Reduced Risk Of Breast Cancer Research Articles

Linking physical activity to breast cancer via inflammation, Part 2: The effect of inflammation on breast cancer risk.

This review synthesized and appraised the evidence for an effect of inflammation on breast cancer risk. Systematic searches identified prospective cohort and Mendelian randomization studies relevant to this review. Meta-analysis of 13 biomarkers of inflammation were conducted to appraise the evidence for an effect breast cancer risk; we examined the dose-response of these associations. Risk of bias was evaluated using the ROBINS-E tool and the quality of evidence was appraised with Grading of Recommendations Assessment, Development, and Evaluation. Thirty-four observational studies and three Mendelian randomization studies were included. Meta-analysis suggested that women with the highest levels of C-reactive protein had a higher risk of developing breast cancer (RR=1.13, 95% CI=1.01, 1.26) compared to women with the lowest levels. Women with highest levels of adipokines, particularly adiponectin (RR=0.76, 95% CI=0.61, 0.91) had a reduced breast cancer risk, although this finding was not supported by Mendelian randomization analysis. There was little evidence of an effect of cytokines, including TNF- and IL-6, on breast cancer risk. The quality of evidence for each biomarker ranged from very low to moderate. Beyond CRP, the published data do not clearly support the role of inflammation in the development of breast cancer.

Abstract P4-03-23: Comparison of Breast Cancer vs Cardiovascular Disease Risk and Uptake of Chemoprevention vs Statins in a Cohort of Predominantly Hispanic Women Undergoing Screening Mammography

Abstract Background: Atherosclerotic cardiovascular disease (ASCVD) and breast cancer are two of the most diagnosed chronic diseases among women in the U.S. Although prevention of ASCVD with statins is widely practiced, breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) is underutilized in the primary care setting, despite significant evidence in randomized controlled trials demonstrating its clinical benefits. We compared the risk of ASCVD and breast cancer among predominantly Hispanic women undergoing screening mammography, as well as uptake of statins and SERMs/AIs for ASCVD and breast cancer risk reduction, respectively, among high-risk women. Methods: We conducted a retrospective cohort study among 1,655 English or Spanish-speaking women, age 40-79 years, with no prior history of breast cancer, who underwent screening mammography from 2014 to 2016 at Columbia University Irving Medical Center in New York City. Participants completed a survey collecting data on sociodemographic and breast cancer risk factors and had available data in the electronic health record (EHR) for calculating ASCVD risk, including systolic blood pressure, total and HDL cholesterol, history of diabetes, treatment for hypertension, and current smoking status. The main outcomes included 5-year and lifetime invasive breast cancer risk according to the Gail model, and 10-year and lifetime ASCVD risk score according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) ASCVD risk calculator. High-risk was defined as a 5-year invasive breast cancer risk 1.67% and 10-year ASCVD risk 7.5%. Secondary outcomes included uptake of chemoprevention with SERMs or AIs and statins among women at high-risk for breast cancer and ASCVD, respectively, based upon medication lists in the EHR. We compared mean lifetime risk of breast cancer vs ASCVD for the entire cohort using a paired t-test, and the proportion of high-risk women taking statins vs chemoprevention using McNemar’s test. Results: Among 1,655 evaluable women, mean age was 58 years (SD=10.1 years), with 76% Hispanic, 6% non-Hispanic White, 3% non-Hispanic Black, 2% Asian, and 13% other. About half (48%) of women met high-risk criteria for ASCVD compared to 15% who met high-risk criteria for breast cancer. Among all women, mean lifetime ASCVD risk was higher than mean lifetime breast cancer risk (10.71% vs. 5.46%, p< 0.001). Among women at high risk for ASCVD or breast cancer, respectively, statin uptake was higher compared to SERM/AI uptake for breast cancer chemoprevention (84% vs. 7%, p< 0.001). Overall, fewer Hispanic compared to non-Hispanic women met high-risk criteria for ASCVD (47% vs. 51%, respectively) and breast cancer (9% vs. 34%, respectively). Conclusions: In a population of predominantly Hispanic women undergoing screening mammography, we found that more women met high-risk criteria for ASCVD compared to breast cancer. Among women at high risk for ASCVD, statin uptake was about 12-fold higher compared to uptake of breast cancer chemoprevention among women at high risk for breast cancer. Given significant underutilization of breast cancer chemoprevention, placing this in the context of prevention of other chronic diseases, such as statins for ASCVD, may enhance uptake of SERMs or AIs in the primary care setting. Citation Format: Luisa Nilan, Mary M. McDermid, Jacquelyn N. Amenta, Julia E. McGuinness, Katherine D. Crew, Rita Kukafka. Comparison of Breast Cancer vs Cardiovascular Disease Risk and Uptake of Chemoprevention vs Statins in a Cohort of Predominantly Hispanic Women Undergoing Screening Mammography [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-23.

Long-term adherence to healthful and unhealthful plant-based diets and breast cancer risk overall and by hormone receptor and histologic subtypes among postmenopausal females

BackgroundEpidemiological studies assessing the influence of vegetarian diets on breast cancer (BC) risk have produced inconsistent results. Few studies have assessed how the incremental decrease in animal foods and the quality of plant foods are linked with BC. ObjectivesDisentangle the influence of plant-based diet quality on BC risk between postmenopausal females. MethodsTotal of 65,574 participants from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale) cohort were followed from 1993–2014. Incident BC cases were confirmed through pathological reports and classified into subtypes. Cumulative average scores for healthful (hPDI) and unhealthful (uPDI) plant-based diet indices were developed using self-reported dietary intakes at baseline (1993) and follow-up (2005) and divided into quintiles. Cox proportional hazards models were used to estimate adjusted HR and 95% CI. ResultsDuring a mean follow-up of 21 y, 3968 incident postmenopausal BC cases were identified. There was a nonlinear association between adherence to hPDI and BC risk (Pnonlinear < 0.01). Compared to participants with low adherence to hPDI, those with high adherence had a lower BC risk [HRQ3 compared withQ1 (95% CI): 0.79 (0.71, 0.87) and HRQ4 compared with Q1 (95% CI): 0.78 (0.70, 0.86)]. In contrast, higher adherence to unhealthful was associated with a linear increase in BC risk [Pnonlinear = 0.18; HRQ5 compared with Q1 (95% CI): 1.20 (1.08, 1.33); Ptrend < 0.01]. Associations were similar according to BC subtypes (Pheterogeneity > 0.05 for all). ConclusionsLong-term adherence to healthful plant foods with some intake of unhealthy plant and animal foods may reduce BC risk with an optimal risk reduction in the moderate intake range. Adherence to an unhealthful plant-based diet may increase BC risk. These results emphasize the importance of the quality of plant foods for cancer prevention.This trial was registered at clinicaltrials.gov (NCT03285230).

Abstract OT1-15-01: SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE)

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-15-01.

Abstract P3-03-14: Comparing risk of breast cancer and cardiovascular disease and uptake of chemoprevention and statins among racially/ethnically diverse women with atypical hyperplasia or lobular carcinoma in situ

Abstract Background: Chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) has been shown in randomized controlled trials to decrease breast cancer incidence by 50-65% among women at high risk for breast cancer. However, chemoprevention uptake remains low among high-risk women. Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) derive the greatest benefit from SERMs and AIs for breast cancer risk reduction. A potential barrier to chemoprevention uptake is competing comorbidities, including atherosclerotic cardiovascular disease (ASCVD). We calculated risk of breast cancer and ASCVD among women with AH or LCIS and assessed uptake of chemoprevention and statins among women who met high-risk criteria for both breast cancer and ASCVD. Methods: We conducted a retrospective cohort study among women, age 40-74 years, with AH or LCIS diagnosed in 2007-2015 at Columbia University Irving Medical Center (CUIMC) in New York City. Eligible women had sufficient data in the electronic health record (EHR) to calculate 5 and 10-year invasive breast cancer risk according to the Breast Cancer Surveillance Consortium (BCSC) risk calculator, including age, race/ethnicity, first-degree family history of breast cancer, breast biopsy results, and mammographic density. We calculated 10-year ASCVD risk using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) ASCVD risk calculator using additional EHR data, including systolic blood pressure, total and HDL cholesterol, history of diabetes, treatment for hypertension, and current smoking status. High-risk criteria to determine eligibility for SERMs/AIs and statins was defined as a 5-year invasive breast cancer risk 1.67% and 10-year ASCVD risk 7.5%, respectively. We compared mean 10-year risk of breast cancer vs. ASCVD using a paired t-test and uptake of SERMs/AIs vs. statins among women at high risk for breast cancer and ASCVD, respectively, using McNemar’s test. Results: Among 298 evaluable women, mean age was 58.2 years (standard deviation [SD], 8.34), with 33% non-Hispanic White, 41% Hispanic, 9% non-Hispanic Black, 6% Asian, and 11% other/unknown race/ethnicity. About 98% of women met high-risk criteria for breast cancer and 30% were high risk for ASCVD. Mean 10-year risk of breast cancer was higher than mean 10-year risk of ASCVD (9.14% vs. 6.69%, p&amp;lt; 0.001). Among women who met high-risk criteria for both breast cancer and ASCVD, uptake of statins was higher compared to SERMs/AIs (58% vs. 21%, p&amp;lt; 0.001). Comparing non-Hispanic Whites vs. racial/ethnic minorities, mean 10-year breast cancer risk was higher (12.12% vs. 7.71%, p&amp;lt; 0.001), but there were no statistically significant differences in ASCVD risk or uptake of chemoprevention or statins. Conclusions: Among women with AH or LCIS, mean absolute risk of breast cancer was higher compared to risk of ASCVD, however, uptake of statins was higher compared to chemoprevention with SERMs or AIs. To address under-utilization of chemoprevention among high-risk women, use of SERMs or AIs should be placed in the context of medications used for other chronic diseases, such as statins for ASCVD. Citation Format: Luisa Nilan, Jacquelyn N. Amenta, Julia E. McGuinness, Rita Kukafka, Katherine D. Crew, Kehinde Lawal. Comparing risk of breast cancer and cardiovascular disease and uptake of chemoprevention and statins among racially/ethnically diverse women with atypical hyperplasia or lobular carcinoma in situ [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-14.

Abstract GS4-08: 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer

Abstract We have previously shown in a phase 3 trial that tamoxifen 5 mg/day for 3 years decreased by 52% the incidence of recurrence of invasive breast cancer or DCIS after a median follow-up of 5.1 years in women with excised non invasive breast disease, including atypical ductal hyperplasia, DCIS or LCIS (DeCensi et al. JCO 2019; 37:1629). Toxicity was negligible with only an extra hot flash per day in the tamoxifen arm compared with the placebo arm. These findings were incorporated into the ASCO clinical practice guidelines for breast cancer risk reduction as an alternative option to standard doses and duration of tamoxifen or aromatase inhibitors in women with non-invasive disease (Visvanathan et al. JCO 2019; 37:3152). In the present study we update the findings on breast cancer recurrence after a median of 9.14 years (interquartile range, IQR, 7.16-10.73) and a total of 10.57 person years of follow up to see if the treatment effect is retained with more events and after a median of approximately 6 years from treatment cessation. We conducted a national multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. Between November 1, 2008, and March 31, 2015, 1,160 women were screened and 500 aged 75 years of age or younger were included in the study. Women with high-grade or comedo/necrotic DCIS received adjuvant radiotherapy of 50 Gy in 25 courses. The mean age was 54 years (standard deviation, 9 years), and 55% of participants were postmenopausal. The mean (SD) body mass index, kg/m2, was 25.7 (4.8) on tamoxifen and 25.3 (4.2) on placebo. Twenty percent had ADH, 11% had LCIS, and the remaining 69% had DCIS. After a median follow-up of 9.14 years, there were 22 neoplastic events (invasive breast cancer or DCIS) with tamoxifen and 37 with placebo (annual rate 11.09, 95% CI, 7-30-16.84 on T vs 19.71, 95% CI, 14.28-27.21 on P per 1,000 person-years; hazard ratio, 0.56; 95% CI, 0.33 to 0.95; P = .03), which resulted in a 5-year number needed to treat of 18. Overall, 71% of the recurrences were invasive breast cancer. The follow-up was updated with the most recent visit within 12 months in two thirds of the participants, so an update of all participants will be performed by Sept 30th with full analysis of neoplastic events, annual risk rate ratio, serious adverse events and deaths. Moreover, an updated analysis of potential effect modifiers will be conducted, including menopausal status, baseline estradiol levels, menopausal symptoms, BMI, smoking status and Ki-67 of the primary lesion. In conclusion, our findings indicate that low dose tamoxifen given for 3 years still significantly prevents recurrences from non-invasive breast cancer after a median of 6 years from treatment cessation, providing a valid prevention/interception option in this disease group. Supported by Ente Ospedaliero Ospedali Galliera, Genova, Italy, the Italian Ministry of Health (RFPS-2006-1-339898), the Italian Association for Cancer Research (IG 2008 Grant No. 5611), and the Italian League against Cancer (LILT 7-08). Citation Format: Andrea De Censi, Matteo Lazzeroni, Matteo Puntoni, Luca Boni, Aliana Guerrieri Gonzaga, Tania Buttiron Webber, Marianna Fava, Irene Maria Briata, Livia Giordano, Maria Digennaro, Laura Cortesi, Fabio Falcini, Franca Avino, Francesco Millo, Katia Cagossi, Elisa Gallerani, Alessia De Simone, Anna Cariello, Giuseppe Aprile, Maria Renne, Bernardo Bonanni. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-08.

Abstract PD12-04: PD12-04 Impact of Race and Body Mass Index on Breast Cancer Diagnoses

Abstract Background Breast cancer (BC) is the most common cancer among women and the second most common cause of cancer-related mortality among women. Much attention has been paid to factors that increase the risk of developing BC. Among these are weight, typically defined by body mass index (BMI), and race. Elevated BMI has not only been shown to increase the risk of BC in some patients but has also been associated with increased rates of hormone receptor (HR) positive BC, particularly among postmenopausal patients. In premenopausal patients, an inverse relationship has been established between obesity and BC. In fact, a 2008 meta-analysis of obesity and malignancy evaluated almost 8,000 cases of premenopausal BC and showed a BC risk reduction of 8% for every 5 kg/m2. However, this study was not inclusive of African American (AA) patients. AA women are more likely to be obese than any other racial group in the US. They are also at higher risk of aggressive breast cancers, and at an earlier age. We sought to evaluate the relative risk of breast cancer diagnosis among obese vs nonobese patients of different races, as well as the rate of HR positivity in patients diagnosed with BC. Methods BMI, age, and self-declared race were collected from the electronic health record for all female patients presenting to our health system located in Louisiana and Mississippi between 2012 and 2022. This same data was collected for female patients who were diagnosed with BC in the same time period (n=9123), as well as HR positivity vs HR negativity. Patients less than 50 years old were considered premenopausal, and patients greater than 50 years old were considered postmenopausal. BMI greater than 30 was used to define obesity. The relative risk of BC was calculated for demographic groups according to premenopausal or postmenopausal status, White or Black/African American race, and BMI less than or greater than 30. The relative risk of HR positive BC was calculated among the same demographic groups. Discussion Data collected across the largest health system in Louisiana and Mississippi shows that a higher BMI is linked to an increased risk of BC, regardless of age or race. This was seen across both stratifications and was statistically significant except in postmenopausal AA women. This is contrary to what is frequently published in the literature that premenopausal obesity is protective against BC. Additionally, this data demonstrates that there is not a link between obesity and HR+ BC. This data did show that obesity in younger white patients may be protective against HR+ BC, which is aligned with prior research. Conclusion The association between obesity and BC incidence has been well-described in the literature, primarily in the postmenopausal setting. This large, retrospective analysis confirms that association, but also shows a strong association in premenopausal patients. Unlike other studies, this review did not show an association between obesity and HR positivity, and additionally did not show significant differences between AA patients and White patients. This provides needed insight into the inequities faced by AA women with BC. Further studies should be done to evaluate the association of socioeconomic status with BC subtypes. Table 1: Breast cancer cases (5/1/2012-5/1/2022) among women by BMI, age group, and race Table 2: Hormone receptor positivity (5/1/2012-5/1/2022) among women with breast cancer by BMI, age group, and race Citation Format: Victoria Chung, Ruby Maini, Rabia Cattie, Susan Olet, Melanie Sheen. PD12-04 Impact of Race and Body Mass Index on Breast Cancer Diagnoses [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-04.

Abstract P3-03-07: The Breast Cancer Prevention Clinic: A Single Institution’s Experience

Abstract The Breast Cancer Prevention Clinic: A Single Institution’s Experience Authors: Joe J. Stephenson MD1, LeAnn Perkins, FNP-BC, DipACLM1, Erinn Crowe, RN, BSN, OCN1, Regina Franco, MSN, NP-C, DipACLM1, Pamela Cloys, MSN, ANP-C1, Carmen Hancock, MSN, APRN, FNP-C, AOCNP1, Marie Smith, MS1 1Prisma Health Cancer Institute, Center for Integrative Oncology &amp; Survivorship Background: Roughly 1 in 8 women will be diagnosed with invasive breast cancer in their lifetime1. Some women have higher risk for developing breast cancer due to numerous factors such as elevated risk modeling scores, a history of chest radiation therapy, a history of atypical cells on a breast biopsy or a pathogenic genetic mutation. Enhanced surveillance to detect cancers early and addressing modifiable lifestyle risks are helpful to mitigate risks. Methods: The Prisma Health’s Breast Cancer Prevention Clinic (BCPC) approaches prevention by monitoring non-modifiable risks with regular surveillance and education on optimizing lifestyle habits to decrease modifiable risks. Established in 2017, the BCPC team now includes multiple medical oncologists and nurse practitioners, allowing the clinic to be offered any day of the week. During the visit, patients receive a personal risk assessment. Recommendations are given for surveillance imaging, risk-reducing endocrine therapy, and risk-reducing lifestyle modifications such as diet, alcohol consumption, and exercise routines. Family history is also reviewed to recommend Genetic Counseling if appropriate. In March 2022, a statement was added to patient mammograms, generating referrals for those with calculated elevated risk (a calculated lifetime risk &amp;gt;20% using the Tyrer-Cuzick or International Breast Cancer Intervention Study model and/or a 5-year risk &amp;gt;1.7% using the National Cancer Institute Breast Cancer Risk Assessment Tool or Gail model). Results: In a 12-month period from June 1, 2021 through May 31, 2022, 56.2% of patients were referred based on family history, 26.9% for higher-risk breast pathology, 8.1% for calculated elevated risk, 4.4 % for a pathogenic genetic variant that increases breast cancer risk and 4.1% for mammographic identification risk modeling. Following the BCPC visit, referrals for patients may include imaging such as mammograms, MRIs, genetic counseling or testing, or surgical evaluations. Referrals for lifestyle modifications may include nutrition, exercise navigation, mindfulness classes, or Sexual Health Evaluations. From June 2021 through May 2022, 41.4% of patients were referred for a breast MRI, 26.6% were referred to genetic counselors for genetic testing recommendations, 11.1% were referred to nutrition or exercise services, 8.42% were referred for a Bone Density Scan (DXA), 4% were referred to a Breast Surgeon and 3.7% were referred to the Genetic Management Clinic. Additionally, 79.5% of patients were referred to the High-Risk Breast Lifetime Clinic for continued monitoring and surveillance for early detection of breast cancer, continued reinforcement of lifestyle modifications, and management of risk-reduction endocrine therapy. Conclusion: The unique structure of this model allows for enhanced surveillance through greater use of evidence-based cancer prevention, early detection methods, and increased education for lifestyle medicine practices with the overall goals of reducing breast cancer risk, earlier breast cancer detection, and increasing quality of life. Reference List 1. DeSantis C, Ma J, Gaudet, M, et al. Breast cancer statistics, 2019. CA: A Cancer Journal for Clinicians. 2019;69(6), 438-451. https://doi.org/10.3322/caac.21583. Citation Format: Joe Stephenson, LeAnn Perkins, Erinn Crowe, Regina Franco, Carmen Hancock, Pamela Cloys, Marie Smith. The Breast Cancer Prevention Clinic: A Single Institution’s Experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-07.

Epidemiology and Risk Factors for Breast Cancer: 21st Century Advances, Gaps to Address through Interdisciplinary Science.

Research methods to study risk factors and prevention of breast cancer have evolved rapidly. We focus on advances from epidemiologic studies reported over the past two decades addressing scientific discoveries, as well as their clinical and public health translation for breast cancer risk reduction. In addition to reviewing methodology advances such as widespread assessment of mammographic density and Mendelian randomization, we summarize the recent evidence with a focus on the timing of exposure and windows of susceptibility. We summarize the implications of the new evidence for application in risk stratification models and clinical translation to focus prevention-maximizing benefits and minimizing harm. We conclude our review identifying research gaps. These include: pathways for the inverse association of vegetable intake and estrogen receptor (ER)-ve tumors, prepubertal and adolescent diet and risk, early life adiposity reducing lifelong risk, and gaps from changes in habits (e.g., vaping, binge drinking), and environmental exposures.

Maternal lifestyle and nutrient intakes during pregnancy and exclusive breastfeeding in relation to risk factors for breast cancer: The Japan Environment and Children's Study

Breastfeeding has many benefits for infant growth and maternal health, such as reducing breast cancer risk. However, data on maternal factors influencing breastfeeding are insufficient. To clarify the associations between maternal lifestyle and diet during pregnancy and exclusive breastfeeding (EBF), we conducted a prospective study of pregnant women within the framework of the Japan Environment and Children's Study (a nationwide birth cohort study). Of 97,413 pregnant women recruited between January 2011 and March 2014, 27,775 with a singleton first live birth whose dietary data during pregnancy and lactation data were complete were eligible. Using logistic regression, we evaluated the associations between lifestyle factors including smoking and prepregnancy body mass index and intake of nutrients (macronutrients, isoflavones, and dietary fiber), some of which are known risk factors of breast cancer, and EBF for one month postpartum (initiation of EBF). To investigate the associations of these factors with EBF for 6 months (continuation of EBF), 9582 women who had successfully completed one-month EBF were further followed up. Smoking and prepregnancy obesity were inversely associated with the initiation and continuation of EBF. Intakes of protein, fat, isoflavone, and dietary fiber were positively associated (p trend = 0.0001 for dietary fiber), and carbohydrate intake was inversely associated with the initiation of EBF. Dietary fiber intake was also associated with the continuation of EBF (p trend = 0.048). These findings indicate that maternal lifestyles during pregnancy affect lactation performance. Lifestyle adjustments during pregnancy may have favorable effects on maternal and children's health through successful breastfeeding.

Hereditary Women’s Cancer: Management and Risk-Reducing Surgery

Hereditary women's syndromes due to inherited mutations result in an elevated risk of developing gynecological cancers over the lifetime of affected carriers. The BRCA 1 and 2 mutations, Lynch syndrome (LS), and mutations in rare hereditary syndromes increase this risk and require more effective management of these patients based on surveillance and prophylactic surgery. Patients need counseling regarding risk-reducing surgery (RRS) and the time required to perform it, considering the adverse effects of premenopausal surgery and the hormonal effect on quality of life, bone density, sexual activity, and cardiological and vascular diseases. Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard for BRCA-mutated patients. An open question is that of endometrial cancer (EC) risk in patients with BRCA1/2 mutation to justify prophylactic hysterectomy during RRSO surgical procedures. RRS provides a 90-95% risk reduction for ovarian and breast cancer in women who are mutation carriers, but the role of prophylactic hysterectomy is underinvestigated in this setting of patients. In this review, we evaluate the management of the most common hereditary syndromes and the benefits of risk-reducing surgery, particularly exploring the role of prophylactic hysterectomy.

Association between employer-based health promotion programs and adherence to breast cancer screening in Texas

Breast cancer is the most common cancer diagnosed among women in Texas. Although adherence to recommended screening mammogram guidelines enables early detection and reduces breast cancer risks, screening mammogram adherence is low in Texas. With the rising percentage of women in the workforce, employer-based health promotion programs could be an effective measure in increasing mammogram adherence, thereby reducing breast cancer risk in Texas. Although employer-based health programs are common in the state, little is known about their effectiveness in increasing screening mammogram adherence among age-eligible employed females. The study survey was administered using Qualtrics and the study participants were representative of the Texas population. The study population included 318 females from Texas who were 50–74 years old. Among those who had access to employer-based health promotion programs, 65.4 % were adherent and 34.6 % were non-adherent to the guidelines. Population-weighted survey logistic regression analysis showed no significant association between access to employer-based health promotion programs and mammogram adherence for employed women (AOR: 0.85 [0.15–4.79], p-value = 0.86). However, access to healthcare coverage (AOR: 7.58 [2.89–19.88], p-value < 0.001), those who disagree with the fatalistic belief that everything causes cancer (AOR: 2.99 [1.45–6.19], p-value < 0.001), and those who perceive cancer screening important (AOR: 12.36 [2.26–67.47], p < 0.05) were found as significant determinants of mammogram adherence among females in Texas. The study concluded that access to employer-based health promotion programs alone was insufficient to improve breast cancer screening. The employers and the insurance companies, with support from the government, should develop a comprehensive program that addresses all structural and psychosocial barriers to employee breast cancer screening adherence.

Should Acellular Dermal Matrices Be Used for Implant-based Breast Reconstruction after Mastectomy? Clinical Recommendation Based on the GRADE Approach.

A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints, and establish recommendation for the use of ADMs for subpectoral one-/two-stage IBBR (compared with no ADM use) for adult women undergoing mastectomy for breast cancer treatment or risk reduction using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: the panel members suggest subpectoral one- or two-stage IBBR either with ADMs or without ADMs for adult women undergoing mastectomy for breast cancer treatment or risk reduction (with very low certainty of evidence). The systematic review has revealed a very low certainty of evidence for most of the important outcomes in ADM-assisted IBBR and the absence of standard tools for evaluating clinical outcomes. Forty-five percent of panel members expressed a conditional recommendation either in favor of or against the use of ADMs in subpectoral one- or two-stages IBBR for adult women undergoing mastectomy for breast cancer treatment or risk reduction. Future subgroup analyses could help identify relevant clinical and pathological factors to select patients for whom one technique could be preferable to another.

Consumption and supplementation of vitamin E in breast cancer risk, treatment, and outcomes: A systematic review with meta-analysis

Robust evidence have shown diet or dietary components in playing a direct role on cancer chemoprevention such as breast cancer (BC), and also prevention against cancer therapy side effects. In this context, vitamin E isoforms have been associated with tumor suppression pathways, mainly related to proliferation, invasion, metastasis, tumor metabolism and chemoresistance. Therefore, we performed a systematic review with meta-analysis to assess the effects of vitamin E consumption and/or supplementation on breast cancer risk, treatment, and outcomes. The studies were selected in the electronic databases PubMed, Science Direct, Scopus and Web of Science. A total of 22 articles were selected, which nine manuscripts we perform the meta-analysis. The summary effect estimate did not indicate any significant association between consumption versus non-consumption of total vitamin E and breast cancer risk. After assessing the effects of vitamin E supplementation on breast cancer risk, only two had data for comparison and vitamin E supplementation presented no impact on breast cancer risk. However, the summary effect estimate from the included studies indicated that vitamin E consumption was inversely associated with breast cancer recurrence in the control group. There are no significant results regarding dietary or supplemental vitamin E intake and BC risk reduction. Finally, regarding recurrence, survival, and mortality, the results indicated that vitamin E consumption was inversely associated with breast cancer recurrence, although no association was found for breast cancer mortality.

Association of food groups and dietary pattern with breast cancer risk: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis of current evidence for the association between food groups, dietary patterns, and breast cancer risk among the Asian population. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We performed a systematic literature search up to December 2022 in English in the PubMed, Web of Science, Embase, and Cochrane databases. Risk ratios (RRs) with 95% confidence intervals (CIs) were extracted as effect sizes. Publication bias was estimated by two different funnel plot methods. We collected the data from 15 cohort studies and 34 case-control studies meeting the search criteria. The meta-analysis found that the consumption of fruits and, likewise, vegetables were associated with a 29% lower risk of breast cancer, respectively [RR=0.71 (0.55, 0.93); RR=0.71 (0.53, 0.95)]. By contrast, no significance was found between meat, soy foods, and green tea consumption and breast cancer risk (P>0.05). However, soy protein and isoflavone intake could lower breast cancer risk by 35% and 32%, respectively [RR=0.65 (0.51, 0.83); RR=0.68 (0.55, 0.82)]. As for the dietary pattern, high adherence to a healthy dietary pattern and, similarly, to a healthy eating index was associated with a 38% and 51% reduction in breast cancer risk, respectively [RR=0.62 (0.44, 0.88; RR=0.49 (0.27, 0.87)], while high adherence to an unhealthy dietary pattern was associated with a 44% increased risk [RR=1.44 (1.06, 1.96)]. Considering alcohol consumption, a 75% increased risk of breast cancer was found [RR=1.75 (1.33, 2.30)]. The present meta-analysis found that high intakes of fruits, vegetables, soy protein, and soy isoflavone significantly reduced the risk of breast cancer, while high intake of alcohol had a significantly increased risk. Meat, soy food, and green tea consumption were not significantly associated with breast cancer risk. Considering dietary patterns, high adherence to a healthy eating index and a healthy dietary pattern may reduce breast cancer risk. Conversely, adherence to unhealthy dietary patterns may increase breast cancer risk. However, further studies are needed to confirm the associations between dietary patterns and breast cancer in the Asian population.

Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort.

Nonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD.Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures.Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78-0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74-0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59-1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92-1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar.Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted. We examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer.

Abstract P065: Effects of metformin on breast tissue inflammation in premenopausal women with components of metabolic syndrome

Abstract Background: Obesity, with increasing worldwide prevalence, is associated with increased breast cancer burden. The association is attributed to multiple metabolic disturbances including chronic inflammation due to dysfunctional adipose tissue. Features of local breast adipose tissue inflammation such as macrophage infiltration and an enriched pro-inflammatory gene signature were recently reported in mouse models of obesity and in women with high adiposity or metabolic disorders. Strategies that can reduce obesity-induced chronic inflammation may lead to reduction of breast cancer risk. Metformin, a widely used anti-diabetic drug, exerts favorable effects on multiple metabolic disturbances. This study aims to evaluate the clinical effects of metformin on breast tissue inflammation. Methods: Macrophage infiltration and polarization were determined in breast core needle biopsies collected at baseline and 6 months after agent intervention from a Phase II randomized, double-blind, placebo-controlled trial of metformin in premenopausal women with components of metabolic syndrome. Macrophage infiltration was assessed using a pan macrophage marker (CD68) by immunohistochemistry (IHC). M1 and M2 macrophages were assessed using CD40 and CD206 surface markers, respectively, by IHC. The primary endpoint is the change in macrophage density in breast adipose tissue. Secondary endpoints include the change in macrophage density in breast stroma and epithelium tissues, the proportion of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages in breast adipose, stroma, and epithelium tissues. Results: Baseline biopsies from 76 participants (40 in the metformin arm and 36 in the placebo arm) were available for CD68 analysis. The baseline CD68 density was 22.48 ± 3.25, 67.26 ± 9.68, 418.81± 71.02 (mean±SE) per mm2 in breast adipose, stroma, and epithelium tissues, respectively. Biopsies from 71 participants (34 in the metformin arm and 37 in the placebo arm) were available for CD68 analysis at 6 months. Comparing to placebo, metformin intervention led to a significant reduction in CD68 density in breast adipose tissue (p = 0.01) but did not change the CD68 density in breast epithelium and stroma tissues. Conclusion: Metformin intervention resulted in favorable changes in macrophage infiltration in breast adipose tissue in premenopausal women with component of metabolic syndrome. Studies are ongoing to evaluate the effects of metformin on macrophage polarization. Citation Format: Liane E. Pinto, Sara Centuori, Jose Guillen-Rodriguez, Denise J. Roe, Edgar Tapia, Pavani Chalasani, H-H. Sherry Chow. Effects of metformin on breast tissue inflammation in premenopausal women with components of metabolic syndrome. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P065.

Abstract C097: Association between a healthy lifestyle index and breast cancer risk among post-menopausal women in the Multiethnic Cohort (MEC) Study

Abstract Consistent evidence supports maintaining a healthy weight, engaging in physical activity, and limiting alcohol consumption as potential strategies for reducing breast cancer risk. Sleep duration and sedentary behavior are also emerging breast cancer risk factors. While these cardiometabolic factors have been associated with an increased risk of breast cancer, prior studies have primarily investigated these factors separately. The association between a healthy lifestyle index (HLI) and breast cancer risk, particularly across racially and ethnically diverse postmenopausal women, has not been well studied. Within the Multiethnic Cohort study, ongoing analyses are examining associations between an HLI and risk of invasive breast cancer among 65,813 eligible postmenopausal women (African American [18.7 %], Native Hawaiian [6.7 %], Japanese American [28.2%], Latina [21.1%], and White [25.3%]). During a median follow-up of 23 years, 4,571 incident invasive breast cancer cases were diagnosed between baseline (1993-1996) and the end of follow-up (2017). Self-reported baseline information on seven lifestyle factors was used to create an HLI based on the sum of scores (max HLI score=23): Healthy Eating Index 2010 (HEI 2010) score divided into quartiles (scored 1-4), metabolic equivalents (METs) of moderate and vigorous physical activity (1-3), time spent sedentary (1-3), smoking status and duration (1-5), alcohol consumption (1-3), body mass index (BMI) (1-3) and sleep duration (1-2). Preliminary analyses included descriptive statistics as well as age- and race and ethnicity-adjusted Cox proportional hazards models of invasive breast cancer to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for the association with HLI score (tertiles, (T)) using age as the timescale. The mean HLI score in the overall population was 15.3 [Standard Deviation (SD): 2.1] with 51.4% of the analytic population in an HLI score tertile of ≥18 to 23 (T3; most healthy) and 13.2% in the lowest HLI score tertile ≥7 to &amp;lt;15 (T1; least healthy). The mean HLI scores by race/ethnicity were the following: African American 16.5 [SD: 2.5], Native Hawaiian 16.7 [SD: 2.6], Japanese American 18.2 [SD: 2.2], Latina 17.3 [SD: 2.2] and White 17.2 [SD: 2.6] women. Preliminary findings suggest that overall, women in HLI score T3 had on average, a BMI of 23.6 [3.7] (mean [SD] kg/m2), dietary intake HEI 2010 scores between 60-78.9, exerted &amp;gt; 6 METs of moderate and strenuous activity, spent &amp;lt; 6 hours a day sedentary, consumed less than 4.9 grams of ethanol per day, slept between 7 to 8 hours and were never smokers. In initial age- and race and ethnicity-adjusted analyses, postmenopausal women with an HLI score in T2 (HR: 0.90 [95% CI:0.82-0.98]) and in T3 (HR: 0.81 [95% CI: 0.74–0.89]) (p-trend &amp;lt;0.001) were at reduced risk of breast cancer compared to women in T1. Ongoing analyses include race and ethnicity stratified and fully adjusted multivariable Cox proportional hazards regression. Citation Format: Bethany T. Ogbenna, Iona Cheng, James Butler III, Typhanye Dyer, Xin He, Loic Le Marchand, Lynne Wilkens, Cher Dallal. Association between a healthy lifestyle index and breast cancer risk among post-menopausal women in the Multiethnic Cohort (MEC) Study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C097.

Breast cancer risk for women with diabetes and the impact of metformin: A meta-analysis.

Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM). Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021. A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users. Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users. These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.

A novel Bayesian adaptive design incorporating both primary and secondary endpoints for randomized IIB chemoprevention study of women at increased risk for breast cancer

BackgroundOur randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint.MethodsIn this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67).ResultsWe present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint.DiscussionOur approach balances trial speed and the need for information on the single, key secondary endpoint.