Improve Breast Cancer Outcomes Research Articles

The worldwide impact of HER2-targeted treatments in women with breast cancer: An epidemiological modeling study.

543 Background: HER2-targeted therapies (trastuzumab, pertuzumab, and T-DM1) have revolutionized the treatment and epidemiological landscape of HER2+ breast cancer, resulting in population-level increases in survival and decreases in disease recurrence. The aim of this epidemiological modeling study was to quantify the estimated global impact of HER2-targeted therapies, by estimating the number of women diagnosed with HER2+ early breast cancer (eBC) who have avoided (or will avoid) metastatic disease recurrence following treatment. Methods: We used data and projections from cancer registries, observational studies, clinical trials, and drug sales volumes (ie, utilization) to create annual country-level synthetic cohorts of patients diagnosed with HER2+ eBC, for the years 2004-2033 in 185 countries. The real-world uptake of HER2-targeted treatments and treatment flow was estimated in the main scenario. The impact of chemotherapy alone was estimated in the counterfactual scenario, assuming 100% chemotherapy worldwide. The occurrence of distant recurrences was modeled in both scenarios using weighted transitional probability averages based on invasive disease-free survival curves from clinical trials. Results: In total, during the 3-decade study period, we predicted that 11.9 million (M) women would be diagnosed with HER2+ eBC, out of which 7.5M were estimated to be treated with HER2-targeted therapies in a real-world uptake scenario. In the counterfactual scenario with only chemotherapy available, a total of 2.9M women were estimated to experience a metastatic disease recurrence, compared to only 2.1M women in the base scenario of predicted real-world uptake of HER2+ targeted therapies. This corresponds to a reduction of 26% or 768,000 women who may avoid metastatic recurrence since the introduction of HER2-targeted therapies (Table). Conclusions: HER2+ targeted therapies have substantially improved breast cancer outcomes and continue to contribute to the reduction in breast cancer recurrence rates. Further research may elucidate treatment-related reductions in costs to society as a result of population-level improvements in disease outcomes for breast cancer survivors. Given the expected rise in the burden of breast cancer globally, therapeutic advances and increased treatment utilization may further accelerate global patient benefit. [Table: see text]

Impact of centralization of initial breast cancer care on time to surgery.

e13511 Background: Evidence suggests that centralization of care in high(er) volume facilities is an effective strategy to improve patient outcomes. However, particularly in the case of breast cancer, concerns about the potential impact on timely access to care have limited its promotion. Leveraging a natural experiment afforded by New York’s statewide implementation of a policy in 2009 restricting Medicaid reimbursement for breast cancer surgery provided at low-volume hospitals (<30 breast cancer surgeries annually), we examined the effect of centralization of care on days from breast cancer diagnosis to initial treatment. Methods: From a linked dataset merging NY state tumor registry with hospital discharge data, we identified 71,135 women diagnosed with Stage 1-3 incident breast cancer who underwent surgery as first course of treatment during the pre-policy (2004-08) and post-policy (2010-13) periods. Multivariable difference-in-difference models were used to estimate the policy effect on the probability of experiencing delayed care (>60 days) between diagnosis and initial surgical treatment by Medicaid beneficiaries before and after policy implementation relative to the experience of commercially or otherwise insured women unaffected by the policy change. Results: The cohort consisted of 8435 Medicaid beneficiaries (4070 pre-/4365 post-policy) and 62,700 non-Medicaid women (34,909 pre-/28,610 post-policy). The mean time to surgery pre- and post-policy was 34 (SD=37.2) and 45.5 (SD=41.3) days for Medicaid beneficiaries and 27.5 (SD=27.7) and 36 (SD=28.4) days for non-Medicaid patients. Multivariate estimates indicate that, regardless of insurance status, the more recently treated patients were more likely to wait >60 days to initial treatment (OR=1.5, 95% CI=1.43-1.59, p<0.001) suggesting a temporal trend of longer time to treatment unrelated to the centralization policy. Regardless of the policy period, Medicaid beneficiaries were more likely to experience delayed care than commercially insured women (OR=1.75; 95% CI=-1.59 to 1.92, p<0.001). Difference-in-difference estimates, however, indicate that the adjusted probability of delayed care among Medicaid patients (from 14.3% to 20.5%) was not significantly larger than that of patients not affected by the policy (from 8.8% to 12.6%). Controlling for time trends and policy effects, age, race, ethnicity, comorbidities, urbanicity, tumor size, nodal status and hormone receptor status, Black women (OR=1.74, 95%CI=1.63-1.85), those of other races (OR=1.15; 95%CI=1.01-1.24), and Hispanic women (OR=1.34; 95%CI=1.24-1.44) were more likely to experience delayed care than their white or non-Hispanic counterparts. Conclusions: Given these findings and growing evidence of better survival among breast cancer patients treated at high(er) volume hospitals, centralization of breast cancer care may be one effective approach to improving breast cancer outcomes.

Leveraging Area Deprivation to Improve Breast Cancer Outcomes

Leveraging Area Deprivation to Improve Breast Cancer Outcomes

Short-term changes in ultrasound tomography measures of breast density and treatment-associated endocrine symptoms after tamoxifen therapy

Although breast density decline with tamoxifen therapy is associated with greater therapeutic benefit, limited data suggest that endocrine symptoms may also be associated with improved breast cancer outcomes. However, it is unknown whether endocrine symptoms are associated with reductions in breast density after tamoxifen initiation. We evaluated treatment-associated endocrine symptoms and breast density change among 74 women prescribed tamoxifen in a 12-month longitudinal study. Treatment-associated endocrine symptoms and sound speed measures of breast density, assessed via novel whole breast ultrasound tomography (m/s), were ascertained before tamoxifen (T0) and at 1–3 (T1), 4–6 (T2), and 12 months (T3) after initiation. CYP2D6 status was genotyped, and tamoxifen metabolites were measured at T3. Using multivariable linear regression, we estimated mean change in breast density by treatment-associated endocrine symptoms adjusting for age, race, menopausal status, body mass index, and baseline density. Significant breast density declines were observed in women with treatment-associated endocrine symptoms (mean change (95% confidence interval) at T1:−0.26 m/s (−2.17,1.65); T2:−2.12 m/s (−4.02,−0.22); T3:−3.73 m/s (−5.82,−1.63); p-trend = 0.004), but not among women without symptoms (p-trend = 0.18) (p-interaction = 0.02). Similar declines were observed with increasing symptom frequency (p-trends for no symptoms = 0.91; low/moderate symptoms = 0.03; high symptoms = 0.004). Density declines remained among women with detectable tamoxifen metabolites or intermediate/efficient CYP2D6 metabolizer status. Emergent/worsening endocrine symptoms are associated with significant, early declines in breast density after tamoxifen initiation. Further studies are needed to assess whether these observations predict clinical outcomes. If confirmed, endocrine symptoms may be a proxy for tamoxifen response and useful for patients and providers to encourage adherence.

Abstract P1-06-03: Differences in Breast Cancers among American-Indians and Whites in the United States

Abstract Differences in Breast Cancers among American-Indians and Whites in the United States Background - The United States has made substantial progress in improving breast cancer (BC) outcomes over the years, but unfortunately, this improvement has not impacted all races equally. BC death rates have not improved significantly for American Indian (AI) women, whereas, it significantly decreased for White women. In addition, AI women were more likely to be diagnosed at a younger age with a late-stage disease. We sought to determine the reasons for these disparities. Methods - This is a retrospective cohort study using a hospital registry database (the National Cancer Data Base) (NCDB). We identified female AIs and non-Hispanic Whites in the US diagnosed with BC between the years 2004 and 2016. We compared patient and tumor characteristics between the 2 groups and its effect on age and stage at diagnosis. We also determined hazard ratios (HRs) for overall survival using Cox regression models, both before and after adjustment for covariates. Results – Data on 6,866 AIs and 1,987,324 White women diagnosed with BC were analyzed. The mean (SD) age at diagnosis was significantly younger for AI than for White women (57.72 ± 12.23 vs. 61.87 ± 13.21). AI women traveled double the distance to their treatment facilities, lived in lower median income zip codes, reported a higher percentage of no insurance, and higher comorbidities than Whites. Furthermore, AIs were less likely to be diagnosed with Stage 0 and I BCs, had a larger tumor size, greater number of positive lymph nodes at diagnosis, and higher proportion of triple negative and HER2-positive BCs than Whites. Whites were more likely to have other cancers diagnosed prior to or after their BC diagnosis. All the above tests for comparisons were significant (p-value < 0.001). Correlation between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AIs and Whites. Unadjusted overall survival (OS) was significantly worse for AIs as compared to Whites (HR=1.07; 95% CI: 1.01-1.14, p-value = 0.025). After adjustment of all covariates including age, travel distance, median income of residential zip code, insurance status, cancer sequence, comorbidities, stage, tumor size, number of positive lymph nodes, grade, histology, and hormonal/HER2 status, OS was not significantly different between AIs and Whites (HR=1.04; 95% CI: 0.90-1.20, p-value = 0.601). Conclusion - Our study showed significant differences in patient and tumor characteristics among AI and White BC patients which adversely impacted BC outcomes in AIs. Survival was lower in AIs, but when adjusted for various covariates, the survival difference disappeared. Improvement in BC outcomes in AIs will involve not only improved and early access to screening to identify patients at younger ages and earlier stages at diagnosis, but also long term plans to provide affordable and the full spectrum of cancer care closer to home. Citation Format: Anu Gaba, Li Cao, Rebecca Renfrew, Janet Wernisch, Abe Sahmoun, Sanjay Goel, Ross Crosby. Differences in Breast Cancers among American-Indians and Whites in the United States [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 P1-06-03.

Abstract PD1-04: Neighborhood Deprivation Index and Survival in Breast Cancer in the United States

Abstract Introduction: Socioeconomic status (SES) of the individual and neighborhood plays an important role in patients’ (pts) access to the health system and eventually in the outcomes of their disease. Owing to the inequalities in opportunities, education, income, and developmental infrastructures, the area with deprived individual and neighborhood SES may be associated with a poor prognosis of certain malignancies and worse outcomes. We analyzed the association between Neighborhood Deprivation Index (NDI) and survival of early-stage breast cancer (BC). Methods: The NDI created by the National Cancer Institute includes variables from dimensions, such as, wealth and income, education, occupation, and housing conditions which have been used for our analysis. We analyzed the impact of NDI in quintiles (qn). We queried the SEER database from 2010-2016 for all early-stage BC pts and studied the overall survival (OS) and disease-specific survival (DSS) of BC in association with NDI. Cox multivariate regression modeling was performed to measure the association between NDI and OS/DSS. Kruskal-Wallis test was used for comparison for continuous and Chi-Square test was used for categorical variables. All analyses were adjusted for age, race, grade, insurance, surgery (SX), radiation (RN), and chemotherapy (CT). Statistics were performed using SAS. Results: Out of the 88,572 early-stage BC pts, 27.4 % (n= 24,307) were in the most deprivation (MD) qn, 26.5% (n= 23,447) were in the average deprivation (AD) qn, 17% (n= 15,035) were in the above average deprivation (AA) qn, 15.6% (n= 13,838) were in the least deprivation (LD) qn and 13.5% (n= 11,945) were in the below average deprivation (BA) qn. The median age of pts in the LD qn was 59 and MD qn was 61 yrs, p< 0.001. There was a predominance of racial minorities in the MD and AA qn with Blacks being 13-15% and Hispanics being 15% compared to only 8% Blacks and 6% Hispanics in the LD qn (p< 0.001). There was a higher percentage of uninsured pts in the MD qn compared to LD qn (2.2% vs 1.7%, p< 0.001). There were more rural areas in MD qn compared to LD qn (25.9% vs only 0.7%, p< 0.001). There were more pts with grade III disease in MD qn compared to LD qn (34% vs 31.9%, p< 0.001). 96.1% pts underwent SX in MD qn vs 97.1 % had SX in LD qn, p< 0.001. Similarly, 49.7% underwent RN in MD qn vs 56.5% had RN in the LD qn, p< 0.001. Greater percentage of pts received CT in MD qn compared to LD qn (44.6% vs 42.1%, p< 0.001). There was a higher percentage of more aggressive cancers such as triple-negative breast cancer (TNBC) and HER2 positive (HER2+) in MD qn compared to LD qn (14.5%, 17.7% vs 11.7%, 16.5% respectively, p< 0.001). In multivariate analysis, in the overall cohort, those who live in AA qn and MD qn have inferior OS and DSS when compared to those who live in LD qn (OS in AA: Hazard Ratio (HR) 1.3, 95% CI: 1.2-1.4; OS in MD: HR 1.2, 95% CI: 1.1-1.3; DSS in AA: HR 1.3, 95% CI: 1.2-1.5; DSS in MD: HR 1.2, 95% CI: 1.1-1.4, all p< 0.001). Similar results in OS and DSS were observed in hormone receptor-positive HER2 negative (HR+) and HER2+ subtypes, but not in TNBC (Table 1). The 5-year OS rates and DSS rates were also comparatively low in AA qn and MD qn compared to LD qn (OS: AA- 84%, MD- 85%, LD- 98%; DSS: AA- 91%, MD- 92%, LD- 95%, all p< 0.001). Conclusion: Early-stage BC pts from areas with worse NDI have poor OS and DSS, after accounting for the demographic, clinicopathological, treatment-related factors. Investments in poor-resource neighborhoods and policies focusing on improving the SES of areas with high deprivation need to be implemented to reduce health care disparities and improve breast cancer outcomes. Table: Overall Survival and Disease Specific Survival Citation Format: Arya Mariam Roy, Anthony George, Kristopher Attwood, Shipra Gandhi. Neighborhood Deprivation Index and Survival in Breast Cancer in the United States [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 PD1-04.

Cascade Analysis for Women Presenting With Breast Concerns to a Zonal Hospital in Mwanza, Tanzania.

In Tanzania, high breast cancer mortality can be attributed to delays in diagnosis and treatment initiation. We adapted the cascade analysis method to depict sequential steps along the breast cancer care pathway in a tertiary hospital in Mwanza, to identify where correction of loss to attrition would have the biggest impact on improving outcomes. This prospective cohort included adult women presenting with breast concerns between February 2020 and January 2022. Five cascade steps beginning with patients' initial clinical breast assessment (CBA) through cancer treatment were identified: (1) CBA, (2) ordering diagnostic test(s), (3) completion of diagnostic test(s), (4) receipt of final diagnosis, and (5) initiating cancer treatment. Overall, 721 eligible women with a median age of 42.8 years (IQR, 32.5-55.0) were included. Median time from presentation to treatment initiation was 35 days (IQR, 20-63). For step 1, 39.1% (n = 282) of patients were diagnosed with a benign concern and removed from the cascade. Completion rates for steps 2-4 were 95.0%, 90.2%, and 91.0, respectively. There were 156 (45.6%) patients diagnosed with breast cancer, and for step 5, 71.2% of patients initiated cancer treatment. In steps 2, 3, 4, and 5, there was a loss of 22, 41, 34, and 45 patients, respectively. If loss was eliminated at steps 2, 3, 4, or 5, an additional 6, 12, 11, or 45 patients, respectively, would have completed the pathway. Initiating cancer treatment was identified as the step with the biggest loss and, if remedied, would have the biggest impact on improving breast cancer outcomes at Bugando Medical Centre. These results will inform future programs focused on reducing overall loss in the system and supporting patients with breast cancer.

Abstract P6-05-25: HT Helper: A Mobile App to Promote Hormone Therapy Adherence among Breast Cancer Patients

Abstract Background: Adjuvant hormonal therapy (HT) is highly effective and appropriate for nearly all women with hormone receptor-positive tumors, making such treatment the most widely prescribed therapy for patients with this type of breast cancer. Despite its proven benefits in reducing cancer recurrence and improving survival, HT adherence is suboptimal (less than 80%). About 33% of patients do not take their medication as prescribed and are at increased risk of disease recurrence and lower survival. Smartphone ownership has increased substantially over the past decade, providing an extraordinary opportunity for innovation in the delivery of tailored interventions to improve patients’ adherence to hormonal therapy. Purpose: We present preliminary results of a pilot study to test the feasibility of an intervention consisting of a theory-based, bilingual, culturally tailored, and interactive mobile app + patient navigation to empower patients’ self-monitoring and management by facilitating patient education, self-efficacy, early identification and reporting of side effects, delivery of self-care advice, and timely feedback through direct communication between the patient and the oncology team. Methods: This is a 2-group parallel, randomized control trial recruiting patients (120) receiving hormone therapy treatment and attending the breast clinic at the Mays Cancer Center (MCC). The intervention group receives two components: 1) the HT Helper phone app; and 2) assistance from a patient navigator who will provide educational, psychosocial support and reinforcement, address common barriers, and facilitate the interaction with the medical team as needed. The control group receives the usual care and information provided by the MCC’s breast clinic to patients undergoing HT. The app and navigation support are based on Social Cognitive Theory and principles of motivational interviewing. Patients are assessed at baseline, three and six months. The primary outcome is HT adherence. Additional variables of interest include self-efficacy, social support, depression, side effects, anxiety, and quality of life. We also assess app usability and satisfaction. Results: We have recruited 108 patients, 56 in the intervention group and 52 in the control group. The mean age is 57.5 years, 58.3% are Latinas, 41.7% have less than high school education, 54.2% have a family income of less than $50,000/year and 52.8% have Medicare/Medicaid. In addition to descriptive data, we will present results of the 3-month and 6-month follow-ups. Conclusion: The anticipated outcome of this innovative, multi-communication study is a scalable, evidence-based, and easily adaptable intervention with potentially broad use to patients using oral anticancer agents. The intervention has the potential to improve breast cancer outcomes by reducing recurrence, improving quality of life and survival, and reducing healthcare costs. The ultimate goal of this innovative, multi-communication intervention is to improve overall survival and life expectancy, enhance quality of life, and decrease healthcare costs. Citation Format: Vivian Cortez, Patricia Chalela, Armida Flores, Sandra Sivak, Edgar Munoz, Ysabel Lew, Virginia Kaklamani, Kate I. Lathrop, Devasena Inupakutika, David Akopian, Amelie Ramirez. HT Helper: A Mobile App to Promote Hormone Therapy Adherence among Breast Cancer Patients [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 P6-05-25.

Abstract P2-13-02: COBRA: Characteristics and Outcomes of patients with BReast cancer in phAse I trials at Gustave Roussy Cancer center

Abstract Background: Breast cancer (BC) is the most frequent cancer and the second leading cause of cancer death for women. Although there is a need of new treatments to improve BC outcome, patients with BC are still under-represented in early phase trials, possibly because of the availability of numerous approved treatments and widely recruiting phase II and III trials. We aim to characterize the molecular profile, outcome and prognostic factors of patients with BC treated in a phase I trial at our institution. Methods: We retrospectively analyzed medical records of every BC patients treated consecutively in a phase I trial in the Early Drug Development Department (DITEP) at Gustave Roussy Cancer Center. Multivariate logistic regression models were used to determine the association between known prognostic factors such as ECOG, LDH or albumin levels, number of previous lines of treatment, metastatic sites and duration of treatment. When available, molecular profile was also reviewed. Results: Between April 1st 2008 and December 31th 2021, 4682 patients were enrolled and treated in a phase I trial in our department. Among them, 272 were treated for BC (5.8%): 271 women and 1 man, in 74 different trials. The median number of BC patients treated per year was 16.5 (min 1; max 33). Median time between consented date and C1D1 was 14 days (min 1; max 63). Median age at C1D1 was 50 years old (min 24; max 82). 5 patients (1.8%) were treated in an adjuvant setting (therapeutic vaccine) while all the others were metastatic. 12 patients (4.5%) had brain metastases and 127 patients (47.6%) had liver metastases. 186 patients (70%) had only 1 or 2 metastatic sites, and 81 (30%) had three or more sites. Triple negative was the most common subtype, representing 132 patients (48.5%), 125 (46%) were ER+ and 15 (5.5%) Her2+. Patients received a median number of 3 prior lines before enrollment (min 0; max 19). Overall, only 78 patients (28%) had a genetic testing: 30.7% had a germline BRCA1/2 mutation. 146 patients (54%) had a molecular profile (liquid biopsy or tissue sample) before their enrollment and among them 32,9% were oriented in a trial according to their specific profile. Regarding the type of treatments received: 21.7% were immunotherapy, 73.6% were targeted therapies (46.7% in monotherapy, 26.9% in different combinations with immunotherapy, chemotherapy, radiotherapy or endocrine treatments), 2.9% were chemotherapy and 1.8% endocrine therapy. The overall response rate was 11.1% (0.4% complete response, 10.7% partial response, 37.5% stable disease, 43.8% progressive disease and 7.6% not evaluable). Main reasons for discontinuation of treatment were: progressive disease (80.5%), toxicity (9.6%) and end of trial (6.6%). Median duration of treatment was 2 months (min 0; max 44), only 28.6% of patients were still treated after 3 months of trial and 10% at 6 months. At data cut off (June 21st 2022) median overall survival was 11 months. All patients had discontinued the trial by the time of the analysis: median number of lines of subsequent treatment was 2 (min 0; max 10) and 31 patients (11%) were enrolled in another phase I trial in our center. In a multivariate analysis, there was no prognostic factor associated with duration of treatment whether it was albumin (p=0.76) or LDH levels (p=0.68), ECOG (p=0.67), number of prior lines of treatment (p=0.79) or number of metastatic site (p=0.05). Conclusion: These results are consistent with prior published data as only few patients with BC are addressed for inclusion in a phase I trial, despite response rates and survival rates similar to other phase I patients. We did not find any specific factor associated with duration of treatment. It is likely that a thorough molecular profile could open more treatment options and access to phase I trials. Citation Format: Lauren Seknazi, Arthur Geraud, Vincent Goldschmidt, Capucine Baldini, Stéphane Champiat, Christophe Massard, Sophie Postel-Vinay, Aurelien Marabelle, Rastilav Bahleda, Antoine Hollebecque, Cristina Smolenschi, Anas Gazzah, Jean-Marie Michot, Patricia Martin-Romano, Aurore Vozy, Perrine Vuagnat, François-Xavier Danlos, Arnaud Bayle, Linda Mahjoubi, Barbara Pistilli, Yohann Loriot, Santiago Ponce-Aix, Kaissa Ouali. COBRA: Characteristics and Outcomes of patients with BReast cancer in phAse I trials at Gustave Roussy Cancer center [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 P2-13-02.

Cascade genetic testing (CGT) female first-degree relatives (FDR) of men with germline BRCA2 mutations (gBRCA2mut) and prostate cancer (PCa): A cost-effectiveness analysis.

110 Background: g BRCA2mut are associated with increased risk of PCa, breast cancer (BC), and ovarian cancer (OC). ~5% of men with metastatic PCa have g BRCA2mut. CGT is recommended for their relatives as there are implications for cancer prevention and early detection strategies. Little is known about CGT initiated by men with PCa. Here we evaluate the cost-effectiveness of CGT in FDR of men with PCa and g BRCA2mut. Methods: A decision-analytic model was created with TreeAge software to compare BC and OC outcomes for female FDRs who underwent CGT for g BRCA2mut versus no CGT. Our theoretical cohort contained 100,000 females, a conservative estimate of patients who could benefit from CGT. We used literature derived estimates to determine the percentage of patients that would pursue risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, both surgeries, or surveillance after CGT. Outcomes included BC or OC diagnoses, survivorship, and cancer death. We derived all probabilities, costs, utilities, and life expectancies from the literature and discounted quality adjusted life years (QALYs) at a rate of 3%. Incremental cost-effectiveness (ICER) was calculated to determine the cost per QALY gained and set the willingness-to-pay threshold at $100,000/QALY. We assessed the robustness of the model with sensitivity analyses. Results: In our theoretical cohort, CGT of female FDRs resulted in 12,910 less BC diagnoses and 6,360 less BC deaths. CGT was associated with lower BC death rates (26.1%) compared to no CGT (35.8%). CGT was not associated with reduction in OC diagnoses or deaths. Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$4,190.10 per QALY, saving an estimated $595 million. We found that CGT in females was the dominant strategy in 100% of the samples, once uncertainty was incorporated into our model inputs via Monte Carlo simulation. The cost-effectiveness of CGT for male FDRs will be presented at the meeting. Conclusions: In this study, CGT of female FDRs of men with PCa and g BRCA2mut was the dominant strategy to improve BC outcomes, including increased survivorship and reduced BC development. Despite a lack of demonstrated benefit for OC, CGT was associated with reduced costs and increased QALYs. CGT for female FDRs of patients with PCa and g BRCA2mut may be a cost-effective approach for identifying and informing individuals with potentially harmful mutations. [Table: see text]

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial

Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P+ T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). Dual blockade with P+ T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.

Centralization of Initial Care and Improved Survival of Poor Patients With Breast Cancer.

Poor women with breast cancer have worse survival than others, and are more likely to undergo surgery in low-volume facilities. We leveraged a natural experiment to study the effectiveness of a policy intervention undertaken by New York (NY) state in 2009 that precluded payment for breast cancer surgery for NY Medicaid beneficiaries treated in facilities performing fewer than 30 breast cancer surgeries annually. We identified 37,822 women with stage I-III breast cancer during 2004-2008 or 2010-2013 and linked them to NY hospital discharge data. A multivariable difference-in-differences approach compared mortality of Medicaid insured patients with that of commercially or otherwise insured patients unaffected by the policy. Women treated during the postpolicy years had slightly lower 5-year overall mortality than those treated prepolicy; the survival gain was significantly larger for Medicaid patients (P = .018). Women enrolled in Medicaid had a greater reduction than others in breast cancer-specific mortality (P = .005), but no greater reduction in other causes of death (P = .50). Adjusted breast cancer mortality among women covered by Medicaid declined from 6.6% to 4.5% postpolicy, while breast cancer mortality among other women fell from 3.9% to 3.8%. A similar effect was not observed among New Jersey Medicaid patients with breast cancer treated during the same years. A statewide centralization policy discouraging initial care for breast cancer in low-volume facilities was associated with better survival for the Medicaid population targeted. Given these impressive results and those from prior research, other policymakers should consider adopting comparable policies to improve breast cancer outcomes.[Media: see text].

The effect of natural products combination on MCF-7 cells exceeds tamoxifen therapeutic dose effects in vitro

Cancer remains to be one of the most severe sicknesses globally. Cases have kept rising over the years. Breast cancer (BC), which is among the leading types of cancers and predominantly affects women, is the second leading cause of cancer mortality. Researchers have developed interventions over the years; however, the BC survival rate has not improved since the 1980s. This has created the need for novel drug interventions that would manage and treat BC more effectively. This study focused on using a combination of natural product extracts such as phytoestrogen (Ziziphus jujube) and Tannin nanoparticles (NP99) together, which we have referred to as (Z.NP99) and tamoxifen (Tam) as one of the leading BC drugs since the 70s, in treating BC. The effectiveness of Tam if used alone in the treatment and if combined with Z.NP99 was evaluated using MCF-7 cells in vitro. The findings showed that the combination treatment of Z.NP99 affected the proliferation and viability of MCF-7 cells more than Tam at a 10 μg/mL dose. Moreover, Z.NP99 with Tam stimulated the maximum reduction of MCF-7 proliferation and viability in a time-dependent manner. Furthermore, Tam and Z.NP99 augmented the DNA fragmentation percentage combined with the upregulation of the apoptotic genes. Additionally, the results showed that the apoptotic impact of Z.NP99 and Tam on MCF-7 cells may be intermediated by down-regulating some genes such as Claudin-1 followed by down-regulating mRNA expression of MMP-9, VEGF, and BCL-2 genes of treated cells. Combining Tam with Z.NP99 considerably enhanced the effectiveness of conventional therapy. As a result, this study suggested that the Z.NP99 was ideal for developing effective natural treatments that would improve BC outcomes.

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models

Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.

Updates in combined approaches of radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer

Breast cancer is the most prevalent non-skin cancer diagnosed in females and developing novel therapeutic strategies to improve patient outcomes is crucial. The immune system plays an integral role in the body's response to breast cancer and modulating this immune response through immunotherapy is a promising therapeutic option. Although immune checkpoint inhibitors were recently approved for the treatment of breast cancer patients, not all patients respond to immune checkpoint inhibitors as a monotherapy, highlighting the need to better understand the biology underlying patient response. Additionally, as radiotherapy is a critical component of breast cancer treatment, understanding the interplay of radiation and immune checkpoint inhibitors will be vital as recent studies suggest that combined therapies may induce synergistic effects in preclinical models of breast cancer. This review will discuss the mechanisms supporting combined approaches with radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer. Moreover, this review will analyze the current clinical trials examining combined approaches of radiotherapy, immunotherapy, chemotherapy, and targeted therapy. Finally, this review will evaluate data regarding treatment tolerance and potential biomarkers for these emerging therapies aimed at improving breast cancer outcomes.

Imaging Surveillance Options for Individuals With a Personal History of Breast Cancer: AJR Expert Panel Narrative Review.

Annual surveillance mammography is recommended for breast cancer survivors on the basis of observational studies and meta-analyses showing reduced breast cancer mortality and improved quality of life. However, breast cancer survivors are at higher risk of subsequent breast cancer and have a fourfold increased risk of interval breast cancers compared with individuals without a personal history of breast cancer. Supplemental surveillance modalities offer increased cancer detection compared with mammography alone, but utilization is variable, and benefits must be balanced with possible harms of false-positive findings. In this review, we describe the current state of mammographic surveillance, summarize evidence for supplemental surveillance in breast cancer survivors, and explore a risk-based approach to selecting surveillance imaging strategies. Further research identifying predictors associated with increased risk of interval second breast cancers and development of validated risk prediction tools may help physicians and patients weigh the benefits and harms of surveillance breast imaging and decide on a personalized approach to surveillance for improved breast cancer outcomes.

The Effect of Two Interventions to Increase Breast Cancer Screening in Rural Women.

Simple SummaryThis research tested the effectiveness of a mailed DVD and mailed DVD + PN (patient navigation) to increase mammography screening compared to usual care in rural women. Women in the combined DVD + PN were over 5 times more likely to have received a mammogram 12 months after the intervention.Guideline-based mammography screening is essential to lowering breast cancer mortality, yet women residing in rural areas have lower rates of up to date (UTD) breast cancer screening compared to women in urban areas. We tested the comparative effectiveness of a tailored DVD, and the DVD plus patient navigation (PN) intervention vs. Usual Care (UC) for increasing the percentage of rural women (aged 50 to 74) UTD for breast cancer screening, as part of a larger study. Four hundred and two women who were not UTD for breast cancer screening, eligible, and between the ages of 50 to 74 were recruited from rural counties in Indiana and Ohio. Consented women were randomly assigned to one of three groups after baseline assessment of sociodemographic variables, health status, beliefs related to cancer screening tests, and history of receipt of guideline-based screening. The mean age of participants was 58.2 years with 97% reporting White race. After adjusting for covariates, 54% of women in the combined intervention (DVD + PN) had a mammogram within the 12-month window, over 5 times the rate of becoming UTD compared to UC (OR = 5.11; 95% CI = 2.57, 10.860; p < 0.001). Interactions of the intervention with other variables were not significant. Significant predictors of being UTD included: being in contemplation stage (intending to have a mammogram in the next 6 months), being UTD with other cancer screenings, having more disposable income and receiving a reminder for breast screening. Women who lived in areas with greater Area Deprivation Index scores (a measure of poverty) were less likely to become UTD with breast cancer screening. For rural women who were not UTD with mammography screening, the addition of PN to a tailored DVD significantly improved the uptake of mammography. Attention should be paid to certain groups of women most at risk for not receiving UTD breast screening to improve breast cancer outcomes in rural women.

Improving Invasive Breast Cancer Care Using Machine Learning Technology

Breast Cancer (BC) is the most common malignancy in women worldwide. In the United States, the lifetime risk of developing an invasive form of breast cancer is 12.5% among women. BC arises in the lining cells (epithelium) of the ducts or lobules in the glandular tissue of the breast. The goal of the present study was to use Machine Learning (ML) as a novel technology to assess and compare the invasive forms of BC including, infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mucinous carcinoma. To achieve this goal, we used ML algorithms and collected a dataset of 334 BC patients available at https://www.kaggle.com/amandam1/breastcancerdataset and interpreted this dataset based on the form of BC, age, sex, tumor stages, surgery type, and survival rate. Among the 334 patients, 70% were diagnosed with infiltrating ductal carcinoma, 27% with infiltrating lobular carcinoma, and 3% with mucinous carcinoma. Overall, out of 334 BC patients: 64 (19.16%) were in stage I, 189 (56.59%) in stage II, and 81 (24.25%) in stage III. Sixty-six, 67, 96, and 105 patients underwent lumpectomy, simple mastectomy, modified radical mastectomy, and other types of surgery, respectively. The survival rates were 83.4% for stage I, 79.1% for stage II, and 77% for stage III. Findings from the present study demonstrated that ML provides an important tool to curate large amount of BC data, as well as a scientific means to improve BC outcomes.

Determinants and Effectiveness of Extending the Duration of Adjuvant Hormone Therapy beyond 5 Years in Patients with Breast Cancer.

The proportion of patients with breast cancer extending adjuvant hormone therapy beyond 5 years has increased dramatically in recent years, which is associated with improved patient outcomes.

Patient Navigation Can Improve Breast Cancer Outcomes among African American Women in Chicago: Insights from a Modeling Study.

African American (AA) women experience much greater mortality due to breast cancer (BC) than non-Latino Whites (NLW). Clinical patient navigation is an evidence-based strategy used by healthcare institutions to improve AA women's breast cancer outcomes. While empirical research has demonstrated the potential effect of navigation interventions for individuals, the population-level impact of navigation on screening, diagnostic completion, and stage at diagnosis has not been assessed. An agent-based model (ABM), representing 50-74-year-old AA women and parameterized with locally sourced data from Chicago, is developed to simulate screening mammography, diagnostic resolution, and stage at diagnosis of cancer. The ABM simulated three counterfactual scenarios: (1) a control setting without any navigation that represents the "standard of care"; (2) a clinical navigation scenario, where agents receive navigation from hospital-affiliated staff; and (3) a setting with network navigation, where agents receive clinical navigation and/or social network navigation (i.e., receiving support from clinically navigated agents for breast cancer care). In the control setting, the mean population-level screening mammography rate was 46.3% (95% CI: 46.2%, 46.4%), the diagnostic completion rate was 80.2% (95% CI: 79.9%, 80.5%), and the mean early cancer diagnosis rate was 65.9% (95% CI: 65.1%, 66.7%). Simulation results suggest that network navigation may lead up to a 13% increase in screening completion rate, 7.8% increase in diagnostic resolution rate, and a 4.9% increase in early-stage diagnoses at the population-level. Results suggest that systems science methods can be useful in the adoption of clinical and network navigation policies to reduce breast cancer disparities.