PB.11: Identifying women at high risk of developing breast cancer: implications of adjusting for inter-observer variability in visual analogue scale assessment of percentage breast density

e12626 Background: Morphological evaluation of tumor lymphocyte infiltration (TIL) in breast cancer (BC) is gaining importance in the clinical setting, as it provides good prognostic information. Most institutions adhere to TIL working group guidelines for evaluating TIL, while having to settle on an acceptable error margin due to its subjective nature, which leads to intra and inter-observer scoring discordance. We aimed to analyze both at our institution, using experienced and inexperienced examiners, with a continuous variable scoring system. Methods: 209 BC core needle biopsy (CNB) samples were stained using hematoxylin-eosin. The percentage of stromal TIL was scored using a numerical variable ranging from 1 to 100. The examination group consisted of two experienced pathologists (pathologist A and B) and one inexperienced examiner - a medical oncology resident with a learning process containing study of the TIL working group analysis criteria and about 100 samples analysed together with an experienced pathologist Pathologist A and the resident analyzed the study samples twice, pathologist B once. Intraclass correlation coefficient (ICC) was used to measure overall intra and inter-observer agreement. Statistical analysis was performed using Google Sheets and Python. Results: 203 CNB samples were analysed (6 were excluded due to inadequate quality or an inconclusive diagnosis). Patients were aged 26 to 79 years (median 49). Sample size ranged from 1 to 16 mm (median 8). The proportion of BC subtypes was: luminal A-like 18%, luminal B-like 39%, HER2+ 10%, luminal B-like HER2+ 12%, TNBC 18%, not defined 2%. The highest proportion of high stromal TIL (≥50%) was seen in HER2+ (30%) and TNBC (22%) subtypes, as observed by pathologist A. We found good intra and inter-observer ICC (Table). Conclusions: Acceptable intra and inter-observer variability was observed in experienced pathologists, suggesting that the proposed methodology could reliably be used in clinical practice, research and trials. Interestingly, variability analysis of scores from a trained non-pathologist has also produced good results. However, it is important to note that inexperienced scoring could be prone to errors, for example counting non-lymphocyte cells as such, not recognizing regions of necrosis or sample damage, or not distinguishing between the tumor and peripheral stroma. Intraclass correlation: two-way random, single score (ICC2); pathologist A and resident (R) first and second analysis (A1, A2, R1, R2); pathologist B analysis (B1). Interpretation of ICC: <0.50 poor; 0.50-0.75 moderate; 0.75-0.90 good (0.75 = minimal acceptable value for a reliable clinical measurement); >0.90 excellent. Clinical trial information: 2018-000547-11. [Table: see text]

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Persistent inter-observer variability of breast density assessment using BI-RADS® 5th edition guidelines

Clinical Imaging ◽

10.1016/j.clinimag.2021.11.034 ◽

2021 ◽

Author(s):

Leah H. Portnow ◽

Dianne Georgian-Smith ◽

Irfanullah Haider ◽

Mirelys Barrios ◽

Camden P. Bay ◽

...

Keyword(s):

Breast Density ◽

Observer Variability ◽

Inter Observer Variability ◽

Density Assessment

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Breast Cancer in Young Women after Treatment with Irradiation for Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v108.11.3333.3333 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3333-3333

Author(s):

Linda Lee ◽

Melania Pintilie ◽

David Hodgson ◽

Michael Crump

Keyword(s):

Breast Cancer ◽

High Risk ◽

Breast Density ◽

Young Women ◽

Cumulative Incidence ◽

Breast Mri ◽

Increased Risk

Abstract BACKGROUND: Women who are survivors of Hodgkin’s Lymphoma (HL) are at increased risk of developing breast cancer (BCa) as a long-term complication due to the use of extended field (mantle) irradiation (RT) of disease above the diaphragm. Many young women are at significantly increased risk of BCa prior to the age at which routine screening mammography is recommended for the general population. The sensitivity of mammography is lower in these women, in part due to increased breast tissue density characteristic of young pre-menopausal women. Currently, there is a paucity of information on the optimal screening modality and surveillance frequency for these women. METHODS: We reviewed the current BCa screening strategies used for this high risk group at our centre and described the incidence, method of detection, and characteristics of secondary BCas in a cohort of 115 women who received supradiaphragmatic RT for HL before age 30 between 1965 and 2000 at Princess Margaret Hospital (PMH) and who subsequently accepted long-term follow-up in a high-risk screening clinic. RESULTS: Median age at treatment was 22 (range 9–30). Radiation fields were mantle in 106 women, modified mantle in 6, and involved field in 3 (median dose delivered: 35 Gy, range 15–60). RT alone was used for 44 patients while 71 received combined modality therapy, of which 45 (65%) received MOPP. Treatment induced amenorrhea occurred in 15 women (median age 38); hormone replacement therapy was subsequently used by 9. Of the 107 women who participated in annual radiographic BCa screening, 95 were screened with mammogram alone, 1 with breast MRI alone, 8 with mammogram and MRI, and 3 with mammogram and ultrasound. Median age at first mammogram was 36; however, median age decreased with more recent year of HL diagnosis (age 40 for women diagnosed before 1985 compared to age 33 for women diagnosed after 1985, p<0.0001). Women with high breast density received MRI screening more often (p=0.02); however, breast density was not significantly associated with previous breast radiation dose or age at last follow-up. Twelve women were diagnosed with BCa in this cohort, following active breast surveillance for a median of 5 years (representing 584 person-years). The 20-year cumulative incidence of breast cancer was 10.9% (95% CI 5.3–18.8%) in this group of women. This was comparable to the 20-year cumulative incidence of breast cancer of 12% (95% CI 8–17%) in all 448 women with HL treated with supradiaphragmatic radiation before age 30 at PMH during the same time period. BCa occurred after a median of 17 years after treatment for HL (range 13–28). Median age at BCa diagnosis was 40 (range 31–51). Seven cancers were detected by physical exam (6 node-positive invasive BCas, 1 in-situ BCa) and 5 were detected on annual mammograms (1 node-positive invasive BCa, 4 in-situ BCas). CONCLUSIONS: Although women in the more recent treatment cohort are receiving their first mammogram at a younger age, the majority of BCas were still detected clinically, and these BCas had less favorable pathological characteristics. More frequent breast imaging should be considered in women who have had supradiaphragmatic RT for HL. Prospective evaluation of breast MRI as a screening strategy for HL survivors has been initiated at PMH in an effort to detect BCa at an earlier stage.

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Correlation of mammographic breast density with Ki-67 expression in benign breast epithelial cells obtained by random periareolar fine needle aspiration of high risk women

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1011 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1011-1011

Author(s):

Q. J. Khan ◽

B. F. Kimler ◽

E. J. Smith ◽

A. P. O’Dea ◽

P. Sharma ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Mammographic Density ◽

Breast Density ◽

Fine Needle Aspiration ◽

Needle Aspiration ◽

Mammographic Breast Density ◽

Ki 67 ◽

Fine Needle ◽

Cytologic Atypia

1011   >Background: Known risk factors for breast cancer development include elements incorporated into the Gail risk model, mammographic breast density and cytologic atypia detected by Random Periareolar Fine Needle Aspiration (RPFNA). Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. We have previously shown that Ki-67 expression is higher in RPFNA specimens of benign breast cells exhibiting cytologic atypia. It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA. Methods: 344 women at high risk of developing breast cancer (based on personal or family history) seen at The University of Kansas Medical Center high risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment, plus a mammogram were included in the study. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by Chi-square test and continuous variables were analyzed by non-parametric test and linear regression. Results: 40% of women were premenopausal, 7% perimenopausal and 53% were postmenopausal. Median age was 49 years, median 5 year Gail Risk was 2.2%, and median Ki-67 was 1.9%. Median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality and number of cells collected, but was unrelated to Gail risk (as observed previously). Breast density was higher in pre-menopausal women (p=0.001), those with lower BMI (p< 0.001), and lower 5-year Gail risk (p=0.012); Breast density showed no correlation with Ki-67 expression or cytomorphology. Conclusion: Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers for breast cancer chemoprevention trials. No significant financial relationships to disclose.

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The inter-observer variability of breast density scoring between mammography technologists and breast radiologists and its effect on the rate of adjuvant ultrasound

European Journal of Radiology ◽

10.1016/j.ejrad.2016.02.023 ◽

2016 ◽

Vol 85 (5) ◽

pp. 957-962 ◽

Cited By ~ 1

Author(s):

Roei D. Mazor ◽

Avital Savir ◽

David Gheorghiu ◽

Yuliana Weinstein ◽

Ifat Abadi-Korek ◽

...

Keyword(s):

Breast Density ◽

Observer Variability ◽

Inter Observer Variability

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Intra- and Inter-observer Variability in Ultrasound-based Diagnosis of Normal-tissue Toxicity in Breast Cancer Radiotherapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2010.07.585 ◽

2010 ◽

Vol 78 (3) ◽

pp. S245

Author(s):

E.J. Yoshida ◽

H. Chen ◽

M. Torres ◽

F. Andic ◽

H. Liu ◽

...

Keyword(s):

Breast Cancer ◽

Normal Tissue ◽

Observer Variability ◽

Cancer Radiotherapy ◽

Normal Tissue Toxicity ◽

Breast Cancer Radiotherapy ◽

Inter Observer Variability

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BRCA1 and BRCA2 germline mutation carriers have a lower breast density compared to high risk women without such mutations

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1517 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1517-1517

Author(s):

P. Sharma ◽

J. R. Klemp ◽

B. F. Kimler ◽

Q. J. Khan ◽

E. J. Smith ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Breast Density ◽

Genetic Factors ◽

Mammographic Breast Density ◽

Mutation Status ◽

High Risk Women ◽

Mutation Carriers ◽

Chi Square Analysis

1517 Background: High mammographic breast density, a known risk factor for breast cancer is influenced by both genetic and non genetic factors. It is not clear if there are differences in breast densities between BRCA1/2 mutation carriers and high-risk non carriers. The aim of this study was to compare breast density in high-risk women with and without BRCA1/2 mutation. Methods: Women at high risk for development of breast cancer (based on family history, prior precancerous disease or prior breast cancer) who underwent genetic testing at the University of Kansas Breast Cancer Prevention Center between 1998 and 2005 were identified under an IRB approved protocol. BRCA1/2 full sequencing was performed at Myriad Genetic Laboratories. The earliest digitized mammogram of these subjects was identified from a preexisting mammogram database. All mammograms had to be prior to/at least one year from any chemoprevention intervention. For subjects with prior breast cancer, mammogram of the uninvolved breast was used. Breast density was assessed on the left craniocaudal mammographic view by computer assisted method, Cumulus. Frequencies of categorical variables were assessed using chi-square analysis. Continuous variables were assessed using Mann-Whitney non parametric test. Multiple regression analysis was used to investigate whether differences are due to variables other than mutation status. Results: The study population consisted of 284 high-risk women who underwent BRCA1/2 testing and for whom a mammogram was available. 30 (11%) had BRCA1 and/or 2 deleterious mutation. There was no difference between mutation carriers and non-carriers for BMI, 5 year Gail risk, parity, menopausal status and HRT use. Mutation carriers were younger (median age 42 vs. 46, p=0.020) and more likely to have a positive family history (100% vs. 85%, p=0.020). Older age (p<0.001), higher BMI (p<0.001) and having a BRCA1/2 mutation (p=0.025) were significantly associated with a lower breast density. Conclusion: Among high risk women, possession of a deleterious BRCA1/2 mutation is associated with lower breast density after adjusting for factors known to affect breast density. This suggests that breast density may be governed by genetic factors other than BRCA1/2 mutation status. No significant financial relationships to disclose.

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