Risk Of Cancer Recurrence Research Articles

Guideline concordance of recurrence risk assessment for early breast cancer in a county-level setting in China.

e23263 Background: Guideline-centric risk-based decision-making is crucial for the treatment of HR+HER2- and HER2+ early breast cancer (eBC). However, the consistency of recurrence risk assessment (RA) between real-life clinical practice and guidelines in China has not been thoroughly investigated. As part of the interim analysis of CHASE001 (NCT05544123), we explored the guideline concordance of RA for HR+HER2- and HER2+ eBC in a county-level setting in China. Methods: Cohorts of HR+HER2- and HER2+ eBC patients (pts) from a county-level observational study (CHASE001) were included in this analysis. Clinical recurrence risk were collected for each patient. Descriptive statistics reported the proportion of pts classified into each risk level under real-life assessment by healthcare professionals (HCPs) (H-low/intermediate/high) and guideline-consistent assessment (G-low/intermediate/high). To investigate the factors associated with lower consistency, univariate (UVA) and multivariate logistic regression analysis (MVA) were performed. Results: 1254 HR+HER2- and 841 HER2+ eBC pts from 26 county-level hospitals were included in this analysis. A comparison between recurrence risk under HCPs assessment (HA) and guideline-consistent assessment (GA) revealed divergence. In HR+HER2- cohort, the proportions of pts classified as low, intermediate (int), and high clinical risk for recurrence under HA/GA were 27.2%/2.0%, 48.0%/57.4%, 24.8%/40.6%, respectively. Notably, 36.8% of pts classified as G-int were categorized as H-low, while 47.5% G-high pts were classified as H-int/low. On UVA and MVA, pT1 stage, histological grade 1 and Ki67 < 20% were associated with G-int/H-low; whereas lymphovascular invasion and pN1 were associated with G-high/H-lower. Among 562 G-int/high premenopausal pts, 280 (49.8%) achieved ovarian function suppression (OFS) and the OFS rates were 46.1% in G-int and 55.3% in G-high pts. In HER2+ cohort, the proportions of pts classified as low, int and high risk under HA/GA were 17.2%/0%, 48.2%/51.2% and 34.6%/48.8%. In pts with pN0, 17.2% were classified as H-low and 12% as H-high. In pts with positive lymph nodes (LN+), 11% were classified as H-low and 31% as H-int. Dual anti-HER2 target therapy was administered in 72% of pts with LN+. In both cohorts, HCPs who were medical oncologists had higher consistency with guideline for high-risk evaluation compared to surgical oncologists, whereas surgical oncologists showed higher consistency for int-risk evaluation compared to medical oncologists. Conclusions: This analysis highlights differences in clinical practice between county-level HCPs and guideline recommendations, revealing a significant underestimation of breast cancer recurrence risk. Further efforts should be made to enhance guideline adherence and promote guideline-centric clinical risk-based decision-making at county-level hospitals. Clinical trial information: NCT05544123 .

Comparative analysis of genomic tests for the prediction for late recurrence risk in hormone receptor–positive invasive breast cancer in a sample of Colombian patients.

e13092 Background: Approximately 70% of invasive breast cancers are hormone receptor-positive, requiring 5 years of endocrine therapy as the gold standard treatment. However, extended endocrine therapy (EET) may be needed, considering the late recurrence risk up to 15 years post-diagnosis. Different genomic tests predict the risk of recurrence. The 70-gene signature classifies patients as low or high risk during the first 5-years after diagnosis. The 12-gene test identifies high and low-risk patients for distant relapse up to 15 years, while a third test, based on 7-gene expression, assesses distant relapse risk up to 10 years. These tests assist clinicians in defining the need for EET. This study aims to compare the results of these genomic tests to determine late recurrence and distant relapse risks after 5 years, guiding EET indications. Methods: This is a retrospective descriptive transversal study involving 27 female patients diagnosed with hormone receptor-positive invasive breast cancer, treated in the same oncologic center in Colombia. All patients were first tested with the 70-gene genomic profile, with 15 patients undergoing the 12-gene test and 12 cases undergoing the 7-gene assay approximately 5 years later. Concordance between test results was assessed, and socio-demographic variables were descriptively analyzed. Results: The mean age was 54.4 years (SD=11.7). Invasive ductal carcinoma comprised 77.7% and invasive lobular carcinoma 22.22%. The 70-gene profile identified 21 cases (77.7%) as low-risk. Among those, 87.5% had a high-risk result with the 12-gene test, and 60% had a high-risk score with the 7-gene test. Conclusions: The findings support the utility observed in the sub-analysis of the NSABP-B42 study, showing that a low-risk result in the 70-genes signature, means high risk of late recurrence and the need for EET, emphasizing the importance of further evaluation and validation of genomic tests in predicting breast cancer recurrence risks. Larger sample sizes are necessary to confirm these results and establish their clinical relevance in oncology practice.

Breast Cancer Local Recurrence Risk in Implant-Based Breast Reconstruction with Macrotexturized and Microtexturized Prosthesis: A Multicentric Retrospective Cohort Study

Abstract Background Nowadays, implant-based breast reconstruction is a common technique after mastectomy. The widespread use of implant employment is prompting significant concerns regarding the oncological safety of prostheses and the potential impact of surface texture on the recurrence of local breast cancer. This article examines the oncological outcomes associated with postmastectomy breast reconstructions using micro- and macrotexturized implants, focusing on the incidence and relative risk (RR). Methods A retrospective cohort study was conducted on patients admitted to Multimedica group (IRCCS, San Giovanni Hospital, Milan) and ICH groups (Humanitas Clinical Institute, Milan) between January 2003 and September 2020. Minimum follow-up considered was of 1 year.Patients submitted to either complete or nipple-spearing mastectomy, who underwent breast reconstruction with macrotexturized or microtexturized prosthesis, were included in group A and B, respectively. Results A total of 646 patients met the basic inclusion and exclusion criteria. Group A included 410 (63.5%) patients and group B included 236 (36.5%). Cancer recurrence absolute risk in group A was 5.6 ± 2.2% and in group B was of 2.1 ± 1.8%. RR for breast cancer recurrence in group A compared to group B was of 2.65; confidence interval 95% (1.02; 6.87). Statistical analysis identified a higher local recurrence risk in patients reconstructed with macrotexturized prosthesis (p-value 0.036). Conclusion This study detected a higher risk for local breast cancer recurrence associated to macrotexturized breast implants employment. Further investigations are required to verify these outcomes.

The role of exercise in aromatase inhibitor-induced arthralgia.

Aromatase inhibitors are prescribed in breast cancer due to their associated lower rate of cancer recurrence compared to tamoxifen. However, aromatase inhibitor-induced arthralgia (AIIA) is one of the leading causes of treatment nonadherence, increasing the risk of cancer recurrence. The pathophysiology of AIIA is poorly understood, and although current recommendations for AIIA include lifestyle changes and analgesics depending on the severity of symptoms, there is no established effective treatment. The aim of this study is to explore the presentation and mechanism of AIIA and investigate the feasibility and efficacy of different exercise interventions (aerobic, resistance, aerobic and resistance combined, and yoga or tai chi) in patients with AIIA to guide the development of formal exercise prescription guidelines. Findings indicate that a mixed-modality regimen of aerobic and resistance exercises is feasible and safe and may serve the most benefit in improving joint pain, functionality, and quality of life. More specifically, the weekly regimen should consist of 150 min of aerobic exercise with two sessions of at least six resistance exercises, 8 to 12 repetitions, three sets each. Supplementary yoga and tai chi may be recommended twice a week depending on a patient's target symptoms. Yoga was associated with improved physical functionality, whereas tai chi was related to improvements in mental health. However, the feasibility and impact of combined aerobic and resistance exercise protocols with yoga or tai chi in our target population were not investigated in this review. The use of large, randomized controlled trials is recommended for future studies.

Use of beta-blockers in patients with ductal carcinoma in situ and risk of invasive breast cancer recurrence: a Swedish retrospective cohort study

BackgroundRetrospective observational studies suggest a potential role of beta-blockers as a protective strategy against progression and metastasis in invasive breast cancer. In this context, we investigated the impact of beta-blocker exposure on risk for progression to invasive breast cancer after diagnosis of ductal cancer in situ (DCIS).MethodsThe retrospective study population included 2535 women diagnosed with pure DCIS between 2006 and2012 in three healthcare regions in SwedenExposure to beta-blocker was quantified using a time-varying percentage of days with medication available. The absolute risk was quantified using cumulative incidence functions and cox models were applied to quantify the association between beta-blocker exposure and time from DCIS diagnosis to invasive breast cancer, accounting for delayed effects, competing risks and pre-specified confounders.ResultsThe median follow-up was 8.7 years. One third of the patients in our cohort were exposed to beta-blockers post DCIS diagnosis. During the study period, 48 patients experienced an invasive recurrence, giving a cumulative incidence of invasive breast cancer progression of 1.8% at five years. The cumulative exposure to beta-blocker was associated with a reduced risk in a dose-dependent manner, though the effect was not statistically significant.ConclusionOur observational study is suggestive of a protective effect of beta-blockers against invasive breast cancer after primary DCIS diagnosis. These results provide rationales for experimental and clinical follow-up studies in carefully selected DCIS groups.

Associations between low- and high-fat dairy intake and recurrence risk in people with stage I-III colorectal cancer differ by sex and primary tumour location.

We previously demonstrated that intake of low-fat dairy, but not high-fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I-III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low- and high-fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow-up of 5.0 years, 331 recurrences were detected. A higher intake of low-fat dairy was associated with a reduced risk of recurrence (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34-0.77) than in women (HR: 0.84, 95% CI: 0.47-1.49). A higher intake of high-fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03-2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54-1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low-fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high-fat dairy intake may be specifically important in people with colon cancer.

Abstract PO2-14-07: Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women

Abstract Background: Breast cancer prognosis is influenced by tumor biomarker expression. For example, tumors that express the estrogen receptor (ER+) have a lower hazard of recurrence in the first five years following treatment than tumors that do not express the estrogen receptor. Identifying additional biomarkers that are prognostic of breast cancer recurrence may aid in risk stratification and the development of targeted therapies. The androgen receptor (AR) is one such candidate biomarker. While some previous studies have found lower breast cancer mortality associated with AR expression, others have shown no association. However, these studies were conducted in populations exclusively or primarily comprised of postmenopausal women. Since menopause is associated with an increased concentration of androgens relative to estrogens, the role of AR may differ in premenopausal women. Methods: Using the Predictors of Breast Cancer Recurrence cohort (N=5,959)—a prospective cohort study of premenopausal women diagnosed with stage I–III primary breast cancer between 2002 and 2011 and registered in the Danish Breast Cancer Cooperative Group (DBCG) clinical database—we measured the association between tumor AR expression and breast cancer recurrence. The majority of the cohort (77%) had ER+ tumors and were intended to be treated with tamoxifen. Primary paraffin-embedded tumors were collected from treating hospitals, and 2–3 cores were included in a tissue microarray for immunohistochemistry. AR staining of each core was automatically scored using a trained software application and quantified as the percent of tumor nuclei with positive staining. Patients were considered to have AR positive (AR+) tumors if the maximum score across replicate cores was >1% positive. Otherwise patients were classified as having AR negative (AR−) tumors. Patients were followed from breast cancer diagnosis until the first of recurrence, death, emigration, another malignancy, or 10 years. The DBCG defines breast cancer recurrence as any breast cancer diagnosed after the initial course of treatment, including contralateral breast cancers. The association between AR expression and breast cancer recurrence was computed as an unadjusted risk ratio and corresponding 95% confidence interval. Results: Among the 4,658 cohort members with available tumor tissue, 72% had AR+ tumors; 720 recurrences occurred over the 10-year follow-up. Patients with AR+ tumors were less likely to experience a recurrence than patients with AR− tumors [14% vs. 18% respectively; unadjusted risk ratio=0.80, 95% CI: (0.70, 0.92)]. Conclusion: AR expression in primary tumor tissue was associated with a lower risk of breast cancer recurrence in a large population-based cohort of premenopausal women. Additional analyses adjusting for clinical factors, examining the association by breast cancer subtype, and accounting for time to recurrence are forthcoming. Citation Format: Rebecca Nash, Anders Kjærsgaard, Kristina Christensen, Thomas Ahern, Lindsay Collin, Stephen Hamilton-Dutoit, Lauren McCullough, Joellen Schildkraut, Henrik Sørensen, Kevin Ward, Kirsten Woolpert, Timothy Lash, Deirdre Cronin-Fenton. Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women [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 PO2-14-07.

Abstract PO4-17-01: Patient Perception and Decision-Making in HER2+ Early Breast Cancer Management: Insights from the ASKHER2 European Survey

Abstract Background Breast cancer remains the most prevalent cancer in women globally, with Human Epidermal Growth Factor Receptor 2 positivity (HER2+) observed in 15-30% of initial breast cancer cases. Adjuvant treatment for HER2+ early breast cancer has notably reduced mortality and recurrence rates. However, the heterogeneity of the disease and in conveying risk information by healthcare providers (HCPs) leaves many women uncertain about their individual risk of recurrence and potential treatment (tx) options. Evidence shows that fear of recurrence, uncertainty about prognosis, and inadequate risk/benefit information can affect patients' decisions during their tx phase. Therefore, it is important to better understand the perceptions, attitudes, and behaviors regarding the risk of recurrence in women with HER2+ early breast cancer. Methods A protocol-driven, direct-to-patient online survey (30 questions total) was administered in France, Germany, Italy, Portugal, Spain, and Sweden via patient advocacy groups and panels. Women aged 18 years and above with either early-stage (eBC) (stages I-III) or metastatic (mBC) (stage IV) as the result of recurrence from an initial diagnosis of locally advanced HER2+ breast cancer were eligible to participate. The implementation of soft quotas ensured a representative sample size. This abstract presents the results of the survey. Results A total of 622 participants completed the survey between July 2022 and February 2023. Majority of participants (70%) were between 40 and 65 years of age. Almost 85% had eBC (N=527), 62% had been diagnosed with HER2+ eBC for ≥ 2 years, and 68% were undergoing breast cancer tx at the time of the survey. The main worries and concerns that were reported by participants when asked about their tx plan were risk of recurrence (27%), fear of dying (22%) and risk of tx failure (14%). Among eBC participants, 40% perceived their personal risk of recurrence to be moderate, 18% perceived it to be high, while 21% did not know their personal risk. Most eBC participants (72%) preferred short and simple explanations from the medical team about the risk of cancer recurrence, while 4% preferred not to receive this information. Overall, 30% of participants said they had fully discussed the risk of recurrence with their doctor, while 20% had no discussion. Almost all participants (97%) wanted to be involved in their tx decision, 49% completely and 48% partially. To reduce this risk of recurrence, participants with eBC were willing to change their diet habits (77%), exercise more frequently (74%), take additional tx (65%) or undergo surgery (60%). Most participants (69%) were willing to take additional tx even if it would reduce their risk of recurrence by less than 50%. Participants were most willing to tolerate fatigue (53%), followed by hot flashes (51%) and joint pain (44%), as the most acceptable side effects if they had to take additional treatments with the potential benefit of reducing risk of recurrence. Conclusion The multinational large direct-to-patient ASKHER2 survey reflects participants’ experience and highlights concerns of patients with HER2+ breast cancer, notably on their recurrence risk. To mitigate this risk, patients exhibited a willingness to modify lifestyle habits and consider additional tx. A fraction of participants considered they had thoroughly discussed these risks with their HCPs, while the vast majority desired active involvement in their treatment decisions. These results underscore the ongoing need for HCPs to discuss the risk of recurrence in a clear way, addressing the full potential of treatment options in eBC and mBC, to enable patients to participate in this patient-centered approach of the decision-making process. Citation Format: Matteo Lambertini, Christian Jackisch, Olivier Trédan, Maria Vidal, Mário Fontes-Sousa, Antonios Valachis, Rosanna D’Antona, Marcelo Ruz, Eugenia Krone, Miriam Brice, Erwan Berjonneau, Soraia Matos, Olivia Dialla, Laure Guéroult-Accolas. Patient Perception and Decision-Making in HER2+ Early Breast Cancer Management: Insights from the ASKHER2 European Survey [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 PO4-17-01.

Abstract PS04-06: Breast cancer recurrence among women with pre-diagnostic major depression and co-existing substance abuse disorder: A retrospective study in the United States Veterans Health Administration Cohort

Abstract Background: Our prior study observed a 34% higher risk of breast cancer (BC) recurrence among women with major depressive disorder (MDD) at the time of their BC diagnosis compared to women without MDD after adjusting for sociodemographic, clinical, and prognostic factors. Given the high prevalence of substance abuse disorders among individuals with MDD and the positive association between alcohol use and mortality among BC survivors, we were interested to examine whether the risk of BC recurrence was compounded for women with both conditions. Objective: To investigate whether pre-diagnostic substance abuse disorders modify the association between MDD and BC recurrence. Methods: We established a retrospective cohort of women (age ≥ 18 years) with incident, early-stage BC diagnosed from 2010 through 2019 using the VHA’s electronic medical record database. A two-year window was used to identify women with MDD and co-existing substance abuse disorders prior to their BC diagnosis. We examined potential interactions between MDD and alcohol abuse and MDD and other substance abuse using multivariable proportional hazards regression, accounting for competing risk of death. Our outcome of interest was BC recurrence. The reference group for all analyses was women with BC alone. The models were adjusted for patient characteristics including age, race, ethnicity, marital status, rurality of primary residence, priority group rating (proxy for socioeconomic status), any homelessness or economic problems, comorbidity burden, body mass index, smoking status, receipt of a screening mammography, year of BC diagnosis, cancer stage, cancer subtype, and cancer treatment. Subgroup analyses were conducted by cancer subtype. Results: Our cohort comprised 6,045 women with BC, of whom 1,754 (29%) had a pre-diagnostic MDD diagnosis and 1,509 (25%) had a substance abuse disorder. Among women with MDD, 386 (22%) abused alcohol and 336 (19%) abused other substances. The median length of follow-up from BC diagnosis was 4.5 years (IQR=4.8 years). The average age at BC diagnosis was 57 years (SD=11 years) overall, 56 years (SD=10 years) among women with MDD, and 57 years (SD=9 years) among women with substance abuse disorders. On multivariable analysis, MDD (HR=1.33; 95% CI: 1.14, 1.53), alcohol abuse disorder (HR=1.37; 95% CI: 1.12, 1.68), and other substance abuse disorders (HR=1.33; 95% CI: 1.13, 1.56) were independent risk factors for BC recurrence. Further, there was a statistically significant interaction between pre-diagnostic MDD and alcohol abuse disorder (p-interaction=0.003). Women with BC who had both pre-diagnostic MDD and alcohol abuse disorder were at a 65% (HR=1.65; 95% CI: 1.29, 2.11) higher risk of BC recurrence compared to women with BC alone. A statistically significant interaction was also observed between pre-diagnostic MDD and other substance abuse disorders (p-interaction < 0.001). Women with BC who had both pre-diagnostic MDD and other substance abuse disorders were at a 90% (HR=1.90; 95% CI: 1.50, 2.42) higher risk of BC recurrence compared to women with BC alone. In subgroup analyses, the interaction between MDD and alcohol abuse disorders (p-interaction=0.001) and MDD and other substance abuse disorders (p-interaction < 0.001) was limited to women with estrogen receptor positive cancer but not estrogen receptor negative cancer. Conclusion: Women with incident BC who have prior diagnoses of both MDD and substance abuse disorder are at higher risk of recurrence than women with either exposure independently. Further research is needed to examine the etiology of our findings and to evaluate whether this newly defined risk group would benefit from closer monitoring and more tailored treatment options. Citation Format: Maya Aboumrad, Kala Visvanathan. Breast cancer recurrence among women with pre-diagnostic major depression and co-existing substance abuse disorder: A retrospective study in the United States Veterans Health Administration Cohort [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 PS04-06.

Abstract PO3-02-03: Ketogenic diet and letrozole to inhibit PI3K signaling in ER+ breast cancer

Abstract Obesity is associated with an increased risk of breast cancer recurrence, similar in magnitude to the reduction in risk seen with the use of adjuvant chemotherapy. However, whether and how obesity causes that increased risk of recurrence remains unknown. Plausible mechanisms include obesity-mediated increases in estrogen signaling, inflammatory conditions resulting from obesity, or effects on insulin or other growth factor signaling pathways resulting from the insulin-resistant state that often accompanies obesity. While phosphatidyl inositol 3-kinase (PI3K) signaling is the normal, biological effector of insulin signaling, abnormal activation of PI3K is of particular concern in breast cancer, where it is associated with resistance to endocrine therapies and HER2-targeted therapies. We hypothesize that at least part of the adverse outcome associated with obesity results from aberrant activation of PI3K signaling in tumors. This may confer resistance to established therapies, or directly stimulate tumor growth (particularly in tumors with existing PI3K pathway mutations), or both. We tested a dietary intervention designed to alter insulin resistance pathophysiology coupled with endocrine therapy in the well-established neoadjuvant treatment paradigm in breast cancer. This will allow us to study the effects of the dietary intervention directly on tumor biology. The primary objective of this neoadjuvant study was to assess feasibility and tolerability of 2 weeks of a very low-carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+ disease. Up to 36 patients will be enrolled for this pilot and feasibility study (24 in the treatment group and 12 controls). Baseline metabolic parameters will be measured and the treatment group will begin a dietitian-supervised 2-week diet to induce a ketogenic state, along with letrozole 2.5 mg daily. The control group will receive only letrozole. At the end of 2 weeks, patients will proceed with surgical treatment of their breast cancer. We will report the primary outcome measure of feasibility, assessed by determining 1) the proportion of patients in the diet group achieving ketosis, 2) adherence to the diet and 3) participant-reported measures of stress, fatigue, and emotional health. For both groups, cell proliferation will be measured in a tumor biopsy obtained from the surgical specimen and compared with the pre-treatment diagnostic biopsy. Correlative studies will evaluate tumor markers of insulin/PI3K signaling before and after the intervention and between diet and control. Citation Format: Brent Rexer, Vandana Abramson, Sara Nunnery, Sonya Reid, Laura Kennedy, Melinda Sanders, Jessica Bennett, Paula Gonzalez-Ericsson, Violeta Sanchez. Ketogenic diet and letrozole to inhibit PI3K signaling in ER+ 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 PO3-02-03.

Abstract PO4-19-12: Trial in progress: An Observational Study to Examine Changes in Metabolic Syndrome Components in Patients With Breast Cancer Receiving (Neo)Adjuvant Aromatase Inhibitors

Abstract Background: (Neo) adjuvant systemic therapy has been shown to adversely impact metabolic health manifested as weight gain, dyslipidemia, and insulin resistance, which ultimately lead to the development of metabolic syndrome (MetS). MetS increases the risk of development for type 2 diabetes mellitus and cardiovascular disease and is associated with an increased risk of breast cancer recurrence, death due to breast cancer, and all-cause mortality. We have previously reported that 76% of metabolically healthy women receiving (neo) adjuvant chemotherapy will develop MetS at a median of 15 weeks. The impact of aromatase inhibitors (AIs) on metabolic health has not been systematically assessed in a longitudinal study. We hypothesize that AIs in the (neo) adjuvant setting will alter metabolic parameters and have embarked on a clinical trial to study this. Methods: This is a prospective observational study that will include: postmenopausal patients with newly diagnosed, early-stage hormone receptor (HR)-positive breast cancer with planned (neo)adjuvant treatment with an AI. Participants will be excluded if they have received or have planned treatment with (neo)adjuvant chemotherapy or are currently receiving antidiabetic medications or cholesterol-lowering agents. All patients will undergo a baseline assessment that includes: BMI, physical exam inclusive of blood pressure, waist circumference, assessment of body fat, lipid profile, insulin, metabolic biomarkers, and completion of the Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES). Following institution of an AI, reassessment of the aforementioned tests will be repeated after 4 months and 12 months of therapy. The primary endpoint is the change in insulin resistance (as measured by HOMA-IR, homeostatic model assessment for insulin resistance) at 4 months. Secondary endpoints include the change in HOMA-IR at 12 months and the change in individual MetS components, metabolic biomarkers, anthropometric measurements, as well as FACT-ES scores from baseline to 4- and 12-months of AI treatment. The mean paired differences will be calculated for HOMA-IR measurements as well as for the secondary endpoints, and the 1-sided paired t-test will be used to test for statistical significance. One-way analysis of covariance will be used to compare means while adjusting for age, race/ethnicity, and BMI. Using a 1-sided paired t-test for the mean difference in HOMA-IR measurements from baseline to 4 months, we will have 80% power to detect an effect size of 0.405 with 40 patients (α = 0.05). Enrollment began in April 2023 and is ongoing. Contact alevee@coh.org for more information. Given the increased recognition of the importance of metabolic health in breast cancer outcomes, this data will inform future trials that focus on maintaining metabolic health in breast cancer survivors. Citation Format: Alexis LeVee, Nora Ruel, Victoria Seewaldt, Joanne Mortimer. Trial in progress: An Observational Study to Examine Changes in Metabolic Syndrome Components in Patients With Breast Cancer Receiving (Neo)Adjuvant Aromatase Inhibitors [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 PO4-19-12.

Abstract PO5-07-07: The biological basis of breast MRI background parenchymal enhancement in women with high breast cancer risk

Abstract Introduction: The amount and degree of the fibroglandular tissue (FGT) enhancement on breast MRI, known as background parenchymal enhancement (BPE), is an emerging marker of breast cancer risk. Higher qualitative and quantitative BPE levels have been shown to correlate with both future risk of initial breast cancer diagnosis and breast cancer recurrence after treatment. Furthermore, adjuvant and preventative therapies such as radiation and endocrine therapy have been shown to lower BPE in many women, potentially serving as a marker of treatment efficacy. However, the biological basis of BPE remains unclear and elucidation of this mechanism could identify novel targeted prevention strategies. The goal of this study was to assess the association of BPE levels with markers of inflammation, vascularity, proliferation, and estrogen sensitivity in a cohort of high-risk women. Materials and Methods: In this IRB-approved retrospective study, we identified asymptomatic high-risk women who underwent at least one dynamic contrast-enhanced (DCE) breast MRI within one year of prophylactic bilateral mastectomy. Qualitative BPE assessments were obtained from clinical reports. Quantitative BPE measures were obtained using in-house semi-automated software: whole breast FGT was first segmented on pre-contrast images, percent enhancement (PE) was calculated for each voxel as (S1-S0)/S0 × 100%, where S0 and S1 are pre- and early post-contrast signal intensity, respectively, and quantitative BPE was then defined as the mean PE of the FGT. Additionally, the BPE volume ratio was calculated as the fraction of FGT that had a PE >50%. Histopathology markers of inflammation (COX-2), vascularity (VEGF), proliferation (Ki-67), and estrogen receptor status (ER) were prospectively measured on archived mastectomy specimens of each breast. BPE metrics were correlated with histopathological markers using Spearman’s rank correlation, with and without adjustment by menopausal status of the patient. All tests were based on generalized estimating equations models to account for the non-independence of the two breasts per patient. A p-value < 0.05 was considered significant. Results: We identified 56 women (median age: 39; range: 26-63 years) for this study, of which 39% were post-menopausal (N=22). Distribution of qualitative BPE levels were 41% minimal (N=23), 29% mild (N=16), 18% moderate (N=10), and 12% marked (N=7). Qualitative BPE and quantitative BPE markers were moderately positively correlated (r=0.37-0.54, p< 0.01). Table 1 lists the correlations between BPE metrics and histopathology markers. After adjusting for menopausal status, qualitative BPE was positively associated with ER (r=0.27, p=0.02) and VEGF (r=0.24, p< 0.01; r=0.21, p=0.02 adjusted). Quantitative BPE and BPE volume ratio were both positively correlated with VEGF (p< 0.04) and negatively correlated with COX2 (p< 0.05). No significant associations were observed between BPE and Ki-67. Discussion: Our study suggests that increased BPE on MRI positively correlates with increased vascularity and higher estrogen receptor expression but not inflammation or proliferation within normal breast tissue in high-risk women. These findings, along with established associations between BPE and cancer risk, could be useful to select and assess efficacy of targeted preventative treatments. Table. Spearman rank correlations between BPE metrics and histopathological markers. Citation Format: Pegah Khoshpouri, Anum Kazerouni, Sana Parsian, Daniel Hippe, Olivia Walsh, Lisa Koch, Savannah Partridge, Habib Rahbar. The biological basis of breast MRI background parenchymal enhancement in women with high breast cancer risk [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 PO5-07-07.

Abstract ED03-03: Impact of exercise on breast cancer outcomes

Abstract Background: Exercise may improve breast cancer outcomes; however, current research is limited in its ability to inform clinical exercise trials and clinical oncology practice. The purpose of this presentation is to summarize the current research on exercise and breast cancer outcomes using a framework proposed to improve the clinical utility of this research. The Exercise as Cancer Treatment (EXACT) Framework organizes and characterizes the critical aspects of a clinical oncology setting to allow for a more systematic and clinically informative approach to the study of exercise as a cancer treatment. The EXACT Framework proposes that two key clinical oncology variables—tumor/disease status (i.e., primary tumor present, primary tumor removed, metastatic disease present) and treatment status (i.e., treatment naïve, actively being treated, previously treated)—are critical for understanding the effects of exercise on cancer outcomes, but few studies have addressed these variables. Application of the EXACT Framework to existing studies may improve their interpretation and identify directions for future research. Results: Presently, there are no adequately powered randomized controlled trials that have examined the effects of exercise on breast cancer outcomes in any clinical oncology scenario, although secondary analysis of smaller phase II trials have been reported. Preclinical research using rodent models has generally shown that exercise slows the growth and spread of treatment naïve breast tumors through various mechanisms including immune response, tumor metabolism, apoptosis, and DNA synthesis and repair. More recently, these preclinical studies have enhanced their clinical utility by including an existing cancer treatment in their design and have generally shown that exercise enhances the delivery and/or efficacy of concurrent cancer treatments through mechanisms related to improved tumor vasculature and perfusion. Most human evidence on exercise and breast cancer outcomes has been gleaned from secondary analysis of observational studies involving healthy cohorts or breast cancer survivor cohorts. These studies have generally included early-stage breast cancer patients who received heterogeneous cancer treatments. Physical activity data was typically collected either well before diagnosis and/or well after treatments. Overall, these studies have generally shown that higher prediagnosis and postdiagnosis physical activity are associated with a lower risk of breast cancer recurrence and mortality. Discussion: There is a disconnect between the clinical oncology scenarios addressed by animal and human studies of exercise and breast cancer outcomes. Moreover, most studies do not adequately address treatment combinations and sequencing. Future observational studies of exercise and breast cancer outcomes may improve their clinical utility by: (a) recruiting breast cancer patients with the same tumor/disease status receiving the same or similar first-line treatment protocols, (b) collecting detailed data on all planned and unplanned cancer treatments, (c) assessing exercise in relation to those cancer treatments (i.e., before, during, between, after) rather than in relation to the cancer diagnosis (i.e., various time periods before and after diagnosis), (d) collecting data on cancer-specific outcomes (e.g., disease response, progression, recurrence) in addition to mortality, and (e) conducting subgroup analyses based on cancer treatments received. Conclusions: Preclinical and observational studies may contribute important knowledge regarding the role of exercise as a cancer treatment; however, modifications to study design and analysis are necessary if they are to inform clinical research and practice. The ultimate goal of precision exercise oncology is to provide the right exercise prescription to the right breast cancer patient at the right time postdiagnosis. Citation Format: K. Courneya. Impact of exercise on breast cancer outcomes [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 ED03-03.

Abstract PO2-01-13: Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women

Abstract Introduction Premenopausal women diagnosed with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) face a significantly higher risk of cancer recurrence and mortality compared to older women, particularly those diagnosed under the age of 40. The underlying causes behind this disparity remain largely unknown. Material and methods We retrospectively select tumour samples from patients (pts) diagnosed with HR+/HER2- EBC at Hospital Clinic (Barcelona, Spain) from May 2014 to March 2020 who had a PAM50/Prosigna assay (Veracyte) previously performed. This assay examines the expression of 50 genes involved in important breast cancer signaling pathways, as well as the intrinsic subtypes (IS) and the Risk of Recurrence (ROR) score. Our primary objective was to compare the distinct clinicopathological and molecular characteristics of HR+/HER2- EBC between two age groups: patients under 40 years old (Young EBC or YEBC) and those 40 years old and above (Older EBC or OEBC). Disease-free survival (DFS) was defined as the time between diagnosis and the first recurrence. Comparisons between groups were carried out using chi-square tests (categorical variables). Additionally, we performed a two-class unpaired Significance Analysis of Microarrays (SAM) with a false discovery rate (FDR) less than 5% to identify genes with significantly different expression between YEBC and OEBC. The statistical significance level was set at less than 0.05. Results A total of 441 tumor samples from 420 patients were included in the analysis, with 5% (22/441) corresponding to YEBC. With a median follow-up of 64.5 months, there were 20 breast cancer (BC) recurrences (4.8%), 12 second cancers (2.9%) and 5 BC-related deaths (1.2%), all occurring in the OEBC group. Table 1 provides an overview of the main clinico-pathological and molecular characteristics. YEBC tended to have larger tumors, with 45.5% (10/22) measuring over 2 cm compared to 36.1% (151/419) in OEBC (p=0.376). YEBC also had a higher proportion of grade 3 tumors (18.18% versus 3.1% in OEBC, p=0.418) and lower expression of estrogen receptor (ER) as determined by immunohistochemistry (mean of 72.28% vs 88.36%, p=0.004). Regarding the PAM50 IS, there was a difference observed between YEBC and OEBC (p < 0.001). Specifically, YEBC patients exhibited a tendency towards a higher proportion of Luminal B tumors (54.6% versus 38.9% in OEBC, p=0.144), as well as non-Luminal subtypes such as Basal-like (18.2% versus 0.95% in OEBC, p< 0.001) and HER2E (4.6% versus 0.7% in OEBC, p=0.186). YEBC tended to have higher ROR (p=0.167), and to receive chemotherapy in a higher proportion, especially in the intermediate-risk group (p=0.004). In YEBC tumours, SAM analysis (p < 0.05) showed an overexpression of genes mainly related with proliferation (i.e., RRM2, MELK, MIK67), cell cycle progression (i.e., KNTC2, CDC20, MYBL2) and apoptosis inhibition (i.e., BIRC5). In OEBC there were an overexpression of genes related with the oestrogen receptor-signalling pathway (i.e., ESR1, NAT1, FOXA1, PGR). Luminal B tumours in YEBC showed an upregulation of genes related to proliferation, migration, and poor prognosis (i.e., KRT17, KRT5) compared to OEBC. However, since there were no recurrences in the YEBC group, differences in terms of DFS between the groups could not be calculated. Principio del formulario Final del formulario Conclusions YEBC exhibited a more advanced stage and a more aggressive intrinsic phenotype compared to OEBC. Additionally, these tumors showed a tendency to upregulate genes involved in proliferation, cell cycle progression, and survival, while downregulating genes related to hormone signaling pathways. These molecular characteristics may help explain the worse prognosis of YEBC compared to OEBC. However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies Citation Format: Francisco Javier Muñoz-Carrillo, José Antonio Sola, Carme Crous, Esther Sanfeliu, Isabel Garcia-Fructuoso, Elia Seguí, Teresa Gorría, Raquel Gómez-Bravo, Barbara Adamo, Tomás Pascual, Olga Martínez-Sáez, Francesco Schettini, Pablo Rivera, Rosalía Cayuela, Montserrat Muñoz, Núria Chic, Maria Vidal. Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women [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 PO2-01-13.

Abstract PO5-01-10: Evaluating a computer-aided platform for predicting recurrence and survival in an Oncotype Dx tested breast cancer cohort

Abstract Background: Oncotype DX Breast Recurrence ScoreÒ (ODXRS) is a widely used predictive measure of breast cancer recurrence risk and chemotherapy benefit for patients with estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-) breast cancers. ODXRS testing incurs additional costs and delays. These drawbacks could be obviated by innovative computer-aided technologies within digital pathology workflows. Such technologies could be developed to perform a wide variety of diagnostic and prognostic tests on digital whole slide images (WSIs) of hematoxylin and eosin (H&E)-stained tissue alone. This would save time, cost, and sample tissue whilst still providing critical prognostic information for patient management. Q-Plasia OncoReader Breast (QPORB) is a computer-aided solution which extracts information from H&E WSIs to provide diagnostic and prognostic information for breast cancer specimens. Aims: The aim of this study was to identify whether the computer aided QPROB platform could successfully predict breast cancer recurrence from H&E WSIs alone in line with recurrence predicted by ODXRS. Methods: H&E slides corresponding to tissue blocks sent for ODXRS testing from primary breast cancer resection/excision specimens from St James’s University Hospital, Leeds, UK (n=137 cases, 1 slide per case) were collected, anonymized, and scanned at x20 magnification on an Aperio AT2 scanner. Relevant pathological and clinical data were collected from electronic pathology reports and patient records. These data included ODXRS and recurrence events. QPORB analyzed each case/slide and generated a digital biomarker profile from the H&E images alone, combining statistical physics and tumor biology to quantify malignant cell cycle deformation. QPORB’s biomarker profile and ODXRS for each case was compared to disease-free survival (DFS) and overall survival (OS). Kaplan-Meier survival analyses were performed. Confounding factors (age, tumor grade, invasive tumor size and Charlson Comorbidity Index) were accounted for. Results: Results of three QPORB-generated indices - two putatively associated with overall cell cycle signature and one with G1 deformation, and their combined overall biomarker profile did not predict DFS in this cohort. However, with regards to OS, all three indices and the combined biomarker profile predicted OS over a median follow-up period of 5 years (P=0.044). 5% of WSIs (7/137) did not meet the criteria to be analyzed by QPORB and 4% (6/137) could not be analyzed by QPORB (attrition). While ODXRS similarly predicted OS but not DFS, the follow-up duration was suboptimal. Conclusion: While QPORB indices evaluated in this work, putatively associated with overall cell cycle signature and G1 deformation, did not predict breast cancer recurrence on a par with ODXRS, it has shown promising results as potential adjunct device to provide an estimate of OS for breast cancer patients eligible for ODXRS testing. Future work will expand on this observational cohort, blindly validate these findings, and extend the work to encompass all breast cancer molecular subtypes. Citation Format: Satabhisa Mukhopadhyay, Elizabeth Walsh, Rebecca Millican-Slater, Andrew Hanby, Joanne Stephenson, Tathagata Dasgupta, Nicolas Orsi. Evaluating a computer-aided platform for predicting recurrence and survival in an Oncotype Dx tested breast cancer cohort [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 PO5-01-10.

HIITING CANCER BACK: THE EFFECTS OF ONE MONTH OF HIGH INTENSITY INTERVAL TRAINING ON INFLAMMATION, BODY COMPOSITION, AND CARDIORESPIRATORY FITNESS IN CANCER SURVIVORS

INTRODUCTION/AIMS Chronic inflammation, low fitness, and unfavourable body composition are often side effects of anti-cancer therapies and are associated with an increased risk of cancer recurrence. However, the response of these variables to high intensity interval training (HIIT), and the relationship among these predictors of cancer recurrence, is yet to be explored in cancer survivors. The aim of this study was to investigate the effect of one month of HIIT on inflammation, body composition, and cardiorespiratory fitness and explore the relationships among these variables in breast, prostate, and colorectal cancer survivors. METHODS Survivors (n=131) of breast, prostate, and colorectal cancer (60.1±10.3 years, 26.9±4.9 kg/m2, 67% female) completed one month of HIIT (12 sessions: 4x4min at 85-95% peak heart rate (HRpeak), interspersed with 3-minutes at 50-75% HRpeak). Body composition via dual-energy X-ray absorptiometry, cardiorespiratory fitness via V̇O2peak, and fasted blood were measured at baseline and at one month. Blood was analysed for inflammatory factors (interleukin (IL)-6, IL-10), and tumour necrosis factor alpha (TNF-α)). RESULTS HIIT resulted in significant reductions in IL-6, IL-10, TNF-α (-37-39%, p<0.001) and significant increases in leg lean mass (+400g, p=0.008) and absolute V̇O2peak (+0.2 L/min, p<0.001). Despite this, the only significant association among the changes in these variables was a weak correlation between IL-10 and absolute V̇O2peak (rs=0.256, p=0.013). CONCLUSION One month of HIIT elicited significant improvement in markers of systemic inflammation, body composition, and cardiorespiratory fitness. However, improvements in these variables were not strongly related and occur independent of each other. The findings of this study demonstrate 4x4 HIIT is an effective prescriptive tool to elicit rapid improvements in physiological markers, through apparent independent pathways. Therefore, exercise physiologists working with cancer survivors should consider utilising 4x4 HIIT to their exercise prescriptions as a time efficient means to reduce the risk of cancer recurrence and improve survivorship.

The Effect of a Mental Health Intervention on Health Behaviors among Cancer Survivors

The Effect of a Mental Health Intervention on Health Behaviors among Cancer Survivors

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.

Perspectives on shorter durations of anti-HER2 therapy in early-stage HER2-positive breast cancer: a patient survey.

Despite previous studies proposing shorter durations of anti-HER2 therapy for selected patients with HER2-positive early breast cancer (EBC), 12-months remains standard of care. A survey was performed to assess patient perspectives and willingness to participate in studies evaluating shorter durations of anti-HER2 therapy. Patients with HER2-positive EBC completing or having previously completed anti-HER2 therapy, were recruited by healthcare professionals at The Ottawa Hospital Cancer Centre to participate in an anonymous online survey. The primary objective was to learn about patients' perspectives on shorter durations (less than 12-months) of anti-HER2 therapy. Secondary objectives were to explore patients' interest in clinical trials of shorter durations of anti-HER2 therapy and the degree of increased breast cancer risk they would accept with a shorter treatment duration. Responses were received from 94 eligible patients. Most patients received Trastuzumab alone (78%, 73/94), while 13% (12/94) received trastuzumab and pertuzumab. Side effects were experienced by 52% (46/89), the most common being; fatigue (61%, 28/46), myalgia (37%, 17/46), and diarrhea (24%, 11/46). Most patients (88%, 78/89) did not find treatment bothersome. Regarding perspectives on shorter durations of anti-HER2 therapy, most (79%, 74/94) respondents stated they would agree to less treatment if it were possible to receive fewer treatments with the same cancer benefits. 56% of patients were interested in clinical trials, however, about half stated they would not be accepting of any increase in breast cancer recurrence risk. Trials to investigate who can safely and effectively be treated with shorter durations of anti-HER2 therapy are needed. This study provides important insights to patients' perspectives on shorter durations of anti-HER2 treatment, and their concerns regarding potential increased cancer risk with less treatment.

Association between pre-diagnosis recreational physical activity and risk of breast cancer recurrence: the California Teachers Study.

Studies have reported inverse associations of pre-diagnosis recreational physical activity (RPA) level with all-cause and breast cancer (BCa)-specific mortality among BCa patients. However, the association between pre-diagnosis RPA level and BCa recurrence is unclear. We investigated the association between pre-diagnosis RPA level and risk of BCa recurrence in the California Teachers Study (CTS). Stage I-IIIb BCa survivors (n = 6,479) were followed with median of 7.4years, and 474 BCa recurrence cases were identified. Long-term (from high school to age at baseline questionnaire, or, age 55years, whichever was younger) and baseline (past 3 years reported at baseline questionnaire) pre-diagnosis RPA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of BCa recurrence overall and by estrogen receptor (ER)/progesterone receptor (PR) status. Long-term RPA was not associated with BCa recurrence risk (ptrend = 0.99). The inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was marginally significant (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.79, 95% CI = 0.60-1.03; ptrend = 0.07). However, the association became non-significant after adjusting for post-diagnosis RPA (ptrend = 0.65). An inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was observed in ER-PR- cases (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.31, 95% CI = 0.13-0.72; ptrend = 0.04), but not in ER+ or PR+ cases (ptrend = 0.97). Our data indicates that the benefit of baseline RPA on BCa recurrence may differ by tumor characteristics. This information may be particularly important for populations at higher risk of ER-PR- BCa.