph node metastases and no tumor in the thyroid glands were found at routine autopsy. Special thyroid reexamination revealed the small primary carcinomas. In this autopsy series, no thyroid follicle inclusions have been found in cervical lymph nodes in the absence of a primary thyroid carcinoma. The metastases were generally occult, and sometimes multiple, contralateral, and bilateral. In the entire autopsy series, only one occult thyroid carcinoma was the cause of death; 517 other persons with occult papillary carcinoma of the thyroid reached the end of their lifespan without awareness or manifestation of the presence of the tumor.

Ischemic heart disease mortality in Hispanics, American Indians, and non-Hispanic whites in New Mexico, 1958-1982.

To describe trends in mortality from ischemic heart disease in New Mexicos Hispanic, American Indian, and non-Hispanic white populations, we used vital records data collected from 1958 through 1982. We calculated age-adjusted and age-specific mortality rates for ischemic heart disease for each of the states principal ethnic groups. Death certificate data were used in combination with population estimates based on the censuses of 1960, 1970, and 1980. Age-adjusted mortality rates for ischemic heart disease among Hispanics, American Indians, and non-Hispanic white men were consistent with nationwide patterns of rising mortality rates during the 1960s followed by declining rates. Mortality rates from ischemic heart disease in all three ethnic groups in New Mexico were lower than national rates for whites. Rates for Hispanics in New Mexico were lower than for non-Hispanic whites; rates for American Indians were the lowest among the three groups. These data support previous observations that Hispanics and American Indians in the Southwest are at decreased risk for mortality from ischemic heart disease in comparison with U.S. whites.

External Validation of Medicare Claims for Breast Cancer Chemotherapy Compared With Medical Chart Reviews

Background:Although Medicare claims data have been increasingly used to examine the patterns and outcomes of cancer chemotherapy, their external validity has not been well studied. Objectives:We sought to validate Medicare claims for chemotherapy compared with medical chart reviews. Patients and Methods:We completed medical chart reviews for 1228 women who were diagnosed with breast cancer at age 65 and older between 1993 and 1999 in New Mexico that were linked with Medicare claims data, achieving an estimated sensitivity of more than 90% and a 0.05 level of precision. Results:Of the 150 subjects identified by Medicare claims as receiving chemotherapy within 6 months of diagnosis, 75% were confirmed by medical records as having received chemotherapy. Of the remaining 25% of cases without chart verification, (1) 33 cases had 7 or more claims for chemotherapy and also had specific chemotherapy drugs indicated in Medicare data, representing 22% (33/150) of all cases that received chemotherapy according to Medicare claims and (2) 4 cases had 1 to 6 claims for chemotherapy, representing 3% (4/150) of all cases with claims for chemotherapy. Of those 1078 subjects who did not receive chemotherapy according to Medicare claims, more than 99% were confirmed by chart reviews. Observed agreement on chemotherapy between Medicare claims and chart reviews was 94% and overall reliability (kappa) was 0.69 (95% confidence interval = 0.63–0.76). Conclusions:Of cases identified as receiving chemotherapy by Medicare claims, 97% had strong evidence and only 3% had weak evidence for receiving this therapy.