Early-stage Hormone Receptor-positive Breast Cancer Research Articles

Evaluation of a complex survivorship intervention incorporating electronic patient-reported outcomes in early stage breast and gynecologic cancer: Results from the Linking You to Support and Advice (LYSA) randomized controlled trial.

1505 Background: Expert consensus supports a multidisciplinary strategy in cancer survivorship care to enhance patient outcomes and quality of life. We hypothesized that introducing a women’s survivorship clinic into routine follow up care would be feasible, and associated with improved symptom management and quality of life (QOL). Methods: LYSA was a multisite randomized controlled trial with parallel arms (experimental and active comparator), co-designed with public and patient involvement. Eligibility: early-stage hormone receptor-positive breast or gynaecologic cancer (GYN) within 12 months of completing primary therapy, and internet access (NCT05035173). Experimental arm attended a nurse-led clinic targeting symptom management, and dietetic consultation. Electronic patient-reported outcome (ePRO) assessments were undertaken at baseline, and bimonthly to 12 months. An online trigger alert system facilitated symptom management. Active comparator arm attended the nurse-led clinic at baseline and end of study. Primary endpoint (feasibility): Proportions of participants completing baseline and follow up ePRO surveys, and engaging in healthcare consultations after ePRO triggers. Pilot efficacy endpoints: changes in cancer-related symptom (PROMIS, PRO-CTCAE, Fear of Cancer Recurrence), health-related QOL Questionnaires (EORTC-QLQ, EQ5D5L) . Sample size target (n=200) facilitated feasibility outcomes. Between arm differences were estimated using generalized linear model, adjusted for baseline outcome. Results: 200 women were randomized, March 2021-August 2022 across two sites; 84% breast and 16% GYN. Consent was obtained in clinic (51%), video call (33%) or phone (16%). Median age was 54 (range 23-78). Of the 173 participants completing the study (n = 90 experimental, 83 comparator), all completed both baseline and end of study surveys. Following symptom triggers (experimental arm), there were 322 study nurse visits across 86 participants, and 243 dietician visits across 73 participants. Engagement with healthcare and other supportive resources was approximately twice more than comparator arm, due to referral. There were no notable between-arm differences with respect to EQ5D5L items at study end. However, experimental arm participants had better EORTC Total scores at study end relative to comparator (difference in means -3.87 95%CI -6.58 to -1.16, p=0.005). There were also significant (p < 0.05) differences observed between the arms for 8/12 symptom items reflecting less fatigue, anxiety and depression in experimental arm at study end. Conclusions: The LYSA trial met its primary feasibility endpoint, with high rates of ePRO completion. Secondary endpoint analysis is ongoing including an economic analysis and future studies. Clinical trial information: NCT05035173 .

Abstract PO4-01-13: Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database

Abstract Background:Adjuvant endocrine therapy is the most important treatment modality as long as one, which can reduce the mortality risk and the recurrence risk for patients with hormone receptor-positive breast cancer. Currently, few studies has reported the association in poor adherence with overall survival(OS) or disease-free-survival(DFS). However, the use of prescription coverage in previous studies to describe patient adherence to endocrine therapy may not be representative of the patient's actual medication. Additionally, previous studies did not distinguish between interruption and discontinuation of endocrine therapy, which is different to clinician. This research used rigorous follow-up data and aims on the effects of discontinuation and interruption on patients with early-stage hormone receptor-positive breast cancer. Methods: Based on the Breast Cancer Information Management System (BCIMS), we identified patients diagnosed with stage I-III breast cancer with hormone receptor-positive and received endocrine therapy during January 1, 1990 to January 1, 2018 in West China Hospital (WCH), Sichuan University, China. Briefly, all patients diagnosed with breast cancer were included and prospectively followed from the diagnosis at WCH or the first visit to WCH for breast cancer. Information, including demographic characteristics, medical history, laboratory results, pathological information, treatments and clinical outcomes, were obtained from clinical records and interviews. Kaplan-Meier analysis, Time-Dependent Cox Regression Model, and subgroup analysis were performed to evaluate the effectiveness of interruption or discontinuation of endocrine therapy. And “X-tile” software is used to select cutoff values in survivorship data. Results:A total of 3,418 eligible patients were included with 8.13(±1.96) years median follow-up. Of these patients, 19.5% did not adhere to standard endocrine regimens, with 6.9% discontinuing and 12.7% discontinuing. The multivariate cox analysis indicates that discontinuation group (DFS:HR=9.71, [95%CI]5.21-18.34,P <0.001; OS:HR=10.41, [95%CI]5.63-19.24,P <0.001) increased the risk of death and breast cancer events compared to the adherence group, but not shown statistical significance difference in the interruption (DFS:HR=1.03,[95%CI]0.23-4.66, P =0.975; OS:HR=1.17, [95%CI]0.26-5.28,P =0.840). We further analyzed the interruption and discontinuation group respectively. In the interruption group, we found cutoff value with 30 months in survival risks but didn't find statistical significance difference in DFS and OS compared to the adherence groups. For the discontinuation group, we divided the patients into low-risk and high-risk groups according to cutoff value (23 months), the final results showed that the high-risk group who took the endocrine therapy less than 23 months had increased the rate of OS(HR=23.98,[95%CI]11.71-49.14, P< 0.001) and DFS(HR=24.03,[95%CI]11.51-50.18, P< 0.001). Conclusion:This study found that interruption of endocrine therapy may not affect prognosis of HR+ breast cancer patients, but prolonged discontinuation increases the risk of relapse and death. Therefore, clinicians should educate patients taking endocrine therapy and encourage those who discontinue the drug to take the drug again as soon as possible. A.Kaplan-Meier Curve for OS B.A.Kaplan-Meier Curve for DFS Kaplan-Meier Curve for OS and DFS in the Interruption Group according to the events location Kaplan-Meier Curve for OS and DFS in the Discontinuation Group according to the total duration of medication Citation Format: Ya Huang, Jie Chen, Yunhao Wu. Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database [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 PO4-01-13.

Abstract PO4-11-11: Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation

Abstract Background: Fertility preservation and family planning are pressing survivorship concerns for many young, reproductive-aged women with hormone receptor-positive (HR+) early-stage breast cancer. Following primary treatment, patients typically receive 5-10 years of adjuvant endocrine therapy (ET), during which pregnancy is contraindicated and fertility may decrease. The first-of-its-kind POSITIVE trial (NCT02308085) sought to challenge this archetype by prospectively evaluating the impact of temporary ET interruption to allow patients to attempt conception. Participants (n=516) received 18-30 months of ET followed by a 3-month washout period prior to initiating a 2-year break from therapy to attempt pregnancy. Results demonstrated that short-term disease outcomes were not impacted by temporarily pausing therapy to allow women who desire conception to attempt pregnancy. This survey-based study aimed to evaluate community oncologists’ perceptions of the POSITIVE trial data, ET interruption, and fertility preservation efforts. Methods: US-based oncologists convened at three live meetings in March and April 2023 to review clinical updates presented at SABCS 2022. Participant characteristics and demographic data were collected via an online survey prior to the respective meetings. Perceptions/reactions to clinical updates were captured using audience response system technology. Data were summarized using descriptive statistics. Results: Among 157 respondents, 82.8% identified as community providers, with 17.9 mean years of clinical experience. On average, participants reported that 85.4% of their time is allocated towards direct patient care, with approximately 21 patients seen per clinic day. Most respondents (85.8%) indicated that they only refer patients to a fertility specialist if the patient initiates fertility preservation discussions and nearly half (45.7%) reported that within the last year, 20% or less of their patients have discussed fertility concerns with them prior to initiating therapy. Additionally, over three-quarters of respondents (79.9%) indicated that 10% or less of their patients with breast cancer underwent fertility preservation within the last year. Prior to reviewing the POSITIVE trial data, 51.3% of respondents reported that they would be most likely to offer therapy interruption to patients with low- or intermediate-risk disease, while 19.8% would do so for all patients regardless of risk status. After reviewing the POSITIVE trial data, 59.3% of respondents would offer therapy interruption to patients with low- or intermediate-risk disease, while 30% would do so for all patients regardless of risk status. Notably, a majority of respondents (54.8%) indicated that they would recommend a therapy interruption of 12 months or less, while 11.1% would opt for 19-24 months. Conclusions: Findings demonstrate that the onus of initiating discussions surrounding fertility and reproductive topics is often placed on patients, and many patients do not proactively address these matters or undergo fertility preservation prior to initiating treatment. Overall, respondents viewed the POSITIVE trial favorably, as evidenced by their increased willingness to consider temporary ET interruption for all patients following their review of the study data. Although the POSITIVE trial allowed up to 2 years of therapy interruption, respondents preferred a treatment break of 12 months or less. With the adoption of the POSITIVE strategy into routine clinical practice, younger women with HR+ breast cancer may no longer be faced with the difficult choice of pursuing potentially life-saving therapy or starting/expanding a family, thereby addressing a current unmet survivorship need among this patient population. However, it remains to be seen how many physicians will offer this approach, who is the ideal candidate, and what the appropriate ET interruption length will be. Citation Format: Brooke Leon, Robert Bone, Yolaine Jeune-Smith, Sigrun Hallmeyer, Bruce Feinberg. Provider perceptions of the POSITIVE trial, endocrine therapy interruption, and fertility preservation [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 PO4-11-11.

Abstract PO2-01-08: Differential HOXB13 gene expression and promoter methylation analysis in breast cancer

Abstract Background: The Breast Cancer Index (BCI) is a gene expression-based signature comprising two functional biomarker panels: the Molecular Grade Index (MGI) and BCI (H/I), which is a ratio of the HOXB13 and IL17BR gene expression. Several studies have shown that BCI (H/I) is a predictive biomarker for extended adjuvant endocrine therapy benefit in hormone receptor-positive (HR+) early-stage breast cancer. Molecular mechanisms underlying endocrine responsiveness remain to be fully explored. The objective of this analysis is to evaluate the correlation between gene expression and methylation in breast cancer patients displaying different HOXB13 mRNA expression levels from The Cancer Genome Atlas (TCGA) project. Methods: Data from methylation microarrays and mRNA sequencing were examined in combination with clinical metadata from 1,095 TCGA breast cancer patients. After removing outliers, HR+ samples were ordered based on their HOXB13 expression levels and the top 10% of samples (HOXB13-high; n=95) and bottom 10% (HOXB13-low; n=95) were selected for further analysis. Differentially expressed genes (DEGs) were determined by comparing all protein-coding genes between the HOXB13-high and HOXB13-low sets, based on an absolute log-fold change above 2 and a Benjamini-Hochberg adjusted p-value threshold of 0.01. Among the subset of samples with matching methylation data (n=60 for the HOXB13-high group and n=48 for the HOXB13-low group), hypo-methylated and hyper-methylated differentially methylated probes (DMPs) were identified based on at least 10% change of β (i.e., average promoter methylation) and a Benjamini-Hochberg adjusted p-value threshold of 0.01. Motif and transcription factor (TF) enrichment analyses were identified at a minimum incidence of 10 and a lower boundary of 1.5 for the 95% confidence interval of the odds ratio. Results: Our analysis identified a total of 613 DEGs between the HOXB13-high and HOXB13-low groups. Gene ontology analysis of DEGs revealed a statistically significant enrichment of genes associated with PTK6 regulated cell cycle, oncogene-induced cellular senescence, and regulation of T cell activation. Analysis of protein-protein interactions of differentially expressed genes revealed differences in key biological processes including changes in cell cycle regulation, p53 pathway, and IL-17 signaling. A total of 5,295 hyper-methylated and 580 hypo-methylated DMPs were discovered when comparing HOXB13-high and HOXB13-low samples. Changes in global methylation patterns enabled classification of breast cancer samples with high or low HOXB13 expression with an accuracy of 0.90. Reconstruction of gene regulatory networks from DNA methylation and transcriptome profiles elucidated significant pairs of DMPs and differentially expressed genes. Specifically, a total of 197 differentially expressed genes were attributed to hyper-methylated DMPs, including genes involved in response to estrogen, activation of HOX genes during differentiation, and drug-mediated inhibition of CDK4/6 activity. Additionally, 8 differentially expressed genes were attributed to hypo-methylated DMPs and were associated with proteasomal protein catabolic processes. Lastly, motif analysis of transcriptional factors for the hyper-methylated DMPs revealed enrichment of binding motifs attributed to FOXA1, ESR1, XBR1, and FOXP1. Conclusion: A comprehensive and comparative analysis of mRNA expression levels and methylation patterns between TCGA breast cancer samples with high and low expression of HOXB13 revealed key signaling pathways and biological processes that may provide insights on the molecular mechanism of HOXB13 in the regulation of response to endocrine therapy in HR+ breast cancer. Citation Format: Natalia Siuliukina, Yi Zhang, Kai Treuner, Mark Pegram. Differential HOXB13 gene expression and promoter methylation analysis in 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 PO2-01-08.

Abstract 890: Multimodal modeling of digitized histopathology slides improves risk stratification in hormone receptor-positive breast cancer patients

Abstract In early-stage hormone receptor-positive breast cancer, genomic risk scores identify patients who stand to benefit from up-front chemotherapy but introduce financial and logistical hurdles to care. We assembled a cohort of 5,244 patients with 11,671 corresponding whole-side images of breast tumors stained with hematoxylin and eosin. We developed a multimodal machine learning model to infer risk of distal metastatic recurrence from routine clinical data. Specifically, the model interprets text from the pathologist’s report using a large language model and uses self-supervised vision transformers to interpret the corresponding whole-slide image. Tensor fusion joins the modalities to infer Genomic Health’s Oncotype DX recurrence score. Inferred recurrence score from the multimodal model correlated with measured score with a concordance correlation coefficient of 0.64 (95% C.I. 0.59 - 0.69) in the withheld test set, compared to 0.55 (95% C.I. 0.49 - 0.61) and 0.56 (95% C.I. 0.52 - 0.60) for the linguistic and visual unimodal models, respectively. The multimodal model attains an area under the precision-recall curve (AUPRC) of 0.69 (AUROC=0.88) for identifying high-risk disease in the full-information setting (when images and pathology reports with quantitative hormone receptor status and grade are available) in a withheld test set, compared to AUPRC of 0.61 and 0.66 for the linguistic and visual models, respectively. By comparison, in the same full-information setting, the clinical nomogram introduced by Orucevic et al. in 2019 achieves an AUPRC of 0.48. We suggest the operating point at which precision is 94.4% and recall is 33.3%. Digitized whole-slide images of routine breast biopsies and their associated synoptic pathology reports contain much of the information necessary to stratify patients by risk of distal metastatic recurrence, when modeled appropriately. Our model could enable hospitals to rapidly triage the need for genomic risk testing, possibly precluding one third of orders without loss of accuracy. This helps allocate scarce resources for genomic tests and valuable weeks prior to beginning therapy while maintaining the standard of precision oncology. Citation Format: Kevin M. Boehm, Antonio Marra, Jorge S. Reis-Filho, Sarat Chandarlapaty, Fresia Pareja, Sohrab P. Shah. Multimodal modeling of digitized histopathology slides improves risk stratification in hormone receptor-positive 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 890.

Impact of the Breast Cancer Index for Extended Endocrine Decision-Making: First Results of the Prospective BCI Registry Study.

The Breast Cancer Index (BCI) test assay provides an individualized risk of late distant recurrence (5-10 years) and predicts the likelihood of benefitting from extended endocrine therapy (EET) in hormone receptor-positive early-stage breast cancer. This analysis aimed to assess the impact of BCI on EET decision-making in current clinical practice. The BCI Registry study evaluates long-term outcomes, decision impact, and medication adherence in patients receiving BCI testing as part of routine clinical care. Physicians and patients completed pre-BCI and post-BCI test questionnaires to assess a range of questions, including physician decision-making and confidence regarding EET; patient preferences and concerns about the cost, side effects, drug safety, and benefit of EET; and patient satisfaction regarding treatment recommendations. Pre-BCI and post-BCI test responses were compared using McNemar's test and Wilcoxon signed rank test. Pre-BCI and post-BCI questionnaires were completed for 843 physicians and 823 patients. The mean age at enrollment was 65 years, and 88.4% of patients were postmenopausal. Of the tumors, 74.7% were T1, 53.4% were grade 2, 76.0% were N0, and 13.8% were HER2-positive. Following BCI testing, physicians changed EET recommendations in 40.1% of patients (P<.0001), and 45.1% of patients changed their preferences for EET (P<.0001). In addition, 38.8% of physicians felt more confident in their recommendation (P<.0001), and 41.4% of patients felt more comfortable with their EET decision (P<.0001). Compared with baseline, significantly more patients were less concerned about the cost (20.9%; P<.0001), drug safety (25.4%; P=.0014), and benefit of EET (29.3%; P=.0002). This analysis in a large patient cohort of the BCI Registry confirms and extends previous findings on the significant decision-making impact of BCI on EET. Incorporating BCI into clinical practice resulted in changes in physician recommendations, increased physician confidence, improved patient satisfaction, and reduced patient concerns regarding the cost, drug safety, and benefit of EET.

Validation of the Prognostic Performance of Breast Cancer Index in Hormone Receptor-Positive Postmenopausal Breast Cancer Patients in the TEAM Trial.

Patients with early-stage hormone receptor-positive (HR+) breast cancer face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is significantly prognostic for overall (0-10 years) and late (5-10 years) distant recurrence (DR) risk in N0 and N1 patients. Here, BCI prognostic performance was evaluated in HR+ postmenopausal women from the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. 3,544 patients were included in the analysis (N = 1,519 N0, N = 2,025 N+). BCI risk groups were calculated using pre-specified cutoff points. Kaplan-Meier analyses and log-rank tests were used to assess the prognostic significance of BCI risk groups based on DR. Hazard ratios (HR) and confidence intervals (CI) were calculated using Cox models with and without clinical covariates. For overall 10-year DR, BCI was significantly prognostic in Ni0 (N = 1,196) and N1 (N = 1,234) patients who did not receive prior chemotherapy (P < 0.001). In patients who were DR-free for 5 years, 10-year late DR rates for low- and high-risk groups were 5.4% and 9.3% (N0 cohort, N = 1,285) and 4.8% and 12.2% (N1 cohort, N = 1,625) with multivariate HRs of 2.25 (95% CI, 1.30-3.88; P = 0.004) and 2.67 (95% CI, 1.53-4.63; P < 0.001), respectively. Late DR performance was substantially improved using previously optimized cutoff points, identifying BCI low-risk groups with even lower 10-year late DR rates of 3.8% and 2.7% in N0 and N1 patients, respectively. The TEAM trial represents the largest prognostic validation study for BCI to date and provides a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ patients with early-stage breast cancer.

Combined modality treatment of early breast cancer. Literature review

The object of the study was to conduct a systematic literature review on combined modality treatment for early-stage breast cancer using postoperative and intraoperative radiation therapy, and consider new treatment approaches for early breast cancer.Material and Methods. The search for sources relevant to the review topic was carried out in the Medline, Cochrane Library, and Elibrary systems. A total of 905 studies on combination treatments for early breast cancer were identified, of which 43 were included in the review.Results. Data analysis showed that the rate of local relapses in early breast cancer was lower in patients who underwent breast-conserving surgery in combination with adjuvant radiation therapy than in patients without adjuvant radiation therapy. Research is ongoing on radiotherapy deintensification using intraoperative radiation therapy for patients at low risk of recurrence. Ongoing clinical trials support the omission of radiotherapy after breast-conserving surgery for elderly women with hormone receptor-positive early-stage breast cancer, who receive adjuvant endocrine therapy. Understanding the characteristics of the tumor process will allow us to personalize the treatment of patients with early breast cancer, reduce the risk of local relapses, and avoid unnecessary treatment-related complications.Conclusion. To improve survival in breast cancer patients is only possible by maximizing the tumor control. The effectiveness of adjuvant radiation therapy, which is an integral component in the combined modality treatment of early breast cancer, has been proven. However, third-generation studies discuss the feasibility of identifying a low-risk group of patients with a favorable clinical prognosis, who receive adequate endocrine therapy, and additional radiation do not provide a significant survival benefit.

ASO Visual Abstract: Trends in Locoregional Therapy in Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer by Frailty and Life Expectancy.

ASO Visual Abstract: Trends in Locoregional Therapy in Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer by Frailty and Life Expectancy.

Trends in Locoregional Therapy in Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer by Frailty and Life Expectancy.

In women ≥ 70 years of age with T1N0 hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, breast surgery type and omission of axillary surgery or radiation therapy (RT) do not impact overall survival. Although frailty and life expectancy ideally factor into therapy decisions, their impact on therapy receipt is unclear. We sought to identify trends in and factors associated with locoregional therapy type by frailty and life expectancy. Women ≥ 70years of age with T1N0 HR+/HER2- breast cancer diagnosed in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 2010 and 2015 were stratified by validated claims-based frailty and life expectancy measures. Therapy trends over time by regimen intensity ('high intensity': lumpectomy + axillary surgery + RT, or mastectomy + axillary surgery; 'moderate intensity': lumpectomy + RT, lumpectomy + axillary surgery, or mastectomy only; or 'low intensity': lumpectomy only) were analyzed. Factors associated with therapy type were identified using generalized linear mixed models. Of 16,188 women, 21.8% were frail, 22.2% had a life expectancy < 5 years, and only 12.3% fulfilled both criteria. In frail women with a life expectancy < 5 years, high-intensity regimens decreased significantly (48.8-31.2%; p<0.001) over the study period, although in 2015, 30% still received a high-intensity regimen. In adjusted analyses, frailty and life expectancy < 5 years were not associated with breast surgery type but were associated with a lower likelihood of axillary surgery (frailty: odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76-0.96; life expectancy < 5 years: OR 0.22, 95% CI 0.20-0.25). Life expectancy < 5 years was also associated with a lower likelihood of RT receipt in breast-conserving surgery patients (OR 0.30, 95% CI 0.27-0.34). Rates of high-intensity therapy are decreasing but overtreatment persists in this population. Continued efforts aimed at appropriate de-escalation of locoregional therapy are needed.

282P Analysis of Prosigna in hormone receptor-positive early-stage breast cancer cohort after 8 years of experience at a single institution

282P Analysis of Prosigna in hormone receptor-positive early-stage breast cancer cohort after 8 years of experience at a single institution

Association of Sarcopenia With Toxicity-Related Discontinuation of Adjuvant Endocrine Therapy in Women With Early-Stage Hormone Receptor–Positive Breast Cancer

Sarcopenia, an age-related decline in muscle mass and physical function, is associated with increased toxicity and worse outcomes in women with breast cancer (BC). Sarcopenia may contribute to toxicity-related early discontinuation of adjuvant endocrine therapy (aET) in women with hormone receptor-positive (HR+) BC but remains poorly characterized. This multicenter, retrospective cohort study included consecutive women with stage 0-II HR+ BC who received breast conserving therapy (lumpectomy and radiation therapy) and aET from 2011 to 2017 with a 5-year follow-up. Skeletal muscle index (SMI, cm2/m2) was analyzed using a deep learning model on routine cross-sectional radiation simulation imaging; sarcopenia was dichotomized according to previously validated reports. The primary endpoint was toxicity-related aET discontinuation; logistic regression analysis evaluated associations between SMI/sarcopenia and aET discontinuation. Cox regression analysis evaluated associations with time to aET toxicity, ipsilateral breast tumor recurrence (IBTR), and disease-free survival (DFS). A total of 305 women (median follow-up, 89 months) were included with a median age of 67 years and early-stage BC (12% stage 0, 65% stage I). A total of 60 (20%) women experienced toxicity-related aET discontinuation. Sarcopenia was associated with toxicity-related early discontinuation of aET (odds ratio, 2.18; P=.036) and shorter time to aET toxicity (hazard ratio [HR], 1.62; P=.031). SMI or sarcopenia were not independently associated with IBTR or DFS; toxicity-related aET discontinuation was associated with worse IBTR (HR, 9.47; P=.002) and worse DFS (HR, 4.53; P=.001). Among women with early-stage HR+ BC who receive adjuvant radiation therapy and hormone therapy, sarcopenia is associated with toxicity-related early discontinuation of aET. Further studies should validate these findings in women who did not receive adjuvant radiation therapy. These high-risk patients may be candidates for aggressive symptom management and/or alternative treatment strategies to improve outcomes.

Targeting psychological and menopausal factors linked to non-adherence to anti-estrogen therapy in women with early-stage hormone-receptor positive breast cancer: Aweb-based feasibility study of Finding My Way.

Key Points Reduced adherence to anti‐estrogen therapy (AET; tamoxifen and aromatase inhibitors) in women with early‐stage hormone‐receptor‐positive (HR+) breast cancers leads to adverse clinical outcomes. Modifiable psychological factors (e.g., depressive symptoms and anxiety) and menopausal symptoms (e.g., sleep disturbance and hot flashes) are linked with diminished adherence. An intervention targeting psychological and menopausal symptoms has potential to improve AET adherence. We conducted a pilot study to evaluate the feasibility of a remotely administered behavioral intervention in women with early‐stage HR+ breast cancer taking AET at‐risk for non‐adherence with psychological and menopausal symptoms. Findings from this preliminary study show that a web‐based behavioral intervention is feasible and may be a potential method of reducing risk for AET non‐adherence in some patients.

Adjuvant Endocrine Therapy in Premenopausal Women With Hormone Receptor-Positive Early-Stage Breast Cancer: Risk Stratification in a Real-World Setting

BackgroundOvarian function suppression (OFS) and hormone therapy (HT) represent an adjuvant option in premenopausal hormone receptor-positive early breast cancer (HR+EBC). The SOFT-TEXT trials showed improved outcomes upon receiving aromatase inhibitors (AIs)/OFS. MethodsIn order to estimate the magnitude of absolute improvements, we conducted a retrospective study applying composite risk (CR) to 237 premenopausal HR+EBC patients. ResultsOverall, 119 of these received tamoxifen (T)/OFS and 118 received AIs/OFS. The median age was 45 years (ys). After a median follow up of 65 months, recurrence was 6.7% in T patients and 10.2% in AI ones. CR (cutoff: 2.67) and ET duration (five-year cutoff) was found to have a significant impact on DFS. Invasive disease-free survival (IDFS) at 5 ys amounted to 82.9% for a CR>2.67 and 95% with CR</=2.67 (p 0.0046). Five-year IDFS was 98.3% in patients who had completed 5-year HT compared to 54.6% of those who had stopped before 5 years (P < .0001). Excluding patients who had discontinued therapy due to disease relapse, IDFS difference at 5 years remained statistically significant (p=0.03) between the two groups, with an iDFS rate of 86.5% at 5 years in the second group. Adverse events of different grades were reported in 116 and 112 patients in the T/OFS group and the AIs/OFS, respectively. Early discontinuation due to toxicity was 3.8%. Seven patients (19.4%) discontinued therapy due to pregnancy desire (6 in the T group, 1 in the AI one); of these, one patient relapsed. ConclusionIn a real-world setting, treatment options for premenopausal patients who are candidates for HT and OFS should take risk status into account. Therefore, every effort should be made to maintain patient adherence to treatment in order to manage toxicities and improve outcomes.

Persistence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor-positive (HR +) breast cancer

PurposeExtending adjuvant endocrine therapy (ET) beyond the standard 5 years offers added protection against late breast cancer recurrences in women with early-stage hormone receptor-positive (HR +) breast cancer. Little is known about treatment persistence to extended ET (EET) and the role that genomic assays may play. In this study, we evaluated persistence to EET in women who had Breast Cancer Index (BCI) testing.MethodsWomen with stage I-III HR + breast cancer who had BCI testing after at least 3.5 years of adjuvant ET and ≥ 7 years of follow-up after diagnosis were included (n = 240). Data on medication persistence was based on prescriptions in the electronic health record.ResultsBCI predicted 146 (61%) patients to have low – BCI (H/I)-low – and 94 (39%) patients to have high likelihood of benefit from EET (BCI (H/I)-high). Continuation of ET after BCI occurred in 76 (81%) (H/I)-high and 39 (27%) (H/I)-low patients. Non-persistence rates were 19% in the (H/I)-high and 38% in the (H/I)-low group. The most common reason for non-persistence was intolerable side effects. Patients on EET underwent more DXA bone density scans than those who stopped ET at 5 years (mean 2.09 versus 1.27; p < 0.001). At a median follow-up of 10 years from diagnosis, there were 6 metastatic recurrences.ConclusionsIn patients who continued ET after BCI testing, the rates of persistence to EET were high, particularly in patients with predicted high likelihood of benefit from EET. Use of EET is associated with increased use of DXA scans.

Are we there yet? Optimal duration of endocrine therapy in women with postmenopausal early-stage hormone receptor-positive breast cancer.

Are we there yet? Optimal duration of endocrine therapy in women with postmenopausal early-stage hormone receptor-positive breast cancer.

Trends and outcomes of systemic therapy in hormone receptor-positive early-stage male breast cancer: A propensity score analysis.

557 Background: Male breast cancer (MBC) is a rare disease. Research on trends and survival outcomes in systemic treatment for MBC is limited. This study aims to describe trends and survival outcomes of different systemic treatments in hormone receptor-positive (HR+) early MBC and to assess the factors related to treatment selection. Methods: We identified stage I-III HR+ invasive MBC patients who have undergone surgery and systemic therapy diagnosed during 2004-2014 from the National Cancer Database (NCDB). Treatment groups include: endocrine therapy (ET), chemotherapy (ET), combination therapy (ET+CT), and None. Using Cochran-Armitage trend tests to describe the temporal trends of different treatments. Performing propensity score models to evaluate overall survival. Conducting a logistic regression to analyze factors associated with ET+CT. Results: Among 6217 patients included (median follow-up 50.1months), 1290 (20.7%) patients received no systemic therapy (None), 705 (11.3%) patients only received CT, 2358 (37.9%) patients only received ET, and 1864 (30.0%) patients received ET+CT. From 2004 to 2013, there was a significant increase in the use of ET ( P(trend) &lt; .001), which was accompanied by a decrease in CT and no treatment (all P(trend) &lt; .001). And the use of ET+CT showed no significant change. After using overlap weighting (OW) to control confounders, multivariable cox regression analysis showed that ET+CT was associated with improved survival compared with ET (hazard ratio [HR], 0.46; P&lt; .001). Sensitivity analyses (including the inverse probability of treatment weighting (IPTW) (HR,0.49; P &lt; .001), IPTW with stabilized weight (HR,0.49; P&lt; .001), propensity score matching (PSM) (HR,0.51; P &lt; .001), PS regression adjustment (HR,0.47; P &lt; .001), and PS stratification (HR 0.44; P &lt; .001)) and exploratory subgroup analyses (except for well-differentiated, stage I, and breast conservation + radiotherapy subgroups) indicated similar outcome. Factors associated with receiving ET+CT include younger age, private insurance, Charlson Comorbidity Index was 0, poorer differentiation, higher stage, mastectomy and radiotherapy, estrogen receptor-positive and progesterone receptor-negative, and HER2-positive. Conclusions: ET+CT was associated with improved survival compared with ET in HR+ early MBC patients, except for some low-risk subgroups.

Omitting axillary staging in selected patients: Rationale of Choosing Wisely in breast cancer treatment

Axillary surgery for breast cancer has continually evolved, with sentinel lymph node biopsy for clinically node-negative women with invasive breast cancer having long replaced axillary lymph node dissection. The information obtained from axillary staging has been important in providing prognostic information and guiding adjuvant treatment recommendations. However, recent studies suggest that sentinel lymph node biopsy should be omitted in select low-risk patients whose axillary surgery provides minimal prognostic value. This was highlighted by the Society of Surgical Oncology Choosing Wisely Guidelines, advocating against routine axillary staging in older women with early-stage hormone receptor-positive breast cancer. Since the guideline release, ongoing research has continued to identify the subset of low-risk patients who would benefit from the omission of axillary staging and improve adherence to Choosing Wisely to prevent overtreatment in older people.

Metformin, placebo, and endocrine therapy discontinuation among participants in a randomized double-blind trial of metformin vs placebo in hormone receptor-positive early-stage breast cancer (CCTG MA32).

The MA32 study investigated whether 5 years of metformin (versus placebo) improves invasive disease-free survival in early-stage breast cancer (BC). Non-adherence to endocrine therapy (ET) and medications for chronic conditions is common and increases with drug toxicity and polypharmacy. This secondary analysis evaluates rates and predictors of early discontinuation of metformin, placebo, and ET among participants with HR-positive BC. Patients with high-risk non-metastatic BC were randomized to 60months of metformin (850mg BID) or placebo BID. Patients were administered bottles of metformin/placebo every 180days. Metformin/placebo adherence was defined as a bottle dispensed at month 48 or later. The ET adherence analysis included patients with HR-positive BC who received ET with start and stop date reported, with adherence defined as > 48months of use. Associations of covariates with study drug and ET adherence were examined using multivariable models. Among the 2521 HR-positive BC patients, 32.9% were non-adherent to study drug. Non-adherence was higher among patients on metformin vs placebo (37.1% vs 28.7%, p < 0.001). Reassuringly, ET discontinuation rates were similar between treatment arms (28.4% vs 28.0%, p = 0.86). Patients who were non-adherent to ET were more likely to discontinue study therapy (38.8% vs 30.1%, p < 0.0001). In a multivariable analysis, study drug non-adherence was increased with metformin vs placebo (OR: 1.50, 95% CI 1.25-1.80; p < 0.0001); non-adherence to ET (OR: 1.47, 95% CI 1.20-1.79, p < 0.0001); grade 1 or greater GI toxicity during the first 2years; lower age; and higher body mass index. While non-adherence was higher among patients on metformin, it was still considerable among patients on placebo. Reassuringly, treatment arm allocation did not impact ET adherence. Attention to global medication adherence is needed to improve BC and non-oncological outcomes in cancer survivors. ClinicalTrials.gov: NCT01.

Using Oncotype DX breast recurrence score® assay to define the role of neoadjuvant endocrine therapy in early-stage hormone receptor-positive breast cancer

PurposeThe role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need.MethodsWe assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay.ResultsWe observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0–25 may omit chemotherapy without compromising outcomes.ConclusionThese data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting.