Ezabenlimab (BI 754091), an anti-PD-1 antibody, in patients with advanced solid tumours.

BACKGROUND: Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics and antitumour activity of ezabenlimab at the recommended Phase II dose in patients with selected advanced solid tumours. STUDY DESIGN: Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States. Study 1381.4 (NCT03433898) was conducted in Japan. Study 1381.3 (NCT03780725) was conducted in the Netherlands. The primary endpoints were: number of patients experiencing dose-limiting toxicities (DLTs) in the first cycle (dose escalation parts), number of patients with DLTs during the entire treatment period and objective response (dose expansion part of Study 1381.1). RESULTS: Overall, 117 patients received ezabenlimab intravenously every 3 weeks (80 mg, n = 3; 240 mg, n = 111; 400 mg, n = 3). No DLTs were observed and the MTD was not reached. Fifty-eight patients (52.3%) had grade ≥ 3 adverse events, most commonly anaemia (10.8%) and fatigue (2.7%). In 111 assessed patients treated with ezabenlimab 240 mg, disease control rate was 56.8% and objective response rate was 16.2%. Three patients had complete response; at data cut-off (November 2021) one remained in response and was still receiving ongoing treatment (duration of response [DoR]: 906 days). Partial responses occurred across several tumour types; DoR ranged from 67 to 757 days. CONCLUSIONS: Ezabenlimab was well tolerated and associated with durable antitumour activity in multiple solid tumours, comparable to other immune checkpoint inhibitors in similar patient populations and treatment settings.

Mental health and social connection among older lesbian and bisexual women.

OBJECTIVE: To assess differences in psychosocial and mental health outcomes between older lesbian and bisexual women compared to heterosexual women. DESIGN: Cross sectional study. SETTING: The study was carried out in the California Teachers Study, a prospective cohort study. PARTICIPANTS: Self-identified heterosexual (n = 35,846), lesbian (n = 710), and bisexual (n = 253) women 50 years of age and older were enrolled. MEASUREMENTS: Validated questionnaires were used to measure social connection, overall happiness, and depression. Logistic regression modeling was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing lesbian and bisexual women separately to heterosexual women in relation to psychosocial and mental health outcomes. RESULTS: After controlling for age and marital status, older bisexual women were significantly more likely to report lack of companionship (OR = 2.00; 95% CI, 1.30-3.12) and feeling left out (OR = 2.33; 95% CI, 1.36-3.97) compared to older heterosexual women. The odds of reporting feeling isolated from others was significantly higher in lesbian (OR = 1.56; 95% CI, 1.06-2.30) and bisexual women (OR = 2.30; 95% CI, 1.37-3.87) than in heterosexual women. The OR (95% CI) for reporting not being very happy overall was 1.96 (CI, 1.09-3.52) in bisexual women and 1.40 (0.92-2.14) in lesbian women compared to heterosexual women. The likelihood of reporting diagnosed depression was significantly higher in lesbian women (OR = 1.65; 95% CI, 1.38-1.97) and bisexual women (OR = 2.21; 95% CI, 1.67-2.93) compared to heterosexual women. CONCLUSION: Inclusion of lesbian and bisexual women in aging research is essential to understand their unique mental and other health needs, including those specific to bisexual women.

Urinary cadmium and timing of menarche and pubertal development in girls.

BACKGROUND: Cadmium (Cd) is a developmental toxicant that is released into the environment during industrial processes. Previous animal studies suggest that Cd may impact the onset of puberty. OBJECTIVES: To determine whether Cd exposure, measured as urinary Cd concentration, was associated with ages at menarche and pubertal development. METHODS: A cohort of 211 girls, ages 10-13 years at baseline, was followed for up to two years. Girls completed an interview and self-assessment of Tanner stages of breast development and pubic hair growth. They were followed monthly until menarche. Urinary Cd concentrations were measured in overnight urine specimens. Multivariable Cox regression was used to evaluate the association between urinary Cd and age at menarche and cumulative logit regression was used to evaluate the associations between urinary Cd and breast development and pubic hair growth. RESULTS: The baseline geometric mean creatinine-adjusted Cd concentration was 0.22 µg/g creatinine (geometric standard deviation = 1.6) and decreased with increasing age (p-trend = 0.04). Cd levels were higher among Asian than White girls or girls of other/mixed race/ethnicity (p = 0.04). In multivariable analyses, girls with urinary Cd ≥ 0.4 µg/L were less likely to have attained menarche than girls with urinary Cd < 0.2 µg/L (hazard ratio = 0.42; 95% confidence interval, 0.23-0.78). Urinary Cd was negatively associated with pubic hair growth (p-trend = 0.01) but not with breast development (p-trend = 0.72) at baseline. CONCLUSIONS: These findings suggest that a higher Cd body burden may delay some aspects of pubertal development among girls.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Asian American Women's Experiences of Discrimination and Health Behaviors during the COVID-19 Pandemic.

The COVID-19 pandemic exacerbated racism experienced by Asian Americans, especially women and older individuals. Little is known about how discriminatory experiences during the pandemic have influenced health behaviors among Asian Americans. Between 10/2021 and 6/2022, we surveyed 193 Asian American women in the San Francisco area. Participants were asked to report types of discrimination they experienced since March 2020. We explored bivariable associations of discrimination and changes in health behaviors and healthcare utilization. Most women were Chinese American (75%) and over 45-years-old (87%). The top three discriminatory experiences reported were being treated with less respect (60%), being treated unfairly at restaurants/stores (49%), and people acting as if they are better (47%). Chinese American women (vs. non-Chinese Asian American women) reported higher frequencies of being threatened/harassed (40% vs. 22%). Women who reported any discriminatory experience (vs. none) were more likely to report less physical exercise (42.7% vs. 26.3%) and canceling/rescheduling medical appointments (65.0% vs. 45.1%). Our findings begin to elucidate Asian American women's experiences of discrimination since the pandemic and provide evidence of the harmful impacts of anti-Asian racism on health behaviors.

Predictors and impact of survivorship care plans and survivorship care visits.

PURPOSE: We performed this study to characterize the population at the Lifespan Cancer Institute (LCI) who received a survivorship care plan (SCP) with or without a survivorship care visit (SCV) to determine both the impact on specialty referrals and the demographic and clinical predictors of SCPs and SCVs. METHODS: We retrospectively reviewed EMR records on 1960 patients at LCI between 2014 and 2017 for SCPs and SCVs and extracted demographics, distress thermometer (DT) scores collected at the time of initial presentation, and subsequent referrals. We evaluated the bivariate associations of SCP and SCV with continuous and categorical factors and assessed the adjusted effect of these factors on receipt of SCP and SCV independently. All analyses were performed in R v4.0.2. RESULTS: SCPs were completed in 740 (37.8%) patients, and of those, 65.9% had a SCV. The mean age was 63.9, 67% were female, and 51.2% were married or partnered. Patients treated for breast, lung, and prostate cancers most received an SCP. Compared to SCP alone, the SCV was associated with more specialty referrals. Those who were younger and had breast cancer were more likely to receive a SCP, and those who were younger and female and had breast cancer were more likely to receive a SCV. CONCLUSIONS: Gender, age, and type of cancer are significant predictors of receipt of SCP and SCV. Patients who received either SCP, SCV, or both were more likely to receive specialty referrals than those who received neither. IMPLICATIONS FOR CANCER SURVIVORS: Identifying predictive factors of SCP and SCV can help facilitate earlier receipt of specialty services and specialty referrals as needed.

Oncologists' confidence in knowledge of fertility issues for young women with cancer.

We sought to identify factors associated with greater cancer-related fertility knowledge in a national survey of oncologists. We surveyed 344 oncologists from a sampling pool drawn randomly from the AMA Masterfile. We conducted multiple linear regression to determine the relationship between confidence in knowledge and oncologists' characteristics. Respondents' average age was 48.5, and 75.3% were male. The average confidence in knowledge summary score was 23.8 (SD 6.4, range 8-40). In multivariable regression, confidence was higher among oncologists with more information resources, a sense of responsibility to discuss fertility issues and among gynecologic oncologists vs. other oncology specialties. Physician age, gender, and practice setting were not associated with fertility-related knowledge. Oncologists lack confidence in their knowledge of fertility issues in young women with breast cancer. Increasing professional responsibility to discuss fertility and greater information access could improve the depth and breadth of education regarding fertility issues among oncologists and their young patients.

Richard Hader Visionary Leader Award 2021 Visionary Leader Elvira Fardella-Roveto.

The following manuscript is the winning 2021 Richard Hader Visionary Leader Award entry submitted to Nursing Management in recognition of Elvira Fardella-Roveto, RN, FNP-BC, assistant vice president and administrator of St. Mary's Home Care in New York.

Integration of electronic pathology reporting with clinical trial matching for advanced prostate cancer.

INTRODUCTION: Racial/ethnic diversity in prostate cancer (CaP) clinical trials (CTs) is essential to address CaP disparities. California Cancer Registry mandated electronic reporting (e-path) of structured data elements from pathologists diagnosing cancer thereby creating an opportunity to identify and approach patients rapidly. This study tested the utility of an online CT matching tool (called Trial Library) used in combination with e-path to improve matching of underrepresented CaP patients into CTs at time of diagnosis. METHODS: This was a nonrandomized, single-arm feasibility study among patients with a new pathologic diagnosis of high-risk CaP (Gleason Score ≥8). Eligible patients were sent recruitment materials and enrolled patients were introduced to Trial Library. RESULTS: A total of 419 case listings were assessed. Patients were excluded due to physician contraindication, not meeting baseline eligibility, or unable to be reached. Final participants (N = 52) completed a baseline survey. Among study participants, 77% were White, 10% were Black/Hispanic/Missing, and 14% were Asian. The majority of the study participants were over 65 years of age (81%) and Medicare insured (62%). Additionally, 81% of participants reported using the Internet to learn about CaP. The majority (62%) of participants reported that Trial Library increased their interest in CT participation. CONCLUSIONS: The current study demonstrated that leveraging structured e-path data reporting to a population-based cancer registry to recruit men with high risk CaP to clinical research is feasible and acceptable. We observed that e-path may be linked with an online CT matching tool, Trial Library. Future studies will prioritize recruitment from reporting facilities that serve more racially/ethnically diverse patient populations.

Improving Advance Care Planning in a Resident Primary Care Clinic.

INTRODUCTION: Two-thirds of chronically ill patients do not have an advance directive. The primary aim of this study was to develop an intervention to increase the documentation of advance directives in elderly adults in an internal medicine resident primary care clinic. The secondary aims were to improve resident confidence in discussing advance care planning and increase the number of discussions. METHODS: The study was a pre- and postintervention study. The study intervention was a 30-minute educational session on advance care planning. Study participants were patients aged 65 years and older who were seen in an internal medicine residency primary care clinic over a 6-month period and internal medicine residents. Clinic encounters were reviewed for the presence of advance care planning discussions before and after the intervention. Resident confidence was measured on a Likert scale. RESULTS: Two hundred ninety-five eligible patients were seen in the clinic from January 1, 2017, to June 30, 2017, and included in the analysis performed between 2017 and 2018. The mean number of documented advance care planning discussions increased from 2.24 (95% confidence interval [CI]: 1.0-4.9) during the preintervention period to 8.94 (95% CI: 5.94-13.24]) during the postintervention period (P = .0011). Following the intervention, residents overall reported increased confidence in discussing advance care planning. CONCLUSION: A relatively modest intervention to increase advance care planning discussions is feasible in an internal medicine primary care clinic and can improve the confidence of residents with end-of-life discussion.

Insights from Adopting a Data Commons Approach for Large-scale Observational Cohort Studies: The California Teachers Study.

BACKGROUND: Large-scale cancer epidemiology cohorts (CEC) have successfully collected, analyzed, and shared patient-reported data for years. CECs increasingly need to make their data more findable, accessible, interoperable, and reusable, or FAIR. How CECs should approach this transformation is unclear. METHODS: The California Teachers Study (CTS) is an observational CEC of 133,477 participants followed since 1995-1996. In 2014, we began updating our data storage, management, analysis, and sharing strategy. With the San Diego Supercomputer Center, we deployed a new infrastructure based on a data warehouse to integrate and manage data and a secure and shared workspace with documentation, software, and analytic tools that facilitate collaboration and accelerate analyses. RESULTS: Our new CTS infrastructure includes a data warehouse and data marts, which are focused subsets from the data warehouse designed for efficiency. The secure CTS workspace utilizes a remote desktop service that operates within a Health Insurance Portability and Accountability Act (HIPAA)- and Federal Information Security Management Act (FISMA)-compliant platform. Our infrastructure offers broad access to CTS data, includes statistical analysis and data visualization software and tools, flexibly manages other key data activities (e.g., cleaning, updates, and data sharing), and will continue to evolve to advance FAIR principles. CONCLUSIONS: Our scalable infrastructure provides the security, authorization, data model, metadata, and analytic tools needed to manage, share, and analyze CTS data in ways that are consistent with the NCI's Cancer Research Data Commons Framework. IMPACT: The CTS's implementation of new infrastructure in an ongoing CEC demonstrates how population sciences can explore and embrace new cloud-based and analytics infrastructure to accelerate cancer research and translation.See all articles in this CEBP Focus section, "Modernizing Population Science."

Using Marketing Automation to Modernize Data Collection in the California Teachers Study Cohort.

BACKGROUND: Like other cancer epidemiologic cohorts, the California Teachers Study (CTS) has experienced declining participation to follow-up questionnaires; neither the reasons for these declines nor the steps that could be taken to mitigate these trends are fully understood. METHODS: The CTS offered their 6th study questionnaire (Q6) in the fall of 2017 using an integrated, online system. The team delivered a Web and mobile-adaptive questionnaire to 45,239 participants via e-mail using marketing automation technology. The study's integrated platform captured data on recruitment activities that may influence overall response, including the date and time invitations and reminders were e-mailed and the date and time questionnaires were started and submitted. RESULTS: The overall response rate was 43%. Participants ages 65 to 69 were 25% more likely to participate than their younger counterparts (OR = 1.25; 95% CI, 1.18-1.32) and nonwhite participants were 28% less likely to participate than non-Hispanic white cohort members (OR = 0.72; 95% CI, 0.68-0.76). Previous questionnaire participation was strongly associated with response (OR = 6.07; 95% CI, 5.50-6.70). Invitations sent after 2 pm had the highest response (OR = 1.75; 95% CI, 1.65-1.84), as did invitations sent on Saturdays (OR = 1.48; 95% CI, 1.36-1.60). CONCLUSIONS: An integrated system that captures paradata about questionnaire recruitment and response can enable studies to quantify the engagement patterns and communication desires of cohort members. IMPACT: As cohorts continue to collect scientific data, it is imperative to collect and analyze information on how participants engage with the study.See all articles in this CEBP Focus section, "Modernizing Population Science."

Incident invasive breast cancer, geographic location of residence, and reported average time spent outside.

There have been reports of greater breast cancer incidence and mortality at northern compared with southern latitudes postulated to be related to vitamin D exposure. Among 71,662 participants in the Women's Health Initiative Observational Study (WHIOS) free of cancer at baseline (1993-1998), associations were explored between incident invasive postmenopausal breast cancer (n = 2,535), over approximately 8.6 years follow-up, and the following: (a) region of residence at birth, age 15 years, age 35 years; (b) region of residence at WHIOS baseline; and (c) clinic center solar irradiance. Hazard ratios and 95% confidence intervals (CI) for breast cancer were estimated after adjustment for individual level confounders. There was no difference in breast cancer risk by region of earlier life, baseline residence, or solar irradiance measured in Langelys (gm-cal) per cm(2). There was an observed 15% decreased risk among women residing in areas of low versus high solar irradiance measured in Watts per m(2) (95% CI, 2-26%). However, the associated P(trend) of 0.20 was not significant. Conversely, women who reported spending on average <30 minutes versus >2 hours outside in daylight year round at WHIOS year 4 follow-up (n = 46,926), had a 20% (95% CI, 2-41%; P(trend) = 0.001) increased risk of breast cancer. In conclusion, region of residence and geographic solar irradiance are not consistently related to risk of breast cancer and may not be sufficient proxy measures for sunlight/vitamin D exposure. The observed association between time spent outside and breast cancer risk support the hypothesis that vitamin D may protect against breast cancer.

Alcohol and folate intake and breast cancer risk in the WHI Observational Study.

BACKGROUND: Alcohol increases breast cancer risk. Epidemiological studies suggest folate may modify this relationship. OBJECTIVE: To examine the relationship among breast cancer, alcohol and folate in the Women's Health Initiative-Observational Study (WHI-OS). METHODS: 88,530 postmenopausal women 50-79 years completed baseline questionnaires between October 1993 and December 1998, which addressed alcohol and folate intake and breast cancer risk factors. Cox proportional hazards analysis examined the relationship between self-reported baseline alcohol and folate intake and incident breast cancer. RESULTS: 1,783 breast cancer cases occurred over 5 years. Alcohol was associated with increased risk of breast cancer (RR = 1.005, 95%CI 1.001-1.009). Risk increased with consumption of alcohol (up to 5 g/d, adjusted HR = 1.10, 95%CI 0.96-1.32; >5-15 g/d HR = 1.14, 95%CI 0.99-1.31; and >15 g/d HR = 1.13 95%CI 0.96-1.32). We found no significant interaction between alcohol and folate in our adjusted model. CONCLUSIONS: We found no evidence for folate attenuating alcohol's effect on breast cancer risk in postmenopausal women. Our results may be due to misclassification of folate intake or the relatively short follow-up period.

Heavy Metals in California Women Living in a Gold Mining-Impacted Community.

Gold mining activities occurred throughout the foothills of the Sierra Nevada Mountains in California, leaving behind persistent toxic contaminants in the soil, dust, and water that include arsenic and cadmium. Despite a high level of concern among local residents about potential exposure and high breast cancer rates, no biomonitoring data has been collected to evaluate the levels of heavy metals. We conducted a study to characterize the urinary levels of heavy metals among women in this region by working with the community in Nevada County. Sixty women provided urine samples and completed a questionnaire. We examined levels of arsenic, cadmium, and other metals in relation to the length of residency in the area, age, dietary factors, recreational activities, and smoking. We compared urinary metal levels in participants to levels in the United States National Health and Nutrition Examination Survey (NHANES). Overall, study participants had higher urinary levels of arsenic than women in the national sample. Cadmium levels were similar to the national average, although they were elevated in women ≥35 years who had lived in the region for 10 years or more. Arsenic levels were higher among women who smoked, ate fish, ate home-grown produce, and who reported frequent hiking or trail running, although these differences were not statistically significant. This study established a successful community-research partnership, which facilitated community dialogue about possible human health consequences of living in a mining-impacted area.

Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy.

PURPOSE: Young women who undergo chemotherapy for breast cancer face serious consequences to their reproductive health. Research in this area has previously focused on men, or on childhood cancer survivors. We sought to explore self-report of reproductive health counseling in young women undergoing chemotherapy for breast cancer. PATIENTS AND METHODS: A total of 166 premenopausal women aged < or = 50 years were recruited from oncology offices in academic and private practices in four northeastern states, as part of a randomized controlled clinical trial aimed at stress reduction. Women were asked a variety of questions regarding diagnosis and treatment, including whether they received any counseling regarding early menopause and fertility issues. RESULTS: Sixty-eight percent and 34% of women reported recalling a discussion with a physician regarding early menopause or fertility, respectively. In multivariate analysis, hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause. Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility, whereas older age and anxiety in medical situations were associated with decreased odds. CONCLUSION: Many women fail to recall discussions regarding the reproductive health impact of chemotherapy. Demographic, psychological, and disease-related variables are related to recalling such discussions. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer. Future research should explore this issue further.

Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS).

RATIONALE: Cryptogenic ischemic strokes constitute 20-30% of ischemic strokes, the majority of which are embolic strokes of undetermined source. The standard preventive treatment in these patients is usually acetylsalicylic acid. AIM: The Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) is designed to determine whether the oral thrombin inhibitor dabigatran, taken within three-months after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of recurrent stroke and to characterize the safety of dabigatran in this setting. DESIGN: Prospective, randomized, double-blind, multicenter trial in approximately 6000 patients and 550 centers with embolic stroke of undetermined source. Subjects are randomized to dabigatran or acetylsalicylic acid and treated for an expected minimum of six-months and up to approximately three-years. It is an event-driven trial aiming for 353 adjudicated primary outcome events. STUDY OUTCOMES: The primary efficacy outcome is time to first recurrent stroke (ischemic, hemorrhagic, or unspecified). Key secondary outcomes are time to first ischemic stroke and time to first occurrence in the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death. The primary safety outcome is major hemorrhage, including symptomatic intracranial hemorrhage. DISCUSSION: Acetylsalicylic acid is the most common antithrombotic given to patients with embolic strokes of undetermined source to reduce recurrence risk. This trial will determine whether anticoagulation with dabigatran is more effective than acetylsalicylic acid, and acceptably safe.

Phytoestrogens: potential benefits and implications for breast cancer survivors.

Phytoestrogens are a group of plant-derived substances that are structurally or functionally similar to estradiol. There has been much interest in the potential role of phytoestrogens in cancer prevention and treatment of estrogen-deficient states. This review summarizes the evidence for phytoestrogen risks and benefits relevant to the breast cancer survivor, including prevention of a second primary breast cancer or metastatic disease, reduction in menopausal symptoms, and interactions with tamoxifen. Epidemiological data suggest a breast cancer protective role for phytoestrogens, and there is some supporting clinical data, but they are far from conclusive. In addition, there is some evidence that genistein, the most prevalent isoflavone in soy, can stimulate estrogen receptor-positive (ER+) breast cancer growth and interfere with the antitumor activity of tamoxifen at low levels. Given current knowledge, women who have ER+ tumors should not increase their phytoestrogen intake. Several studies suggest an inhibitory effect on ER- breast cancer cell growth, and it may be reasonable for women with ER- tumors to safely consume soy and possibly other phytoestrogens. However, the optimal amount and source are not clear. More research is needed to clarify the role of phytoestrogens in breast cancer prevention and in treating estrogen-deficient diseases in women who have had breast cancer.