Incidence Of Invasive Breast Cancer Research Articles

Abstract P4-07-06: Circulating lipids and breast cancer survival in the Malmö diet and cancer study

Abstract Rationale: Overweight and obesity are associated with inferior prognosis in breast cancer. The explanation is considered multifactorial, and dyslipidemia may be a contributing factor. The purpose of this study was to examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods: Circulating lipid levels were measured in the blood sampled upon enrollment in the female MDCS cohort (N=17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991-2014. The follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or five years of follow-up. We estimated the incidence rates of recurrence at five years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results: We enrolled 850 eligible patients. During the five years of follow up, 90 invasive recurrences with over 3,807 person-years occurred. In multivariable analyses, high levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR= 2.30 [95% CI: 1.13-4.68]). However, high levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR= 1.23 [95%CI: 0.68-2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR= 1.34 [95%CI: 0.70-2.58]) or all-cause mortality (tertile 3 vs. 1, HR=1.12 [95%CI: 0.61-2.05]). Conclusion: High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcome. These results warrant further investigation into the importance of lipid-regulation in breast cancer patients. Citation Format: Sixten Harborg, Thomas P Ahern, Maria Feldt, Ann H Rosendahl, Deirdre Cronin-Fenton, Olle Melander, Signe Borgquist. Circulating lipids and breast cancer survival in the Malmö diet and cancer study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-06.

The association between the incidence of post-menopausal breast cancer and residential greenness

BackgroundThere is little data as to whether exposure to residential greenness is associated with the incidence of breast cancer. Lack of physical activity and obesity are two of the accepted risk factors for postmenopausal breast cancer and living near green areas may contribute to an active lifestyle and maintaining a normal body mass index and, consequently, residential greenness may be associated with lower incidence rates. ObjectivesThe objective of this study was to determine whether there was an association between past exposure to residential greenness and the incidence of invasive postmenopausal breast cancer among Canadian women living in Montreal, Quebec, in the mid-2000s. MethodsWe conducted a population-based, case-control study of incident postmenopausal breast cancer in Montreal, Canada, and herein we show analyses by level of greenness surrounding participants’ homes. Incident cases were identified between 2008 and 2011 from all but one hospital that treated breast cancer in the Montreal area. Population controls were identified from provincial electoral lists of Montreal residents and frequency-matched to cases on age. Residential greenness was estimated using the maximum daily normalized difference vegetation index averaged over the growing season (“maximum NDVI”). Maximum NDVI was assigned at the home address of recruitment for the years 1992–1998 (about 15 years before diagnosis), and we measured subjects’ personal information, exposure to NO2 and ultrafine particles, and area-wide variables to control for potential confounding effects. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer associated with residential greenness were estimated using logistic regression models adjusting for various combinations of potential confounders. We assessed the functional form of maximum NDVI using natural cubic splines. ResultsWe found that the response functions between incident postmenopausal breast cancer and maximum NDVI were consistent with linearity. The age-adjusted and fully-adjusted ORs, per increase in the interquartile range (IQR=0.13) of maximum NDVI measured with a 250 m buffer around residences, were 0.95 (95%CI: 0.86–1.04) and 1.00 (95%CI: 0.84–1.11), respectively. For maximum NDVI measured using a 1000 m buffer (IQR=0.05), these were 0.98 (95%CI: 0.94–1.02) and 0.99 (95%CI: 0.95–1.03), respectively. ConclusionsOur findings suggest that exposure to NDVI evaluated where participants were interviewed is not associated with the risk of incident postmenopausal breast cancer.

Statin use and patterns of breast cancer recurrence in the Malmö Diet and Cancer Study

BackgroundAccumulating evidence suggests that statins have a beneficial effect on breast cancer prognosis. Previous studies have reported a positive association between statin use and breast cancer survival; however, the relationship between statin use and patterns of breast cancer recurrence remains unclear. Patients and methodsWe identified all Malmö Diet and Cancer Study (MDCS) participants diagnosed with incident invasive breast cancer between 2005 and 2014. The follow-up period began at breast cancer diagnosis and continued until the first invasive breast cancer recurrence event, death, emigration or the end of the follow-up (June 8, 2020). We estimated incidence rates (IRs) of recurrence and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for disease recurrence to compare post-diagnosis statin users with non-users. ResultsThe final study cohort consisted of 360 eligible patients with a median follow-up of 8.6 years. Overall, there were 71 recurrences in 2932 total person-years. According to statin use, there were 14 recurrences in 595 person-years among statin users, and 57 recurrences in 2337 person-years in non-users. Statin use was associated with a reduced risk of breast cancer recurrence (HRadj = 0.88 [95% CI: 0.82–0.96]). Regarding the pattern of recurrence, statin use was associated with a reduced risk of distant recurrence (HRadj = 0.86 [95% CI: 0.80–0.94]) but not loco-regional recurrence (HRadj = 0.97 [95% CI: 0.87–1.08]). ConclusionIn the MDCS, statin use was associated with a reduced risk of distant breast cancer recurrence, whereas no association between statin use and loco-regional breast cancer recurrence was found. This site-based difference in disease recurrence may be explained by statin's inhibition of epithelial-mesenchymal transition.

Abstract PO-170: Association between outdoor ambient benzene and invasive breast cancer incidence: The Multiethnic Cohort Study

Abstract Background: Benzene is classified as a Group 1 carcinogen in humans. A major pathway of benzene exposure is through the inhalation of ambient air contaminated by emissions from motor vehicle exhaust, gas stations, industries, tobacco smoke, and other consumer products. Past studies on benzene and breast cancer based on job titles or occupational history have yielded mixed results and the role of ambient benzene and breast cancer risk has been sparsely studied. Within the California component of the Multiethnic Cohort study, we examined the association between outdoor exposure to benzene and breast cancer risk among four major U.S. racial/ethnic groups―African Americans, Latinos, Japanese Americans, and Whites. Methods: Outdoor ambient benzene exposure was estimated from U.S. EPA measurements from air monitoring stations that were within 15 km of residences of 57,589 female MEC participants, largely from Los Angeles County, from time of recruitment (1993-1996) through study end date (12/31/2010). Cox proportional hazards models were used to examine the associations between time-varying benzene exposure and invasive breast cancer risk (cases=2,388), adjusting for age, race/ethnicity, education, smoking pack-years, family history of breast cancer, body mass index, physical activity, parity and age at first live birth, age at menarche, menopausal status, use of hormone therapy, alcohol consumption, intake of total calories, and neighborhood (block group) socioeconomic status. Stratified analyses were conducted by race/ethnicity, smoking history, and hormone receptor status. Results: Outdoor ambient benzene exposure (average median level from 1993-2010 was 0.94 ppb) was associated with an increased risk of breast cancer (per 1 ppb hazard ratio [HR]=1.40, 95% confidence interval [CI]: 1.24-1.58). This positive association was observed across all racial/ethnic groups; HR ranged from 1.23 to 1.67 (p values were <0.001 in African Americans, Japanese Americans, and Whites). Analysis by smoking status at baseline showed significant increased risk among former smokers (HR=1.53, 95% CI:1.22-1.91) and never smokers (HR=1.33, 95% CI: 1.12-1.58) but this risk did not reach statistical significance among current smokers (HR=1.27, 95% CI: 0.91-1.79) (Pheterogeneity=0.56). A larger effect estimate of benzene was observed for hormone receptor negative (HR=1.66; 95% CI: 1.18-2.33) than for hormone receptor positive (HR=1.28, 95% CI: 1.10-1.50) breast cancer (Pheterogeneity=0.02). Conclusions: Benzene exposure adversely impacted the risk of breast cancer across all racial/ethnic groups but appeared to be more prominent for hormone receptor negative breast cancer after adjusting for covariates mentioned above. Additional large population-based studies with breast cancer subtypes are needed to further determine benzene's role in breast cancer development. Citation Format: Ugonna Ihenacho, Jun Wu, Chiu-Chen Tseng, Juan Yang, Scott Fruin, Timothy Larson, Salma Shariff-Marco, Loic Le Marchand, Daniel Stram, Beate Ritz, Iona Cheng, Anna H. Wu. Association between outdoor ambient benzene and invasive breast cancer incidence: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-170.

Abstract PO-171: Local economic and racial/ethnic segregation and breast cancer risk: The Multiethnic Cohort Study

Abstract Introduction: Residential segregation has been documented to contribute to health inequities. The Index of Concentration at the Extremes (ICE) is a local measure of residential segregation that can capture economic, racial, and combined racialized economic residential segregation. ICE measures have only recently been examined in cancer studies, few of which have focused on breast cancer risk and none among Asian American or Pacific Islander (AAPI) groups. In the Multiethnic Cohort Study (MEC), we examined the associations of neighborhood ICE measures with breast cancer incidence among 101,811 female participants in five racial/ethnic groups (African American, Latino, Japanese American, Native Hawaiian, and White). Methods: ICE measures were developed based on 1990 U.S. census tract-level data, categorized in quintiles based on Los Angeles county and Hawai'i state-specific distributions, and assigned to the residential census tract of MEC female participants residing, at study baseline, in California (CA) (primarily Los Angeles, n=56,880), and Hawai'i (HI) (n=44,931). Separate ICE measures were created for household income, education, race/ethnicity, and combined household income and race/ethnicity. Women, aged 45-75 at enrollment, completed a comprehensive lifestyle questionnaire and were followed from baseline (1993-1996) to earliest date of invasive breast cancer diagnosis (n=6,398), death, or end-of-follow-up (12/31/2014). Invasive breast cancer incidence was modeled using Cox proportional hazards regression adjusted for demographics, family history of breast cancer, reproductive and lifestyle factor factors. Stratified analyses were conducted by race/ethnicity and stage at diagnosis. Results: For women in CA MEC, there were significantly higher risks of breast cancer for those living in neighborhoods with more versus less concentrated privilege [Q5 v Q1 Hazard Ratios (HR): ICE income 1.16 (1.03-1.31), ICE education 1.21 (1.05-1.39)]. In stratified analyses, these patterns of associations were seen for African Americans, Latinos, and Japanese Americans. Risks were also higher among Japanese American women living in neighborhoods with greater concentrations of Whites versus AAPI [Q5 v Q1 ICE Race HR: 1.77 (1.22-2.57)] and for Latino women living in neighborhoods with greater concentrations of high income-White households versus low income-Hispanic households [Q4 v Q1 ICE Race + Income HR: 1.48 (1.20-1.82)]. For women in HI MEC, those living in neighborhoods with higher versus lower ICE income or ICE education had higher risk of localized stage at diagnosis and lower risk of regional & distant diagnosis (p Het <0.01). No associations were found among White or Native Hawaiian women. Conclusions: Our findings suggest economic residential segregation plays an important role in breast cancer risk among African American, Latino, and Japanese American women. This study also highlights the importance of examining racial and racialized economic residential segregation separately across racial/ethnic groups. Citation Format: Jenna Khan-Gates, Salma Shariff-Marco, Katherine Lin, Pushkar Inamdar, Juan Yang, Yuqing Li, Meera Sangaramoorthy, Christopher Haiman, Loïc Le Marchand, Lynne R Wilkens, Scarlett L Gomez, Iona Cheng. Local economic and racial/ethnic segregation and breast cancer risk: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-171.

Racial disparities in mortality outcomes among women diagnosed with breast cancer in Maryland: Impact of cardiovascular disease and clinical characteristics.

Although racial disparities in breast cancer (BC) mortality have been well documented in the United States, little is known about the impact of coexisting cardiovascular disease (CVD) and other clinical factors on Black-White survival disparities after the diagnosis of BC. This study examined the associations of race, CVD, and clinical factors at diagnosis with the hazard of BC and CVD-related mortality among patients with BC identified from the Maryland Cancer Registry. A total of 36,088 women (25,181 Whites and 10,907 Blacks) diagnosed with incident invasive BC between 2007 and 2017 were included. Subdistribution hazard ratios (sdHRs) for CVD-related and BC mortality were estimated with Fine and Gray regression models, which accounted for the influence of competing events. After a median follow-up of 5.8 years, 8019 deaths occurred; 3896 were BC deaths, and 1167 deaths were CVD-related. Black women had a higher hazard of BC mortality (sdHR, 1.66; 95% confidence interval [CI], 1.55-1.77) and CVD mortality (sdHR, 1.33; 95% CI, 1.17-1.51) in comparison with White women. Associations with CVD mortality were significantly stronger among Black women aged 50 to 59 years (sdHR, 2.86; 95% CI, 1.84-4.44; P for interaction < .001). Among Black women with CVD, the hazard of BC death was 41% higher in comparison with White women. By treatment, a significant association with CVD mortality was observed only among Black women undergoing surgery and radiation (sdHR, 1.61; 95% CI, 1.22-2.13). Clinicians should consider the impact of younger age, preexisting CVD, and BC treatments among Black patients. Early identification of those at risk for worse survival may improve surveillance and outcomes.

Circulating lipids and breast cancer prognosis in the Malm\xf6 diet and cancer study

PurposeExamine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS).Patients and methodsCirculating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort (N = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B).ResultsWe enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]).ConclusionHigh pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes.

Neighborhood disadvantage and individual-level life stressors in relation to breast cancer incidence in US Black women

BackgroundResearch on psychosocial stress and risk of breast cancer has produced conflicting results. Few studies have assessed this relation by breast cancer subtype or specifically among Black women, who experience unique chronic stressors.MethodsWe used prospective data from the Black Women’s Health Study, an ongoing cohort study of 59,000 US Black women, to assess neighborhood- and individual-level psychosocial factors in relation to risk of breast cancer. We used factor analysis to derive two neighborhood score variables after linking participant addresses to US Census data (2000 and 2010) on education, employment, income and poverty, female-headed households, and Black race for all households in each residential block group. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors.ResultsDuring follow-up from 1995 to 2017, there were 2167 incident invasive breast cancer cases (1259 estrogen receptor positive (ER +); 687 ER negative (ER−)). For ER− breast cancer, HRs were 1.26 (95% CI 1.00–1.58) for women living in the highest quartile of neighborhood disadvantage relative to women in the lowest quartile, and 1.24 (95% CI 0.98–1.57) for lowest versus highest quartile of neighborhood socioeconomic status (SES). For ER+ breast cancer, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR = 0.83, 95% CI 0.70–0.98). With respect to individual-level factors, childhood sexual abuse (sexual assault ≥ 4 times vs. no abuse: HR = 1.35, 95% CI 1.01–1.79) and marital status (married/living together vs. single: HR = 1.29, 95% CI 1.08–1.53) were associated with higher risk of ER+, but not ER− breast cancer.ConclusionNeighborhood disadvantage and lower neighborhood SES were associated with an approximately 25% increased risk of ER− breast cancer in this large cohort of Black women, even after control for multiple behaviors and lifestyle factors. Further research is need to understand the underlying reasons for these associations. Possible contributing factors are biologic responses to the chronic stress/distress experienced by individuals who reside in neighborhoods characterized by high levels of noise, crime and unemployment or the direct effects of environmental toxins.

Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer

BackgroundThe incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis.MethodsThe expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively.ResultsBy univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3.ConclusionsCPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.

Mammographic density, endocrine therapy and breast cancer risk: a prognostic and predictive biomarker review.

Mammographic density, endocrine therapy and breast cancer risk: a prognostic and predictive biomarker review.

Risk of Secondary Breast Cancer in Female Non-Hodgkin Lymphoma Survivors: 40 Years of Follow-Up Assessed by Treatment Modality

Survivors of non-Hodgkin lymphoma (NHL) are at increased risk of treatment associated secondary malignancies. We quantified the risk of developing a secondary breast cancer (SBC) in female NHL survivors with over 40 years of follow-up, and evaluated differences in risk by treatment modality.Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio), which accounts for patient years at risk, and absolute excess risk of SBC were assessed in 65,123 female patients diagnosed with NHL as a first malignancy between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Only invasive disease was considered SBC, ductal carcinoma in situ was excluded. Follow up was available through 2016. SIRs were also evaluated for patients stratified by age at and latency from diagnosis.In all, 7,010 (10.8%) patients received radiotherapy alone (RT), 30,393 (46.7%) received chemotherapy alone (CT), and 7,845 (12.0%) received chemotherapy and radiation (CRT). In total, there were 1,480 female SBCs with NHL survivors having a lower incidence of SBC than the endemic rate (O/E 0.91, 95 % CI 0.87-0.96, P < 0.05. Patients treated with RT were at a higher risk of SBC than those who did not receive RT (O/E 1.02, 95% CI 0.93-1.12 vs O/E 0.87, 95% CI 0.82-0.93 respectively; P < 0.05). When stratified by treatment groups (No therapy, RT alone, CT alone, and CRT) there was a significantly higher risk of SBC in the CRT group than any other treatment group (O/E 1.18, 95% CI 1.03-1.34, P < 0.05). When patients were stratified by age at diagnosis, there was a significantly increased risk of SBC in patients who were diagnosed at age < 25 years irrespective of RT status with O/E ratios of 3.07 and 3.97 in the RT and no RT groups, respectively. However, there was no significant difference between these two treatment groups. This effect decreased with increasing age at diagnosis of NHL. The risk of developing SBC was significantly higher at > 10 years from NHL diagnosis (O/E 1.12) compared to < 10 years (O/E 0.82).This is the largest study to examine SBC risk in patients with NHL. These results demonstrate that survivors of NHL have a lower incidence of invasive breast cancer compared to the general population. Patients treated with RT did have an increased risk over those with no RT; however, this did not exceed endemic breast cancer rate. The use of CRT and time > 10 years from NHL diagnosis were associated with higher risk of developing an SBC. Importantly, women diagnosed with NHL < 25 yrs of age had a higher rate of SBCs regardless of RT use. These results may help inform breast cancer screening protocols for women with a history of NHL.

PROFICIENT STRIDES AND INHERENT LIMITATIONS IN CURRENT DIAGNOSTIC STRATEGY OF BREAST MASS

Breast masses might be a mass discovered by patients incidentally during breast self-examination or else by the physician during routine physical examination. These masses have a variable etiology and nature. while, Fibroadenoma considered the most common benign breast mass, contrary, invasive ductal carcinoma is the most common malignancy [1]. Although, the vast majority of these masses are benign, still breast cancer is the furthermost frequently resulting malignancy in females worldwide having an age-standardized incidence rate (ASR) of 39.0 per 100,000 females, and the second leading cause of cancer deaths in women [2-4]. In spite of most breast cancers occur in women older than 50 years, one third of women diagnosed with breast cancer between 1996 and 2000 were younger than 50 years [5,6]. Contempt of medical advances and assuring treatment regime, morbidity and mortality due to breast cancer has seen no signicant changes in developing countries. In the US in 2020, estimations reach 276,480 new cases of invasive breast cancer in women ,and an additional 48,530 cases of ductal carcinoma in situ diagnosed in women [7]. Also, an estimated mortality of 42,170 female patients with breast cancer will occur in 2020. Invasive female breast cancer incidence rates trends increased slightly, by 0.3% per year [2,6,8]. This might probably be due to lack of systematic screening and early detection

Associations between obesity, metabolic health, and the risk of breast cancer in East Asian women.

This study examined the associations between metabolic syndrome(MetS), obesity, their combination as a metabolic obesity phenotype, and the risk of breast cancer in East Asian postmenopausal women. A total of 3,095,336 postmenopausal cancer-free women aged 40-79 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. The incidence of invasive breast cancer was followed up until 2018. The presence of obesity (body mass index[BMI] ≥25 kg/m2), MetS, and each component of MetS was investigated. Obesity and MetS were associated with breast cancer risk, but when the effects of obesity and MetS were mutually adjusted, the associations were attenuated, especially for MetS. Only elevated fasting blood glucose levels and waist circumference increased the risk of breast cancer after adjusting for BMI. Compared to metabolically healthy normal-weight women, metabolically unhealthy normal-weight women, metabolically healthy obese, and metabolically unhealthy obese women had an increased risk of breast cancer. Obesity and MetS were independently associated with an increased risk of breast cancer in postmenopausal women, despite the relationship between MetS and breast cancer appearing to result from a partial association with BMI. Postmenopausal women should be encouraged to control their weight and metabolic health.

Racial/ethnic differences in postmenopausal breast cancer risk by hormone receptor status: The multiethnic cohort study.

There are racial/ethnic differences in the incidence of hormone receptor positive and negative breast cancer. To understand why these differences exist, we investigated associations between hormone-related factors and breast cancer risk by race/ethnicity in the Multiethnic Cohort (MEC) Study. Among 81 511 MEC participants (Native Hawaiian, Japanese American, Latina, African American and White women), 3806 estrogen receptor positive (ER+) and 828 ER- incident invasive breast cancers were diagnosed during a median of 21 years of follow-up. We used Cox proportional hazards regression models to calculate associations between race/ethnicity and breast cancer risk, and associations between hormone-related factors and breast cancer risk by race/ethnicity. Relative to White women, ER+ breast cancer risk was higher in Native Hawaiians and lower in Latinas and African Americans; ER- disease risk was higher in African Americans. We observed interaction with race/ethnicity in associations between oral contraceptive use (OC; Pint .03) and body mass index (BMI; Pint .05) with ER+ disease risk; ever versus never OC use increased risk only in Latinas and positive associations for obese versus lean BMI were strongest in Japanese Americans. For ER- disease risk, associations for OC use, particularly duration of use, were strongest for African Americans (Pint .04). Our study shows that associations of OC use and obesity with ER+ and ER- breast cancer risk differ by race/ethnicity, but established risk factors do not fully explain racial/ethnic differences in risk. Further studies are needed to identify factors to explain observed racial/ethnic differences in breast cancer incidence.

Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative.

Research findings remain inconsistent whether caffeine consumption is associated with invasive breast cancer. We aimed to examine the association between caffeine intake from coffee and tea and incident invasive breast cancer among postmenopausal women. We included 79 871 participants in the Women's Health Initiative Observational Study in the current analysis. Incident invasive breast cancers were identified through September 30, 2015. Caffeine intake (mg/day) from caffeinated and decaffeinated coffee and tea was estimated based on self-reported frequency (cups/day) and average caffeine amount in each beverage. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to explore whether associations of caffeine intake from coffee and tea with invasive breast cancer were different by age, race and ethnicity, smoking status, body mass index, history of hormone therapy use, alcohol intake and subtypes of breast cancer. During a median follow-up of 16.0 years, 4719 incident invasive breast cancers were identified. No significant association was found between caffeine intake from coffee and tea and invasive breast cancer incidence after adjusting for demographic, lifestyle and reproductive factors: HRs (95% CIs) for increasing quartiles of caffeine intake compared to the lowest were 1.03 (0.94, 1.12), 1.04 (0.95, 1.13) and 1.03 (0.94, 1.13), respectively (P-for-trend=.54). No significant associations of coffee and tea intake (cups/day) with overall breast cancer risk were found. Our findings are consistent with others showing no clear association of caffeine consumption with invasive breast cancer among postmenopausal women.

906Can mammographic density add value to the Gail model in risk-stratifying women in BreastScreen Australia?

Abstract Background There is significant interest in personalised, risk-based breast cancer screening. This requires high quality risk assessment. The ‘Gail model’ risk assessment tool has been validated on over 40,000 BreastScreen Australia participants. We assess whether adding mammographic density (MD) information improves risk stratification on that cohort. Methods We used questionnaire data, baseline MD readings (using AutoDensity) and linked screening and cancer registry records from 40,158 BreastScreen Australia participants aged 50–69 years (via the lifepool cohort). We investigated incident invasive breast cancer rates by quintiles of Gail model scores, MD, and combinations of Gail and MD. Results Gail scores and MD values were weakly correlated (r≤0.02). Gail and MD were each strong predictors of incident breast cancer, but stronger predictors when used in combination. For example, the odds ratio for incident invasive breast cancer was 3.6 (95%CI 2.5-6.3) for the 17% of women in the upper two quintiles of both Gail and MD scores compared to the 17% of women in the lower two quintiles of both scores. In comparison, the odds ratio for breast cancer between same-size (each 17%) upper and lower groups for Gail score alone was 2.5 (95%CI 1.8-3.4), and for MD 1.9 (95%CI 1.2-2.9). Conclusions Combining Gail and MD categories improves risk stratification on BreastScreen Australia participants, compared to using Gail or MD alone. Key messages While questionnaire data and MD measures are each strong predictors of future invasive breast cancer among BreastScreen Australia participants, risk prediction is stronger when questionnaire and MD measures are combined.

Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index

Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older. To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI). This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020. Breast Imaging Reporting and Data System breast density category, age, and BMI. The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density. A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women [95% CI, 10.4-12.5 per 1000 women]; scattered fibroglandular densities: 17.2 per 1000 women [95% CI, 16.1-17.9 per 1000 women]; extremely or heterogeneously dense breasts: 23.7 per 1000 women [95% CI, 22.4-25.3 per 1000 women]) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women [95% CI, 11.6-15.5]; scattered fibroglandular densities: 18.4 per 1000 women [95% CI, 17.0-19.5 per 1000 women]; extremely or heterogeneously dense breasts: 22.5 per 1000 women [95% CI, 20.2-24.2 per 1000 women]). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio [HR], 1.39 [95% CI, 1.28-1.50]; ≥75 years: HR, 1.23 [95% CI, 1.10-1.37]). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 [95% CI, 0.58-0.75]; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36). The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.

Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women.

Surveillance, Epidemiology, and End Results (SEER) data from 1973-2010 have been used to show that minority women have disproportionately higher percentages of breast cancers diagnosed at younger ages in comparison with White women. The authors analyzed SEER 21 invasive breast cancer incidence data for 2014-2017 and National Center for Health Statistics mortality data for 2014-2018 and compared invasive incidence and mortality by age in non-Hispanic Black (NH-Black), Asian American/Pacific Islander (AAPI), Native American, and Hispanic women with those in non-Hispanic White (NH-White) women. They evaluated incidence rates and percentages of invasive breast cancer cases and breast cancer deaths occurring before the age of 50years along with advanced-stage incidence rates and percentages in minority women versus NH-White women. Recent SEER data showed that invasive breast cancers were diagnosed at significantly younger ages in minority women versus NH-White women. Among women diagnosed with invasive breast cancer, compared with NH-White women, minority women were 72% more likely to be diagnosed under the age of 50years (relative risk [RR], 1.72; 95% confidence interval [CI], 1.70-1.75), 58% more likely to be diagnosed with advanced-stage breast cancer under the age of 50years (RR, 1.58; 95% CI, 1.55-1.61), and 24% more likely to be diagnosed with advanced-stage (regional or distant) breast cancer at all ages (RR, 1.24; 95% CI, 1.23-1.25). Among women dying of breast cancer, minority women were 127% more likely to die under the age of 50years than NH-White women. NH-Black, AAPI, Native American, and Hispanic women have higher proportions of invasive breast cancers at younger ages and at advanced stages and breast cancer deaths at younger ages than NH-White women. This study analyzes the most recently available data on invasive breast cancers and breast cancer deaths in US women by age and race/ethnicity. Its findings show that non-Hispanic Black, Asian American/Pacific Islander, Native American, and Hispanic women have a higher percentage of invasive breast cancers at younger ages and at more advanced stages and a higher percentage of breast cancer deaths at younger ages than non-Hispanic White women.

Trends in incidence, treatment, survival and subsequent breast cancer in lobular carcinoma in situ in the Netherlands: A population-based analysis

PurposeWe analysed incidence, treatment, survival, occurrence of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) after lobular carcinoma in situ (LCIS) in the Netherlands. MethodsAll women diagnosed with classic LCIS between 1989 and 2017 were identified from the Netherlands Cancer Registry. We calculated overall (OS), relative survival (RS) and cumulative incidence functions (CIF, accounting for competing risks) of mortality, DCIS and IBC. For IBC, standardised incidence ratios (SIR) of IBC were calculated. Analyses were stratified for surgical treatment. ResultsWe included 1890 patients. Median age was 51 years. Median follow-up was 8.5 years. In 1989–2017, LCIS incidence increased from 41 to 124, surgical treatment decreased from 100% to 41.1 % – mostly BCS. 10-year OS and 20-year RS exceeded 90 % in all subgroups. Overall, 48 (2.5 %) and 270 (14.3 %) patients were diagnosed with DCIS and IBC. IBCs were mostly early-stage. After mastectomy, 13 of 14 IBCs presented contralaterally. In the other groups, 64.8–70.9 % of IBCs presented ipsilaterally, 34.5–53.9 % of these were lobular. The SIR of ipsilateral IBC was highest after no surgery (6.9, 95%CI:4.9–9.4), lowest after mastectomy (0.2, 95%CI:0.4–0.8). ConclusionLCIS incidence increased, surgical treatment decreased. The low mortality risks support consideration of active surveillance. However, the increased IBC incidence suggests careful monitoring.

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n=37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend>0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR=0.90, 95% CI: 0.83, 0.98 comparing≥60 g/d with<1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing≥25 g/d with<1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR=0.98, 95% CI: 0.97, 0.99 per 350mg/d). Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.