Parity and mammographic breast density in relation to breast cancer risk: indication of interaction.

We examined whether the harmful influence of nulliparity on breast cancer risk could be mediated by high mammographic density. Another possibility is that mammographic density and nulliparity act independently or perhaps synergistically on breast cancer risk. Our study population consisted of 129 cases and 517 controls who had been participants in the Nijmegen breast cancer screening programme for 10 years. Breast density was classified with a fully automated technique on digitized mammograms from the screening examination 10 years before diagnosis. Classification was based on the proportion of the breast that was composed of high density: < 5%, 5-25% or > 25%. Data on parity and potential confounders were obtained using a questionnaire, administered at the same examination. We found that nulliparae with low breast density (< 5%) were not at increased risk compared to parous women with low density: OR 1.1 (95% CI 0.2-5.8). Parous women with < 5% density formed the reference category throughout all analyses. The risks for parous women with 5-25% or > 25% density were 2.7 (95% CI 1.3-5.6) and 3.6 (95% CI 1.7-7.7) fold increased, respectively. However, when both factors were present (nulliparity and > or = 5% density), breast cancer risk was 7.1 times higher (95% CI 3.2-15.9). This could indicate that nulliparity and high breast density might work synergistically and that breast density is not just an explanatory factor in the influence of nulliparity on breast cancer risk. It is hypothesized that high breast density (reflecting fibro-glandular tissue with increased epithelial cell proliferation) is more susceptible to carcinogenic effects in the undifferentiated epithelial breast tissue of nulliparae than in the differentiated tissue of parous women. Since there were few data, no firm conclusions can be drawn. If these findings can be confirmed in a larger study population, however, they may have important implications for the prevention and early detection of breast cancer.     

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.     

Risk factors for subsequent invasive breast cancer and breast cancer death after ductal carcinoma in situ: a population-based case-control study in Sweden.

In a case-control study derived from a cohort of 4661 women with a primary carcinoma in situ of the breast, we investigated age at diagnosis, mode of detection, tumor characteristics, and primary therapy, as prognostic factors for developing invasive breast cancer or dying from breast cancer. From all of the women with a primary carcinoma in situ reported to the Swedish Cancer Registry from 1960 through 1992, we selected as cases all of the women with a ductal carcinoma in situ who later died of breast cancer (n = 39) or who developed a subsequent invasive cancer in either breast (n = 118). From this cohort, we also selected controls matched to the cases by year of diagnosis and health care region. We conducted univariate and multivariate analyses to study the association between risk of invasive cancer or death and the different risk factors. Large size, diameter > or = 25 mm [odds ratio (OR), 3.5; 95% confidence interval (CI), 1.1-11.4] and multifocality (OR, 3.9; 95% CI, 1.2-12.7) increased the risk of breast cancer death in univariate analysis. Postoperative radiotherapy (OR, 0.1; 95% CI, 0.0-1.0) and mastectomy (OR, 0.1-95% CI, 0.0-0.5) lowered the risk of an ipsilateral invasive cancer in multivariate analysis. The risk pattern by treatment category differed between those who had an ipsilateral invasive cancer and those who either had a contralateral cancer or died from breast cancer. The driving forces behind local and generalized disease may differ. Because confounding by indication may influence the effects of different treatments, the results should be interpreted with caution.     

Using mammographic density to improve breast cancer screening outcomes

It is possible that the performance of mammographic screening would be improved if it is targeted at women at higher risk of breast cancer or who are more likely to have their cancer missed at screening, through more intensive screening or alternative screening modalities. We conducted a case-control study within a population-based Australian mammographic screening program (1,706 invasive breast cancers and 5,637 randomly selected controls). We used logistic regression to examine the effects of breast density, age, and hormone therapy use, all known to influence both breast cancer risk and the sensitivity of mammographic screening, on the risk of small (15 mm) screen-detected and interval breast cancers. The risk of small screen-detected cancers was not associated with density, but the risk of large screen-detected cancers was nearly 3-fold for the second quintile and approximately 4-fold for the four highest density categories (third and fourth quintiles and the two highest deciles) compared with the lowest quintile. The risk of interval cancers increased monotonically across the density categories [highest decile odds ratio (OR), 4.65; 95% confidence interval (95% CI), 2.96-7.31]. The risk of small and large screen-detected cancers, but not interval cancers, increased with age. After adjusting for age and density, hormone therapy use was associated with a moderately elevated risk of interval cancers (OR, 1.43; 95% CI, 1.12-1.81). The effectiveness of the screening program could be improved if density were to be used to identify women most likely to have poor screening outcomes. There would be little additional benefit in targeting screening based on age and hormone therapy use.     

Case-control study of increased mammographic breast density response to hormone replacement therapy.

Previous studies have demonstrated an association between current hormone replacement therapy (HRT) use and increased mammographic breast density. Many of these studies have also shown that only 20-35% of women initiating HRT respond in this manner. This subgroup of HRT responders may be at an increased risk of breast cancer. We performed a case-control study to investigate how women who experience increased density in response to HRT (cases) differ from women who do not experience an increase in density with HRT use (controls) with regard to breast cancer risk factors, type of HRT, weight change, and baseline breast density. Participants were female residents of Olmsted County, Minnesota who received routine screening mammograms at the Mayo Clinic. Cases included 172 women identified between the years 1998 and 1999 by Mayo radiologists as having a HRT response. Controls were women who did not experience an increase in mammographic density with HRT use and were matched to cases on age (+/-3 years), menopausal status, duration of HRT, month of initiation of HRT, and months between baseline and follow-up mammograms. Mammograms were obtained from cases and controls before and during HRT therapy. Breast density was read as a four-category Bi-Rads density grade measure and as a quantitative percentage estimate, using a computer-assisted method. Risk factor information was obtained from both chart review and a mammography database of patient-provided information. There was no association between HRT response and first-degree family history of breast cancer [odds ratio (OR), 0.8; 95% confidence interval (CI), 0.4-1.5], parity (OR, 0.8; 95% CI, 0.4-1.7), later age at first birth (OR, 0.8 for age >25 years versus nulliparous women; 95% CI, 0.4-1.8), or history of biopsy (OR, 0.9; 95% CI, 0.6-1.5). There was also no association with baseline weight or change in weight between a woman's baseline and follow-up mammograms. However, there was evidence of an association between HRT response and type of HRT used; women who experienced a mammographic increase in density with HRT had 2.3 greater odds (95% CI, 1.4-3.7) of having taken estrogen-progestin combined therapy than estrogen alone, compared with controls. This association was stronger among women with a baseline weight below the median (OR, 5.2; 95% CI, 1.6-17.6). Also, there was an inverse association between HRT response and baseline density. Because all risk factors examined accounted for only 26% of the variation in the HRT response, genes or other unmeasured factors are thought to be involved.     

The relation of reproductive factors to mortality from breast cancer.

Young women with breast cancer have been reported to have an increased risk of dying from their disease if they have given birth in <2 years before diagnosis. The prognostic factors associated with the tumors of these women have not been thoroughly studied. We examined the tumors of the women who had a recent birth and compared the tumor characteristics with those of women who were nulliparous or had given birth > or =5 years before diagnosis. A follow-up study was conducted of 1174 women <45 years old whose invasive ductal breast cancer was diagnosed from January 1983 to December 1992 in three counties of western Washington. These women had participated previously in a population-based, case-control study. Mean follow-up time was 105.4 months. Histological slides were collected for 79.1% of the tumors and reviewed by the study pathologist. Using immunoperoxidase assays, tumor tissue was tested for prognostic markers for 70.4% of the tumors from the women. Cox proportional hazards models were used to estimate the relative risk of dying from breast cancer associated with reproductive events. Logistic regression was used to obtain estimates of the association between various reproductive factors and tumor characteristics. At the end of follow-up, 48.2% of the women (n = 83) whose last birth occurred in < 2 years of diagnosis had died, compared with 23.3% of nulliparous women (n = 189) and 24.4% of the women (n = 661) whose last birth was > or =5 years before diagnosis. The tumors of the women with a recent birth (<2 years before diagnosis) were more likely to be progesterone receptor negative, odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.2-3.9, to be p53 positive, OR = 2.6, 95% CI = 1.5-4.7, to be of high histological grade, OR = 5.9, 95% CI = 1.7-20.1, to have high mitotic count, OR = 2.2, 95% CI = 1.4-4.4, to be node positive, OR = 2.1, 95% CI = 1.3-3.5, to have a high S phase fraction, OR = 2.3, 95% CI = 1.1-4.8, and to have a high American Joint Committee on Cancer stage (III+), OR = 2.8, 95% CI 1.3-5.8, compared with the tumors of nulliparous women. After adjusting for tumor characteristics and treatment, the risk of mortality associated with a birth in < 2 years of diagnosis of breast cancer remained an independent predictor of mortality, hazard radio (HR) = 2.7, 95% CI = 1.6-4.3. Our study provides evidence that reproductive factors influence the biological behavior of breast cancer in young women and prognosis. Clinicians need to be aware that women who have delivered a child in < 2 years before diagnosis are at increased risk of having tumors with especially adverse prognostic profiles and have a poorer survival rate than women who are nulliparous or whose last birth was some years in the past.     

Lifetime exercise activity and breast cancer risk among post-menopausal women.

Lifetime exercise activity has been linked to breast cancer risk among young women. However, no study has specifically evaluated whether lifetime exercise activity is related to the breast cancer risk of post-menopausal women. We conducted a population-based case-control study of post-menopausal white women (1123 newly diagnosed cases and 904 healthy controls) aged 55-64 who lived in Los Angeles County, California, USA to evaluate this relationship. Although neither exercise activity from menarche to age 40 years, nor exercise after age 40 separately predicted breast cancer risk, risk was lower among women who had exercised each week for at least 17.6 MET-hours (metabolic equivalent of energy expenditure multiplied by hours of activity) since menarche than among inactive women (odds ratio (OR) = 0.55; 95% confidence interval (CI) 0.37-0.83). Exercise activity was not protective for women who gained considerable (> 17%) weight during adulthood. However, among women with more stable weight, breast cancer risk was substantially reduced for those who consistently exercised at high levels throughout their lifetime (OR = 0.42; 95% CI 0.24-0.75), those who exercised more than 4 h per week for at least 12 years (OR = 0.59; 95% CI 0.40-0.88), and those who exercised vigorously (24.5 MET-hours per week) during the most recent 10 years (OR = 0.52; 95% CI 0.32-0.85). Strenuous exercise appears to reduce breast cancer risk among post-menopausal women who do not gain sizable amounts of weight during adulthood.     

Risk factors for breast cancer in Turkish women with early pregnancies and long-lasting lactation--a case-control study

A hospital-based case-control study was carried out among 504 women with breast cancer and 610 controls to analyse the risk factors for breast cancer in Turkey. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor were obtained from logistic regression analysis. Risk factors for breast cancer were found to be long-term lactation (> or = 5 years versus never OR 0.31, 95% CI 0.12-0.79), young age at menarche (< 15 years versus > or = 15 OR 1.72, 95% CI 1.30-2.28), late age at first full-term pregnancy (> or = 30 versus < 20 OR 2.86, 95% CI 1.32-6.21), oral contraceptive use (ever versus never OR 1.51, 95% CI 1.10-2.08), positive family history (positive versus negative OR 2.81, 95% CI 1.35-5.82), and menstrual irregularity (yes versus no OR 1.61, 95% CI 1.05-2.49). The results of the present study will lead to a better understanding of the risk factors for breast cancer in a developing country.     

Sociocultural predictors of breast cancer risk perceptions in African American breast cancer survivors.

Although African American breast cancer survivors are at increased risk for developing breast cancer again, empirical data are not available on breast cancer risk perceptions in these women. This study characterized perceived risk of developing breast cancer in African American breast cancer survivors at risk for having a BRCA1 or BRCA1 (BRCA1/2) mutation and identified factors having significant independent associations with risk perceptions. Participants were 95 African American breast cancer survivors at an increased risk for having a BRCA1/2 mutation. Risk perceptions and sociodemographic, clinical, treatment, and sociocultural factors were collected during a structured telephone interview. Most women reported that they had the same or lower risk of developing breast cancer again compared with other women (53%); however, a substantial minority of women (47%) reported that they had a higher or much higher risk. Factors having significant independent associations with heightened risk perceptions included having a >or=10% prior probability of having a BRCA1/2 mutation [odds ratio (OR), 2.91; 95% confidence interval (95% CI), 1.09-7.72; P = 0.03] and more years of formal education (OR, 2.74; 95% CI, 1.02-7.36; P = 0.05). In addition, women who thought about the past a lot were three times more likely to report heightened risk perceptions compared with those who did not think about the past a lot (OR, 3.72; 95% CI, 1.45-9.57; P = 0.01). These results suggest that it may be important to ensure adequate risk comprehension among African American women as part of genetic counseling for inherited breast-ovarian cancer risk. Discussion of risk perceptions within the context of existing beliefs and values may facilitate this process.     

The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses' Health Study

Shorter alleles of a polymorphic [CAG](n) repeat in exon 1 of the androgen receptor (AR) have been associated with increased risk of prostate cancer and decreased risk of breast cancer. We prospectively assessed the association between the [CAG](n) repeat polymorphism in the androgen receptor and breast cancer risk among Caucasian women in a case-control study nested within the Nurses' Health Study cohort (cases, n = 727; controls, n = 969). In addition, we assessed whether androgen receptor genotype influences endogenous steroid hormone levels in women and whether the associations between androgen receptor alleles and breast cancer risk differed according to established breast cancer risk factors. Women with one or more long AR [CAG](n) repeat alleles (>or=22 repeats) were not at increased risk of breast cancer [odds ratio (OR), 1.06; 95% confidence interval (CI), 0.83-1.35]. Significant associations were not observed between AR genotypes comprised of two short alleles ([CAG](n) or=22: OR, 0.92; 95% CI, 0.62-1.36) or two long alleles ([CAG](n) >or= 25 versus both alleles or=22; OR, 1.70; 95% CI, 1.20-2.40; P for interaction = 0.04). In summary, we observed no overall relation of AR genotype with breast cancer risk among mostly postmenopausal Caucasian women. However, these data suggest that longer AR [CAG](n) repeat alleles may increase breast cancer risk among women with a first-degree family history of breast cancer.     

The influence of family history on breast cancer risk in women with biopsy-confirmed benign breast disease: results from the Nurses' Health Study

BACKGROUND: An association between histologic category of benign breast disease (BBD) and breast cancer risk has been well documented. However, the influence of a positive family history (FH) on breast cancer risk among women with biopsy-confirmed BBD is less certain. METHODS: The authors conducted a nested case-control study of BBD and breast cancer risk among 2005 women who were enrolled in the Nurses' Health Study. Cases were women with breast cancer who had a previous benign breast biopsy (n = 395 women). Controls were women who also had previous biopsy-confirmed BBD but were free from breast cancer at the time the corresponding case was diagnosed (n = 1610 women). BBD slides were reviewed and categorized as either nonproliferative lesions, proliferative lesions without atypia, or atypical hyperplasia (AH). RESULTS: Compared with women who had nonproliferative lesions and no FH, women who had proliferative lesions without atypia and a positive FH had a higher breast cancer risk (odds ratio [OR], 2.45; 95% confidence interval [95% CI], 1.61-3.70) than women with no FH (OR, 1.51; 95% CI, 1.12-2.06; P = .07). Among women who had AH, the OR for the development of breast cancer was 4.38 (95% CI, 2.93-6.55) for those with no FH and 5.37 (95% CI, 3.01-9.58) for those with a positive FH (P = .57). There was no significant interaction between the type of BBD and FH (P = .74). CONCLUSIONS: A positive FH of breast cancer slightly increased the breast cancer risk among women who had proliferative lesions without atypia. The increase in risk of breast cancer associated with FH was not significant among women who had AH.     

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.     

Evaluating organized breast cancer screening implementation: the prevention of late-stage disease?

The objective of our study was to evaluate organized breast cancer screening implementation by measuring the association between screening program enrollment and late-stage disease. Our setting was a health plan using mailed mammography reminders to women ages > or = 40. We conducted yearly cross-sectional summaries of mammography experience and late-stage (regional or distant Surveillance Epidemiology and End Results Reporting (SEER) stage) breast cancer occurrence for all of the health-plan women ages > or = 40 (1986-1998). We estimated the odds of late-stage breast cancer among health-plan and surrounding community women because it was too early to compare changes in mortality. We also estimated the odds of late-stage disease (1995-1998) associated with program enrollment and mammography screening among health-plan women. We found that mammography-within-two-years increased within the health plan from 25.9% to 51.2% among women ages 40-49 and from 32.9% to 74.7% among women ages> or = 50. Health-plan late-stage rates were lower than those in the surrounding community [ages 40-49: odds ratio (OR), 0.87; 95% confidence interval (CI), 0.77-0.99; ages 50-79: OR, 0.86; 95% CI, 0.80-0.92] and declined parallel to the community. Among health-plan cancer cases, women ages > or = 43 who were enrolled in the screening program and who had at least one program mammogram were less likely to have late-stage disease compared with the women not enrolled in the program (OR, 0.31; 95% CI, 0.16-0.61) but the odds of late-stage was also reduced among program-enrolled women not receiving program mammograms (OR, 0.45; 95% CI, 0.21-0.95). We concluded that enrollment in organized screening is associated with increased likelihood of mammography and reduced odds of late-stage breast cancer. Addressing the concerns of un-enrolled women and those without mammograms offers an opportunity for further late-stage disease reduction.     

Influence of patterns of hormone replacement therapy use and mammographic density on breast cancer detection.

BACKGROUND: There is evidence that factors such as current hormone replacement therapy (HRT) use and mammographic density may each lower the sensitivity of mammography and are associated with a greater risk of developing an interval cancer. This study explores this relationship further by examining the influence of patterns of HRT use and the percentage of mammographic density on the detection of breast cancer by classification of interval cancer. METHODS: This study uses a case-case design nested within a cohort of women screened by the Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both those missed at screening but seen on retrospective review (n = 87) or true intervals without visible tumor signs at screening (n = 288) were matched to 450 screen-detected cancers. The association between the percentage of mammographic density, measured by radiologists and a computer-assisted method, and HRT use, ascertained from a mailed questionnaire, and the risk of being diagnosed with an interval cancer was estimated using conditional logistic regression. RESULTS: A monotonic gradient of increasing risk for interval cancers was found for each 25% increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true intervals]. After adjusting for mammographic density, a significantly increased risk for true-interval cancers remained for women taking estrogen alone (OR, 1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined HRT. CONCLUSIONS: Information on mammographic density and HRT use should routinely be collected at the time of screening. Women at risk should be made aware of the lower sensitivity of mammography and offered alternative procedures for screening.     

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.     

Association of symptoms and breast cancer in population‐based mammography screening in Finland

The study purpose was to assess association of symptoms at screening visits with detection of breast cancer among women aged 50–69 years during the period 2006–2010. Altogether 1.2 million screening visits were made and symptoms (lump, retraction, secretion etc.) were reported either by women or radiographer. Breast cancer risk was calculated for each symptom separately using logistic regression [odds ratio (OR)] and 95% confidence intervals (CIs). Of the 1,198,410 screening visits symptoms were reported in 298,220 (25%) visits. Breast cancer detection rate for women with and without symptoms was 7.8 per 1,000 and 4.7 per 1,000 screening visits, respectively, whereas lump detected 32 cancers per 1,000 screens. Women with lump or retraction had an increased risk of breast cancer, OR = 6.47, 95% CI 5.89?7.09 and OR = 2.19, 95% CI 1.92–2.49, respectively. The sensitivity of symptoms in detecting breast carcinoma was 35.5% overall. Individual symptoms sensitivity and specificity ranged from, 0.66 to 14.8% and 87.4 to 99.7%, respectively. Of 5,541 invasive breast cancers, 1,993 (36%) reported symptoms at screen. Breast cancer risk among women with lump or retraction was higher in large size tumors (OR = 9.20, 95% CI 8.08–10.5) with poorly differentiated grades (OR = 5.91, 95% CI 5.03–6.94) and regional lymph nodes involvement (OR = 6.47, 95% CI 5.67–7.38). This study was done in a setting where breast tumors size is generally small, and symptoms sensitivity and specificity in diagnosing breast tumors were limited. Importance of breast cancer symptoms in the cancer prevention and control strategy needs to be evaluated also in other settings.     

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.     

Mammographic breast density and family history of breast cancer

The association between mammographic breast density and breast cancer risk may be the result of genetic and/or environmental factors that determine breast density. We reasoned that if the genetic factors that underlie breast density increase breast cancer risk, then breast density should be associated with family history of breast cancer. Therefore, we determined the association between mammographic density and family history of breast cancer among women in the San Francisco Mammography Registry. Mammographic density was classified using the four BI-RADS criteria: 1 = almost entirely fatty, 2 = scattered fibroglandular tissue, 3 = heterogeneously dense, and 4 = extremely dense. We adjusted for age, body mass index, hormone replacement therapy use, menopause status, and personal history of breast cancer. Compared with women with BI-RADS 1 readings, women with higher breast density were more likely to have first-degree relatives with breast cancer (BI-RADS 2, odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.96 to 1.89; BI-RADS 3, OR = 1.70, 95% CI = 1.19 to 2.40; BI-RADS 4, OR = 1.70, 95% CI = 1.05 to 2.71). Thus, the genetic factors that determine breast density may determine breast cancer risk.     

Effects of mammographic density and benign breast disease on breast cancer risk (United States)

Background: Having either a history of benign breast disease, particularly atypical hyperplasia or extensive mammographic breast density, is associated with increased breast cancer risk. Previous studies have described an association between benign breast disease histology and breast density. However, whether these features measure the same risk, or are independent risk factors, has not been addressed. Methods: This case–control study, nested within the prospective follow-up of the Breast Cancer Detection Demonstration Project, evaluated both benign histologic and mammographic density information from 347 women who later developed breast cancer and 410 age- and race-matched controls without breast cancer. Multivariate logistic regression analyses provided maximum-likelihood estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relative risk of breast cancer associated with each exposure. Results: Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95% CI: 1.3–3.6), and adjusting for benign breast histology, the OR for 75% density was 3.8 (95% CI: 2.0–7.2). Women with nonproliferative benign breast disease and 75% density had an OR of 5.8 (95% CI: 1.8–18.6), and women with <50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1–8.0). Conclusions: In this study, both benign breast disease histology and the percentage of the breast area with mammographic density were associated with breast cancer risk. However, women with both proliferative benign breast disease and 75% density were not at as high a risk of breast cancer due to the combination of effects (p = 0.002) as women with only one of these factors.     

Androgen receptor gene polymorphism and breast cancer susceptibility in The Philippines.

Up to one-third of women with breast cancer have a family history of breast cancer, and approximately 5% of cases are attributed to mutations in high-risk breast cancer susceptibility genes, such as BRCA1 and BRCA2. It is believed that genes of lower penetrance, but of greater prevalence, may also modulate a woman's risk of breast cancer. We studied the association of breast cancer and the trinucleotide repeat polymorphism (CAGn) in exon 1 of the androgen receptor gene (AR) in 299 cases of breast cancer and in 229 hospital-based controls from The Philippines. Women for whom the mean length of the CAG repeat allele was < or = 25 units had approximately one-half of the risk of breast cancer compared with women with a mean repeat length of > or = 26 [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.28-0.8). The association with breast cancer risk was particularly strong among older women (> or = 50 years; OR, 0.2; 95% CI, 0.04-0.94). The association was also observed for the longer of the two AR alleles; there was a 5% increase in breast cancer risk for each unit increase in CAG repeat number. These findings support the theory that short trinucleotide repeat genotypes of the AR gene protect against breast cancer.