Previous Benign Breast Disease Research Articles

Use of artificial intelligence to identify patients to be assessed in a breast clinic on 2-week wait: a retrospective cohort study

Background: The number of urgent referrals from primary care to specialist one stop breast clinics continues to rise beyond the capacity of the 2-week wait service. This study aims to use artificial intelligence (AI) to identify patients with new breast symptoms requiring a biopsy to identify those who should be prioritised for urgent breast clinic assessment. Methods: Data were collected retrospectively for patients attending one stop triple assessment breast clinic at Broomfield hospital between 1 June and 1 October 2021. PHP machine learning software was used to run AI on the data to identify patients who had a core biopsy in clinic. Results: A total of 794 cases were referred to one stop breast clinic for new breast symptoms—37 male (4.6%) and 757 female (95.3%). The average age of the patients included was 43.2 years. Five hundred thirty-six patients (67.5%) presented with a breast lump, 180 (22.7%) with breast pain, 61 (7.7%) with changes to shape or skin and 13 (1.6%) with a lump identified by their general practitioner. The patients who had a biopsy were of increased age [52.8 (SD 17.9) vs. 44.1 (SD 16.8), P<0.001], and had previous mammogram [n=21, (31.8%) vs. n=148 (20.3%), P 0.03], previous benign breast disease [n=9 (13.6%) vs. n=23 (3.1%), P<0.001], and increased use of HRT [n=13 (19.7%) vs. n=53 (6.4%), P<0.001]. The sensitivity and specificity of AI with neural network algorithms were 84% and 90%, respectively. Conclusion: AI was very effective at predicting the presenting symptoms that are likely to result in biopsy and can therefore be used to identify patients who need to be seen urgently in breast clinic.

Clinicopathological profile of breast cancer from Chhattisgarh India: A single-center hospital-based study.

Global breast cancer incidence is increasing at an annual rate of 3·1%. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%). However, the data from different parts of India are still lacking and the study was conducted to assess the burden of disease at tertiary referral centers in central India. Retrospective record analysis (June 2013-June 2017) of data from outdoor clinics and pathology reports. The patients aged <15 yrs, nonresidence of Chhattisgarh, and diagnosed outside the study period were excluded. The triple assessment was used to diagnose all breast lumps (sensitivity 99%). Eighty patients were diagnosed having breast carcinoma. The mean age for breast cancer was 39 ± 3.028 years (ranged 31-50 years). Twenty patients had locally advanced breast carcinoma. The predominant religion was Hindu 55.00%. The referral pathway to seek medical care for breast cancer was via a gynecologist in 40% (32/80). Familial breast cancers were in 0.03% (3/80) of patients. None breast cancer patients have previous histology-proven benign breast disease. The mean size of the breast cancer lump was 3.56 cm (ranged 1.0-11.0 cm). Overlying skin ulceration (n = 2), skin infiltration/peau-d'- orange (n = 2), skin tethering (n = 4), and bloody nipple discharge were found in one patient. Breast cancer was diagnosed during lactation (postnatal period) in one patient. The maximum number of patients have tumor size >5 cm (72.6%). Immunohistochemistry and pathological analysis was done on core biopsy (n = 20) and surgical procedure (n = 60). Modified radical mastectomy was done in 52, breast conservative surgery with Sentinal Lymph node biopsy and axillary lymph node dissection in 6, and toilet mastectomy in two patients. The predominant tumors were solid (n = 79/80), with both solid and cystic types (1/80). The solid and cystic lesion on FNAC was of C3b type, and an excision biopsy revealed medullary carcinoma of the breast. Invasive ductal carcinoma-no special type (IDC-NST) was observed to be the most common histopathologic type (n = 70/80), followed by medullary carcinoma (n = 2), metaplastic carcinoma (n = 1), papillary carcinoma (n = 4), Paget disease with DCIS (n = 1), mucinous carcinoma (n = 1), invasive lobular carcinoma (n = 1). One male patient with breast cancer and two female patient having bilateral breast cancer also have IDC-NST.Scarff Bloom Richardson Grade was predominantly graded 2 in 46.25% (37/80) of breast cancer patients (Grade 1 = 9, Grade 2 = 37, Grade 3 = 34). Lymphovascular (LVI) and perineural invasion (PNI) were predominantly without LVI and PVI. (Lymphovascular present and perineural invasion present = 4, Lymphovascular present and perineural invasion absent = 32, Lymphovascular absent and perineural invasion absent = 42, Lymphovascular absent and perineural invasion present = 2). Histological examination of axillary lymph nodes showed the presence of malignant cells in all. Triple-negative breast carcinoma was 26.58% (21/79). Most breast cancer presented at stage II A = 37.5% (30/80) and II B = 28.7% (23/80) of the AJCC staging system. The clinico-epidemio and histological profile of breast cancer in Chhattisgarh is similar to other parts of India. Scarff Bloom Richardson Grade was predominantly grade 2 in 46.25% (37/80) contrary to Grade III (70%) in other series from India.

Developing and validating an individualized breast cancer risk prediction model for women attending breast cancer screening.

Several studies have proposed personalized strategies based on women's individual breast cancer risk to improve the effectiveness of breast cancer screening. We designed and internally validated an individualized risk prediction model for women eligible for mammography screening. Retrospective cohort study of 121,969 women aged 50 to 69 years, screened at the long-standing population-based screening program in Spain between 1995 and 2015 and followed up until 2017. We used partly conditional Cox proportional hazards regression to estimate the adjusted hazard ratios (aHR) and individual risks for age, family history of breast cancer, previous benign breast disease, and previous mammographic features. We internally validated our model with the expected-to-observed ratio and the area under the receiver operating characteristic curve. During a mean follow-up of 7.5 years, 2,058 women were diagnosed with breast cancer. All three risk factors were strongly associated with breast cancer risk, with the highest risk being found among women with family history of breast cancer (aHR: 1.67), a proliferative benign breast disease (aHR: 3.02) and previous calcifications (aHR: 2.52). The model was well calibrated overall (expected-to-observed ratio ranging from 0.99 at 2 years to 1.02 at 20 years) but slightly overestimated the risk in women with proliferative benign breast disease. The area under the receiver operating characteristic curve ranged from 58.7% to 64.7%, depending of the time horizon selected. We developed a risk prediction model to estimate the short- and long-term risk of breast cancer in women eligible for mammography screening using information routinely reported at screening participation. The model could help to guiding individualized screening strategies aimed at improving the risk-benefit balance of mammography screening programs.

Breast Density of Mammography is Correlated with Reproductive Risk Factors Regardless of Menopausal Status: A Cross-Sectional Study of the Korean National Screening Program.

Objective:To clarify the limitations of mammography screening for women with dense breasts, we examined breast density and its effects on screening results. Patients and Methods:We performed a cross-sectional, observational study on women who underwent mammography. Data from the National Cancer Screening Program(NCSP) from 2009 to 2013 were used. The study population consisted of participants with high breast density. We used a logistic regression analysis to evaluate the relationships between breast density and reproductive factors and screening results according to menopause status. Results:High breast density was reported for 57.5% of all participants (3,417,319 participants). Screening results indicated breast density of <25%, 25-50%, 51-75%, and ≥76% for 16.4%, 26.3%, 37.8%, and 19.5%, respectively, of participants. According to the screening results, high breast density was correlated with high deferment and recall rates. Reproductive factors, especially parity, breastfeeding, and use of oral contraceptives, had consistent effects on screening results of premenopausal and postmenopausal women. Regardless of menopausal status, age, early onset of menarche (15 years or younger), fewer live births (≤1 birth), and previous benign breast disease were correlated with increased breast density. In postmenopausal women, early-onset menopause and longer-term hormone replacement therapy (≥2 years) also independently increased breast density.Conclusion:Breast density influenced screening results, which could increase the rate of recall. Breast density was also influenced by reproductive factors, with patterns similar to those of breast cancer risk, regardless of menopausal status. We need to identify high-risk women with high density who would probably benefit from supplemental breast cancer screening.

Health and health belief factors associated with screening and help-seeking behaviours for breast cancer: A systematic review and meta-analysis of the European evidence.

The aim of this systematic review was to identify health or health belief factors associated with mammography attendance or with self-initiated medical help-seeking for breast cancer symptoms among women in Europe. Five databases were searched for articles published between 2005 and 2018. Meta-analyses were conducted for 13 factors related to screening attendance and two factors associated with help-seeking behaviour. Where there were too few studies to include in the meta-analysis, a narrative synthesis was undertaken. Sixty-five studies were included. Never having had cervical screening (d=-.72, p<.001) and higher perceived barriers to mammography (d=-.40, p<.001) were associated with lower levels of screening attendance. Possessing health insurance (d=.49, p<.001), greater perceived benefits (d=.31, p<.001) and motivation (d=.36, p=.003) towards screening, and higher perceived seriousness (d=.24, p=.019) and susceptibility (d=.20, p=.024) towards breast cancer were associated with a higher level of screening attendance. Presenting with a non-lump symptom was associated with a longer time to presentation (d=.32, p<.001). The narrative synthesis revealed that previous benign breast disease was associated with a higher level of screening attendance but with a longer time to presentation. The review identified key similarities in factors associated with screening and help-seeking behaviours which offer scope for combined interventions aimed at women that target both behaviours. Furthermore, the review highlighted that fewer studies have focused on help-seeking behaviour, despite two thirds of breast cancer cases being self-detected. Future research should further examine predictors of help-seeking behaviour including a focus on modifiable factors, such as BMI, and physical activity.

Clinical and histologic characteristics of breast cancers in women with previous pathologic diagnosis of benign breast disease in Spain.

Women with a benign breast disease (BBD) have an increased risk of subsequent breast carcinoma. Information is scarce regarding the characteristics of breast carcinomas diagnosed after a BBD. Our aim was to point out the differences in clinical and histologic characteristics of breast carcinomas diagnosed in women with and without a previous pathologic diagnosis of BBD in the context of population-based mammography screening. Retrospective cohort study of all women aged 50-69years who were screened at least once in a population-based screening program in Spain, between 1994 and 2011 and followed up until December 2012. The mean follow-up was 6.1years. We analyzed 6645 breast carcinomas, of whom 238 had a previous pathologic diagnosis of BBD. Information on clinical and histologic characteristics was collected from pathology reports. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95%CI) of occurrence of selected histologic characteristics of breast carcinomas in women with and without a previous BBD. Women with a previous BBD had a higher proportion of ductal carcinoma insitu (DCIS) compared with women without a BBD (22.1% and 13.6%, respectively). Among those diagnosed with an invasive breast carcinoma, women with previous BBD were more likely to be diagnosed with carcinomas sized >2cm (OR=1.46; 95%CI=1.03-2.08), metastatic positive (OR=2.66; 95%CI=1.21-5.86), and with a high Ki-67 proliferation rate (OR=1.93; 95%CI=1.24-2.99). No differences were found across histologic subtypes of BBD. Screening participants with a previous pathologic diagnosis of BBD had a higher proportion of DCIS. However, invasive carcinomas detected in women with a BBD were associated with clinical and histologic characteristics conferring a worst prognosis.

Comparison of the association of mammographic density and clinical factors with ductal carcinoma in situ versus invasive ductal breast cancer in Korean women

BackgroundIn spite of the increasing incidence of in situ breast cancer, the information about the risk factors of in situ breast cancer (DCIS) is scarce as compared to the information available for invasive ductal breast cancer (IDC), with inconsistent findings regarding the difference in risk factors between DCIS and IDC.MethodsWe enrolled 472 women with IDC and 90 women with DCIS and 1088 controls matching for age and menopausal status. Information on risk factors was collected through self-administered questionnaire. Percent mammographic dense area (PDA), absolute mammographic dense area (ADA), and nondense area were assessed using a computer-assisted thresholding technique. Odds ratio (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression model with adjustment for covariates.ResultsLater age at menarche and regular physical exercise were associated with decreased risk of IDC, whereas alcohol consumption, previous benign breast disease, and family history of breast cancer were associated with increased risk of IDC. For DCIS, previous benign breast disease and alcohol consumption were associated with the increased risk, and regular physical exercise was associated with decreased risk. Increase of ADA by 1-quartile level and PDA increase by 10% were associated with 1.10 (95% CI: 1.01, 1.21) and 1.10 (95% CI: 1.01, 1.19) times greater risk of IDC, respectively. The increase of ADA by 1-quartile level and PDA increase by 10% were associated with 1.17 (95% CI: 0.91, 1.50) times and 1.11 (95% CI:0.90,1.37) times greater risk of DCIS, respectively, but the associations were not statistically significant. There was no significant difference in the association with risk factors and mammographic density measures between IDC and DCIS (P > 0.1).ConclusionsDifferential associations of DCIS with mammographic density and risk factors as compared with the associations of IDC were not evident. This finding suggests that IDC and DCIS develop through the shared causal pathways.

Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening

Background:Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer.Methods:The cohort included 42 928 women first screened at the age of 50–51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams.Results:The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively.Conclusions:Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.

Abstract P6-10-19: Clinicopathologic features of breast cancers that develop in women with previous benign breast disease

Abstract Background Women with benign breast disease (BBD) have an increased risk for breast cancer (BC). Almost 30% of all BCs develop in women with prior BBD. Information about the features of the expected BCs after BBD would enable individualized surveillance and prevention strategies for these women. We sought to characterize BCs developing in a large cohort of women with BBD. Methods Our cohort includes 13,485 women who underwent breast biopsy for mammographic or palpable concern between 1967-2001. Biopsy slides were reviewed and classified as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed. Results With a median follow-up of 15.8 years, 1273 women developed BC. Most BCs were invasive (81%), among which 61% were ductal, 13% mixed ductal/lobular, and 14% lobular. Two thirds were intermediate or high-grade, and 29% were node positive. Cancer characteristics were similar across the three histologic categories of BBD, with similar frequency of DCIS and invasive disease, tumor size, time to invasive BC, histologic type of BC, nodal positivity and HER2 positivity. Women with AH had a higher frequency of ER+ BC (91%) vs women with PD (80%) or NP (85%), p=0.02. Conclusion A substantial proportion of all BCs develop in women with prior BBD. We show that the majority of BCs after BBD are invasive tumors of ductal type, with a substantial proportion node positive. 84% of cancers were ER-positive. Chemoprevention should be strongly encouraged in higher-risk women with BBD. Citation Format: Visscher DW, Frost MH, Hartmanan LC, Frank RD, Vierkant RA, McCullough AE, Winham SJ, Vachon C, Ghosh K, Brandt KR, Farrell AM, Tarabishy Y, Hieken TJ, Haddad TC, Kraft RA, Radisky DC, Degnim AC. Clinicopathologic features of breast cancers that develop in women with previous benign breast disease. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-19.

Clinicopathologic features of breast cancers that develop in women with previous benign breast disease.

Women with benign breast disease (BBD) have an increased risk of developing breast cancer (BC). Nearly 30% of all BCs develop in women with prior BBD. Information regarding features of the expected number of BCs after BBD would enhance individualized surveillance and prevention strategies for these women. In the current study, the authors sought to characterize BCs developing in a large cohort of women with BBD. The current study cohort included 13,485 women who underwent breast biopsy for mammographic or palpable concerns between 1967 and 2001. Biopsy slides were reviewed and classified as nonproliferative disease, proliferative disease without atypia, or atypical hyperplasia. BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed. With median follow-up of 15.8 years, 1273 women developed BC. The majority of BCs were invasive (81%), of which 61% were ductal, 13% were mixed ductal/lobular, and 14% were lobular. Approximately two-thirds of the BC cases were intermediate or high grade, and 29% were lymph node positive. Cancer characteristics were similar across the 3 histologic categories of BBD, with a similar frequency of ductal carcinoma in situ, invasive disease, tumor size, time to invasive BC, histologic type of BC, lymph node positivity, and human epidermal growth factor receptor 2 positivity. Women with atypical hyperplasia were found to have a higher frequency of estrogen receptor-positive BC (91%) compared with women with proliferative disease without atypia (80%) or nonproliferative disease (85%) (P = .02). A substantial percentage of all BCs develop in women with prior BBD. The majority of BCs after BBD are invasive tumors of ductal type, with a substantial number demonstrating lymph node positivity. Of all the BCs in the current study, 84% were estrogen receptor positive. Prevention therapy should be strongly encouraged in higher-risk women with BBD.

Evaluating 17 breast cancer susceptibility loci in the Nashville breast health study

Genome-wide association studies have discovered multiple genetic loci associated with breast cancer risk. Investigating these loci would be helpful to evaluate previous findings and identify causal variants for breast cancer. We evaluated index SNPs in 17 of these loci in a study of 1,511 cases and 1,454 controls of European descent. We investigated the overall association with breast cancer and among subtypes defined as ER+ (estrogen receptor positive), ER- (estrogen receptor negative) and triple-negative breast cancer (TNBC). Combined effects of SNPs on breast cancer risk were assessed via a genetic risk score. We evaluated the contribution of both genetic variants and traditional risk factors to a breast cancer risk assessment model. Five of the 17 SNPs were significantly associated (P≤0.05) with overall breast cancer in the same direction as previously reported: rs13387042 (2q35/TNP1), rs4973768 (3p24/SLC4A7), rs2046210 (6q25/ESR1), rs1219648 (10q26/FGFR2), and rs4784227 (16q12/TOX3). When stratified by breast cancer subtype, all five SNPs were associated (P<0.05) with ER+ cancer, three with ER- cancer (rs13387042, rs1219648, and rs4784227), and one with TNBC (rs1219648). A GRS, based on those five significant SNPs, showed strong association with overall breast cancer with ORs (95% CI) of 1.48 (1.22-1.79), 1.85 (1.52-2.25) and 2.26 (1.82-2.80), respectively, for each quartile, (P=2.0×10(-15)). Traditional risk factors, including previous benign breast disease, breast cancer family history and parity, were significantly associated with breast cancer risk in the present study. These factors, together with the GRS, were used to build a breast cancer risk assessment model with a c statistic of 0.6321 from receiver operating characteristic analysis. The contribution of the GRS to the model was greater than prior benign breast disease, family history and parity with the c statistic change of 0.0374, 0.0324, 0.0103, 0.0012, respectively. Our study demonstrates that five SNPs were associated with overall breast cancer, with stronger association for ER+ than ER- cancer as previously reported, and suggests that a risk assessment model incorporating the GRS from five loci is useful in identifying women at high risk of breast cancer.

Time Perspective and Perceived Risk as Related to Mammography Screening

The present study explored the relation of time perspective to perceived risk for breast cancer and mammography screening. Women free from breast cancer (N = 194), eligible for mammography screening in terms of age, completed the Zimbardo Time Perspective Inventory (Zimbardo & Boyd, 1999) and measures of perceived risk, attitude toward performing mammography screening, intention to get a mammogram, and mammography screening behavior. Hierarchical multiple regression analysis revealed that perceived risk of breast cancer (β= .18, p < .01) and intention to be screened (β = .35, p < .01) were significantly associated with mammography screening, after controlling for the effects of sociodemographic (e.g., age, education, and economic level) and health-related variables (e.g., family history of breast cancer and previous benign breast disease). Path analyses including the main psychological variables indicated that perceived risk was indirectly related to intention via attitude (β = .17, p < .01), and to mammography screening through attitude and intention (β = .06, p < .01). Attitude was indirectly related to mammography screening via intention (β = .20, p < .01). Also, a significant indirect association was observed between future orientation and mammography screening, via perceived risk (β = .10, p < .01). Theoretical implications of study findings and suggestions for future research on use of mammography are presented.

Mammography Screening within the Context of the Theory of Planned Behavior: The Role of Personality Traits and Personal Factors

The present study examined the associations between optimism, personal characteristics and theory of planned behavior (TPB) components for mammography screening. Most of the results were in line with TPB which proposed that intention would be the most proximal determinant of a behavior and the effects of other factors including attitudes and perceived behavioral control on behavior would be mediated through intention. However, a number of demographic and health-related factors, including age and a previous benign breast disease emerged as independent factors associated with mammography screening, providing evidence that personal factors should be taken into account in future applications of the TPB when examining mammography screening behavior.

Evaluation of a breast cancer risk prediction model expanded to include category of prior benign breast disease lesion

Benign breast diseases (BBD) encompass several histologic subtypes with various risks of subsequent breast cancer. Information on previous benign breast disease biopsies has been incorporated into breast cancer risk prediction models; however, the type of histologic lesion has not been taken into account. Given the substantial heterogeneity in breast cancer risk dependent on the type of benign lesion, the authors evaluated whether incorporating this level of detail would improve the discriminatory power of risk classification models. By using data from the Nurses' Health Study, a breast cancer nested case-control study (240 cases; 1036 controls), the authors determined predictors of categories of BBD lesions and developed imputation models. The type of BBD, imputed for each cohort member who reported a diagnosis, was added to a modified version of the Rosner-Colditz breast cancer risk prediction model. Compared with the model that included only previous BBD (yes/no), the model that included categories of BBD was significantly improved (P<.0001). Overall, including the category of BBD increased the concordance statistic from 0.628 to 0.635. By using risk reclassification, inclusion of the type of BBD resulted in a 17% increase in incidence per increase of 1 risk decile, holding the model without BBD type risk decile constant. Although the current data suggested that the inclusion of BBD category may improve breast cancer risk classification, the clinical utility of such a model will depend on the consistency of histologic classification of benign breast disease lesions.

Abstract A74: Association between FGFR2 SNPs, breast cancer risk factors, and clinical and pathological features of breast tumors in the Western New York Exposures and Breast Cancer (WEB) study

Abstract A74 Previous observations indicate that FGFR2 is involved in estrogen-related breast carcinogenesis and is amplified and overexpressed in breast cancer, the levels of expression being higher in ER-positive than ER-negative cell lines and tumors. In two recent genome-wide association studies (GWAS), SNPs in intron 2 of FGFR2 were associated with breast cancer risk with ORs of about 1.6. To date, 2 studies have found stronger associations of FGFR2 SNPs with ER+, PR+, lower grade, node positive breast tumors and one study found a positive correlation with family history of breast cancer. Here we investigated 4 SNPs (rs11200014, rs1219648, rs2420946, rs2981579) in intron 2 of FGFR2 in order to replicate the GWAS findings and assess the association with breast cancer risk factors, and clinical and pathological features of breast tumors in a population-based case-control study, the Western New York Exposures and Breast Cancer study. Genomic DNA and SNP genotyping was performed by allelic discrimination real time PCR for 991 cases and 1698 controls. Demographics, reproductive history, lifetime alcohol consumption and smoking were queried by interview. Clinical and pathological characteristics of 803 tumors were abstracted from hospital records. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). We confirmed the overall association of variant alleles of FGFR2 intron 2 SNPs with breast cancer risk (OR 1.52, CI 1.20-1.94) as well as previously reported associations with ER+ (1.36, 1.11-1.67), PR+ (1.47, 1.19-1.83), lower grade tumors (1.57, 1.10-2.25) and family history of breast cancer (2.00, 1.50-2.67). We also found an association with negative node tumors in our sample set (1.29, 1.05-1.58). Additionally, we observed associations with Ki67- (1.33, 1.16-1.52), lower stage (1.42, 1.21-1.66) and smaller size (1.39, 1.21-1.59) tumors. Also, all four SNPs were associated with older age (1.96, 1.47-2.61), higher education (1.51, 1.17-1.94), higher postmenopausal BMI (1.53, 1.15-2.05), younger age at menarche (1.48, 1.05-2.08), lower number of births (2.55, 1.77-3.68), and previous benign breast disease (2.28, 1.76-2.95). Marginal association with alcohol drinking (OR 1.46, CI 0.92-2.32) and significant association with smoking status (OR 1.94, 1.37-2.75) were found. This is the first study that comprehensively investigates interactions of FGFR2 SNPs with breast cancer risk factors, and clinical and pathological features of breast tumors in relation to breast cancer risk. Our results support the hypothesis that FGFR2 is involved in estrogen-related breast carcinogenesis, suggested by the association with ER+ tumors and reproductive history. Moreover, lifestyle exposures like alcohol and smoking seem to modulate the association of FGFR2 SNPs and breast cancer, perhaps through estrogen related mechanisms as well, although further studies are needed to elucidate these mechanisms. Supported by the following grants: DAMD-17-03-1-0446, DAMD-17-00-1-0417 and NCI-RO1CA92040 Marian C was supported by an AVON-AACR International Scholar in Breast Cancer Research Award Citation Information: Cancer Prev Res 2008;1(7 Suppl):A74.

Participant characteristics on an international NCIC CTG breast cancer prevention trial

1531 Background: Antagonizing estrogen with tamoxifen has set the precedent for preventing breast cancer. Aromatase inhibitors reduce contralateral breast cancer in the adjuvant setting more than tamoxifen. The goal of MAP.3 is to determine whether exemestane reduces invasive breast cancers in post-menopausal women at risk for the disease. Methods: NCIC CTG MAP.3 is a randomized placebo controlled double blind trial of exemestane versus placebo. Recruitment began in September 2004 in North America and Spain. Criteria for entry on MAP.3 include: a Gail score of 1.66%; previous benign breast disease including LCIS; age over 60. The target sample size for the trial is 4560. Baseline characteristics of women enrolled thus far on MAP.3 were reviewed to determine whether their projected risk of breast cancer is consistent with the assumptions made in designing the trial. Results: Baseline characteristics are available on the 1784 women enrolled to MAP.3 to date. Over 70% of participants are over 60 years old (mean 64; SD=8.2 years) and the majority of the women are Caucasian (85%). The average 5-year risk of breast cancer is 2.7% (median, 2.2%). However, a greater proportion of women over 60 (30%) have a substantially lower Gail score (&lt;1.66) compared to women less than 60 years of age (8%). Few women in the MAP.3 cohort have been enrolled on a basis of a history of prior breast atypical hyperplasia or LCIS (8%), or DCIS treated with mastectomy (2%). Nearly half the MAP.3 participants (45%) have at least one first degree relative with malignant breast cancer, and 7.5% of these women have 2 or more first degree relatives with the disease. Conclusions: The risk profile of the women on MAP.3 will determine the event rate and therefore the time to trial unblinding and analysis. This initial description of the MAP.3 population enrolled thus far indicates a slightly lower baseline breast cancer risk in comparison to the risk profile of those enrolled in previous breast cancer prevention trials with tamoxifen or raloxifene (NSABP P1, IBIS-1 and STAR). Reasons for this difference are being explored. [Table: see text]

Benign breast disease, recent alcohol consumption, and risk of breast cancer: a nested case–control study

IntroductionAlcohol consumption is a well-established risk factor for breast cancer. Some studies have suggested that the risk of breast cancer associated with alcohol consumption is greater for women with a history of benign breast disease (BBD). We hypothesized that among women with biopsy-confirmed BBD, recent alcohol consumption would increase the risk of breast cancer in women with proliferative breast disease to a greater extent than in women with nonproliferative breast disease.MethodsWe conducted a nested case–control study in the Nurses' Health Study I and II. The cases (n = 282) were women diagnosed with incident breast cancer, with a prior biopsy-confirmed breast disease. The controls (n = 1,223) were participants with a previous BBD biopsy, but without a diagnosis of breast cancer. Pathologists reviewed benign breast biopsy slides in a blinded fashion and classified the BBD as nonproliferative, proliferative without atypia, or atypical hyperplasia, according to standard criteria.ResultsWomen with nonproliferative breast disease consuming ≥ 15 g of alcohol per day had a nonsignificant 67% increased risk of breast cancer (odds ratio = 1.67; 95% confidence interval 0.65 to 4.34) compared with nondrinkers. There was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent in women with proliferative BBD than among women with nonproliferative BBD (P for interactio n = 0.20).ConclusionContrary to our a priori hypothesis, there was no evidence that recent alcohol consumption increased the risk of breast cancer to a greater extent among women with proliferative BBD than among women with nonproliferative BBD.

Anaesthesia for breast surgery

surgery, there are numerous others: for example, benign lump excision, abscess incision and drainage, breast reduction or augmentation, and reconstructive procedures after mastectomy. Breast cancer is the most frequent cancer in women and is responsible for 20% of cancer deaths; its incidence in women > 50 years is 1 in 400 per year. Its prevalence has increased dramatically due to improved survival and introduction of screening programmes. Risk factors for breast cancer include age, environment, earlier menarche and later menopause, age at first pregnancy, family history, previous benign breast disease, radiation, life-style (diet, weight, alcohol intake), oral contraceptives and hormone replacement therapy. Some 5–8% of breast cancers are genetic, the associated genes being BRCA-1, BRCA-2 and P53.

Pathologic features of breast cancers in women with previous benign breast disease.

To compare pathologic features of the cancers arising after different types of benign breast disease (BBD), we reviewed the invasive breast cancer slides of 169 women with a previous benign biopsy result. Lesions were categorized previously as nonproliferative, proliferative without atypia, or atypical hyperplasia. Pathologic features of the cancers were evaluated without knowledge of the previous BBD category. Estrogen and progesterone receptor immunohistochemistry was performed on available tissue blocks. The median times between a benign result and cancer were 100, 124, and 92 months for women with nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia, respectively. Cancers in the 3 groups did not differ significantly in tumor size, axillary lymph node status, or histologic grade, and there was no significant difference in the distribution of histologic types of breast cancer. Lymphatic vessel invasion, extensive intraductal component, and hormone receptor status did not differ among BBD categories. The pathologic features of breast cancers that develop in women with a previous benign biopsy result do not vary according to the histologic category of the previous BBD.

P53 gene mutations in women with breast cancer and a previous history of benign breast disease

Mutations of the p53 tumour suppressor gene are the most common genetic lesions in human cancers and have been reported in breast cancer as part of the Li-Fraumeni syndrome. In the present study, we determined frequencies and types of the p53 mutations in breast cancer tissues in women with a history of benign breast disease (BBD) identified in Florence, Italy, with ( n = 6) or without ( n = 10) a family history of breast cancer. Among the cases with a family history of breast cancer and BBD, 2 out of 6 had p53 gene mutations in cancer samples. 1 patient had a mutation at codon 248 and the other had double mutations at codons 243 and 241. In these cases, the p53 gene was also analysed in the tissue samples from previous BBD lesions; however, no mutations were observed (0 out of 6). These results suggest that the p53 mutations occur during advanced stages of tumour progression. In sporadic breast cancer cases with a history of BBD, p53 point mutations were observed in four samples (4 out of 10). Two of these mutations turned out to be silent changes and one of the samples showed triple mutations at amino acid positions 267, 277 and 296. No p53 gene mutations were found in the breast tumour tissues of 10 additional women from the same area with a family history of breast cancer, but no previous BBD (0 out of 10). Family history of breast cancer does not appear to affect the frequency of p53 mutations in women with a previous history of BBD.