Turning the Page on Breast Cancer in Ohio: Lessons learned from implementing a multilevel intervention to reduce breast cancer mortality among Black women.

BACKGROUND: Turning the Page on Breast Cancer (TPBC) uses a multilevel approach to reduce breast cancer (BC) mortality among Black women. TPBC intervenes by (1) improving health care facilities' ability to conduct effective BC screening, follow-up, and treatment; (2) involving community-based organizations; and (3) providing education and personal risk information through a culturally relevant website. Ohio has among the worst BC mortality rates in the United States for Black women. TPBC is in its third year of providing targeted interventions in 12 Ohio counties with particularly high BC rates among Black women. METHODS: TPBC enrolls health care facilities, collects organizational and patient data, and conducts key informant interviews to inform the provision of appropriate evidence-based interventions. TPBC engages Black communities through community-based organizations and social media advertising. The TPBC website offers BC information, connects Black women to community BC resources, and provides access to a risk-assessment tool. RESULTS: TPBC has provided tailored information packets, evidence-based interventions, and systematic support for improving the tracking and follow-up of breast health care among patients in 10 clinical partnerships. The project has provided education at community events monthly since mid-2021. The TPBC website (http://endbreastcancerohio.org) is promoted through social media (primarily Facebook) and community events to reach Black women aged 25-70 years. To date, 4108 unique users have visited the website, of whom 15.9% completed the risk assessment. CONCLUSIONS: Novel strategies are needed to address persistent disparities in BC outcomes among Black women. TPBC demonstrates the potential effectiveness of multiple methods of community-based, clinic-based, and web-based engagement. PLAIN LANGUAGE SUMMARY: Turning the Page on Breast Cancer (TPBC) aims to reduce breast cancer mortality among Black women in Ohio by conducting multilevel, community-engaged interventions in 12 counties. Women are provided risk information and education at virtual and in-person community events and through a community-friendly website that was launched in November 2020. Almost 4000 women have visited the website, which offers community-targeted information, urges screening for individuals at elevated risk, and offers access to patient navigation services; 655 users have used a breast cancer risk-assessment tool on the site. Community-based organizations conduct educational efforts. TPBC partners with health care facilities, which are taught to improve their ability to conduct effective breast cancer screening, follow-up, and treatment. So far, TPBC has provided educational information, evidence-based intervention lists, tailored information packets, and ongoing quarterly support to partners in 10 counties. Evaluation will focus on aggregated data for screening and genetic testing referral at the clinic level.

Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.

PURPOSE: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. METHODS: Appalachian women's survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene-environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. RESULTS: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between "Appalachian self-identity" variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. CONCLUSIONS: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

Participants' barriers to diagnostic resolution and factors associated with needing patient navigation.

BACKGROUND: Patient navigation (PN) may improve cancer care by identifying and removing patient-reported barriers to care. In 2012, the American College of Surgeons Commission on Cancer (CoC) announced that health care facilities seeking CoC accreditation must have PN processes in place by January 1, 2015. Given these unfunded mandates, hospitals are looking for cost-effective ways to implement PN. This study examined demographic and psychosocial predictors of barriers to diagnostic resolution among individuals with a cancer screening abnormality enrolled in the Ohio Patient Navigation Research Project. METHODS: Data were obtained from patients who received care at 1 of 9 Ohio Patient Navigation Research Project intervention clinics. Descriptive statistics and logistic regression models were used. RESULTS: There were 424 participants, and 151 (35.6%) reported a barrier to diagnostic resolution within 90 days of study consent. The most commonly reported barriers were misconceptions about a test or treatment (16.4%), difficulty in communicating with the provider (15.0%), and scheduling problems (11.5%). Univariate analyses indicated that race, education, employment, income, insurance, clinic type, friend support, and physical and psychological functioning were significantly associated with reporting a barrier to diagnostic resolution. Multivariate analyses found that comorbidities (odds ratio, 1.65; 95% confidence interval, 1.04-2.61) and higher intrusive thoughts and feelings (odds ratio, 1.25; 95% confidence interval, 1.10-1.41) were significantly associated with reporting a barrier to diagnostic resolution. CONCLUSIONS: The results suggest that demographic and psychosocial factors are associated with barriers to diagnostic resolution. To ensure compliance with the CoC mandate and provide timely care to all patients, CoC-accredited facilities can systematically identify the patients most likely to have barriers to care and assign them to PN.

Comparative Effectiveness of Two Interventions to Increase Colorectal Cancer Screening for Those at Increased Risk Based on Family History: Results of a Randomized Trial.

BACKGROUND: First-degree relatives (FDR) of patients with colorectal cancer are at risk for colorectal cancer, but may not be up to date with colorectal cancer screening. We sought to determine whether a one-time recommendation about needing colorectal cancer screening using patient navigation (PN) was better than just receiving the recommendation only. METHODS: Participants were FDRs of patients with Lynch syndrome-negative colorectal cancer from participating Ohio hospitals. FDRs from 259 families were randomized to a website intervention (528 individuals), which included a survey and personal colorectal cancer screening recommendation, while those from 254 families were randomized to the website plus telephonic PN intervention (515 individuals). Primary outcome was adherence to the personal screening recommendation (to get screened or not to get screened) received from the website. Secondary outcomes examined who benefited from adding PN. RESULTS: At the end of the 14-month follow-up, 78.6% of participants were adherent to their recommendation for colorectal cancer screening with adherence similar between arms (P = 0.14). Among those who received a recommendation to have a colonoscopy immediately, the website plus PN intervention significantly increased the odds of receiving screening, compared with the website intervention (OR: 2.98; 95% confidence interval, 1.68-5.28). CONCLUSIONS: Addition of PN to a website intervention did not improve adherence to a colorectal cancer screening recommendation overall; however, the addition of PN was more effective in increasing adherence among FDRs who needed screening immediately. IMPACT: These findings provide important information as to when the additional costs of PN are needed to assure colorectal cancer screening among those at high risk for colorectal cancer.

The CITIES Project: Understanding the Health of Underrepresented Populations in Ohio.

BACKGROUND: Ohio, the catchment area of The Ohio State University Comprehensive Cancer Center (OSUCCC), includes diverse populations with different cancer profiles. As part of the National Cancer Institute (NCI)-funded initiative to conduct population health assessments in cancer center catchment areas, the OSUCCC surveyed residents, focusing on factors contributing to cancer disparities in Ohio populations. METHODS: Two sampling strategies were used: (i) probability sampling of mailing lists and (ii) convenience sampling at community events, coupled with phone/in-person/web surveys. Survey items were chosen along multilevel framework constructs, used in concert with other funded NCI-Designated Cancer Centers. Multivariable logistic regression models investigated predictors associated with health behaviors, cancer beliefs, knowledge, and screening. RESULTS: The sample of 1,005 respondents were white (46.6%), African American (24.7%), Hispanic (13.7%), Somali (7.6%), and Asian (7.5%). A total of 216 respondents were Appalachian. Variations in cancer attitudes, knowledge, and behaviors were noted by racial/ethnic and geographic group. Multivariable models identified individuals with less financial security as less likely to exercise or be within guidelines for screening, but more likely to smoke and have a poor diet. At the community-level, measures of poverty were highest in Appalachia, whereas children in female-headed households were greater in urban minority areas. CONCLUSIONS: This population health assessment reinforced the diversity of the OSUCCC catchment area. These populations are ripe for implementation science strategies, focusing in communities and clinics that serve vulnerable populations. IMPACT: Understanding attitudes, knowledge, and behaviors of this population can assist tailoring outreach and research strategies to lessen the cancer burden.

Disparities in breast cancer tumor characteristics, treatment, time to treatment, and survival probability among African American and white women.

African American (AA) women have a 42% higher breast cancer death rate compared to white women despite recent advancements in management of the disease. We examined racial differences in clinical and tumor characteristics, treatment and survival in patients diagnosed with breast cancer between 2005 and 2014 at a single institution, the James Cancer Hospital, and who were included in the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Cancer Registry in Columbus OH. Statistical analyses included likelihood ratio chi-square tests for differences in proportions, as well as univariate and multivariate Cox proportional hazards regressions to examine associations between race and overall and progression-free survival probabilities. AA women made up 10.2% (469 of 4593) the sample. Average time to onset of treatment after diagnosis was almost two times longer in AA women compared to white women (62.0 days vs 35.5 days, p < 0.0001). AA women were more likely to report past or current tobacco use, experience delays in treatment, have triple negative and late stage breast cancer, and were less likely to receive surgery, especially mastectomy and reconstruction following mastectomy. After adjustment for confounding factors (age, grade, and surgery), overall survival probability was significantly associated with race (HR = 1.33; 95% CI 1.03-1.72). These findings highlight the need for efforts focused on screening and receipt of prompt treatment among AA women diagnosed with breast cancer.

Do cervical cancer screening rates increase in association with an intervention designed to increase mammography usage?

OBJECTIVES: To assess cervical cancer screening behaviors among underserved women participating in an intervention designed to increase mammography use. METHODS: This was a randomized trial of 897 women from three racial groups (white, African American, Native American) living in a rural county in North Carolina. Baseline and followup surveys were completed by 815 women; 775 women provided data to be included in these analyses. The intervention group received an educational program focused on mammography delivered by a lay health advisor, and the control group received a physician letter/brochure focusing on Pap tests. RESULTS: Women in both the intervention (OR 1.70; 1.31, 2.21, p < 0.001) and control groups (OR 1.38; 1.04, 1.82, p = 0.025) significantly increased cervical cancer screening rates within risk appropriate guidelines. No differences by racial group were documented. Women categorized in the high-risk group for developing cervical cancer (>2 sexual partners, age <18 years at first sexual intercourse, smoker; treated for sexually transmitted disease [STD] or partner with treated STD) significantly (OR 1.88; 1.54, 2.28, p < 0.001) increased Pap test completion. However, a nonsignificant increase (OR 1.25; 0.87, 1.79, p = 0.221) in Pap test completion was demonstrated in women categorized as low risk for cervical cancer. CONCLUSIONS: This study suggests that women in an intensive behavioral intervention designed to increase mammography use may also increase Pap test completion, similar to a minimal intervention focused only on increasing Pap test completion. These results have implications for the design and evaluation of behavioral intervention studies.

Colorectal cancer screening in 3 racial groups.

OBJECTIVES: To understand predictors of colorectal cancer (CRC) screening in African Americans, European Americans, and Native Americans as these groups differ in CRC incidence and mortality. METHODS: Participants were surveyed for knowledge, beliefs, and behaviors related to CRC. RESULTS: Predictive regression modeling found, after adjusting for race, CRC risk, and CRC worry, the odds of screening within guidelines were increased for men, those receiving doctor's recommendation, those with polyp/tumor history, those under 70, those with more knowledge about CRC, and those with fewer barriers to screening. CRC screening rates did not differ by race. CONCLUSIONS: These results reiterate the importance of knowledge, barriers, and physician recommendation for CRC screening in all racial groups.

Participation in cancer trials: recruitment of underserved populations.

One approach to address cancer health disparities is to focus on the under-representation by minority populations in cancer trials. Recruitment strategies include: 1) characterizing the target populations, 2) involve members of the population in planning, 3) take the message to the population, 4) give something back to the community, 5) enhance credibility with a community spokesperson, 6) identify and remove barriers, 7) improve staff sensitivity, and 8) educate the population about the trial. To recruit minorities to clinical trials, we have developed the Accrual to Clinical Trials (ACT) framework for understanding and enhancing the recruitment of participants to cancer trials.

Effects of tomato and soy on serum adipokine concentrations in postmenopausal women at increased breast cancer risk: a cross-over dietary intervention trial.

CONTEXT: Breast cancer risk among postmenopausal women increases as body mass index increases. Practical preventive methods to reduce risk of breast cancer are lacking. Few studies have investigated the effects of carotenoids and isoflavones on circulating adipokines in postmenopausal women. OBJECTIVE: The aim was to examine the effects of lycopene- and isoflavone-rich diets on serum adipokines. DESIGN: This was a 26-week, two-arm, longitudinal crossover trial. SETTING: Participants were recruited from clinics at The Ohio State University Comprehensive Cancer Center. PARTICIPANTS: Seventy postmenopausal women at increased breast cancer risk participated in the study. The mean age and body mass index of participants was 57.2 years and 30.0 kg/m(2), respectively; the study was comprised of 81.4% whites. INTERVENTIONS: The interventions included 10 weeks of consumption of a tomato-based diet (≥25 mg lycopene daily) and 10 weeks of consumption of a soy-based diet (≥40 g of soy protein daily), with a 2-week washout in between. MAIN OUTCOME MEASURES: Changes in serum adiponectin, leptin, and the adiponectin to leptin ratio were examined for each intervention through linear mixed models, with ratio estimates corresponding to postintervention adipokine concentrations relative to preintervention concentrations. RESULTS: After the tomato intervention, among all women, adiponectin concentration increased (ratio 1.09, 95% confidence interval (CI) 1.00-1.18), with a stronger effect observed among nonobese women (ratio 1.13, 95% CI 1.02-1.25). After the soy intervention, adiponectin decreased overall (ratio 0.91, 95% CI 0.84-0.97), with a larger reduction observed among nonobese women (ratio 0.89, 95% CI 0.81-0.98). Overall, no significant changes in leptin or the adiponectin to leptin ratio were observed after either intervention. CONCLUSIONS: Increasing dietary consumption of tomato-based foods may beneficially increase serum adiponectin concentrations among postmenopausal women at increased breast cancer risk, especially those who are not obese. Additional studies are essential to confirm these effects and to elucidate the specific mechanisms that may make phytonutrients found in tomatoes practical as breast cancer chemopreventive agents.

Effects of a walking intervention using mobile technology and interactive voice response on serum adipokines among postmenopausal women at increased breast cancer risk.

Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin, and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m(2) or >30 kg/m(2)) and randomized to a 12-week, two-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were IVR + coach and IVR + no-coach condition. Pre-post changes in serum adiponectin, leptin, and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95 % confidence intervals [CI]) corresponding to postintervention adipokine concentrations relative to preintervention concentrations. While postintervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (ratio = 0.86, 95 % CI 0.74-1.01, and ratio = 0.94, 95 % CI 0.87-1.01, respectively) and increase in A/L ratio = 1.09, 95 % CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention.

Favorable effects of low-fat and low-carbohydrate dietary patterns on serum leptin, but not adiponectin, among overweight and obese premenopausal women: a randomized trial.

PURPOSE: The most effective dietary pattern for breast cancer prevention has been greatly debated in recent years. Studies have examined hypocaloric diets, with particular emphasis on macronutrient composition, yielding inconclusive data. The objective of this study was to examine the effects of calorie-restricted low-fat and low-carbohydrate diets (LFD and LCD, respectively) on circulating adipokines among overweight and obese premenopausal women. METHODS: Seventy-nine overweight and obese premenopausal women were randomized to either LFD or LCD, with increased physical activity, for 52 weeks. Serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L) were measured at baseline, and at weeks 34 and 52 to assess intervention effects. RESULTS: While there were no significant changes in serum adiponectin concentrations following the LCD and LFD interventions, leptin concentrations significantly decreased by week 34 of the intervention period (LCD: 35.3%, P = 0.004; LFD: 30.0%, P = 0.01), with no difference by intervention arm. At week 52, these reductions were statistically non-significant, indicating a return to baseline levels by the end of the intervention. While there were non-significant increases in the A/L ratio following the LCD and LFD intervention arms, the overall trend, across groups, was marginally significant (P = 0.05) with increases of 16.2% and 35.1% at weeks 34 and 52, respectively. CONCLUSIONS: These findings suggest that caloric-restricted LCD and LFD dietary patterns favorably modify leptin and possibly the A/L ratio, and lend support to the hypothesis that these interventions may be effective for obesity-related breast cancer prevention through their effects on biomarkers involved in metabolic pathways. CLINICAL TRIAL REGISTRATION NUMBER: NCT01559194.

A walking intervention for postmenopausal women using mobile phones and Interactive Voice Response.

We conducted a feasibility study of a 12-week walking intervention administered through an Interactive Voice Response (IVR) system and mobile phones. We also examined the added benefit of a human coach. Post-menopausal women (n = 71) were given a daily-steps goal, which they monitored using a pedometer. Each day, they answered an automated call from the IVR system to their mobile phone and provided assessments of walking goals and mood. Every evening, they called the IVR system to report their steps, answered a brief questionnaire and received a message with a helpful hint. Participants took less time to complete a one-mile walk after the intervention, compared to baseline (0.77 min, SE = 0.22, P < 0.001). In addition, a significant loss in body weight (0.93 kg, SE = 0.31) and body-mass index (0.28 kg/m(2), SE = 0.11) were observed. The key psychometric measures of exercise goal setting (0.67 units, SE = 0.12) and exercise planning (0.48 units, SE = 0.09) also improved from baseline (both P < 0.001). However, results in the coach and no-coach conditions were not significantly different. The study suggests that mobile phones can be used to deliver an effective, low-cost walking intervention, irrespective of the addition of a human coach.

Human papillomavirus vaccine knowledge and hypothetical acceptance among women in Appalachia Ohio.

OBJECTIVE: To assess hypothetical acceptance of the human papillomavirus (HPV) vaccine for themselves and a daughter age 9-12 years among Appalachia Ohio women. METHODS: Women with an abnormal Pap smear and randomly selected women with a normal Pap smear from 17 clinics completed an interview in 2006-2008. RESULTS: From 1131 original study participants, 807 (71%) completed a survey about the HPV vaccine for their daughters and themselves. Nearly half, 380 (47%), of the participants had heard of a vaccine to prevent cancer, and 362 (95%) of respondents had heard of HPV. The participants were then told that the FDA had approved a vaccine to prevent HPV. Only 379 (38%) participants identified girls ages 9-12 years as a group who should get the vaccine. After being given the official HPV vaccine recommendation statement, 252 (31%) wanted the vaccine; 198 (25%) were "not sure"; and 353 (44%) did not want the vaccine for themselves. With respect to giving the HPV vaccine to a daughter ages 9-12 years, participants responded "yes" 445 (55%); "not sure" 163 (20%); or "no" 185 (23%). Numerous reasons were provided supporting and opposing vaccine acceptance for themselves and for a daughter. Their physician's recommendation for the HPV vaccine increased vaccine acceptance to 86% for themselves and 90% for a daughter. CONCLUSION: Knowledge, acceptance, and barriers about the HPV vaccine vary among women living in Appalachia Ohio. Physician recommendation is a key facilitator for vaccine diffusion in this region.

The Ohio Patient Navigation Research Program: does the American Cancer Society patient navigation model improve time to resolution in patients with abnormal screening tests?

BACKGROUND: Patient navigation (PN) has been suggested as a way to reduce cancer health disparities; however, many models of PN exist and most have not been carefully evaluated. The goal of this study was to test the Ohio American Cancer Society model of PN as it relates to reducing time to diagnostic resolution among persons with abnormal breast, cervical, or colorectal cancer screening tests or symptoms. METHODS: A total of 862 patients from 18 clinics participated in this group-randomized trial. Chart review documented the date of the abnormality and the date of resolution. The primary analysis used shared frailty models to test for the effect of PN on time to resolution. Crude HR were reported as there was no evidence of confounding. RESULTS: HRs became significant at 6 months; conditional on the random clinic effect, the resolution rate at 15 months was 65% higher in the PN arm (P = 0.012 for difference in resolution rate across arms; P = 0.009 for an increase in the HR over time). CONCLUSIONS: Participants with abnormal cancer screening tests or symptoms resolved faster if assigned to PN compared with those not assigned to PN. The effect of PN became apparent beginning six months after detection of the abnormality. IMPACT: PN may help address health disparities by reducing time to resolution after an abnormal cancer screening test.

Patterns of cellular and HPV 16 methylation as biomarkers for cervical neoplasia.

Aberrant promoter methylation of biologically relevant genes in cervical cancer and uneven CpG distribution within the human papillomavirus 16 (HPV 16) enhancer region have been reported. Cervical samples and questionnaires from 151 women screened for cervical cancer in Appalachian Ohio were analyzed. Methylation was measured by bisulfite sequencing in candidate gene sites in ESR1, DCC, p16, and LINE1 elements. Among 89 HPV 16-positive women, CpG sites in the E6 promoter and enhancer regions and the L1 region of the HPV 16 genome were measured. Methylation levels were compared by cervical cytology and HPV 16 status. HPV methylation was low regardless of cytology status, however E6 methylation was significantly higher in women with normal cytology. ESR1 and DCC methylation were significantly higher in HPV 16-positive women. Increased methylation at sites in the E6 promoter region was associated with lower odds of abnormal cytology. Increased methylation in candidate genes was associated with higher odds of abnormal cytology, particularly DCC region 2.4, DCC region 2.6, ESR1 region 3.2, and LINE1 site 1.2. HPV 16 genome CpG methylation was low except for the L1 region. In general, lower HPV 16 methylation and higher candidate gene methylation levels were associated with higher odds of abnormal cytology.

Effects of tomato- and soy-rich diets on the IGF-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer.

To determine whether dietary modifications with tomato products and/or a soy supplement affected circulating levels of insulin-like growth factor (IGF)-1 and other markers of cell signaling in postmenopausal women at risk for developing breast cancer. Eligible and consented postmenopausal women at high risk for developing breast cancer were enrolled in a 26-week, two-arm (tomato and soy, 10 weeks each) longitudinal dietary intervention study in which each woman served as her own control. Changes in biochemical endpoints including IGF-I, IGF-binding protein (IGFBP)-3, estradiol, sex hormone-binding globulin (SHBG), C-peptide, and insulin were measured for each intervention arm. Carotenoid and isoflavone levels were measured to assess adherence. Significant increases in carotenoid and isoflavone levels during the tomato and soy study arms, respectively, suggested that women were adherent to both arms of the intervention. The tomato-rich diet had little effect on cell-signaling biomarkers previously associated with breast cancer risk. However, results of the soy intervention showed that concentrations of IGF-I and IGFBP-3 increased by 21.6 and 154.7 µmol/L, respectively (P = 0.001 for both) and SHBG decreased by 5.4 µmol/L (P < 0.001) after consumption of the soy protein supplement. Increased soy protein intake may lead to small, but significant, increases in IGF-I and IGFBP-3. Soy consumption also led to a significant decrease in SHBG, which has been hypothesized to promote, rather than prevent, cancer growth. Previous epidemiologic studies, however, have confirmed protective effect of soy on breast cancer. Additional investigation about the effect of soy on breast cancer risk and its mechanism of action is warranted.