Improved Breast Cancer Survival Research Articles

Predicting locoregional recurrence in triple-negative breast cancer using novel molecular subtyping.

e12549 Background: Triple-negative breast cancer (TNBC) presents a poorer prognosis compared to other breast cancer subtypes, characterized by a higher likelihood of early recurrence and increased incidence of visceral metastases. Evidence from numerous randomized clinical trials indicates that postmastectomy radiotherapy (PMRT) reduces locoregional recurrence (LRR) and improves breast cancer survival in TNBC. Previous reports creatively divided TNBC into four molecular subtypes for personalized treatment. The present study aims to elucidate patterns of LRR in different subtypes of TNBC after PMRT. Methods: From 2019 to 2022, data from 349 AJCC 7th edition stage II-III breast cancer patients treated with mastectomy and PMRT were retrospectively analyzed. These patients were classified into the basal-like immune-suppressed (BLIS) and non-BLIS groups based on the immunohistochemistry biomarkers. The cumulative incidence function was applied to estimated LRR rates, with death as a competing risk, using Gray's test for comparisons. Results: According to the IHC results, a total of 255 patients belonged to the non-BLIS group and 94 to the BLIS group. The 3-year LRR for the entire cohort was 5.16%. There were 9 cases each in the non-BLIS subtype (3.5%) and BLIS subtype (9.6%). The cumulative incidence of LRR between the two groups was significantly different, with a rate of 4.0% in the non-BLIS group and 9.0% in the BLIS group ( P = 0.02). Among the 18 patients with LRR in the whole population, 11 had isolated LRR and 7 were diagnosed with LRR with concurrent distant metastases. The most common area of recurrence in both subtypes was the supraclavicular region. The majority of recurrences occurred within the RT field (in-field), and no isolated out-of-field relapse was observed. In multivariate analysis, independent factors predicting higher LRR were the BLIS subtype (HR = 3.06, P = 0.02). Conclusions: Study results suggest that TNBC of the BLIS subtype is at higher risk for LRR. Immunohistochemistry-based molecular typing may serve as a prognostic biomarker to guide postmastectomy radiotherapy in patients with TNBC. New strategies are needed to improve local control rates in patients with BLIS subtype.

Statin use and risks of breast cancer recurrence and mortality.

Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients. In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis statin use and risks of breast cancer recurrence and breast cancer-specific mortality. Over a median follow-up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post-diagnosis statin use was 2.2 years. Statin use post-diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91-1.21), but was associated with a reduced risk of cancer-specific mortality (HR, 0.85; 95% CI, 0.75-0.96). The reduction was more pronounced in women with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR, 0.71; 95% CI, 0.57-0.88). These findings suggest that post-diagnosis statin use is associated with improved cancer-specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients.

Abstract PO1-09-11: Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer and has been utilized in multiple clinical trials assessing the efficacy of novel therapies. Pathologic complete response (pCR) following NAC is associated with improved survival outcomes in breast cancer and pCR is a commonly used endpoint in clinical trials. Despite improvements in breast cancer survival using modern treatment regimens, Black women continue to experience worse survival outcomes as compared to White women. The objective of this study was to evaluate the association between race and clinical outcomes, specifically pCR rate, recurrence free survival and overall survival, in patients undergoing neoadjuvant chemotherapy at our institution. Methods: We conducted a retrospective review of patients who completed at least 75% of the recommended cycles of neoadjuvant chemotherapy for breast cancer between 2010 and 2016 and underwent surgery. Receptor subtypes were defined as HR+/HER2-negative, HER2+ or triple-negative. The association between race and pCR, defined as ypT0/ypTis ypN0, and survival endpoints of overall survival and recurrence free survival were analyzed using multivariable logistic regression and Cox proportional hazard models. Results: A total of 532 women met the inclusion criteria, 323 (60.7%) were White, 188 (35.3%) were Black and 21 (3.9%) were other/unknown. Median follow-up was 65 months. The receptor subgroups consisted of 195 (36.7%) HR+/HER2-negative cancers, 193 (36.3%) HER2+ cancers and 144 (27.1%) triple-negative cancers. No significant association between race and receptor subtype (p=0.55) or pre-treatment clinical stage (p=0.96) was observed. The overall observed pCR rate was 19% for Black patients and 27% for White patients, demonstrating a significantly different pCR rate by race in multivariate analysis (odds ratio of pCR White vs Black of 1.75; p=0.02). The largest discrepancy in pCR rate between White and Black patients was within subjects with triple-negative disease (pCR rate 44% White patients vs 27% Black patients, p=0.03). There was no association between recurrence free survival and race in univariate analysis (p=0.15). A significant difference in overall survival by race was observed using multivariable Cox proportions hazard model (hazard ratio Black vs White 1.77; p=0.03). Conclusions: In this retrospective analysis of patients receiving neoadjuvant chemotherapy, Black patients experienced a significantly lower pCR rate compared to White patients, with the biggest gap identified within triple-negative breast cancers. During the study period, Black patients also experienced a lower overall survival rate compared to White patients. Differences in the ability to achieve a pCR may be a contributing factor to the worse survival outcomes of Black patients. Citation Format: Chad Livasy, Erin Donahue, Brittany Neelands, Lejla Hadzikadic-Gusic, Terry Sarantou, Mckenzie Needham, Alicia Patrick, Arielle Heeke, Antoinette Tan, Richard White. Racial Differences in Pathologic Complete Response Rate and Overall Survival Following Neoadjuvant Chemotherapy for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-11.

Abstract PO1-02-13: Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA)

Abstract Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) Background: There is accumulating evidence that the RANK/RANKL signaling pathway plays a pivotal role in breast tumorigenesis, particularly in the development of BRCA1-mutated tumors. Targeting the RANK pathway has been shown to attenuate breast cancer (BC) proliferation in vitro and in vivo. Studies using bone modifying agents as adjuvant therapy showed reduced rates of bone metastases and improved BC survival, as well as prevention of treatment-induced skeletal events. The GeparX clinical trial assessed the use of denosumab in patients with primary BC as an adjunct to neoadjuvant chemotherapy for its ability to enhance pathological complete response (pCR) rate and improve outcome. The trial randomized 780 patients twice to a total of 4 treatment groups (to receive or not receive denosumab; to receive nab-paclitaxel 125 mg/m2 weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles, both followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m2 every 2 weeks/every 3 weeks according to the investigator´s choice). Carboplatin was given in triple-negative breast cancer (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in human epidermal growth factor-2-positive (HER2+) BC. Overall, the pCR (ypT0 ypN0) rate was 41% with denosumab vs 43% without; nab-paclitaxel at a dosage of 125 mg/m2 weekly resulted in a significantly higher pCR rate of 45% vs 39% with a dosage of 125 mg/m2 days 1 and 8 every 3 weeks. Research question: Does the germline mutation status of BRCA1/2 and other BC predisposition genes affect treatment outcome in the GeparX study? Methods: Genetic germline analyses assessing pathogenic variants in BRCA1/2 and 16 other BC predisposition genes were performed at the Center for Familial Breast and Ovarian Cancer, Cologne, Germany; 767 patients were included in this secondary investigation (308 TNBC, 306 HER2-/hormone receptor positive [HR+], 153 HER2+). Findings: Germline BRCA1/2 mutations were present in 91/767 patients (11.9%), with a higher mutation prevalence in TNBC (50/308, 16.2%) and HER2-/HR+ BC (37/306, 12.1%), and a low mutation prevalence in HER2+ BC (4/153, 2.6%). Overall, the pCR rate (ypT0 ypN0) was elevated in BRCA1/2 mutation carriers vs non-carriers (49.5% vs 41.1%, respectively; overall: OR 1.40, 95% CI 0.90-2.17; TNBC: OR 1.24, 95% CI 0.67-2.32; HER2-/HR+: OR 1.83, 95% CI 0.86-3.88). Highest pCR rates were observed in TNBC in BRCA1/2 mutation carriers vs non-carriers (60% vs. 54.7%, respectively). Highest pCR rate differences were observed HER2-/HR+ BC in BRCA1/2 mutation carriers vs non-carriers (32.4% vs. 20.8%, respectively). Regarding treatment arms, both BRCA1/2 mutation carriers and non-carriers benefitted most from nab-paclitaxel at a dosage of 125 mg/m2 weekly vs 125 mg/m2 days 1 and 8 every 3 weeks (BRCA1/2 mutation carriers: 55.3% vs 43.2%, respectively; OR 1.63, 95% CI 0.71-3.73; non-carriers: 43.7% vs 38.6%, respectively; OR 1.24, 95% CI 0.91-1.68). No beneficial effect was observed for denosumab vs no denosumab (51.1% vs 47.8% for BRCA1/2 mutation carriers, respectively; OR 1.14, 95% CI 0.50-2.60; 40.3% vs 41.9% for non-carriers, respectively; OR 0.94, 95% CI 0.69-1.27). Of the 617 BRCA1/2-negative patients, 59 patients carried mutations in other BC predisposition genes which did not predict therapy response compared to patients without any mutation. Conclusions: Irrespective of the treatment arm, higher pCR rates were observed in BRCA1/2 mutations carriers vs non-carriers. Both BRCA1/2 mutation carriers and non-carriers benefitted most from weekly nab-paclitaxel. No pronounced effect was observed for denosumab in either group. Key words: GeparX, denosumab, BRCA1/2 germline mutations, therapy response Funding: GeparX was financially supported by Amgen and BMS (Celgene). Citation Format: Rita K. Schmutzler, Theresa Link, Eric Hahnen, Mattea Reinisch, Jan Hauke, Marianne Just, Michael Untch, Corinna Ernst, Oliver Stötzer, Peter A. Fasching, Mohamad Kayali, Pauline Wimberger, Andreas Schneeweiss, Sandra Schmidt, Sabine Seiler, Christian Jackisch, Marc Thill, Kerstin Rhiem, Carsten Denkert, Valentina Nekljudova, Johannes Holtschmidt, Jens-Uwe Blohmer, Sibylle Loibl. Germline mutation status of BRCA1/2 and other breast cancer predisposition genes as predictive and prognostic biomarker: Results of the GeparX study (GeparX-BRCA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-13.

Abstract PO3-10-11: Mujeres Avanzando a la Sobrevida (MAS: women going forward in survival): Breast Cancer Characteristics and Delays in Care in Honduras

Abstract Introduction: Low and middle-income countries have exceedingly high breast cancer mortality rates primarily due to delays to diagnosis and treatment. The Breast Health Global Initiative (BHGI) recommends a diagnostic interval (time from initial provider visit to receiving a diagnosis) of < 60 days. Honduras is one of the poorest countries in the western hemisphere and has a paucity of published breast cancer research. Our objective was to understand delays in breast cancer diagnosis and treatment in Honduras. Methods: We initiated a prospective cohort study (Mujeres Avanzando a la Sobrevida (MAS: Women Going Forward in Survival)) in 2021 at two hospitals in two major cities in Honduras. All patients with newly diagnosed breast cancer were invited to participate. We prospectively collected demographic, cancer, and treatment data through patient interviews and surveys. We also determined several time intervals including: onset of symptoms to initial provider visit (patient interval), initial provider visit to biopsy (diagnostic interval), and biopsy to first treatment (treatment interval). Patients also completed the Unger-Saldana Delay Survey to assess their perceptions of any delays in cancer care and reasons for these delays. Results: We enrolled 95 patients with an average age of 54 years. 73% of patients reported an income of < 1 minimum wage (< 8,448 lempiras/month). 93% were housewives, and 35% were married. The majority of patients had an elementary school education or no education (61%). The most common first symptom was a breast lump (81%). The majority of patients had advanced stage disease (Stage III and IV: 64%). The mean patient interval was 185 days. The mean diagnostic interval was 153 days, and the mean treatment interval was 139 days. Most patients (61%) thought their symptoms were slightly serious or not serious at all, and 78% did not think their symptoms were due to cancer. Most patients (60%) thought they were able to see a physician immediately or soon after symptoms developed (63%). Patient stated reasons for not seeking care earlier included believing their symptoms would self-improve, being unsure which health service to go to, lack of money, and fear. Similarly, most patients (67%) thought the time between seeing their first provider and visiting the cancer hospital was immediate or soon but not immediately. Reasons for this delay included lack of information, lack of money, wait times to appointment or tests, incorrect initial diagnosis, and fear. Conclusion: In this prospective cohort study, nearly two-thirds of patients in Honduras were diagnosed with stage III/IV breast cancer. We found marked delays in patient, diagnostic, and treatment intervals, even though patients perceived their care to be immediate. Importantly, the diagnostic interval far exceeded 60 days, as recommended by the BHGI. This study provides initial insight into delays in breast cancer care in Honduras and provides an opportunity to target obstacles to early diagnosis and treatment and to improve breast cancer survival. Citation Format: Saranya Prathibha, Alejandra Molina, Jorge Siryi, Kristhel Gaitán, Mildred Raudales, Manuel Maldonado, Todd Tuttle, Suyapa Bejarano. Mujeres Avanzando a la Sobrevida (MAS: women going forward in survival): Breast Cancer Characteristics and Delays in Care in Honduras [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-11.

Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer

Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs >30], stage II vs III, and time since diagnosis [<18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. The primary outcome was invasive disease-free survival. Overall survival was a key secondary outcome. A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease-free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease-free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. ClinicalTrials.gov Identifier: NCT02927249.

Abstract 5403: Meeting the Physical Activity Guidelines is associated with increased CD8+ T-cell density in the tumor microenvironment of breast cancer patients

Abstract Background: Our current understanding of how physical activity (PA) is associated with immunity in breast cancer (BC) patients is based on pre-clinical evidence gleaned from mouse models or immune cells in the circulating blood, which may not be reflective of the tumor immune microenvironment (TIME). Whether self-reported PA is associated with immune cell infiltration in the breast TIME, the most relevant site for prognosis, remains a fundamental gap in knowledge. Herein, we examined the association of self-reported PA in the year before BC diagnosis with CD8+ T-cell density in the breast TIME. As prior evidence from healthy adults suggests the relationship between exercise and immunity is not linear, we hypothesized that patients reporting the highest PA level would not have the highest CD8+ T-cell density in their tumor. Methods: We leveraged data and tumor samples from 685 women with BC (548 self-identified Black and 137 self-identified White) enrolled in the Women’s Circle of Health Study and the Women’s Circle of Health Follow-Up Study. CD8+ T-cell density per square millimeter of tumor tissue was derived from IHC staining of tissue microarrays. Weekly PA in the year before diagnosis was categorized as inactive; low active (&amp;lt;7.5 MET hours/week); moderately active [7.5-14.9 MET hours/week, the equivalent of meeting the minimum PA Guidelines (PAG)]; or high active (≥15.0 MET-hours/week, exceeding the minimum PAG). Log transformed mean CD8+ T-cell densities were compared by PA level using t-tests and multivariable linear regression with adjustment for age, race, estrogen receptor status, and tumor grade. Results: Meeting the minimum PA Guidelines was associated with significantly higher CD8+ T-cell density in the breast TIME [120.4 (353.6)] in comparison to inactivity [62.0 (154.5), p=0.02]. Although there were also distinct differences in T-cell density between moderate and low-active patients [120.4 (353.6) versus 69.5 (172.6), p=0.10] and moderate and high-active patients [120.4 (353.6) versus 80.7 (223.3), p=0.051], associations were shy of significance. Multivariable linear regression analyses confirmed that moderately active patients had significantly higher CD8+ T-cell density in comparison to inactive patients, overall (p=0.029), and among Black patients (p=0.021). Conclusions: In comparison to inactivity, BC patients meeting the PAG (moderate activity) had significantly increased CD8+ T-cell density in their tumor, which is associated with better survival outcomes. This new translational knowledge suggests exercise-induced immunomodulation may be an important molecular mechanism underlying the association of PA with improved BC survival. As the immune system is a key player in treatment response and efficacy, further study of the role that PA ancillary to therapy may play in improving treatment and survival outcomes is warranted. Citation Format: Rikki Cannioto, Angela Omilian, Evan Davis, Lucas Mendicino, Scott Abrams, Bo Qin, Chi-Chen Hong, Elisa Bandera, Song Yao, Christine Ambrosone. Meeting the Physical Activity Guidelines is associated with increased CD8+ T-cell density in the tumor microenvironment of breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5403.

Abstract 2137: Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis

Abstract Background: While high-resolution imaging and advancements in therapies have significantly improved breast cancer survival rates, 43,170 breast cancer patients will die in the United States in 2023 alone. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and disproportionately affects BRCA1 mutation carriers and young black women. Black/African American (AA) patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. Persistent cancer racial disparities remain due to a variety of risk factors. The SEER/CDC data show an 8% lower breast cancer incidence rate and a 41% higher mortality rate in Black/AA patients compared to their white counterparts. Methods: Chart review was conducted using Sentara MD Office/EPIC and VOA iKnowMedicine portals to update tumor relapse, metastasis, and survival in 577 TNBC patients. Supported by strong evidence in developmental, evolutionary, and cancer biology, we hypothesize that persistent EGFR/K-RAS/SIAH pathway activation is a major driving force of TNBC malignancy, racial disparity, early relapse, and high mortality. We propose to integrate SIAH expression to augment the existing clinicopathological parameters to improve patient risk stratification, therapy quantification, and relapse/survival prediction at the 1st-line neoadjuvant settings. Results: We report that cancer disparity and high mortality rates are even more pronounced in our racially-diverse communities in Hampton Roads Virginia. We discovered that SIAH is a tumor-specific, therapy-responsive, and prognostic biomarker in TNBC. High SIAH expression in residual tumors reflects tumor-driving EGFR/K-RAS/SIAH pathway activation (ON) that will predict cancer disparity, treatment resistance, early relapse, and poor survival. Low SIAH expression in residual tumors reflect EGFR/K-RAS/SIAH pathway inactivation (OFF) that will predict tumor remission and prolonged survival. Conclusion: We detect a major racial disparity of TNBC patients at Sentara-EVMS-VOA. Our local Black/AA TNBC patients have a 1.6-fold higher mortality rate than their White counterparts. Encouraged by our preliminary data, we aim to develop a SIAH-centered biomarker panel by measuring the EGFR/K-RAS/SIAH pathway activation (ON)/inactivation (OFF), and use SIAH as a new prognostic biomarker to risk stratify patients, detect cancer racial disparities, forecast tumor relapse, and predict patient survival at 1st-line neoadjuvant settings. By targeting SIAH, individualized treatments can be created to allow for increased survival rates in at risk individuals with more aggressive TNBCs. Citation Format: Claire B. Piatak, Taylor N. Drake, Ashleigh Hannah, Jonathan Baker, Caroline L. Dasom, Emily L. Breeding, Janet S. Winston, Billur Samli, Rick Jansen, Michael Danso, Richard A. Hoefer, Amy H. Tang. Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2137.

Unmet Social Needs and Breast Cancer Screening Utilization and Stage at Presentation

Unmet social needs in local populations may hinder the development of targeted cancer control interventions aimed at improving screening utilization and early-stage breast cancer diagnosis to ultimately improve breast cancer survival disparities. To evaluate if (1) city-funded screening mammography is associated with utilization of screening mammography, (2) unmet social needs are associated with utilization of screening mammography, and (3) unmet social needs are associated with later-stage disease at diagnosis. This cohort study included patients with stages I-IV invasive ductal or lobular carcinoma treated at an academic medical center (including both an underserved safety-net hospital [SNH] and a National Cancer Institute-designated academic cancer center [ACC]) from 2020 to 2023. Eligible patients were aged 18 years or older and able to consent. Data were analyzed between July 2023 and September 2023. The Health Leads Social Needs Screening Toolkit, a screening tool that gathers information on the most common social need domains affecting patient health. Univariable and multivariable logistic regression was utilized to evaluate the following primary outcomes: (1) routine screening mammography and (2) American Joint Committee on Cancer 8th edition clinical stage at presentation. Of the 322 women who completed the Health Leads Social Needs Screening Toolkit, 201 (62%) self-identified as Hispanic, 63 (19%) as non-Hispanic Black, and 63 (19%) as non-Hispanic White. Two hundred fifty-five (76%) patients with access to city-funded screening mammography completed a screening mammogram. Patients who presented to the SNH were more likely to present with late-stage disease compared with early-stage disease (15 of 48 [31%] vs 50 of 274 [18%]; P = .04). On multivariable logistic regression, not completing a screening mammography was associated with having an increasing number of unmet social needs (OR, 0.74; 95% CI, 0.55-0.99; P = .047) and an increasing age at diagnosis (OR, 0.92; 95% CI, 0.89-0.96; P < .001). Moreover, increasing unmet social needs was significantly associated with late-stage diagnosis above and beyond screening mammography (OR, 1.38; 95% CI, 1.01-1.89; P = .04). In this cohort study, access to screening mammography did not translate to utilization of screening mammography, increasing unmet social needs were significantly associated with lower rates of screening mammography, and those with increasing unmet social needs were more likely to present with late-stage disease. This association transcended recruitment site (SNH vs ACC), indicating that patients in either hospital setting may benefit from unmet social needs screening to overcome access to care barriers associated with late-stage disease at diagnosis.

Breast conserving surgery versus mastectomy: the effect of surgery on quality of life in breast cancer survivors in Malaysia

BackgroundIn the competitive health care environment, patient satisfaction and quality of life (QoL) have become the subject of interest to evaluate the efficacy of therapeutic interventions as we experience improved breast cancer survival in modern times. The knowledge of the long-term effects of surgery on the QoL in breast cancer patients is currently limited in the Asian setting. The purpose of this longitudinal study is to evaluate the QoL of early-stage breast cancer patients undergoing mastectomy and breast-conserving surgery (BCS).MethodsIn this prospective cohort study, the QoL of 208 patients who underwent mastectomy and the BCS treatment were assessed, using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire. The questionnaire was administered at the baseline, 6 and 12 months following diagnosis. One-way ANCOVA was used for statistical analysis.ResultsA total of 208 female survivors of Stage 0–II breast cancer were included, among them 47.1% underwent BCS and 52.9% underwent mastectomy. Older (63.3%), Chinese women (63.6%), and patients with primary education (71.7%) were more likely to undergo mastectomy. At baseline, no significant differences were observed for QoL in both treatment groups. At 6 months, patients who underwent BCS had better social functioning scales( P = 0.006) and worse symptom scales for dyspnoea (P = 0.031), compared to mastectomy patients. One year after diagnosis, the role functioning score of the mastectomy group was significantly higher than the BCS group, specifically among patients who had undergone chemotherapy (P = 0.034).ConclusionPatients who underwent BCS had better social functioning and worse dyspnoea symptoms compared to patients undergoing mastectomy at six months. During one year, there were only significant improvements in the role functioning among the mastectomy groups compared to the BCS groups. After further stratification, only mastectomy patients who received chemotherapy exhibited improved role functioning compared to patients those who did not undergo chemotherapy. Providing social and physical support postoperatively and monitoring patients for cancer worry, or other symptoms in the long-term survivorship period would be important to ensure optimal QoL.

Hypothetical Interventions on Diet Quality and Lifestyle Factors to Improve Breast Cancer Survival: The Pathways Study.

The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited. This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated. Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced. Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors. We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors.

Conditional survival in breast cancer up to 10 years in the Nordic countries.

Survival in breast cancer (BC) has developed favorably but late recurrences are still a problem. We model survival data from the NORDCAN database and analyze 1-, 5-, and 10-year relative survival and 5/1- and 10/5-year conditional survival in BC from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) between 1971 and 2020. Conditional survival measures survival in those who had survived year 1 to reach year 5 (5/1), or in those who had survived year 5 to reach year 10 (10/5). Almost all survival metrics were best for SE but survival in all countries improved in the course of time approaching the SE levels which were 98.3% for 1-year, 92.3% for 5-year, and 87.8% for 10-year survival. Conditional 10/5-year survival, covering 5 years, was better than 5/1-year survival, covering 4 years. A contributing factor is most likely the high rate of recurrence in period 2-5 years. The difference was observed for all countries but for DK 10/5-year survival approached 1-year survival and for NO and SE 10/5-year survival was only barely better than 5/1-year survival. The explanation to this was the excellent 10/5-year survival in DK compared to SE and particularly to NO. Literature search suggested that the reason for the relatively low 10/5-year survival in NO might be stagnant survival development in old patients. We assume that late mortality is critically limiting survival in BC and either interference with the late metastatic process or effective treatment will be key to future improvements in BC survival.

Evaluation of an Artificial Intelligence System for Detection of Invasive Lobular Carcinoma on Digital Mammography.

Introduction Early breast cancer detection with screening mammography has been shown to reduce mortality and improve breast cancer survival. This study aims to evaluate the ability of an artificial intelligence computer-aided detection (AI CAD) system to detect biopsy-proven invasive lobular carcinoma (ILC) on digital mammography. Methods This retrospective study reviewed mammograms of patients who were diagnosed with biopsy-proved ILC between January 1, 2017, and January 1, 2022. All mammograms were analyzed using cmAssist® (CureMetrix, San Diego, California, United States), which is an AI CAD for mammography. The AI CAD sensitivity for detecting ILC on mammography was calculated and further subdivided by lesion type, mass shape, and mass margins. To account for the within-subject correlation, generalized linear mixed models were implemented to investigate the association between age, family history, and breast density and whether the AI detected a false positive or true positive. Odds ratios, 95% confidence intervals, and p-values were also calculated. Results A total of 124 patients with 153 biopsy-proven ILC lesions were included. The AI CAD detected ILC on mammography with a sensitivity of 80%. The AI CAD had the highest sensitivity for detecting calcifications (100%), masses with irregular shape (82%), and masses with spiculated margins (86%). However, 88% of mammograms had at least one false positive mark with an average number of 3.9 false positive marks per mammogram. Conclusion The AI CAD system evaluated wassuccessful in marking the malignancy in digital mammography. However, the numerous annotations confounded the ability to determine its overall accuracy and this reduces its potential use in real-life practice.

Abstract 1900: Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609)

Abstract Background: Adjuvant radiotherapy (RT) following surgery significantly improves breast cancer survival. However, some patients, particularly minorities, develop early adverse skin reactions (EASRs) or skin toxicities that negatively impact the quality of life (QOL). We assess RT-related EASRs and QOL using clinician-reported outcomes (CROs) and patient-reported outcomes (PROs) in a large multi-racial/ethnic breast cancer population. Methods: This prospective study recruited 1,000 breast cancer patients undergoing RT through the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base between 2011 and 2013. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria for CROs and Skindex-16 (SD-16) for PROs. Results: This study included 405 non-Hispanic whites (NHW), 277 black/African Americans (AA), 241 HW, 62 Asian/Pacific Islanders (ASPI), and 15 others. About 42% and 15% of patients developed RT-induced ONS grade 3+ and 4+ skin toxicities, respectively. RT-induced EASRs differed significantly by race/ethnicity at mid-RT, 1-month, and 2-month post-RT, but not at the end of RT. Total SD-16 scores differ by race/ethnicity at pre-RT, 1-month, and 6-month post-RT, but not at the end of RT. Overall, PROs have a moderate but significant correlation with CROs at the end of RT. Conclusion: RT-induced EASRs differed significantly by race/ethnicity. There was a moderate but significant correlation between PROs and CROs. However, PROs delineated a broader spectrum in capturing the impact of RT on patients’ QOL, which highlights the importance of integrating PROs in accessing RT-induced EASRs, particularly in minorities with worse RT-induced EASRs. Trial Registration: NCT01407770 (09/02/2011) Citation Format: James J. Urbanic, Edward G. Shaw, Cristiane Takita, Jean L. Wright, Edward H. Ip, Lingyi Lu, Luis Baez-Diaz, Doris R. Brown, Jon Strasser, Kathy Baglan, Mark Palmer, Anu Thakrar, Amarinthia E. Curtis, Glenn Lesser, Jennifer J. Hu. Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1900.

Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers: A Systematic Review and Meta-Analysis

Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59-1.21) or CBC risk (RR = 0.95, 95%CI: 0.65-1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18-0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68-1.17) or CBC risk (RR = 0.85, 95%CI: 0.59-1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07-1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41-0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30-0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers.

Breast cancer mammographic screening by different guidelines among women of different races/ethnicities

Mammographic screening is a common diagnostic tool for breast cancer among average-risk women. However, breast cancer screening guidelines differ between societies and organizations. Appropriate adherence to screening guidelines helps early diagnosis and treatment of breast cancer, which subsequently improves breast cancer survival. We used three national guidelines to define adherence recommended by US Preventive Services Task Force (USPSTF), American Cancer Society (ACS), and American College of Radiology (ACR), which included different criteria for age and frequency. (USPSTF: 50–74, biennial; ACS: 45–54, yearly, 55+ biennial; ACR: 40+, yearly) We hypothesized that adherence rates for mammographic screening may be lower among minorities (non-Hispanic black (NHB) and Hispanic/Latino) than among non-Hispanic whites (NHW) regardless of the guideline applied. We conducted a cross-sectional study using nationally representative survey data from the 2020 Health Information National Trends Survey (HINTS). Adherence to mammographic screening among NHW, NHB, and Hispanic/Latino populations were calculated. A total of 1,751 survey samples were used in the final analysis. Adherence rates of each guideline for average-risk woman in this study were as follows: USPSTF - 77.37%, ACS - 68.41%, and ACR - 57.71%. Additionally, our results demonstrated that the adherence rate was higher among NHB when compared with NHW women regardless of which guideline was applied. Multivariate logistic regression analysis indicated that both NHB ethnicity and insurance coverage exhibited strong positive associations with adherence to breast cancer screening. Our findings support other studies’ results that different racial/ethnic and socio-demographic factors can affect screening adherence. Therefore, healthcare providers should promote breast cancer screening especially among NHW/Hispanic women and women lacking insurance coverage.

Changes in geographic accessibility to mammography by state and rural-urban status, United States, 2006-2022.

Although mammography is widely available in the United States, differences in accessibility in rural and urban areas and changes over time are not well described. In this study, we estimated the number and proportion of women aged 45-84 years who had limited travel time-based geographic accessibility to mammography by urban-rural status and state in the contiguous United States in 2006 and 2022. The proportion of women aged 45-84 years with limited accessibility to mammography did not substantially change from 2006 (12.7%; representing 7.5 million women) to 2022 (12.2%; 8.2 million women). Accessibility to mammography varied by state, but in 10 states, more than 26% of the statewide female population aged 45-84 years had limited accessibility in 2022. This proportion was substantially higher in rural areas (50.6% overall; ≥50% in 28 states in 2022) than in urban areas (3.0% overall). Increasing accessibility to mammography could increase utilization of breast cancer screening and, potentially, improve breast cancer survival.

Toxicity Index, patient-reported outcomes, and persistence of breast cancer chemotherapy-associated side effects in NRG Oncology/NSABP B-30

Adjuvant chemotherapy improves breast cancer survival but is associated with bothersome short- and long-term toxicity. Factors associated with toxicity, especially subacute toxicity up to 2 years following chemotherapy, have not been fully elucidated. The NRG Oncology/NSABP B-30 clinical trial compared 3 different doxorubicin-, cyclophosphamide-, and docetaxel-based chemotherapy regimens given over 3–6 months. Patients with hormone receptor-positive breast cancer received subsequent adjuvant endocrine therapy. From baseline through 24 months, 2156 patients completed questionnaires serially. We used multivariable probabilistic index models to identify factors associated with acute (>0–12 months) and subacute (>12–24 months) difficulties with pain, cognition, vasomotor symptoms, and vaginal symptoms. For all symptom domains, presence of symptoms prior to chemotherapy initiation were associated with symptoms in the subacute period (all p < 0.001). In addition, different combinations of patient factors and breast cancer treatments were associated with increased likelihood of pain, vasomotor, and vaginal symptoms in the subacute period. Consideration of pre-treatment symptoms and patient factors, as well as treatments for breast cancer, can facilitate identification of groups of patients that may experience symptoms following completion of chemotherapy. This information may be important for treatment-decision-making when alternative regimens are equivalent in benefit.

Width of excision margins after breast conserving surgery for invasive breast cancer and distant recurrence and survival

One premise of cancer treatment is that if a tumour is cut out but tumour cells remain present or close to the edges (of the cut), the risk of cancer...

A randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): The Aspirin after Breast Cancer (ABC) Trial

360922 Background: In-vitro and in-vivo evidence suggests that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. Thus, we conducted a prospective randomized controlled trial to determine the true benefits and risks of adjuvant aspirin therapy for breast cancer survivors. Methods: The primary objective was to compare the effect of 300 mg aspirin daily versus placebo upon invasive disease-free survival (iDFS) in patients with high-risk, HER2-negative breast cancer. Secondary objectives included effects on overall survival, cardiovascular disease, toxicity, and adherence. Eligible participants included patients aged 18-70 diagnosed with a primary invasive HER2-negative breast cancer. If hormone receptor (HR)–positive, tumors needed to be node positive and diagnosed within the past 10 years. If HR negative, tumors could be node positive or T2-4N0 and diagnosed within the past 18 months. Participants were randomly selected (1:1) to aspirin 300 mg versus placebo daily for 5 years in a double-blinded fashion. Stratification factors include HR status (positive vs. negative), body mass index (&lt; or ≥ 30 kg/m2), and stage (II vs. III). Based upon an accrual goal of 2,936 patients to reach 381 iDFS events, the study was estimated to have 80% power to detect HR 0.75. Results: From January 2017 to December 2020, 3,021 participants were enrolled. Treatment arms were well balanced in terms of key characteristics. In November 2021, the Data Safety and Monitoring Board recommended that the trial be unblinded because the stratified hazard ratio had crossed a pre-specified futility boundary. After 191 iDFS events (aspirin: 107, placebo: 84) and median follow-up of 20 months, the stratified hazard ratio comparing aspirin to placebo was 1.27 (z-score: -1.64), which is greater than the pre-specified hazard ratio of futility 1.03 (z-score &lt; -0.192). There was no difference in the frequency of grade 3/4 adverse events by study arm. Compliance was high and similar across arms. Non-protocol use of aspirin/non-steroidal anti-inflammatory drugs was similar across arms and less than 14%, consistent with prior randomized aspirin trials. Updated results on iDFS events will be provided at presentation. Conclusions: In this double-blinded, placebo-controlled, randomized trial, there was no benefit in breast cancer invasive disease-free survival with the addition of 300 mg aspirin daily. Although inflammation may still play a role in cancer progression, aspirin is not recommended for prevention of breast cancer recurrence. Clinical trial information: NCT02927249.