Low Mammographic Breast Density Research Articles

An analysis of the association between breast density and body mass index with breast cancer molecular subtypes in early breast cancer: data from a Spanish population.

Breast cancer is an important health problem, like obesity and dyslipidemia, with a strong association between body mass index (BMI) and breast cancer incidence and mortality. The risk of breast cancer is also high in women with high mammographic breast density (MBD). The purpose of this study was to analyze the association between BMI and MBD according to breast cancer molecular subtypes. This transversal, descriptive, multicenter study was conducted at three Spanish breast cancer units from November 2019 to October 2020 in women with a recent diagnosis of early breast cancer. Data were collected at the time of diagnosis. The study included 162 women with a recent diagnosis of early breast cancer. The median age was 52years and 49.1% were postmenopausal; 52% had normal weight, 32% overweight, and 16% obesity. There was no association between BMI and molecular subtype but, according to menopausal status, BMI was significantly higher in postmenopausal patients with luminal A (p = 0.011) and HER2-positive (p = 0.027) subtypes. There was no association between MBD and molecular subtype, but there were significant differences between BMI and MBD (p < 0.001), with lower BMI in patients with higher MBD. Patients with higher BMI had lower HDL-cholesterol (p < 0.001) and higher insulin (p < 0.001) levels, but there were no significant differences in total cholesterol or vitamin D. This study showed higher BMI in luminal A and HER2-positive postmenopausal patients, and higher BMI in patients with low MBD regardless of menopausal status.

The Relationship Between Breast Density and Breast Cancer Surgical Outcomes: A Systematic Review.

This study aims to investigate the relationship between mammographic breast density and the surgical outcomes of breast cancer. PubMed, SCOPUS, Web of Science, Science Direct, and the Wiley Library were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Our results included ten studies with a total of 5017 women diagnosed with breast cancer. The follow-up duration ranged from 1 year to 15.1 years. Eight out of the twelve included studies reported that low mammographic breast density was significantly associated with no local recurrence, metachronous contralateral breast cancer, and fewer challenges in the preoperative and intraoperative phases. On the other hand, four studies reported that mammographic breast density is not linked to disease recurrence, survival, re-excision, or an incomplete clinical and pathological response. There is a significant association between low mammographic breast density and reduced challenges in the preoperative and intraoperative phases, as well as no local recurrence and fewer mastectomy cases. However, the link between mammographic breast density and disease recurrence, survival, re-excision, and incomplete clinical and pathological response is less clear, with some studies reporting no significant association. The findings suggest that mammographic breast density may play a role in certain aspects of breast cancer outcomes, but further research is needed to fully understand its impact.

Breast Cancer Incidence After a False-Positive Mammography Result

False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear. To examine long-term outcomes after a false-positive mammography result and to investigate whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result. This population-based, matched cohort study was conducted in Sweden from January 1, 1991, to March 31, 2020. It included 45 213 women who received a first false-positive mammography result between 1991 and 2017 and 452 130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result). The study also included 1113 women with a false-positive result and 11 130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. Statistical analysis was performed from April 2022 to February 2023. A false-positive mammography result. Breast cancer incidence and mortality. The study cohort included 497 343 women (median age, 52 years [IQR, 42-59 years]). The 20-year cumulative incidence of breast cancer was 11.3% (95% CI, 10.7%-11.9%) among women with a false-positive result vs 7.3% (95% CI, 7.2%-7.5%) among those without, with an adjusted hazard ratio (HR) of 1.61 (95% CI, 1.54-1.68). The corresponding HRs were higher among women aged 60 to 75 years at the examination (HR, 2.02; 95% CI, 1.80-2.26) and those with lower mammographic breast density (HR, 4.65; 95% CI, 2.61-8.29). In addition, breast cancer risk was higher for women who underwent a biopsy at the recall (HR, 1.77; 95% CI, 1.63-1.92) than for those without a biopsy (HR, 1.51; 95% CI, 1.43-1.60). Cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR, 1.92; 95% CI, 1.81-2.04) and were more common during the first 4 years of follow-up (HR, 2.57; 95% CI, 2.33-2.85 during the first 2 years; HR, 1.93; 95% CI, 1.76-2.12 at >2 to 4 years). No statistical difference was found for different tumor characteristics (except for larger tumor size). Furthermore, associated with the increased risk of breast cancer, women with a false-positive result had an 84% higher rate of breast cancer death than those without (HR, 1.84; 95% CI, 1.57-2.15). This study suggests that the risk of developing breast cancer after a false-positive mammography result differs by individual characteristics and follow-up. These findings can be used to develop individualized risk-based breast cancer screening after a false-positive result.

The association of metformin and aspirin intake with mammographic breast density: A cross-sectional study.

Our purpose was to investigate the association between Mammographic breast density (MBD), a known strong marker for breast cancer and metformin and aspirin use and duration of use alone or simultaneously, in a sample of Iranian women considering other confounding factors. In a cross-sectional study, 712 individuals were selected out of women referred to two university hospitals for screening mammography. Participants' information was collected with a questionnaire. Four-category density scale (a = almost entirely fatty, b = scattered fibroglandular densities, c= heterogeneously dense, and d = extremely dense) was categorized as low (a&b) and high (c&d) density. The mean age of the participants was 49.80 ± 7.26 years. Sixty-five percent of women belonged to the high and 35% to the low MBD category. Both aspirin and metformin had a significantly negative association with MBD, however, when confounding factors were entered into the models, only aspirin after adjustment for age and BMI had an inverse association with MBD (OR = 0.53, 95% CI: 0.35-0.94). Simultaneous use of metformin and aspirin (OR = 0.44, 95 %CI: 0.17-1.12) was associated with lower MBD. Furthermore, in women who used metformin (OR = 0.23, 95% CI: 0.09-0.62) and aspirin (OR= 0.35, 95% CI: 0.17-0.72) for 2 to 5 years, MBD was significantly lower. However, after the adjustment of confounding factors, these associations were not statistically significant. It seems metformin and aspirin intakes are associated with MBD. However, further studies with more sample size are needed.

Air pollution exposure and mammographic breast density in Tehran, Iran: a cross-sectional study.

BackgroundAir pollution is one of the major public health challenges in many parts of the world possibly has an association with breast cancer. However, the mechanism is still unclear. This study aimed to find an association between exposure to six criteria ambient air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and mammographic breast density (MBD), as one of the strongest predictors for developing breast cancer, in women living in Tehran, Iran.MethodsParticipants were selected from women attending two university hospitals for screening mammography from 2019 to 2021. Breast density was rated by two expert radiologists. Individual exposures to 3-year ambient air pollution levels at the residence were estimated.ResultsThe final analysis in 791 eligible women showed that low and high breast density was detected in 34.8 and 62.2 of participants, respectively. Logistic regression analysis after considering all possible confounding factors represented that an increase in each unit of NO2 (ppb) exposure was associated with an increased risk of breast density with an OR equal to 1.04 (95CI: 1.01 to 1.07). Furthermore, CO level was associated with a decreasing breast density (OR = 0.40, 95CI = 0.19 to 0.86). None of the other pollutants were associated with breast density.ConclusionHigher MBD was associated with an increased level of NO2, as a marker of traffic-related air pollution. Furthermore, CO concentration was associated with a lower MBD, while other criteria air pollutants were not related to MBD. Further studies are needed to evaluate the association between ambient air pollutants with MBD.Supplementary informationThe online version contains supplementary material available at https://doi.org/10.1265/ehpm.22-00027.

Chemoprevention Agents to Reduce Mammographic Breast Density in Premenopausal Women: A Systematic Review of Clinical Trials.

BackgroundHigher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.MethodsWe searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria.ResultsWe identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists.ConclusionsA limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts.

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density

BackgroundWell-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk.MethodsUsing data from a cross-sectional study of 770 women (78% Hispanic, aged 40–61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported “ever” use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use.ResultsWe observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (β = − 6.56, 95% CI = − 9.05 to − 4.06), and dense area (DA) (β = − 9.05, 95% CI = − 14.89 to − 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., β = − 6.86, 95% CI: − 9.67, − 4.05 and β = − 7.07, 95% CI: − 10.97, − 3.17, respectively, for PD) and higher NDA (β = 25.05, 95% CI: 14.06, 36.03; β = 29.76, 95% CI: 14.55, 44.96, respectively).ConclusionsStatin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease.

The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer

PurposeTo evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC). MethodsThe institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson’s Chi Square, Wilcoxon Rank-Sum and logistic regression. ResultsOf 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23–96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts. ConclusionsThe higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.

Involution of Breast Lobules, Mammographic Breast Density and Prognosis Among Tamoxifen-Treated Estrogen Receptor-Positive Breast Cancer Patients.

Mammographic breast density (MD) reflects breast fibroglandular content. Its decline following adjuvant tamoxifen treated, estrogen receptor (ER)-positive breast cancer has been associated with improved outcomes. Breast cancers arise from structures termed lobules, and lower MD is associated with increased age-related lobule involution. We assessed whether pre-treatment involution influenced associations between MD decline and risk of breast cancer-specific death. ER-positive tamoxifen treated patients diagnosed at Kaiser Permanente Northwest (1990–2008) were defined as cases who died of breast cancer (n = 54) and matched controls (remained alive over similar follow-up; n = 180). Lobule involution was assessed by examining terminal duct lobular units (TDLUs) in benign tissues surrounding cancers as TDLU count/mm2, median span and acini count/TDLU. MD (%) was measured in the unaffected breast at baseline (median 6-months before) and follow-up (median 12-months after tamoxifen initiation). TDLU measures and baseline MD were positively associated among controls (p < 0.05). In multivariable regression models, MD decline (≥10%) was associated with reduced risk of breast cancer-specific death before (odds ratio (OR): 0.41, 95% CI: 0.18–0.92) and after (OR: 0.41, 95% CI: 0.18–0.94) adjustment for TDLU count/mm2, TDLU span (OR: 0.34, 95% CI: 0.14–0.84), and acini count/TDLU (OR: 0.33, 95% CI: 0.13–0.81). MD decline following adjuvant tamoxifen is associated with reduced risk of breast cancer-specific death, irrespective of pre-treatment lobule involution.

Mammographic Breast Density of Japanese Women Living in Australia: Implications for Breast Screening Policy.

Background:Mammographic Breast Density (MBD) increases breast cancer risk, lowers sensitivity of mammography and is related to ethnicity. This study compared the MBD of Australian women living in Australia (AW), Japanese women living in Japan (JWJ) and Japan-born women living in Australia (JWA). The outcomes have implications for breast screening policies in Australia. Methods:In this cross-sectional study, mammographic images were collected from a total of 677 women who were examined at BreastScreen NSW or Miyata Hospital, Japan. The images were retrospectively evaluated using the 5th edition Breast Imaging-Reporting and Data System (BI-RADS) to assess the level of MBD. Descriptive analyses and binary logistic regressions were performed. Results:More than 65% of AW had low MBD while the majority of JWJ had high MBD. Among AW, low MBD was found in women aged 40-49 and 50-59. The MBD of JWA showed a similar pattern to JWJ but with a slightly lower MBD. The great majority of JWA aged 40-49 were found to have high MBD compared to women aged 50-59. JWJ were categorised as high MBD regardless of their age. JWA were 5 times more likely and JWJ were 15 times more likely to have high MBD compared to AW. Conclusion:Mammography screening becomes more effective for JW after migration to Australia. For JWA aged 40-49 years, supplemental screening options are indicated to provide better cancer detection. For AW, screening mammography could be equally as effective for AW aged 40-49 years as for those aged 50-59.

Mammographic Breast Density: it’s Role in Tumor Size Assessment with Imaging Techniques

Aims: To study the visual and automatic measurement of mammographic breast density (MBD) and its implications in tumor size assessment using distinct imaging techniques. Methods: Retrospective, observational study of the visual and automatic measurement of mammographic breast density according to the breast imaging data system (BI-RADS) in 212 patients with invasive unifocal breast cancer, excluding microinvasive lesions, who did not receive neoadjuvant chemotherapy. Tumor size assessment is compared using a linear regression according pathologic size with mammographic, US and MR size. The influence of MBD in each technique of pathologic size was seen by Bland-Altman plot. Results: Patient’s mean age was 55, 7±9.9 year-old. The mean size of the lesion stablished by mammography was 16.8± 10.4 (4 -70) mm, by US was 13.6±7.2 (5 – 55) mm and by MR 17.2 ±9.9 (5 – 66) mm. Mean pathologic size was 12.6 ±8.1 (0.3 – 55) mm. Automatic MBD mean was 25.2±16.78. BIRAD assessment with visual and automatic MBD measurements were correlated with a tendency of tumor size overestimation with visual method. Linear regression of tumor size according image techniques with pathologic size showed an adjusted r-square of 27.3% for mammography, 41.8% for US and 51.7% for MR. The best correlation was seen with MR although has a tendency to overestimate tumor size. Only tumor size assessed by mammography was influenced by MBD. With this technique, tumor size was best adjusted for those breasts with lower MBD. Conclusion: Visual measurement overestimates MBD versus automatic measurement according BIRADS categories. MR is the more accurate breast imaging technique for assessing tumor size independently of the BMD, which only influences in the mammographic tumor size estimation.

Prognostic Influence of Preoperative Mammographic Breast Density in Operable Invasive Female Breast Cancer

We aimed to investigate the potential of preoperative mammographic breast density (MBD) as a prognostic factor in breast cancer. Data of 969 patients with primary breast cancer were analyzed. We defined low MBD as fatty or fibroglandular breast, and high MBD as heterogeneously dense or extremely dense breast, respectively. The high MBD group demonstrated a superior overall survival rate compared to the low MBD group (p < 0.001). Favorable prognostic effects of high MBD were observed in subgroups aged >50 years (p < 0.001) and with positive hormone receptor (HRc) and negative human epidermal growth factor receptor 2 (HER2) (p < 0.001). The high MBD group had a higher proportion of patients aged ≤50 years (p < 0.001) and patients with body mass index (BMI) ≤25 kg/m2 (p < 0.001), and a higher proportion of patients who received chemotherapy (p < 0.001). MBD was a significant independent prognostic factor by multivariable analysis (hazard ratio, 0.382; 95% confidence interval, 0.206–0.708). The high MBD group was associated with superior overall survival rates. Preoperative MBD was a strong independent prognostic factor in operable primary invasive female breast cancer, especially in patients with age >50 years and the HRc(+)/HER2(−) subtype. Favorable clinicopathologic features, active treatments, and other factors could contribute to this causality.

Abstract C82: Breast density notification in a racially diverse and immigrant sample of women: Evidence for social disparities in awareness, knowledge, and follow-up

Abstract As mandated by legislation in 31 states, clinical mammographic breast density (MBD) information is currently disclosed to women identified as having heterogeneously or extremely dense breasts on routine mammograms (Breast Imaging-Reporting and Data System [BI-RADS] density categories of C/D, hereafter referred to as high MBD). The New York State legislation, enacted in 2013, informs women about the lower sensitivity of mammography and increased breast cancer risk associated with having dense breasts and advises them to seek risk assessment and additional screening; women with low MBD (BI-RADS density categories of A/B) do not receive density information. The legally mandated MBD information provided to women is ambiguous and written at a high literacy level. Additionally, any follow-up actions on this information taken by women require personal resources, including high educational attainment, health insurance coverage, and access to regular health care provider versed in breast cancer risk assessment and screening guidelines. We investigated the impact of this legislation on women's awareness of MBD, knowledge of its effect on breast cancer risk and detection, and communication with health care providers in a predominately Hispanic and foreign-born sample of 466 women, recruited from a mammography clinic in the Northern Manhattan community of New York City (age range: 40-60 years; 79% Hispanic, 12% African American; 81% foreign-born; 26% less than high school education). Overall 88% of the sample had obtained a prior mammogram since 2013 and 31% had heard about MBD. Awareness of MBD did not differ by risk factors for breast cancer (e.g., family history of breast cancer, breast biopsy, parity-related factors) or psychological factors related to breast cancer screening (breast cancer risk perception and worry). Non-Hispanic white women were significantly more likely to have heard of MBD (81%) than non-Hispanic African American (54%), and Hispanic women (13%). In multivariable logistic regression models, odds of MBD awareness were significantly lower in women who were Hispanic (OR=0.1, 95% CI: 0.04, 0.3 relative to white women), foreign-born (OR=0.3, 95% CI: 0.2, 0.6 relative to U.S.-born), or had lower educational attainment (e.g., OR=0.3, 95% CI: 0.2-0.7 for high school or less vs. college or higher degree). Women with personal high MBD were twice as likely as women with low MBD to be aware of MBD, but adjusting for personal MBD did not substantially alter the associations of race/ethnicity, education, and nativity with MBD awareness. In women who reported awareness of MBD, 47% and 76%, respectively, were able to correctly identify the higher risk and masking potential associated with high MBD, and 31% reported following on MBD information with their health care providers. Racial/ethnic and educational differences in knowledge of MBD impact and health care provider communication were smaller and less consistent. In conclusion, awareness of MBD remains low in women from racial/ethnic minority and lower socioeconomic backgrounds, even in a regularly screened population. These findings underscore the importance of understanding and averting potential unintended disparate consequences of breast density notification. Citation Format: Parisa Tehranifar, Carmen B. Rodriguez, Mariangela Agovino, Karen M. Schmitt. Breast density notification in a racially diverse and immigrant sample of women: Evidence for social disparities in awareness, knowledge, and follow-up [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C82.

Migration History, Language Acculturation, and Mammographic Breast Density.

Background: Breast cancer incidence is lower in many U.S. ethnic minority and foreign-born population groups. Investigating whether migration and acculturation patterns in risk are reflected in disease biomarkers may help to elucidate the underlying mechanisms.Methods: We compared the distribution of breast cancer risk factors across U.S.-born white, African American and Hispanic women, and foreign-born Hispanic women (n = 477, ages 40-64 years, 287 born in Caribbean countries). We used linear regression models to examine the associations of migration history and linguistic acculturation with mammographic breast density (MBD), measured using computer-assisted methods as percent and area of dense breast tissue.Results: The distribution of most breast cancer risk factors varied by ethnicity, nativity, and age at migration. In age- and body mass index-adjusted models, U.S.-born women did not differ in average MBD according to ethnicity, but foreign-born Hispanic women had lower MBD [e.g., -4.50%; 95% confidence interval (CI), -7.12 to -1.89 lower percent density in foreign- vs. U.S.-born Hispanic women]. Lower linguistic acculturation and lower percent of life spent in the United States were also associated with lower MBD [e.g., monolingual Spanish and bilingual vs. monolingual English speakers, respectively, had 5.09% (95% CI, -8.33 to -1.85) and 3.34% (95% CI, -6.57 to -0.12) lower percent density]. Adjusting for risk factors (e.g., childhood body size, parity) attenuated some of these associations.Conclusions: Hispanic women predominantly born in Caribbean countries have lower MBD than U.S.-born women of diverse ethnic backgrounds, including U.S.-born Hispanic women of Caribbean heritage.Impact: MBD may provide insight into mechanisms driving geographic and migration variations in breast cancer risk. Cancer Epidemiol Biomarkers Prev; 27(5); 566-74. ©2018 AACR.

Highlights of This Issue

Causal relationships between thyroid-stimulating hormone (TSH), thyroid hormones, and papillary thyroid cancer (PTC) development remain poorly understood. This nested case–control study measuring concentrations of TSH within prediagnostic serum samples revealed a significantly increased risk of PTC associated with TSH levels below the normal range among women and with TSH levels above the normal range among men. Huang and colleagues observed an inverse association between PTC and TSH levels within the normal range among both men and women. These results could have significant clinical implications for physicians who are managing patients with abnormal thyroid functions and those with thyroidectomy.It is important to protect the privacy of individuals who participate in research. Even if all personal identifying data are removed, individuals can sometimes be reidentified in a dataset. The main purpose of this study was to assess how easy it would be to reidentify specific individuals in a large dataset consisting of 900,000 individuals using dates of exams and diagnosis. Ursin and colleagues used a readily available online tool to assess the number of unique records. At the outset, 94% were unique and therefore reidentifiable. Removing the day in the date reduced this risk to 6%. The authors then added a “fuzzy factor”—a random number—to each month. The number of unique records remained the same, but this made it more difficult to identify one specific individual. In conclusion, data custodians need to start assessing reidentification risks and take measures to reduce risk before sharing large data.To date, findings from epidemiological studies on the therapeutic benefits of metformin and statins in pancreatic cancer have been inconsistent. Such discrepancies are likely a result of methodologic limitations, which include relatively small sample sizes, immortal time bias, and no consideration of interactive effects of metformin and statins. In this large U.S. population–based cohort study, E and colleagues observed that use of statins, but not metformin, was associated with reduced mortality among elderly patients with pancreatic adenocarcinoma, with a 31% reduction for postdiagnostic exposure to statins. These new insights provide crucial data for the planning of randomized clinical trials using statins.In a majority of observational studies, higher vitamin D intakes were associated with lower mammographic breast density among premenopausal women. Breast density is a well-established breast cancer incidence indicator. The purpose of this double-blind, placebo-controlled randomized trial by Brisson and colleagues was to determine whether vitamin D3 supplementation at doses of 1,000, 2,000, and 3,000 IU/day over one year reduces breast density among premenopausal women. Intention-to-treat analysis showed that, after one-year, reduction of breast density with vitamin D3 supplementation was no greater than that seen with placebo. Thus, at doses studied, vitamin D supplementation could not reduce breast cancer incidence through breast density reductions.

Mammographic breast density and risk of breast cancer in women with atypical hyperplasia: an observational cohort study from the Mayo Clinic Benign Breast Disease (BBD) cohort

BackgroundAtypical hyperplasia (AH) and mammographic breast density (MBD) are established risk factors for breast cancer (BC), but their joint contributions are not well understood. We examine associations of MBD and BC by histologic impression, including AH, in a subcohort of women from the Mayo Clinic Benign Breast Disease Cohort.MethodsWomen with a diagnosis of BBD and mammogram between 1985 and 2001 were eligible. Histologic impression was assessed via pathology review and coded as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and AH. MBD was assessed clinically using parenchymal pattern (PP) or BI-RADS criteria and categorized as low, moderate or high. Percent density (PD) was also available for a subset of women. BC and clinical information were obtained by questionnaires, medical records and the Mayo Clinic Tumor Registry. Women were followed from date of benign biopsy to BC, death or last contact. Standardized incidence ratios (SIRs) compared the observed number of BCs to expected counts. Cox regression estimated multivariate-adjusted MBD hazard ratios.ResultsOf the 6271 women included in the study, 1132 (18.0%) had low MBD, 2921 (46.6%) had moderate MBD, and 2218 (35.4%) had high MBD. A total of 3532 women (56.3%) had NP, 2269 (36.2%) had PDWA and 470 (7.5%) had AH. Over a median follow-up of 14.3 years, 528 BCs were observed. The association of MBD and BC risk differed by histologic impression (p-interaction = 0.03), such that there was a strong MBD and BC association among NP (p < 0.001) but non-significant associations for PDWA (p = 0.27) and AH (p = 0.96). MBD and BC associations for AH women were not significant within subsets defined by type of MBD measure (PP vs. BI-RADS), age at biopsy, number of foci of AH, type of AH (lobular vs. ductal) and body mass index, and after adjustment for potential confounding variables. Women with atypia who also had high PD (>50%) demonstrated marginal evidence of increased BC risk (SIR 4.98), but results were not statistically significant.ConclusionWe found no evidence of an association between MBD and subsequent BC risk in women with AH.

Prognostic contribution of mammographic breast density and HER2 overexpression to the Nottingham Prognostic Index in patients with invasive breast cancer

BackgroundTo investigate whether very low mammographic breast density (VLD), HER2, and hormone receptor status holds any prognostic significance within the different prognostic categories of the widely used Nottingham Prognostic Index (NPI). We also aimed to see whether these factors could be incorporated into the NPI in an effort to enhance its performance.MethodsThis study included 270 patients with newly diagnosed invasive breast cancer. Patients with mammographic breast density of <10 % were considered as VLD. In this study, we compared the performance of NPI with and without VLD, HER2, ER and PR. Cox multivariate analysis, time-dependent receiver operating characteristic curve (tdROC), concordance index (c-index) and prediction error (0.632+ bootstrap estimator) were used to derive an updated version of NPI.ResultsBoth mammographic breast density (VLD) (p < 0.001) and HER2 status (p = 0.049) had a clinically significant effect on the disease free survival of patients in the intermediate and high risk groups of the original NPI classification. The incorporation of both factors (VLD and HER2 status) into the NPI provided improved patient outcome stratification by decreasing the percentage of patients in the intermediate prognostic groups, moving a substantial percentage towards the low and high risk prognostic groups.ConclusionsVery low density (VLD) and HER2 positivity were prognostically significant factors independent of the NPI. Furthermore, the incorporation of VLD and HER2 to the NPI served to enhance its accuracy, thus offering a readily available and more accurate method for the evaluation of patient prognosis.

Abstract P5-08-41: Prognostic contribution of mammographic breast density and HER-2 overexpression to the Nottingham prognostic index in patients with invasive breast cancer

Abstract Purpose: To examine the associations between very low mammographic breast density (VLD), HER2, ER and PR status in a more homogenized patient group within matched NPI categories. We also aimed to investigate whether those variables could be added to the NPI to enhance its prognostic and predictive values and better categorize which patients are at higher risk. Materials and methods: A total of 270 patients with invasive breast cancer were included in the final analysis. Patients with mammographic breast density of &amp;lt;10% were considered as VLD. We compared the performance of NPI with and without ER, PR , VLD and/or HER2. Factors first underwent univariate and then multivariate analysis to assess the factors combined until the best fit was obtained. Cox multivariate analysis, time-dependent receiver operating characteristic curve (tdROC), concordance index (c-index) and prediction error (i.e. 0.632+ bootstrap estimator) were used to derive an updated version of NPI. Patients' survival was assessed by the Kaplan-Meier method using a log rank (Mantel-Cox) test. Results: The average NPI value was 4.66 (range 2.12-7.40), the percentage of HER2 positive patients progressively increased from the low to the high prognostic groups of NPI (p&amp;lt;0.001). While MBD, ER and PR status showed no such difference in distribution. Patients showed survival differences in the intermediate and high risk groups of NPI according to VLD and HER2 status (p&amp;lt;0.001 and p=0.02, respectively). Outcome analysis showed that the addition of both factors combined provides improved patient outcome stratification superior to the traditional NPI helping to significantly decrease the percentage of patients in the intermediate patient groups. Conclusion: VLD breasts and HER2 positivity are prognostic factors for breast cancer independent of the NPI. Moreover, their addition to the NPI helps increase its prognostic accuracy and reduces the percentage of patients in the intermediate prognostic group. Citation Format: Masarwah A, Sudah M, Sutela A, Päivi A, Ritva V. Prognostic contribution of mammographic breast density and HER-2 overexpression to the Nottingham prognostic index in patients with invasive breast cancer. [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 P5-08-41.

The reciprocal association between mammographic breast density, hyaluronan synthesis and patient outcome.

Low mammographic breast density (MBD) and increased hyaluronan (HA) synthesis have been shown to have adverse effects on breast cancer prognosis. We aimed at elucidating the background of risk associated with mammographic characteristics, MBD and HA and its synthesizing isoforms in an attempt to uncover potential underlying biological mechanisms. MBD and mammographic characteristics of 270 patients were classified according to percentile density (very low density VLD, ≤25 %; mixed density MID, >25 %) and the BI-RADS 5th edition lexicon. Breast density and mammographic features were correlated with the localization and expression of HA, CD44, and HAS1-3 isoforms, and their combined effect on patients' survivals was explored. VLD showed an increased level of HA-positive carcinoma cells and stromal HA, HAS2, and HAS3. Tumors presenting as masses had more HA-positive carcinoma cells and more stromal HAS2 and HAS3. Indistinct margin tumors showed more stromal HA and HAS3. Patients who combined both VLD breasts with either high HA in carcinoma cells or stroma showed a worse prognosis compared to low levels (carcinoma cells 58.0 vs. 80.5 %, p = 0.001; stroma 64.2 vs. 79.6 %, p = 0.017), while no similar HA-related effect was observed in MID breasts. Our findings suggest a strong reciprocal relationship between low MBD and HA expression and synthesis. The expression of both factors simultaneously leads to an especially adverse prognostic effect which might have an impact on treatment decision in the future. Moreover, HA around cancer cells may inhibit chemotherapy agents and antibody treatments from reaching cancer cells.

Breast composition: Measurement and clinical use

Breast density is a measure of the extent of radiodense fibroglandular tissue in the breast. The risk of developing breast cancer and the risk of missing cancer at screening rise with higher breast density. In this paper, the historical background to breast density measurement is outlined and current evidence based practice is explained. The relevance of breast density knowledge to mammographic practice and image interpretation is considered in the light of clinical assessment and notification of mammographic breast density (MBD). The current work also discusses risk stratification for decision-making regarding screening frequency and better modalities for earlier detection of breast cancer in the dense breast. Automated volumetric approaches are explained while ultrasound, digital breast tomosynthesis, molecular breast imaging, and magnetic resonance imaging are introduced as valuable adjuncts to digital mammography for imaging the dense breast. The work concludes on the important note that screened women should be notified of their breast density, and such notification should be accompanied with clear and adequate information about breast density and cancer risk, strategies associated with lower MBD, as well as best screening intervals and pathways for women with dense breasts. Adoption of these strategies may be crucial to early detection and treatment of cancer and improving survival from the disease.