Biomedical subjects

Michael S Simon

Publications and source records attributed to Michael S Simon.

At least 19 recordsLinked to original sources

PubMed2017

Reanalysis of BRCA1/2 negative high risk ovarian cancer patients reveals novel germline risk loci and insights into missing heritability.

While up to 25% of ovarian cancer (OVCA) cases are thought to be due to inherited factors, the majority of genetic risk remains unexplained. To address this gap, we sought to identify previously undescribed OVCA risk variants through the whole exome sequencing (WES) and candidate gene analysis of 48 women with ovarian cancer and selected for high risk of genetic inheritance, yet negative for any known pathogenic variants in either BRCA1 or BRCA2. In silico SNP analysis was employed to identify suspect variants followed by validation using Sanger DNA sequencing. We identified five pathogenic variants in our sample, four of which are in two genes featured on current multi-gene panels; (RAD51D, ATM). In addition, we found a pathogenic FANCM variant (R1931*) which has been recently implicated in familial breast cancer risk. Numerous rare and predicted to be damaging variants of unknown significance were detected in genes on current commercial testing panels, most prominently in ATM (n = 6) and PALB2 (n = 5). The BRCA2 variant p.K3326*, resulting in a 93 amino acid truncation, was overrepresented in our sample (odds ratio = 4.95, p = 0.01) and coexisted in the germline of these women with other deleterious variants, suggesting a possible role as a modifier of genetic penetrance. Furthermore, we detected loss of function variants in non-panel genes involved in OVCA relevant pathways; DNA repair and cell cycle control, including CHEK1, TP53I3, REC8, HMMR, RAD52, RAD1, POLK, POLQ, and MCM4. In summary, our study implicates novel risk loci as well as highlights the clinical utility for retesting BRCA1/2 negative OVCA patients by genomic sequencing and analysis of genes in relevant pathways.

Adult↗

PubMed2007

Risk of breast cancer associated with short-term use of oral contraceptives.

OBJECTIVE: To estimate breast cancer risk associated with short-term (<6 months) oral contraceptive use, and explore variation in estimates by use characteristics and medical, menstrual, and reproductive history. METHODS: We analyzed data from the Women's Contraceptive and Reproductive Experiences Study. Case subjects were white women and black women, 35-64 years old, diagnosed with invasive breast cancer in July 1994-April 1998. Control subjects identified by random-digit dialing were matched to case subjects by age, race, and study site. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Overall, short-term oral contraceptive use was not associated with breast cancer risk (OR = 1.0; 95% CI = 0.8-1.1). However, significant interaction between short-term use and menopausal status led to an observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI = 1.0-1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6-1.0) associated with short-term use. The association was more pronounced in women with non-contraceptive reasons for use and underlying risk factors for breast cancer. CONCLUSIONS: These associations may result from underlying characteristics of users or unmeasured factors influencing duration of use and breast cancer risk.

Adult↗

PubMed2006

Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years.

Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population.

Adult↗

PubMed2006

Breast cancer risk estimates for relatives of white and African American women with breast cancer in the Women's Contraceptive and Reproductive Experiences Study.

PURPOSE: Family history is a well-recognized risk factor for breast cancer. Familial aggregation and segregation analyses have estimated breast cancer risk based on family history primarily for white women; such information is limited for African American (AA) women. The purpose of this report is to update breast cancer risk estimates associated with a family history of breast cancer for white and AA women. METHODS: We used family cancer history from 2,676 white and 1,525 AA women with breast cancer (probands) in the population-based National Institute of Child Health and Human Development's Women's Contraceptive and Reproductive Experiences (CARE) Study to estimate age-specific breast cancer risks in their first degree adult female relatives. Cumulative hazard curves were calculated for relatives of all probands using Cox proportional hazards models, and were stratified by the proband's race and age at diagnosis and number of relatives affected. RESULTS: Breast cancer risks for white and AA women with a family history of the disease are similar through age 49 years, but diverge afterwards, with higher risks by age 79 in white women than in AA women (17.5% [SE, 0.9%] v 12.2% [SE, 1.1%]; P < .001). These risks increase as the number of affected first degree relatives increases, reaching 25.2% (SE, 3.4%) and 16.9% (SE, 4.0%) in white and AA women with more than one affected relative, respectively (P = .3). CONCLUSION: We found age-related racial differences in breast cancer risk in women with a family history of breast cancer and have updated risk estimates for white and AA women for clinical use.

Adult↗

PubMed2006

Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status.

PURPOSE: The extent to which socioeconomic disadvantages and inadequate health care access account for the disproportionately elevated mortality hazard observed in African American compared with white American patients with breast cancer is poorly defined. METHODS: We identified 20 studies reported between January 1980 and June 2005 that provided survival analyses in patients with breast cancer after adjusting for ethnicity and some measurement of socioeconomic status. These studies also adjusted for age and stage of disease at time of diagnosis. RESULTS: The pooled outcome data yielded estimates for the mortality hazard in 14,013 African American and 76,111 white American patients with breast cancer. Studies varied in their methods for assigning socioeconomic status, with most relying on area-wide measures such as census tract and census block data. The combined analysis (adjusted for age, stage, and socioeconomic status) revealed that African American ethnicity was associated with a statistically significant excess mortality risk in overall survival (mortality hazard, 1.27; 95% CI, 1.18 to 1.38) and in breast cancer-specific survival (mortality hazard, 1.19; 95% CI, 1.10 to 1.29). CONCLUSION: Our pooled analysis demonstrated that African American ethnicity is a significant and independent predictor of poor outcome from breast cancer, even after accounting for socioeconomic status by conventional measures. These findings support the need for further investigation of the biologic, genetic, and sociocultural factors that may influence survival in African American patients with breast cancer.

Black People↗

PubMed2006

Predictors of enrollment in lung cancer clinical trials.

BACKGROUND: Clinical trials may offer patients innovative therapeutic options with potentially better outcomes, which are particularly relevant for patients afflicted with lung carcinoma, because current therapies provide only modest survival benefits. Only approximately 5% of patients with newly diagnosed cancer participate in clinical trials nationwide, and African-American (AA) patients are particularly under-represented. METHODS: To determine predictors of clinical trials enrollment, the authors reviewed the medical records of 427 patients with lung carcinoma (175 AA patients and 252 non-AA patients) who were eligible for clinical trials between 1994 and 1998 at the Karmanos Cancer Institute in Detroit, Michigan. Logistic regression analysis was used to assess the association of patient demographic characteristics and clinical trial enrollment. RESULTS: Ninety-one patients (21%) were enrolled onto a lung cancer clinical trial during the period of the current study. Enrollment was associated significantly with race (P < 0.001), gender (P = 0.048), age (P = 0.005), and insurance type (P = 0.024). After multivariable adjustment, only race and gender remained significant predictors of enrollment. AA patients were less likely to enroll than non-AA patients (odds ratio [OR], 0.485; 95% confidence interval [95% CI], 0.243-0.966), and men were more likely than women to enroll (OR, 1.812; 95% CI, 1.033-3.178). CONCLUSIONS: The current results suggest disparities by race and gender in the enrollment of patients onto lung cancer clinical trials and support the need to improve educational and outreach endeavors that would make clinical trials available to a wider range of eligible patients.

Aged↗

PubMed2006

Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer.

BACKGROUND: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. METHODS: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. RESULTS: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. CONCLUSIONS: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer.

Adenocarcinoma, Mucinous↗

PubMed2005

Racial differences in breast cancer survival in the Detroit Metropolitan area.

African American (AA) women have poorer breast cancer survival compared to Caucasian American (CA) women. The purpose of this analysis was to determine whether socioeconomic status (SES) and treatment differences influence racial differences in breast cancer survival. The study population included 9,321 women (82% CA, 18% AA) diagnosed with local (63%) or regional (37%) stage disease between 1988 and 1992, identified through the Metropolitan Detroit SEER registry. Data on SES were obtained through linkage with the 1990 Census of Population and Housing Summary Tape and cases were geocoded to census block groups. Pathology, treatment and survival data were obtained through SEER. Cox proportional hazards models were used to compare survival for AA versus CA women after adjusting for age, SES, tumor size, number of involved lymph nodes, and treatment. AA women were more likely to live in a geographic area classified as working poor than were CA women (p<0.001). AA women were less likely to have lumpectomy and radiation and more likely to have mastectomy with radiation (p<0.001). After multivariable adjusted analysis, there were no significant racial differences in survival among women with local stage disease, although AA women with regional stage disease had persistent but attenuated poorer survival compared to CA women. After adjusting for known clinical and SES predictors of survival, AA and CA women who are diagnosed with local disease demonstrate similar overall and breast cancer-specific survival, while race continues to have an independent effect among women presenting at a later stage of disease.

Adult↗

PubMed2005

Lifetime recreational exercise activity and breast cancer risk among black women and white women.

BACKGROUND: Physical inactivity is a potentially modifiable breast cancer risk factor. Because few data on this relationship exist for black women, we examined the relationship between breast cancer risk and lifetime and time- or age-specific measures of recreational exercise activity among white women and among black women. METHODS: The Women's Contraceptive and Reproductive Experiences Study was a multicenter population-based case-control study of black women and white women aged 35-64 years with newly diagnosed invasive breast cancer. We collected detailed histories of lifetime recreational exercise activity during in-person interviews with 4538 case patients with breast cancer (1605 black and 2933 white) and 4649 control subjects (1646 black and 3033 white). Control subjects were frequency-matched to case patients on age, race, and study site. We examined associations between exercise activity measures (metabolic equivalents of energy expenditure [MET]-hours per week per year) and breast cancer risk overall and among subgroups defined by race, other breast cancer risk factors, and tumor characteristics by use of unconditional logistic regression. All statistical tests were two-sided. RESULTS: Among all women, decreased breast cancer risk was associated with increased levels of lifetime exercise activity (e.g., average MET-hours per week per year, P(trend) = .002). An average annual lifetime exercise activity that was greater than the median level for active control subjects was associated with an approximately 20% lower risk of breast cancer, compared with that for inactivity (for 6.7-15.1 MET-hours/week/year, odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.71 to 0.93; for > or =15.2 MET-hours/week/year, OR = 0.80, 95% CI = 0.70 to 0.92). The inverse associations did not differ between black and white women (for MET-hours/week/year, P(trend) = .003 and P(trend) = .09, respectively; homogeneity of trends P = .16). No modification of risk was observed by disease stage, estrogen receptor status, or any breast cancer risk factor other than first-degree family history of breast cancer. CONCLUSIONS: This study supports an inverse association between physical activity and breast cancer among black women and among white women.

Adolescent↗

PubMed2005

A comparison of record linkage yield for health research using different variable sets.

As part of a study on childbearing and survival, we linked records of young women with invasive breast cancer identified through three population-based cancer registries, to state birth certificate records. In Michigan prior to 1989, only maternal social security number (SSN) was available for matching; other data became available in 1989 including name, birth date, address, and infant's surname. To examine the quality of the linkage using SSN as the sole matching criterion, we conducted two procedures using data for 1989-1994 to compare linkages identified by SSN, to linkages identified using other available variables. Linkage was conducted using a deterministic approach based on seven variables and 14 steps. In each step a string of relevant variables was created and in successive phases selected variables were substituted or removed with decreasingly stringent requirements. A manual review was done to check for accuracy. Utilizing all available variables, the linkage process yielded 793 matches (live births) among 4496 patients, 780 [98%] of which would have been identified using SSN alone. Five of seven matches identified by SSN were not confirmed by manual review. SSN appears to be fairly accurate for linkage and can be valuable for linking cancer registries to other data sources.

Adult↗

PubMed2005

Racial differences in the familial aggregation of breast cancer and other female cancers.

Although breast cancer familial aggregation has been studied in Caucasians, information for African-Americans is scant. We used family cancer history from the Women's Contraceptive and Reproductive Experiences study to assess the aggregation of breast and gynecological cancers in African-American and Caucasian families. Information was available on 41,825 first and second-degree relatives of Caucasian and 28,956 relatives of African-American participants. We used a cohort approach in which the relative's cancer status was the outcome in unconditional logistic regression and adjusted for correlated data using generalized estimating equations. Race-specific models included a family history indicator, the relative's age, and type. Relative risk (RR) estimates for breast cancer were highest for first-degree relatives, and the overall RR for breast cancer among case relatives was 1.96 (95% CI = 1.68-2.30) for Caucasian and 1.78 (95% CI = 1.41-2.25) for African-Americans. The effect of CARE participants' reference age on their relatives' breast cancer risk was greatest among first-degree relatives of African-American patients with RRs (95% CI) for ages <45 and > or =45 of 2.97 (1.86-4.74) and 1.48 (1.14-1.92), respectively. Among Caucasians, first-degree relatives of case subjects were at greater risk for ovarian cancer, particularly relatives younger than 45 years (RR (95% CI) = 2.06 (1.02-4.12)), whereas African-American first-degree relatives of case subjects were at increased cervical cancer risk (RR (95% CI) = 2.17 (1.22-3.85). In conclusion, these racially distinct aggregation patterns may reflect different modes of inheritance and/or environmental factors that impact cancer risk.

Adult↗

PubMed2005

Racial disparities in treatment and survival of women with stage I-III breast cancer at a large academic medical center in metropolitan Detroit.

African-American (AA) women with breast cancer have higher mortality rates than Caucasian woman, and some studies have suggested that this disparity may be partly explained by unequal access to medical care. The purpose of this study was to analyze racial differences in patterns and costs of care and survival among women treated for invasive breast cancer at a large academic medical center. Subjects included 331 AA and 257 Caucasian women diagnosed with stage I-III breast cancer between 1994 and 1997. Clinical, socio-demographic, and cost data were obtained from the medical record, cancer registry, and hospital financial database. Data were collected on the use of cancer directed treatments (surgery, radiation, chemo and hormonal therapy) up to 1-year post-diagnosis. Survival analyses compared disease-free and overall survival by race adjusting for age, stage, nodal involvement, ER/PR status and a diagnosis of hypertension, diabetes, heart disease and cerebral vascular accident. There were no significant racial differences in treatment utilization and costs. The mean total 1-year treatment costs were US 16,348 dollars for AAs and US 15,120 dollars for Caucasians. While AAs had a significantly higher unadjusted relative risk (RR) of recurrence 2.09 (95% CI: 1.41-3.10) and death 1.56 (95% CI: 1.09-2.25), the multivariate adjusted analyses resulted in no significant differences in recurrence 1.38 (95% CI: 0.85-2.26) or death 1.06 (95% CI: 0.64-1.75). There was no obvious racial disparity in treatment and costs noted. Our findings support the theory that equal treatments produce equal outcomes. Improvement in screening may have an important impact on survival among minority women with breast cancer.

Academic Medical Centers↗

PubMed2004

Reproductive factors and risk of breast carcinoma in a study of white and African-American women.

BACKGROUND: Few studies have investigated the association between reproductive factors and the risk of breast carcinoma among African-American women. The authors assessed whether the number of full-term pregnancies, age at first full-term pregnancy, and total duration of breastfeeding were associated with similar relative risk estimates in white and African-American women in a large multicenter, population-based case-control study of breast carcinoma. METHODS: Case patients were 4567 women (2950 white women and 1617 African-American women) ages 35-64 years with newly diagnosed invasive breast carcinoma between 1994 and 1998. Control patients were 4668 women (3012 white women and 1656 African-American women) who were identified by random-digit dialing and were frequency matched to case patients according to study center, race, and age. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. RESULTS: For white women, the reduction in risk of breast carcinoma per full-term pregnancy was 13% among younger women (ages 35-49 years) and 10% among older women (ages 50-64 years). The corresponding risk reductions for African-American women were 10% and 6%, respectively. Risk decreased significantly with increasing number of full-term pregnancies for both races and both age categories. Duration of lactation was inversely associated with breast carcinoma risk among younger parous white (trend P = 0.0001) and African-American (trend P = 0.01) women. African-American women tended to have more children compared with white women, but parity rates were lower in younger women than in older women in both racial groups. However, breastfeeding was substantially more common in young white women than in young African-American women. CONCLUSIONS: Overall, parity and lactation had similar effects on breast carcinoma risk in white and African-American women. If younger African-American women now are giving birth to fewer children than in the past, without a substantial increase in breastfeeding, breast carcinoma rates may continue to increase at a more rapid rate among these women compared with white women.

Adult↗

PubMed2004

Factors associated with breast cancer clinical trials participation and enrollment at a large academic medical center.

PURPOSE: The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials. PATIENTS AND METHODS: From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment. RESULTS: The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%). CONCLUSION: It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.

Black or African American↗

PubMed2004

Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer.

Animal data indicate that both estrogens and progestins could be carcinogenic and that progestins could serve as tumor promoters. Human studies have not confirmed an increased risk of breast cancer from long-term use of oral contraceptives, but have shown an increased risk from hormone replacement therapy including progestins. The present study analyzed the relationship between breast cancer and use of injectable and implantable progestin-only contraceptives. Analyses were performed on data collected in a population-based, multicenter, case-control study, the Women's Contraceptive and Reproductive Experiences Study of the National Institute of Child Health and Human Development. The study involved 4575 randomly sampled cases with invasive breast cancer diagnosed between 1994 and 1998, and 4682 controls, identified using random digit dialing. We assessed the association between exposure to injectable contraceptives and risk of breast cancer. The use of injectable contraceptives was not associated with an increased risk of breast cancer [odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7, 1.2]. Risk was not increased among current users, defined as women who used injectable contraceptives within 1 year of the reference date (OR = 0.7, 95% CI: 0.4, 1.3) or those who initiated use in the 5 years immediately preceding the reference date (OR = 0.9, 95% CI: 0.5, 1.4), or with use beginning before age 35 (OR = 0.9, 95% CI: 0.6, 1.3). Among users, risk increased with increasing duration of use (p = 0.03). However, short-term users (<6 months duration) were at decreased risk relative to never users (OR = 0.6, 95% CI: 0.4, 1.0). When the short-term users were then excluded from the duration-response analysis, the slope of the duration-response became slightly (and nonsignificantly) negative. Risk was not increased among women with 24 or more months of use relative to never users (OR = 1.4, 95% CI: 0.8, 2.5). No increased risk was seen from implantable contraceptives either, although the sample sizes were small. This study does not support an increased risk of breast cancer associated with the use of injectable or implantable progestin-only contraceptives in women aged 35 to 64.

Absorbable Implants↗

PubMed2004

Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study.

OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship. METHODS: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately. RESULTS: Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3). CONCLUSIONS: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.

Adult↗

PubMed2003

Childbearing and survival after breast carcinoma in young women.

BACKGROUND: Many young patients with breast carcinoma have not started, or completed, their desired families. How childbearing after a diagnosis of breast carcinoma affects survival is of importance to these women and their families. The authors measured relative mortality among young patients with breast carcinoma with and without births occurring after diagnosis. METHODS: The authors conducted a cohort study using data from three population-based cancer registries in the U.S. (Seattle, Detroit, and Los Angeles), linked to birth certificate data in each state. Four hundred thirty-eight women younger than 45 years of age with primary invasive breast carcinoma were identified as having births after diagnosis. In addition, 2775 comparison women, matched on the basis of age at the time of diagnosis, race/ethnicity, diagnosis year, disease stage, and presence of previous nonbreast primary tumors, were identified among those with breast carcinoma without births after diagnosis. Relative mortality was assessed using multivariable statistical methods. RESULTS: After adjustment for stage of disease, age at diagnosis, study region, diagnosis year, and race/ethnicity, women with births occurring 10 months or more after diagnosis had a significantly decreased risk of dying (relative Risk [RR] = 0.54, 95% confidence interval [CI], 0.41-0.71) compared to women without subsequent births. Women pregnant at the time of diagnosis had a mortality rate similar to those who did not give birth (RR = 1.10, 95% CI, 0.80-1.60). CONCLUSIONS: The results of the current study, in light of growing evidence from other studies using various methods, may provide some reassurance to young women with breast carcinoma that subsequent childbearing is unlikely to increase their risk of mortality.

Adult↗

PubMed2003

Infertility drugs and the risk of breast cancer: findings from the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study.

OBJECTIVE: To determine the association between infertility drug use and invasive breast cancer in a population-based case-control study. DESIGN: Multicenter case-control study. SETTING: Women aged 35 to 64 years in metropolitan Atlanta, Detroit, Los Angeles, Philadelphia, and Seattle. PATIENT(S): The 4,575 case patients had histologically confirmed primary invasive breast cancer. The 4,682 control subjects were women without breast cancer identified in the same geographic locations using randomized-digit dialing. INTERVENTION(S): A standardized questionnaire focusing on reproductive health and family history as well as use of oral contraceptives and other hormones and infertility drugs was administered to all subjects. Data on the type of breast cancer were also obtained. MAIN OUTCOME MEASURE(S): Odds ratios examining the association between use of various infertility drugs and invasive breast cancer. RESULT(S): Overall, a history of infertility drug use was not associated with the risk of developing breast cancer. Compared with women who never used any fertility medication, however, women using human menopausal gonadotropin (hMG) for > or = 6 months or for at least six cycles had a relative risk of breast cancer ranging between 2.7 to 3.8. CONCLUSION(S): Long-term use of certain infertility drugs could adversely affect risk of breast cancer. Additional confirmatory studies are needed.

Adult↗