Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.     

Prognosis of premenopausal breast cancer and childbirth prior to diagnosis.

PURPOSE: The time interval between last childbirth and subsequent breast cancer diagnosis is emerging as an important prognostic factor for premenopausal women. PATIENTS AND METHODS: We studied, prospectively, 750 women diagnosed with primary invasive breast cancer before age 45 years who participated in the population-based Australian Breast Cancer Family Study (ABCFS). RESULTS: Median follow-up time was 4.9 years (range, 0.8 to 10.8 years). Compared with nulliparous women, women who gave birth within 2 years prior to diagnosis were more likely to have axillary node-positive (58% v 41%; P =.01), and estrogen receptor-negative (58% v 39%; P =.005) tumors. The unadjusted hazard ratios for death were 2.3 (95% CI, 1.3 to 3.8; P =.002), 1.7 (95% CI, 1.1 to 2.6; P =.03), and 0.9 (95% CI, 0.6 to 1.5; P =.8) for patients who gave birth less than 2 years, 2 to 5 years, and 5 or more years before diagnosis, respectively. After adjusting for tumor characteristics, these hazard ratios were reduced to 1.9 (95%CI, 1.1 to 3.2; P =.02), 1.3 (95% CI, 0.8 to 2.1; P =.3), and 0.9 (95%CI, 0.5 to 1.4; P =.5). Modeling showed that, compared with nulliparous women, the mortality hazard ratio in parous women was 1.9, decreasing by 8% (95%CI, 4% to 13%; P <.001) for each year between last birth and breast cancer diagnosis. CONCLUSION: Proximity of last childbirth to subsequent breast cancer diagnosis is a predictor of mortality independent of histopathological tumor characteristics. Clinicians should be aware that women diagnosed with breast cancer within a few years following childbirth may have a worse outcome than that suggested solely by the standard histopathological prognostic factors of their cancer.     

Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history.

Women who have inherited a germ-line mutation in the BRCA1 or BRCA2 (BRCA1/2) genes have a greatly increased risk of developing breast cancer compared with the general population. However, there is also substantial interindividual variability in the occurrence of breast cancer among BRCA1/2 mutation carriers. We hypothesize that genes involved in endocrine signaling may modify the BRCA1/2-associated age-specific breast cancer penetrance. We studied the effect of alleles at the AIB1 gene using a matched case-control sample of 448 women with germ-line BRCA1/2 mutations. We found that these women were at significantly higher breast cancer risk if they carried alleles with at least 28 or 29 polyglutamine repeats at AIB1, compared with women who carried alleles with fewer polyglutamine repeats [odds ratio (OR), 1.59; 95% confidence interval (CI), 1.03-2.47 and OR, 2.85; 95% CI, 1.64-4.96, respectively]. Late age at first live birth and nulliparity have been associated with increased breast cancer risk. We observed increases in BRCA1/2-associated breast cancer risk in women who were either nulliparous or had their first live birth after age 30 (OR, 3.06; 95% CI, 1.52-6.16). Women were at significantly increased risk if they were nulliparous or had a late age at first live birth and had AIB1 alleles no shorter than 28 or 29 or more AIB1 polyglutamine repeats (OR, 4.62; 95% CI, 2.02-10.56 and OR, 6.97; 95% CI, 1.71-28.43, respectively) than women with none of these risk factors. Our results support the hypothesis that pathways involving endocrine signaling, as measured through AIB1 genotype and reproductive history, may have a substantial effect on BRCA1/2-associated breast cancer risk.     

Is birth history the key to highly educated women's higher breast cancer mortality? A follow‐up study of 500,000 women aged 35–54

A positive relationship has been found between high levels of education and breast cancer mortality. The aim of our study is to determine if the educational gradient in breast cancer mortality persists after adjustment for reproductive history. Register data including the total adult population in Norway were used. A total of 512,353 Norwegian women 35-54 years of age at the Norwegian Census in 1990 were followed with respect to breast cancer deaths until December 31, 2001. The analysis included 2,052 breast cancer deaths in 5.6 million person years. Educational differences in breast cancer mortality were analysed using Cox regression. The age adjusted relative risk of dying from breast cancer for women with >12 years of education compared to women with <10 years was 1.25 (95% confidence limits [CI] = 1.10-1.41). Adjustment for age at first birth with nulliparous as reference category reduced this difference to 1.08 (95% CI = 0.95-1.23). For parous women, age at first birth explained all the educational difference in breast cancer mortality. Among nulliparous women there was a larger positive educational gradient in breast cancer mortality than among parous women (relative risk [RR] = 1.57, 95% CI = 1.15-2.13), indicating that there were differences in other confounders than birth history among the childless.     

Risk factors for hormone receptor-defined breast cancer in postmenopausal women.

The effect of classic breast cancer risk factors on hormone receptor-defined breast cancer is not fully clarified. We explored these associations in a Swedish population-based study. Postmenopausal women ages 50 to 74 years, diagnosed with invasive breast cancer during 1993 to 1995, were compared with 3,065 age frequency-matched controls. We identified 332 estrogen receptor (ER-) and progesterone receptor (PR-) negative, 286 ER+PR-, 71 ER-PR+, 1,165 ER+PR+, and 789 tumors with unknown receptor status. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Women ages >or=30 years, compared with those ages 20 to 24 years at first birth, were at an increased risk of ER+PR+ tumors (OR, 1.5; 95% CI, 1.2-1.8) but not ER-PR- tumors (OR, 1.1; 95% CI, 0.8-1.6). Women who gained >or=30 kg in weight during adulthood had an approximately 3-fold increased relative risk of ER+PR+ tumors (OR, 2.7; 95% CI, 1.9-3.8), but no risk increase of ER-PR- tumors (OR, 1.0; 95% CI, 0.5-2.1), compared with women who gained <10 kg. Compared with never users, women who used menopausal estrogen-progestin therapy for at least 5 years were at increased risk of ER+PR+ tumors (OR, 3.0; 95% CI, 2.1-4.1) but not ER-PR- tumors (OR, 1.3; 95% CI, 0.7-2.5). In conclusion, other risk factors were similarly related to breast cancer regardless of receptor status, but high age at first birth, substantial weight gain in adult age, and use of menopausal estrogen-progestin therapy were more strongly related to receptor-positive breast cancer than receptor-negative breast cancer.     

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.     

Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger

Differences in incidence, prognosis, and treatment response suggest gene expression patterns may discern breast cancer subtypes with unique risk factor profiles; however, previous results were based predominantly on older women. In this study, we examined similar relationships in women ≤ 56 years, classified by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 for 890 breast cancer cases and 3,432 frequency-matched population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) for tumor subtypes were calculated using multivariate polytomous regression models. A total of 455 (51.1%) tumors were considered luminal A, 72 (8.1%) luminal B, 117 (13.1%) non-luminal HER-2/neu+, and 246 (27.6%) triple negative. Triple negative tumors were associated with breast feeding duration (per 6 months: OR = 0.76, 95% CI 0.64-0.90). Among premenopausal women, increasing body size was more strongly associated with luminal B (OR = 1.73, 95% CI 1.07-2.77) and triple negative tumors (OR = 1.67, 95% CI 1.22-2.28). A history of benign breast disease was associated only with increased risk of luminal A tumors (OR = 1.89, 95% CI 1.43-2.50). A family history of breast cancer was a risk factor for luminal A tumors (OR = 1.93, 95% CI 1.38-2.70) regardless of age, and triple negative tumors with higher risks for women <45 (OR = 5.02, 95% CI 2.82-8.92; P for age interaction = 0.005). We found that little-to-no breastfeeding and high BMI were associated with increased risk of triple negative breast cancer. That some risk factors differ by molecular subtypes suggests etiologic heterogeneity in breast carcinogenesis among young women.     

Characteristics of women refusing follow-up for tests or symptoms suggestive of breast cancer

BACKGROUND: Delay in diagnosis of breast cancer can occur at several points on the diagnostic pathway. We examined characteristics of women with breast cancer who before diagnosis actively refused recommended follow-up of tests or symptoms suggestive of breast cancer. METHODS: We identified women aged 50 years or older diagnosed with late-stage (metastatic disease or tumors > or = 3 cm at diagnosis) and a matched sample of women with early-stage (tumors < 3 cm) breast cancer from 1995 to 1999. Using medical records, we investigated clinical characteristics, use of health care, and documentation of care refusal during the 3 years before diagnosis. We used logistic regression models to compare refusers to nonrefusers. RESULTS: Of the 2694 women studied, 7.2% refused provider follow-up advice during the 3 years. These women were more likely to have late-stage breast cancer at diagnosis than were nonrefusers (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.4 to 2.6). They were more likely to be aged 75 years or older (OR = 1.9, 95% CI = 1.4 to 2.7 compared with age 50-64) or to have six or more children (OR = 2.3, 95% CI = 1.3 to 4.2 compared to women with one to two children). Clinical factors associated with refusal included low use of mammography, high use of clinical breast exam, and missed appointments. A minority of women who refused had a reason documented in the medical record; the most frequent reasons were avoidance-denial-fatalism, fear of diagnostic tests, and fear of surgery or disfigurement. CONCLUSIONS: Our results suggest that certain demographic and clinical characteristics are associated with women's refusal of diagnostic testing for breast cancer. Further study is needed on refusers' characteristics and on how such refusals affect outcomes. Efforts aimed at identifying and counseling women with abnormal results who refuse follow-up are warranted.     

Incidence of histologic types of uterine sarcoma in relation to menstrual and reproductive history

To determine whether the occurrence of one or more histologic types of uterine sarcoma is related to events in a woman's reproductive life, a population-based case-control study was conducted. One-hundred sixty-seven women newly diagnosed with uterine sarcoma among residents of 6 geographic regions were compared to 208 women selected at random from the same populations with regard to histories of menstruation, pregnancy and childbearing, and breast feeding, as reported during a telephone interview. Compared to women whose menstrual periods began at age 13, women whose menses began earlier were at increased risk of leiomyosarcoma (OR = 2.0, 95% CI 0.9, 4.3); other histologic types were less strongly associated with early age at menarche. Women with leiomyosarcoma and endometrial stromal sarcoma, but not malignant mixed Müllerian tumors, tended to have ceased menstruating 2-3 years later than controls. None of the histologic types was clearly related to parity or to age at first live birth, but each was inversely related to age at last live birth. Associations were observed between leiomyosarcoma and histories of an induced abortion (OR = 4.2, 95% CI 1.2, 14.2) and of breast feeding after a live birth (OR = 0.5, 95% CI 0.3, 1.0); these relationships were not observed for other morphologic variants. These results suggest possible similarities and differences in menstrual and reproductive risk factors among histologic types of uterine sarcoma, and between these malignancies and the more common breast, endometrial and ovarian carcinomas.     

Effects of Menstrual and Reproductive Factors on the Risk of Breast Cancer: Meta-analysis of the Case-Control Studies in Japan

To elucidate the magnitude of the effect of menstrual and reproductive factors on breast cancer occurrence among Japanese women, we reviewed eight case-control studies previously conducted in Japan and used a quantitative method (meta-analysis) to summarize the data. While individual studies have different methods and populations, the estimated odds ratios (ORs) in the studies were statistically homogeneous for all study variables. It was confirmed that early age at menarche, late age at first birth, and premenopausal status are significantly associated with risk of breast cancer; an estimated combined OR of 0.68 (95% confidence interval (CI): 0.59-0.77) was obtained for women with onset of menstruation after age 16 compared to those before age 14. Nulliparous women had higher risk than women with first birth before age 25 (OR=1.56 95%, CI: 1.27-1.91). The OR for women with first birth after age 35 was 2.26 (95% CI: 1.85-2.77) compared to women at first birth before age 25. Premenopausal women had a higher risk than women with menopause before age 50 (OR=2.21, 95% CI: 1.53-3.20). We also found a significant protective effect of high parity after controlling for age at first birth and the other menstrual factors. The OR estimate for 3 or more births compared to nulliparity was 0.68 (95% CI: 0.54-0.86). The meta-analysis provided quantitative estimates of breast cancer risk among Japanese women with improved precision.     

Differences in estrogen receptor subtype according to family history of breast cancer among Hispanic, but not non-Hispanic White women

BACKGROUND: Pathologic differences have been reported among breast tumors when comparing ethnic populations. Limited research has been done to evaluate the ethnic-specific relationships between breast cancer risk factors and the pathologic features of breast tumors. METHODS: Given that genetic variation may contribute to ethnic-related etiologic differences in breast cancer, we hypothesized that tumor characteristics differ according to family history of breast cancer among Hispanic and non-Hispanic White (NHW) women. Logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (95% CI) to assess this relationship in the population-based, case-control 4-Corners Breast Cancer Study (1,537 cases and 2,452 controls). RESULTS: Among Hispanic women, having a family history was associated with a 2.7-fold increased risk of estrogen receptor (ER) negative (95% CI, 1.59-4.44), but not ER positive tumors (OR, 1.04; 95% CI, 0.71-1.54) when compared with women without breast cancer. In contrast, there was an increased risk for ER positive (OR, 1.89; 95% CI, 1.50-2.38) and a marginally significant increased risk for ER negative tumors (OR, 1.41; 95% CI, 0.92-2.17) among NHW women. When comparing tumor characteristics among invasive cases, those with a family history also had a significantly higher proportion of ER negative tumors among Hispanics (39.2% versus 25.8%; P=0.02), but not among NHWs (16.3% versus 21.1%; P=0.13). CONCLUSIONS: These results may reflect ethnic-specific predisposing genetic factors that promote the development of specific breast tumor subtypes, and emphasize the importance of evaluating the relationship between breast cancer risk factors and breast tumor subtypes among different ethnic populations.     

Reproductive factors and risk of meningioma and glioma

Female sex hormones have previously been suggested as possible risk factors for brain tumors, but published studies have reported conflicting results. We conducted a population-based case-control study of glioma (n=626) and meningioma (n=906) cases and randomly selected controls stratified on age and geographic region (n=1,774) in Denmark, Finland, Norway, Sweden, and the United Kingdom. Unconditional logistic regression was used to estimate odds ratios (OR) for glioma and meningioma in relation to reproductive factors. A decreased glioma risk was associated with ever-pregnancy compared with never-pregnancy [OR, 0.8; 95% confidence interval (95% CI), 0.6-1.0]. Meningioma risk among women ages <50 years was increased in relation to number of pregnancies leading to a live birth (OR, 1.8; 95% CI: 1.1-2.8 for giving birth to 3 children compared with nulliparous women; P(trend) among parous women=0.01). This relation was not found for older women. Breast-feeding among parous women increased the glioma risk (OR, 2.2; 95% CI, 1.3-3.9 for breast-feeding 36 months or more compared with breast-feeding 3 months or less). Menopausal status and age at menopause were not associated with meningioma or glioma risk. Our findings imply that reproductive hormones may influence the occurrence of meningioma and glioma.     

Childbirth and breast cancer prognosis

Although certain risk factors for breast cancer incidence may also effect survival, findings have been inconsistent and the long-term role of childbirth is unknown. We studied the influence of number and timing of births on breast cancer prognosis prospectively. From 1958 to 1997, altogether 32,003 women, born 1932 or later, were notified to the Swedish Cancer Registry due to a primary invasive breast cancer. We obtained information on dates of all childbirths and achieved complete follow-up through 1997 by means of linkage to other nation-wide databases. Proportional hazards analyses were used to compute crude and multivariate hazard ratios (HR) with 95% confidence intervals (CI) of dying from breast cancer. We found a successively worse prognosis for women with a shorter delay between their last birth and breast cancer diagnosis (p for trend <0.0001). Compared to women with their last birth more than 10 years before diagnosis, the multivariate HR of breast cancer death was 1.39 (95% CI 1.17-1.67) for those with breast cancer diagnosis in the 3rd year after last birth and 1.72 (CI 95% 1.42-2.09) for those with diagnosis within 1 year after last birth. This adverse effect on prognosis of childbirth persisted beyond 10 years among women with a first birth before the age of 20 years. A pregnancy has marked adverse effects on the prognosis of a breast cancer diagnosed within 10 years after delivery. These findings suggest that pregnancy influences tumor biology.     

The Investigation of Risk Factors Impacting Breast Cancer in Guilan Province

Introduction: Breast cancer is multifactorial therefore more recognition of risk factors is important in its prevention. Objective: This study was conducted in order to determine the factors influencing breast cancer in women referred to health centers in Guilan province in 2015-2016. Method: In a case- control study, 225 women with breast cancer were investigated. The control group consisted of 225 healthy women of the relatives (third-rank) whose phone numbers were obtained from the patients. Data were collected through telephone interviews. Results: The risk of breast cancer raised in women who have a family history of other cancers (OR= 3.5; 95% CI= 1.96-6.6) ,exposure to X-Ray (OR= 2.5; 95% CI=1.1-5.5), having more than 4 children (OR= 2.695% CI=1.2-4.8), age more than 36 years at first pregnancy(OR=2.3; 95% CI=0.7-5.1),primary levelof education (OR= 5.4;95% CI=2.8-11.2) and inadequate intake of fruit (OR=1.5; 95% CI=1-2.2). Also, presence of the following factors reduced breast cancer risk: regular menstruation (OR= 0.66; CI=0.4- 0.9), duration of breastfeeding more than 12 months, less than 6 months and 7-12 months (OR=0.23; 95% CI=0.09-0.59 , OR=0.29; 95% CI=0.17-0.49 and OR=0.03; 95% CI=0.01-0.08) and parity (OR=0.4; 95% CI=0.27-0.83) In multiple linear regression analysis of higher education (OR=0.16; 95% CI=0.03-0.77), using contraceptives for more than 16 years (OR=2.3; 95% CI=1.4-3.9), family history of other cancers (OR=6.1; 95% CI=1.9-19.3) and a history of X-Ray exposure (OR=4.4; 95% CI=1.07-18.1) were considered as predictive factors. Conclusion: The results of this study emphasize the importance of informing women about breast cancer risk factors. So, identification of these risk factors is required as important means of prevention and treatment of breast cancer.     

Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin.

We investigated the association of oral contraceptive (OC) use and reproductive factors with colorectal cancer risk in a large population-based case-control study. Cases were women ages 20 to 74 years, living in Wisconsin, with a new diagnosis of colon (n = 1,122) or rectal (n = 366) cancer. Control participants were randomly selected from population lists of similarly aged female Wisconsin residents (n = 4,297). Risk factor information was collected through structured telephone interviews. Compared with never users, OC users had an odds ratio (OR) of 0.89 [95% confidence interval (95% CI), 0.75-1.06] for colorectal cancer. OC use associations did not differ significantly between colon and rectal cancer sites; however, when compared with never users, recent OC users (<14 years) seemed at reduced risk of rectal cancer (OR, 0.53; 95% CI, 0.28-1.00). Women with age at first birth older than the median (23 years) had 0.83 times the risk of colon cancer compared with women with age at first birth below the median (95% CI, 0.70-0.98). We observed an inverse trend between increasing parity and rectal cancer risk (P = 0.05). Compared with nulliparous women, women with five or more births had 0.66 times the risk of rectal cancer (95% CI, 0.43-1.02). Compared with postmenopausal women, premenopausal women were at reduced risk (OR, 0.67; 95% CI, 0.47-0.97) of colorectal cancer. No significant associations were observed between colorectal cancer risk and age at menarche or age at menopause. These findings suggest differential roles of reproductive factors in colon and rectal cancer etiology.     

Differences in breast cancer risk factors by tumor marker subtypes among premenopausal Vietnamese and Chinese women.

We evaluated associations between reproductive and lifestyle risk factors with breast cancer tumor marker status in a case-control study. Cases were premenopausal women living in Vietnam and China who were eligible for a clinical trial of oophorectomy and tamoxifen as treatment for breast cancer (n = 682). Controls were nonrelative hospital visitors, matched on age to the cases (n = 649). Immunohistochemical analysis was used to identify the presence of estrogen receptor (ER) and progesterone receptor and the overexpression of HER-2/neu oncogene. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression, adjusted for known confounders. Overall, 280 (61%) tumor samples were ER positive and 176 (38%) were ER negative. HER-2/neu overexpression was detected in 161 (35%) samples, whereas 286 (26%) samples were HER-2/neu negative. We observed an inverse trend between increasing parity and decreasing breast cancer risk (P = 0.002). Women ages > or =25 years at first birth had increased breast cancer risk compared with women ages <25 years at first birth (OR, 1.53; 95% CI, 1.20-1.95). Women who consumed alcohol had increased risk of breast cancer compared with women who did not (OR,1.85; 95% CI, 1.32-2.61). Compared with controls, OR estimates for breast cancer by parity and age at first birth were significantly associated with ER and/or HER-2/neu tumor status by Wald test (P < 0.05). Family history, age at menarche, cumulative lactation, body mass index, and education were not significantly related to breast cancer risk. Our findings support the hypothesis that some breast cancer risk factors differ by ER and HER-2/neu tumor marker subtypes.     

A prospective study of induced abortion and breast cancer in African-American women

OBJECTIVE: There continues to be controversy about whether induced abortion influences the risk of breast cancer. Because case-control studies of this relation are subject to recall bias, there is a need for prospective data. Further, there has been little study of abortion and breast cancer in African-American women. We assessed the relation of abortion to risk of breast cancer in a prospective follow-up study of African-American women. METHODS: Black Women's Health Study participants have been followed by mailed questionnaires every two years since enrollment in 1995. Participants reported 348 incident breast cancers during 205,983 person-years of follow-up. Women who had an induced abortion were compared with women who had never had one, with nulliparous and parous women analyzed separately. Incidence rate ratios (IRR) with two-sided 95% confidence intervals (CI) were derived from Cox regression models that controlled for age, age at first birth, number of births, history of spontaneous abortion, and other factors. RESULTS: Among nulliparous women, the IRR for any induced abortion relative to none was 0.9 (95% CI = 0.5-1.4), and among parous women, the comparable IRR was 1.1 (95% CI = 0.8-1.4). Risk did not vary by number of abortions, age at first abortion, age at diagnosis or a family history of breast cancer in either nulliparous or parous women. CONCLUSIONS: Our findings indicate that induced abortion does not increase breast cancer risk in African-American women.     

Risk factors for breast cancer in nulliparous women

The relation between hormonal and lifestyle factors and breast cancer risk in nulliparae was investigated using data from two case-control studies conducted in Italy between 1983 and 1994. The study included 1041 nulliparae with histologically confirmed incident breast cancer and 1002 nulliparous controls admitted to hospital for a wide range of acute, non-neoplastic, nonhormone-related diseases. In premenopausal nulliparae, there was an inverse relation with age at menarche [odds ratios (OR) 0.45; 95% confidence intervals (CI) 0.24-0.86 for > or = 15 years vs < 12], while no association emerged in postmenopausal. Breast cancer risk increased with age at menopause, the OR being 1.91 (95% CI 1.26-2.90) for nulliparae reporting age at menopause > or = 53 years compared with < 45. Abortion was not related to breast cancer risk, the OR being 0.92 for any spontaneous, 0.97 for any induced and 0.77 for > or = 2 total abortions compared to none. The OR was 1.75 (95% CI 1.03-2.97) for women reporting their first abortion at age > or = 30 years compared with < 30. Oral contraceptives and hormone replacement therapy in menopause were moderately related to risk. The OR was 2.71 (95% CI 1.85-3.95) in nulliparae with a family history of breast cancer and 1.60 (95% CI 1.20-2.14) in those with a history of benign breast disease. Compared with nulliparae reporting a low physical activity, the OR was 0.79 (95% CI 0.54-1.16) for those reporting intermediate/high activity. Breast cancer risk increased with total energy intake, the OR being 1.65 (95% CI 0.99-2.75) in the highest tertile; beta-carotene was inversely related to risk (OR 0.60, 95% CI 0.38-0.95) for the highest tertile. Thus, most risk factors for breast cancer in nulliparae were similar to those in women generally.     

Late-stage breast cancer among women with recent negative screening mammography: do clinical encounters offer opportunity for earlier detection?

BACKGROUND: Opportunities to prevent late-stage breast cancer within the course of usual care are needed. We evaluate whether clinical encounters offer such opportunities. METHODS: Within seven health care plans, we identified 1298 women aged more than 50 years with early (<3 cm), late-stage (> or = 3 cm), or metastatic invasive breast cancer diagnosed during 1995-1999, whose first screening mammogram 13-36 months prior to the diagnosis (index) was negative. We audited all care occurring in the health plans up to 36 months prior to the cancer diagnoses. Ordinal logistic regression compared the frequency of events by disease category. We hypothesized that during the 13-36 months prior to diagnosis, women with late-stage or metastatic breast cancer would have more symptoms and be more likely to have breast-related clinical visits but have less breast screening (clinical breast examination [CBE] or mammography) than women with early-stage disease, thereby indicating clinical opportunities for earlier detection. RESULTS: We found no differences in demographic characteristics across breast cancer stage among the 1298 women. Both before and after the negative index mammogram but during the 13-36 months prior to diagnosis, few women had breast symptoms (5% before index, 8% after), but many sought breast care (86% before index, 90% after) and screening CBE (62% before index, 43% after). Only the occurrence of screening CBE (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.56 to 0.95) or screening mammograms (OR = 0.74, 95% CI = 0.57 to 0.97) after the negative index mammogram reduced odds of more severe disease at diagnosis. CONCLUSION: Although the mortality benefit of CBE, or one compared to two year mammography has not been established, we found that women with late-stage breast cancers undetected by screening mammography did not experience opportunities for earlier detection except through CBE or additional screening mammography.     

Body mass and stage of breast cancer at diagnosis

Obesity is a well-known risk factor for postmenopausal breast cancer. In contrast, the relationship between obesity and stage of breast cancer at diagnosis is less clear. We hypothesized that increased breast size in obese women may delay discovery of breast tumors. Thus, the purpose of our study was to examine whether there is an association between body mass and stage of breast cancer at diagnosis using hospital medical records. Newly diagnosed breast cancer cases (n = 966) in the Baltimore metropolitan area from 1991 to 1997 were included in our study. Patient information including age, ethnicity, weight, height and pathology data were obtained from hospital medical records. High body mass was significantly associated with late stage of breast cancer at diagnosis. Women who were obese (body mass index [BMI] > or = 27.3) were more likely to be at an advanced stage at diagnosis compared with women with a BMI of < 27.3 (multivariate-adjusted odds ratio [OR] 1.57, 95% confidence interval [CI] 1.15-2.14). The association between body mass and stage at diagnosis was stronger among women younger than 50 years (OR 2.34, 95% CI 1.34-4.08) compared with women 50 years or older (OR 1.30, 95% CI 0.89-1.91). Our study suggests that higher body mass is associated with advanced stage of breast cancer at diagnosis. This finding may be of considerable concern, given the increasing prevalence of obesity in women in the United States and the poor prognosis associated with late-stage tumors.