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K E Malone

Publications and source records attributed to K E Malone.

At least 19 recordsLinked to original sources
PubMed2003

ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer.

Recent reports suggest that two ATM gene mutations, 7271T>G and IVS10-6T>G, are associated with a high risk of breast cancer among multiple-case families. To assess the importance of these two mutations in another 'high-risk' group, young women (under age 51) with multiple primaries, we screened a large population-based series of young women with bilateral breast cancer and compared the frequency of these mutations among similar women diagnosed with unilateral breast cancer. The 1149 women included were enrolled in an ongoing population-based case-control study of the genetic factors that contribute to bilateral breast cancer; they were not selected on the basis of family history of cancer. Screening for 7271T>G and IVS10-6T>G ATM gene mutations was conducted using DHPLC followed by direct sequencing. The 7271T>G mutation was detected in one out of 638 (0.2%) women with unilateral breast cancer and in none of the bilateral cases, and the IVS10-6T>G mutation in one out of 511 (0.2%) bilateral and in eight out of 638 (1.3%) unilateral breast cancer cases. Carriers of either mutation were not limited to women with a family history. Given the likelihood that young women with bilateral breast cancer have a genetic predisposition, the observed mutation distribution is contrary to that expected if these two mutations were to play an important role in breast carcinogenesis among individuals at high risk.

Adult↗
PubMed2003

Epidemiologic and molecular risk factors for contralateral breast cancer among young women.

Women diagnosed with a first breast cancer before the age of 45 years have a greater than 5.0-fold risk of developing a second primary contralateral breast cancer (CBC) than women in the general population have of developing a first breast cancer. Identifying epidemiologic or molecular factors that influence CBC risk could aid in the development of new strategies for the management of these patients. A total of 1285 participants in two case-control studies conducted in Seattle, Washington, who were 21-44 years of age when diagnosed with a first invasive breast carcinoma from 1983 to 1992, were followed through December 2001. Of them, 77 were diagnosed with CBC and 907 tumour tissues from first cancers were analysed. Women with body mass indices (BMIs) >/=30 kg m(-2) had a 2.6-fold greater risk (95% CI: 1.1-5.9) of CBC compared to women with BMIs </=19.9 kg m(-2). Women whose first tumour was c-erbB-2 positive had a 1.7-fold (95% CI: 1.0-3.0) excess CBC risk. Body mass index and c-erbB-2 expression may be risk factors for CBC in young women. Further observational studies are needed to confirm these findings and to evaluate whether testing for c-erbB-2 in this population may help identify those at high risk for CBC.

Adult↗
PubMed2003

Hormonal content and potency of oral contraceptives and breast cancer risk among young women.

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.

Adult↗
PubMed2001

Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma.

BACKGROUND: Obesity has been shown to affect breast carcinoma prognosis, with the heaviest women having a higher mortality due to breast carcinoma. Few studies have focused on premenopausal women or the correlation of body mass index (BMI) to tumor characteristics related to prognosis. METHODS: The authors conducted a population-based follow-up study for mortality of 1177 women younger than 45 years of age who had invasive ductal breast carcinoma diagnosed from 1983 through 1992. Histologic slides and/or tumor tissue were collected for pathologic review, immunohistochemistry assays, and bivariate flow cytometric analysis. RESULTS: Women with breast carcinoma who were in the highest quartile of BMI were 2.5 times as likely (95% confidence interval [CI], 1.6-3.9) to die of their disease within 5 years of diagnosis compared with women in the lowest quartile of BMI. The tumors of the women in the highest quartile of BMI were more likely to be estrogen receptor negative (odds ratio [OR], 1.5; 95% CI, 1.0-2.2) and to have a high S-phase fraction (OR, 1.9; 95% CI, 1.2-3.1), high histologic grade (OR, 1.7; 95% CI, 1.0-2.9), high mitotic cell count (OR, 2.0; 95% CI, 1.2-3.1), and large tumor size (2 to < 5 cm: OR, 2.3; 95% CI, 1.5-3.1; or > or = 5 cm: OR, 2.7; 95% CI, 1.5-4.8) compared with the tumors of women whose BMI was in the first quartile. Relative to the large tumors (> or = 2 cm) in women in the lowest BMI quartile, the large tumors in women in the highest BMI quartile were more likely to express markers of high proliferation, indicating they may have grown faster than similar size tumors of the thinnest women. In a multivariate analysis including the tumor characteristics, obesity, as measured by being in the highest quartile of BMI, remained an independent prognostic factor for mortality (hazard ratio, 1.7; 95% CI, 1.0-2.9; P < 0.05. CONCLUSIONS: Our study results indicated that being in the highest quartile of BMI was a strong predictor of mortality in women with breast carcinoma diagnosed at a young age. The tumors of the heavy women were larger and more likely to have markers of high cellular proliferation than those of thinner women.

Adult↗
PubMed2001

Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history.

BACKGROUND: An increased incidence of breast carcinoma has been reported among relatives of individuals who are affected with the rare recessive disorder, ataxia-telangiectasia (A-T), and who are heterozygous for mutations in the ataxia-telangiectasia mutated (ATM) gene. However, most studies of breast carcinoma cases from the general population have failed to find a higher incidence of ATM mutations in cases when compared with controls. METHODS: Genomic DNA samples from 258 individuals were screened for mutations of all types in each of the 62 coding exons of the ATM gene; 142 of these were from breast carcinoma cases with a first-degree family history or early age at diagnosis, 35 were from cases selected for the presence of either known disease-related mutations (n = 25) or missense alterations of unknown consequences (n = 10) in BRCA1 or BRCA2, and 81 were from matched controls. RESULTS: A total of 12 individuals with ATM mutations were identified, 11 among 142 breast carcinoma cases (7.7%; 95% CI, 3.9-13.4%) and 1 among 81 controls (1.2%; 95% CI, 0.0-6.7%) (P = 0.06). All mutations detected were of the missense type; none were predicted to truncate the ATM protein. Among cases, mutations were found exclusively in patients with a family history of breast carcinoma (12.1%; 95% CI, 6.2-20.6%) (P = 0.02). Similar frequencies of ATM mutations were found in 35 additional cases selected for the presence of BRCA1 or BRCA2 mutations when compared with cases overall. CONCLUSIONS: ATM mutations, specifically missense mutations, are more common in breast carcinoma cases selected for first-degree family history and early age at diagnosis.

Adult↗
PubMed2001

Body mass index and asthma in the military population of the northwestern United States.

BACKGROUND: Patients with asthma commonly have other medical problems such as obesity, but it is unclear if obesity independently relates to asthma occurrence. OBJECTIVE: To examine the association between asthma and obesity. METHODS: We studied enrollees aged 17 to 96 years in region 11 of TRICARE, a military managed health care program encompassing Washington, Oregon, and northern Idaho, using an enrollment questionnaire from January 1997 to December 1998. We performed case-control analyses on 2788 asthma cases and 39 637 controls. From these cases and controls, we selected a random sample of 1000 asthma cases and 1000 controls, linking them to a computerized military health record system to verify if medications indicated for asthma therapy were prescribed. After excluding cases not prescribed bronchodilator medications and excluding controls prescribed bronchodilator medications or steroids, we used logistic regression to estimate associations among asthma, body mass index, and demographic, lifestyle, and comorbid risk factors in 386 verified cases and 744 verified controls. RESULTS: Increasing body mass index, younger age, female sex, non-active duty beneficiary status, and arthritis were significant independent predictors of asthma prevalence in both our larger analysis and our verified substudy, whereas stomach ulcer, depression, hypertension, and white race are also independent predictors of asthma prevalence in our larger analysis. CONCLUSIONS: Increasing body mass index is a key factor predicting prevalence of asthma and, if determined to be etiologically related to asthma incidence, is a potentially modifiable risk factor for asthma.

Adolescent↗
PubMed2001

Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer.

BACKGROUND: Women diagnosed with breast cancer have a twofold to sixfold greater risk of developing contralateral breast cancer than women in the general population have of developing a first breast cancer. Tamoxifen therapy reduces this risk, but it is unclear if this benefit exists for both estrogen receptor (ER)-positive and ER-negative contralateral tumors. METHODS: Using data from a population-based tumor registry that collects information on the ER status of breast tumors, we followed 8981 women residing in western Washington State who were diagnosed with a primary unilateral invasive breast cancer during the period from 1990 through 1998 to identify cases of contralateral breast cancer. We restricted our analyses to women who were at least 50 years old and whose first breast cancer had a localized or regional stage; women who received adjuvant hormonal therapy but not chemotherapy (n = 4654) were classified as tamoxifen users, while those who received neither adjuvant hormonal therapy nor chemotherapy (n = 4327) were classified as nonusers of tamoxifen. By reviewing selected patient abstracts, we estimated that 94% of the subjects were classified correctly with respect to tamoxifen use. The risk of contralateral breast cancer associated with tamoxifen use was estimated with the use of Cox regression. All statistical tests were two-sided. RESULTS: Of the 89 tamoxifen users and 100 nonusers of tamoxifen diagnosed with contralateral breast cancer, 112 had ER-positive tumors, 20 had ER-negative tumors, and 57 had tumors with an ER status that was unknown or had not been determined by an immunohistochemical assay. The risk of developing an ER-positive and an ER-negative contralateral tumor among tamoxifen users was 0.8 (95% confidence interval [CI] = 0.5 to 1.1) and 4.9 (95% CI = 1.4 to 17.4), respectively, times that of nonusers of tamoxifen. This difference in risk by ER status was statistically significant (P<.0001). CONCLUSIONS: Tamoxifen use appears to decrease the risk of ER-positive contralateral breast tumors, but it appears to increase the risk of ER-negative contralateral tumors.

Age Factors↗
PubMed2001

Patterns and predictors of the breast cancer detection methods in women under 45 years of age (United States).

OBJECTIVES: Few studies have examined methods by which breast cancers are detected, and only one study has been published on predictors of those methods. This study examined patterns and predictors of breast cancer detection methods during 1990-1992 among women age 20-44. METHODS: In-person interview and medical record data were obtained during a population-based case-control study of 1619 women newly diagnosed with breast cancer in three areas of the United States (US). RESULTS: Seventy-one percent of the cancers were identified by self-detection, 9% by routine clinical breast exam (CBE), and 20% by routine mammography. Cancers detected by mammography and CBE, but not those detected by breast self-exam, were much more likely to be early-stage. Detection by mammography increased with age, and a history of mammography use was associated with detection by mammography or CBE. Several commonly studied predictors of screening utilization in the US population were associated with CBE detection, but were less clearly related to or unrelated to mammography detection. CONCLUSION: Findings suggest that, during the 1990s in the US, most breast cancers among women under age 45, including those age 40-44, were self-detected. Few factors other than age and prior screening are verified predictors of method of breast cancer detection.

Adult↗
PubMed2000

Case-control differences in the reliability of reporting a history of induced abortion.

The authors investigated the possibility that, in interview-based case-control studies, controls are more likely than cases to underreport a history of induced abortion. A case-control study was conducted in White women under 45 years of age who had given birth in Washington State during 1984-1994. The cases were women in three metropolitan counties of Washington State diagnosed with invasive breast cancer during 1984-1994; controls were selected through random digit dialing. A history of induced abortion among study participants was compared between interview data and information collected on the birth record of the last child to whom they gave birth (225 cases, 303 controls). Among women with a prior induced abortion recorded on the birth record, 14.0% of the 43 cases and 14.9% of the 47 controls did not report an induced abortion at interview (difference = -0.9%, 95% confidence interval of the difference: -15, 14). The authors' data do not suggest that controls are more reluctant to report a history of induced abortion than are women with breast cancer.

Abortion, Induced↗
PubMed2000

Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases.

BACKGROUND: There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population-based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes. METHODS: Subjects were drawn from two population-based, case-control studies of breast carcinoma in young women conducted in western Washington State and focused on 1) women diagnosed with breast carcinoma before age 35 years (n = 203); and 2) women with a first-degree family history of breast carcinoma who were diagnosed before age 45 years (n = 225). Similarities and differences between BRCA2 carriers and BRCA1 carriers were analyzed in terms of age at diagnosis, family history status, and disease features. RESULTS: Of cases diagnosed before age 35 years, all of whom were unselected for family history, 9.4% carried germline mutations (3.4% for BRCA2 and 5.9% for BRCA1). Of cases diagnosed before age 45 years who had a first-degree family history of breast carcinoma, 12.0% carried germline mutations (4.9% for BRCA2 and 7.1% for BRCA1). Increased frequencies of mutations were observed in cases with a personal or family history of early age at diagnosis and in those with four or more family members affected with breast carcinoma. BRCA2 mutations were less common than BRCA1 mutations in families with any history of ovarian carcinoma. CONCLUSIONS: Overall, given current constraints on health care resources, these data suggest that screening for germline mutations in these breast carcinoma susceptibility genes may have the greatest impact on overall health care if it is prioritized toward high and moderate risk populations.

Adult↗
PubMed2000

Assessing changes in ages at onset over successive generation: an application to breast cancer.

Decreased age at onset in successive generations has been observed for a number of diseases. Two nonparametric matched and unmatched test statistics are proposed, taking into account not only current age or age at death for unaffected individuals and age at disease onset for affected individuals, but also possible correlations among family members. Both are asymptotically normal with readily estimated variances from the data. A simulation study is conducted to compare the proposed tests with the commonly used paired t-test and log-rank test. It has been shown that the proposed test statistics yield valid conclusions in assessing genetic anticipation under all situations considered. However, the paired t-test is valid only when the censoring distributions are comparable between two generations, whereas the log-rank test is valid when the correlation among family members is weak. As expected, the matched test is most powerful when the data are heterogeneous, and the unmatched and the log-rank tests are most powerful when the data are homogeneous and the correlation is weak. Lastly, a population-based family study of breast cancer conducted at the Fred Hutchinson Cancer Research Center is used for illustration of the proposed and the log-rank tests. The preliminary analysis suggests that there appears a decreased age at onset over the successive generations in breast cancer.

Adolescent↗
PubMed2000

Characteristics of respondents and non-respondents from a case-control study of breast cancer in younger women.

BACKGROUND: This study assessed the nature of potential biases by comparing respondents with non-respondents from a case-control study of breast cancer in younger women. METHODS: The case-control study was conducted in three regions in the US: Atlanta GA, Seattle/Puget Sound WA, and central New Jersey. An abbreviated interview or mailed questionnaire was completed by willing non-respondents, most of whom had refused participation in the main study. RESULTS: Respondents and non-respondents appeared similar with respect to age, race, relative weight, smoking, family history of breast cancer, number of births, age at first birth, and several dietary items. Compared to non-respondents, case and control respondents were of shorter stature, and reported less frequent consumption of doughnuts/pastries. Respondent cases, compared with non-respondent cases, were more highly educated and more likely to have consumed alcohol regularly; similar but not statistically significant tendencies were observed for controls. Respondent cases experienced menarche earlier than non-respondents. Respondent controls were more likely to have used oral contraceptives than non-respondents; a similar but not statistically significant tendency was observed in cases. Comparisons of crude and simulated relative risks using available non-respondents' data generally showed a low impact of non-response on relative risks in this study. CONCLUSIONS: Our results suggest that non-response would not greatly affect relative risk estimates in this study, except possibly regarding height. However, we were limited by the numbers of informative non-respondents and the amount of data collected. Collecting similar information in future studies would be useful, especially since varying methods used to encourage participation may lead to differences in respondents' characteristics.

Adult↗
PubMed2000

Induced abortion in relation to breast cancer among parous women: a birth certificate registry study.

We wished to assess the relation of induced abortion to the subsequent incidence of breast cancer among parous women, using a design that would prevent the possibility of differentially complete reporting of abortion history by women with breast cancer and controls. Our study was conducted within a cohort of women who gave birth to a child during 1984-1994 while residing in 13 counties of western Washington. Cases were women from the cohort diagnosed with breast cancer between 1984 and 1994. From the remaining cohort members, five controls were matched to each woman with breast cancer by year of index birth (ie, the last child born before breast cancer diagnosis) and by age at delivery. We categorized 463 cases and 2,201 controls according to history of induced abortion as recorded on the index birth certificate. The risk of breast cancer was not found to be associated with a prior induced abortion (estimated relative risk (RR) = 0.9, 95% confidence interval (CI) 0.7-1.2). These results suggest that an induced abortion, if followed at some later time by pregnancy and childbirth, does not increase a woman's risk of breast cancer.

Abortion, Induced↗
PubMed1999

Stage of breast cancer in relation to body mass index and bra cup size.

Most studies on women with breast cancer indicate that obesity is positively associated with late-stage disease. Some results have shown a similar relationship between breast size and stage. A recent study found that the association between body mass index (BMI) and stage was limited to cancers that were self-detected, suggesting that the BMI-stage relation may be due to delayed symptom recognition. We examined the relationships between stage and both BMI and breast (bra cup) size, stratified by method of detection, using data from a population-based case-control study of 1,361 women (ages 20-44 years) diagnosed with breast cancer during 1990-1992. Height and weight measurements and information on bra cup size, method of cancer detection and other factors predictive of stage at diagnosis were collected during in-person interviews. A case-case comparison was conducted using logistic regression to estimate odds of regional or distant stage rather than local stage in relation to BMI and bra size. Odds of late-stage disease were increased with higher BMI [adjusted odds ratio (OR) for highest to lowest tertile = 1.46, 95% confidence interval (CI) 1.10-1.93] and larger bra cup size (OR for cup D vs. cup A = 1.61, 95% CI 1.04-2.48). These relationships were not modified by the method of detection. Differences in etiologic effects, rather than differences in detection methods, may explain the relations observed between stage and both BMI and breast size.

Adult↗
PubMed1999

Pregnancy after breast carcinoma: outcomes and influence on mortality.

BACKGROUND: To the authors' knowledge, no previous studies have identified an adverse effect of pregnancy on patient survival after breast carcinoma. However, results are difficult to interpret because of failure to control for stage of disease at the time the pregnancy occurred. METHODS: Study participants were women diagnosed with invasive breast carcinoma between 1983-1992 who previously had participated in a population-based case-control study or, if deceased, proxy respondents. Information regarding subsequent pregnancies was obtained by self-administered questionnaire or telephone interview. Information regarding breast carcinoma recurrences was obtained by questionnaire and from cancer registry abstracts. Women who became pregnant after a diagnosis of breast carcinoma (n = 53) were matched with women without subsequent pregnancies based on stage of disease at diagnosis and a recurrence free survival time in the comparison women greater than or equal to the interval between breast carcinoma diagnosis and onset of pregnancy in the women with a subsequent pregnancy. RESULTS: Sixty-eight percent of women who became pregnant after being diagnosed with breast carcinoma delivered one or more live-born infants. Miscarriages occurred in 24% of the patients who became pregnant compared with 18% of the controls (women without breast carcinoma) of similar ages from the case-control study. Five of the 53 women who had been pregnant after breast carcinoma died of the disease. The age-adjusted relative risk (RR) of death associated with any subsequent pregnancy was 0.8 (95% confidence interval [95% CI], 0.3-2.3). All five deaths occurred among the 36 women who had a live birth (age-adjusted RR = 1.1; 95% CI, 0.4-3.7). CONCLUSIONS: The findings of the current study are based on a small number of deaths but do not suggest that pregnancy after a diagnosis of breast carcinoma has an adverse effect on survival.

Adult↗
PubMed1999

Relation between obesity and breast cancer in young women.

This study was conducted to assess the relation between body size and risk of breast cancer among young women. A case-control study was conducted among women aged 21-45 years living in three counties in Washington State. Cases were women born after 1944 with invasive or in situ breast cancer that was diagnosed between January 1, 1983, and April 30, 1990. Controls were selected using random digit dialing and were frequency-matched to cases on the basis of age and county of residence. Interviews took place between 1986 and 1992. Body size was evaluated using indices from several different time periods. After adjustment for confounders, a decreased risk of breast cancer was found for women in the highest quintile of body mass index (weight (kg)/height (m)2) as compared with the lowest quintile (for maximum lifetime body mass index, odds ratio = 0.69, 95% confidence interval (CI) 0.51-0.94). Age modified the relation between body size and risk of breast cancer. The odds ratio for women in the highest quintile of maximum body mass index who were aged 21-35 years was 0.29 (95% CI 0.16-0.55), as compared with an odds ratio of 1.5 for women aged 36-45 years (95% CI 0.9-2.5) (p for interaction = 0.003). This study supports prior research showing a decreased risk of breast cancer associated with increased body size among premenopausal or young women. More detailed analysis in this study found a strong effect that was limited to the youngest age group (< or = 35 years).

Adult↗
PubMed1999

Hair product use and the risk of breast cancer in young women.

OBJECTIVES: The reported mutagenic and carcinogenic effects of some chemicals present in hair dyes have raised concern that hair dye use could increase breast cancer risk. This case-control study evaluated how detailed aspects of hair coloring and hair spray application by reproductive-age women may affect breast cancer risk. METHODS: Cases were white female residents of three counties of western Washington state 45 years of age or less, who were diagnosed with breast cancer between 1983 and 1990 (n = 844). A sample of similarly aged women residing in the same counties served as controls (n = 960). Information on hair coloring and hair spray use, as well as other exposures, was ascertained during in-person interviews. RESULTS: Breast cancer cases were slightly more likely than controls to report ever having used some type of hair coloring application, including use of rinses, semi-permanent or permanent dyes, as well as bleaching then dyeing or frosting their hair (relative risk [RR] = 1.3, 95% CI = 1.0-1.6, adjusted for age, fullterm pregnancies, family history of breast cancer, and weight). In subgroup analyses, women with exclusive use of just one of these methods of hair coloring application had no elevation in risk (similarly adjusted RR = 1.1, 95% CI = 0.9-1.3), whereas women who used two or more of these methods did have an elevated risk (RR = 1.9, 95% CI = 1.4-2.5). Hair spray use was not related to the risk of breast cancer (ever versus never users: RR = 1.0, 95% CI = 0.8- 1.3). CONCLUSION: The lack of an association between exclusive use of a single type of hair coloring application and breast cancer risk argues that hair coloring application does not influence breast cancer risk among reproductive-age women. Thus, the results of the present study, as well as negative ones from most (but not all) prior studies, are most consistent with the conclusion that neither hair coloring application nor hair spray application influences breast cancer risk.

Adult↗