Use Of Adjuvant Endocrine Therapy Research Articles

Abstract PO4-17-05: Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK

Abstract Background The use of adjuvant radiotherapy (RT) and endocrine therapy (ET) in the management of pure ductal carcinoma in situ (DCIS) remains controversial. We investigate how the use of adjuvant RT after breast conserving surgery (BCS) and use of adjuvant ET (in BCS and mastectomy patients) has changed over time. Methods A prospective cohort SQL database of 11,284 patients (the Sloane Project) diagnosed 2003-2012 with screen-detected DCIS in the UK was interrogated for use of adjuvant RT and ET over time and association with factors reported to be predictive of recurrence (patient age, DCIS nuclear grade, size, comedo necrosis, resection margins), as well as institution of surgery, travel time to radiotherapy facility, Index of Multiple Deprivation and outcome (provided by the National Disease Registration Service, NDRS). RT data by site were confirmed with more recent data from the National Audit of Breast Cancer in Older Patients (NABCOP), which looked at patterns of care and outcomes for women aged 70 years and over, compared with those aged 50-64 in England and Wales. Results Among the 7,949 women (70.6%) treated by BCS, post-operative adjuvant RT was given to 4,939 (62.1%); RT use after BCS increased over time (R2 =0.92; p< 0.01). RT use was associated with year of diagnosis (p < 0.01), younger age at diagnosis (p < 0.01), larger DCIS size (p < 0.01), presence of comedo necrosis (p < 0.01), higher nuclear grade (p < 0.01) and presence of microinvasion (p < 0.01). Adjusted analyses showed the most significant factor for RT after BCS was the surgery institution. Travel time to RT facility, Index of Multiple Deprivation and final radial margin were not associated with RT use. When compared with the more recent data from the NABCOP, a marked variation in radiotherapy use across hospitals remains. Ipsilateral recurrence rate varied significantly by hospital, with some of the difference associated with RT utilisation. ET was prescribed in 1313 women (12%), more often following BCS than mastectomy (p < 0.001), with significant variation by institution and a decline in the use of ET over time. Conclusion Marked geographic variation in the use of RT and ET after surgery for DCIS persists in the UK and is likely due to physician choice rather than other factors such as travel times to RT facilities. This is contributing to geographic variation in ipsilateral recurrence rates, suggesting the need for adoption of more authoritative guidelines to support clinical decision-making. Consistent national practice could provide auditable performance standards for adjuvant therapy of screen detected DCIS and contribute to more uniform patient care. Citation Format: Karen Clements, David Dodwell, Elinor Sawyer, Ramsey Cutress, Nisha Sharma, Abeer Shaaban, Alastair Thompson. Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK [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 PO4-17-05.

Abstract PO4-04-10: Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 trial

Abstract BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the standard of care for hormone receptor-positive (HR+)/Human Epidermal Growth Factor 2 negative (HER2-) metastatic breast cancer (MBC); no consensus actually exists for second-line (2L) treatments. The HERMIONE-13 trial evaluates the adopted therapeutic options after CDK4/6i failure and the potential factors that influence these choices. METHODS: HERMIONE-13 is a retrospective and prospective multicentric observational trial involving 15 Italian Centers. Information about therapies after disease progression to CDK4/6i from January 2016 until December 2020 was collected for the present analysis, aiming at evaluating which are the clinical criteria guiding the choice of 2L therapy after CDK4/6i failure. RESULTS: 114 pts have been enrolled: 14 pts (12.3%) received neoadjuvant treatment, 80 (70.2%) adjuvant therapy, of whom 46 (57.5%) chemotherapy (CT)+ endocrine therapy (ET) and 33 (41.3%) ET alone. Among the 79 pts treated with adjuvant ET, 44 pts (55.7%) showed primary or secondary endocrine resistance. 39 pts (34.2%) received first-line (1L) CDK 4/6i in combination with Fulvestrant (F), the remaining with aromatase inhibitors (AIs). Median duration of 1L CDK4-6i was 10.4 months (interquartile range (IQR) 4.7-17.4). Median age at 2L start was 59.5 years (IQR 51-68). As 2L therapy, 79 pts (69.3%) received CT±targeted therapy (TT) and 35 (30.7%) ET±TT. Visceral metastases at the beginning of 2L were documented in 46 pts (40.4%). Comorbidities were present in 48 (42.9%) of the pts, mainly cardiac diseases (25, 22.3%); 71 pts (63.4%) showed a 1L-related adverse events (AEs) (NA: 2 pts), mainly hematological toxicity (60, 53.6%). Among 79 pts treated with adjuvant ET, 60 (76%) were addressed to 2L CT±TT, while 19 (24%) to an ET-based therapy. A longer duration of 1L was observed in pts treated with 2L ET±TT (12.5 months, 7.2-22.2) in comparison with those treated with CT±TT (8.7 months, 4.2-14.9). The majority of pts treated with 1L F+CDK 4/6i underwent 2L CT-based treatment, as summarized in Table 1. Analyzing the population treated with 2L CT±TT, we observed that median age was 58 years (49-67), slightly lower than that of pts treated with ET±TT (63, 54-69). Among pts with visceral metastases, 30 pts (65.2%) were addressed to 2L CT±TT and 16 pts (34.8%) to ET±TT; CT±TT was also the favorite choice for the majority of pts with concomitant disease (33, 68.8%) and with previous CDK4/6i-related toxicity (47, 66.2%). Among age, visceral metastases, comorbidities, adjuvant treatment, duration of 1L therapy, use of 1L F and 1L related AEs, univariate analysis revealed that previous use of adjuvant ET (p=0.021), 1L F (p< 0.001), duration of 1L treatment (p=0.043) and age at 2L start (p=0.053) are all factors influencing the choice of 2L therapy. At the multivariate logistic regression model, only the use of F in association with CDK4/6i as 1L treatment and age at 2L therapy were associated with the choice between ET±TT vs CT± TT, with a backward selection, as summarized in table 2. CONCLUSION: The preliminary results of our study suggest that previous F in combination with CDK4/6i is a statistically confirmed predictor of choice for subsequent CT, whereas the increase in age is significantly associated with the choice for ET. Further research is needed to investigate the optimal sequencing of treatments following CDK4/6i and to determine predictive factors of response to 2L therapies. Table 1 2L choices in 1L F+CDK 4/6i pts. Table 2 Statistical model with the significant variables. Citation Format: Marina Elena Cazzaniga, Emanuela Rossi, Antonella Turla, Massimo Ambroggi, Alice Baggi, Rossana Berardi, Fulvio Borella, Serena Capici, Federica Cicchiello, Luigi Coltelli, Ugo De Giorgi, Antonella Ferro, Ornella Garrone, Monica Giordano, Elisabetta Landucci, Marco Mazzotta, Gabriella Moretti, Raffaella Palumbo, Francesca Fulvia Pepe, Patrizia Vici, Fable Zustovich, Viola Cogliati. Selection criteria for second-line treatments after Cyclin-dependent kinase 4/6 inhibitors failure in Hormone Receptor positive metastatic breast cancer patients: the preliminary experience of the HERMIONE-13 trial [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 PO4-04-10.

5-year adherence to adjuvant endocrine treatment in Dutch women with early stage breast cancer: A population-based database study (2006-2016).

Hormonal receptor (HR) positive breast tumors are common. Adjuvant hormonal therapy (AHT) with tamoxifen or Aromatase Inhibitors (AIs) is beneficial depending on the stage of the tumor. Despite the fact that AHT has been shown to improve survival and recurrence, Dutch adherence rates, which were mostly dependent on Tamoxifen prescriptions until 2006, plummeted from 80% after one year to 50% after five years. Nonadherence with AHT reduces its effectiveness. This research presents more recent adherence statistics (from 2006 to 2016), on a larger sample (7,996 vs 1,451), as well as factors that influence AHT adherence. In addition to tamoxifen data, AIs are now included. As low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome, it is important to monitor the rate as an indicator of women's burden of disease and the direction of adherence trends. The Netherlands Cancer Registry (NCR) was used to find women with early-stage breast cancer who started AHT within a year of surgery and were linked to the PHARMO Database Network (n =8,679). The Kaplan-Meier approach was used to measure AHT adherence five years after treatment was started, with a 60-day gap between refills as our primary outcome. Furthermore, the Medication Possession Rate (MPR) was determined using a cutoff of ≥80%. Analysis was performed on influential factors of adherence. The proportion of persistent women declined over time to reach 46.6% at the end of the fifth year and 53.3% of the women had a MPR ≥80% during the fifth year. Older and being diagnosed in 2006-2010 were associated with AHT adherence. Dutch 5-year AHT adherence appears to remain poor. Improving AHT adherence in HR+ breast cancer survivors is a critical medical need.

Area Deprivation Index in patients with invasive lobular carcinoma of the breast: associations with tumor characteristics and outcomes.

While investigators have shown associations between socioeconomic status (SES) and outcomes in breast cancer, there is a paucity of such data for invasive lobular carcinoma (ILC), the second most common type of breast cancer. Herein we evaluated the relationship between SES with tumor features and outcomes in stage I-III patients with ILC. We analyzed a prospectively maintained institutional ILC database and utilized the Area Deprivation Index (ADI) to determine neighborhood adversity, an indicator of SES. We used Cox proportional hazards models in Stata 17.0 to evaluate relationships between ADI quintile (Q), race, body mass index (BMI), clinicopathologic features, treatment type, and event-free survival (EFS). Of 804 patients with ILC, 21.4% lived in neighborhoods classified as ADI Q1 (least resource-deprived) and 19.7% in Q5 (most resource-deprived). Higher deprivation was significantly associated with larger tumor size (3.6 cm in Q5 versus 3.1 cm in Q1), increased presence of lymphovascular invasion (8.9% in Q5 versus 6.7% in Q1), and decreased use of adjuvant endocrine therapy (67.1% in Q5 versus 73.6% in Q1). On multivariable analysis, tumor size, receptor subtypes, and omission of adjuvant endocrine therapy were associated with reduced EFS. These data show that patients with ILC and higher ADI experience more aggressive tumors and differences in treatment. More data evaluating the complex relationships between these factors is needed to optimize outcomes for patients with ILC, regardless of SES. ADI is associated with differences in patients with ILC.

Cost-Effectiveness Analysis of MammaPrint® to Guide the Use of Endocrine Therapy in Patients with Early-Stage Breast Cancer.

Gene expression profiling tests can predict the risk of disease recurrence and select patients who are expected to benefit from therapy, while allowing other patients to forgo therapy. For breast cancers, these tests were initially designed to tailor chemotherapy decisions, but recent evidence suggests that they may also guide the use of endocrine therapy. This study evaluated the cost effectiveness of a prognostic test, MammaPrint®, to guide the use of adjuvant endocrine therapy in patients eligible according to Dutch treatment guidelines. We constructed a Markov decision model to calculate the lifetime costs (in 2020 Euros) and effects (survival and quality-adjusted life-years) of MammaPrint® testing versus usual care (endocrine therapy for all patients) in a simulated cohort of patients. The population of interest includes patients for whom MammaPrint® testing is currently not indicated, but for whom it may be possible to safely omit endocrine therapy. We applied both a health care perspective and a societal perspective and discounted costs (4%) and effects (1.5%). Model inputs were obtained from published research (including randomized controlled trials), nationwide cancer registry data, cohort data and publicly available data sources. Scenario and sensitivity analyses were conducted to explore the impact of uncertainty around input parameters. Additionally, threshold analyses were performed to identify under which circumstances MammaPrint® testing would be cost effective. Adjuvant endocrine therapy guided by MammaPrint® resulted in fewer side effects, more (quality-adjusted) life-years (0.10 and 0.07 incremental QALYS and LYs, respectively) and higher costs (€18,323 incremental costs) compared with the usual care strategy in which all patients receive endocrine therapy. While costs for hospital visits, medication costs and productivity costs were somewhat higher in the usual care strategy, these did not outweigh costs of testing in the MammaPrint® strategy. The incremental cost-effectiveness ratio was €185,644 per QALY gained from a healthcare perspective and €180,617 from a societal perspective. Sensitivity and scenario analyses showed that the conclusions remained the same under changed input parameters and assumptions. Our results show that MammaPrint® can become a cost-effective strategy when either the price of the test is reduced (>50%), or the proportion of patients for which treatment is altered (i.e. those with ultra-low risk) increases to >26%. Standard MammaPrint® testing to guide the use of endocrine therapy in our simulated patient population appears not to be a cost-effective strategy compared with usual care. The cost effectiveness of the test can be improved by reducing the price or preselecting a population more likely to benefit from the test.

Abstract P2-03-12: Impact of adjuvant endocrine therapy (ET) omission in ER+ breast cancer (BC) treated with neoadjuvant chemotherapy (NAC)

Abstract Background: Adjuvant endocrine therapy (ET) in ER+ breast cancer (BC) reduces local, distant, and contralateral BC events and improves overall survival (OS). Furthermore, decreased adherence or omission of ET increases the risk of death. However, in ER+ pts with early-stage BC treated with NAC who have a pathologic complete response (pCR), the importance of adjuvant ET may be called into question. We sought to examine the impact of ET omission on the survival of pts with ER+ BC treated with NAC, according to pCR vs residual disease. Methods: We queried the National Cancer Database (NCDB) 2010-2018 for female pts with stage I-III ER+ BC treated with NAC followed by surgery. pCR was defined as ypT0/ypTis, ypN0. The percent receiving adjuvant ET and the impact of adjuvant ET omission on overall survival (OS) in patients with and without pCR were assessed separately based on HER2 expression. OS was analyzed with adjuvant ET as a time-dependent covariate using Cox proportional hazards regression. Results: We identified 34,394 pts treated with NAC for ER+ BC (28,434 ER+/HER2-, 5960 ER+/HER2+). Pts with ER+/HER2+ BC were less likely than pts with ER+/HER2- BC to have received adjuvant ET (61.6% vs 88.8%, p< 0.001). Overall, 4505 (13.1%) had pCR (9.1% of ER+/HER2- and 32.0% of ER+/HER2+). Within each subtype, pts with pCR were significantly less likely to start adjuvant ET after surgery than pts with residual disease (78.4% vs 89.8% for ER+/HER2- and 46.5% vs 68.7% for ER+/HER2+, each p< 0.001), Table 1. Regarding those with residual disease, pts with ER+/HER2+ BC were less likely than ER+/HER2- BC to receive adjuvant ET (68.7% vs 89.8%, p< 0.001). Median follow-up was 4.4 years. Among pts with pCR, 5-year OS was 93.2% (95% CI: 92.1-94.4%) for ER+/HER2- BC and 94.3% (95% CI: 93.1-95.5%) for ER+/HER2+ BC (p=0.08), while among patients with residual disease 5-year OS was 81.7% (95% CI: 81.1-82.2%) and 85.7% (95% CI: 84.5-86.9%) for the two subtypes respectively (p< 0.001). On multivariable analysis, omission of adjuvant ET was significantly associated with poorer OS in patients with residual disease for both ER+/HER2- BC (adjusted HR 1.72, p< 0.001) and ER+/HER2+ BC (adjusted HR 1.63, p< 0.001). In contrast, omission of adjuvant ET was not significantly associated with OS in patients with pCR, regardless of HER2 status (ER+/HER2- adjusted HR 1.28, p=0.20; ER+/HER2+ adjusted HR 1.13, p=0.54), Table 1. Conclusions: In pts receiving NAC for ER+ BC, those with ER+/HER2+ disease were less likely to have received adjuvant ET compared to ER+/HER2- patients, regardless of pCR. In pts with residual disease after NAC, omission of adjuvant ET was associated with significantly higher risk of death. These data provide strong support for interventions to increase utilization of ET, especially for patients with residual disease following NAC. The observation that ET omission did not impact OS in pts with ER+ BC who achieve pCR following NAC is hypothesis generating and may have implications for future de-escalation trials for this subset of patients. Table 1. Differential use of adjuvant endocrine therapy by subtype and pCR and the impact on overall survival Citation Format: Grace M. Choong, Judy C. Boughey, Tanya L. Hoskin, Courtney N. Day, Matthew P. Goetz. Impact of adjuvant endocrine therapy (ET) omission in ER+ breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-12.

Abstract P4-02-17: Impact of low hormone receptor expression on neoadjuvant chemotherapy response and patterns of care in early-stage HER2-negative breast cancer: a US National Cancer Database analysis

Abstract Background: Hormone receptor (HR) low (1-10%) HER2-negative breast cancer (BC) is emerging as a distinct subtype with similarities in clinical outcomes to triple-negative BC. However, there is a lack of consensus on treatment recommendations for chemo-immunotherapy and endocrine therapy in this subset. Here, we present results from a US National Cancer Database (NCDB) analyses of patients with HER2-negative BC evaluating response to neoadjuvant chemotherapy (NAC) and patterns of care by HR expression. Methods: Patients with stage I-III HER2-negative BC diagnosed in 2018 were identified in NCDB, a nationwide oncology outcomes database in the US. Quantitative HR expression was unavailable prior to 2018. Data were categorized into four groups by estrogen receptor (ER) and progesterone receptor (PR) expression: ER< 1% & PR< 1% (HR-Neg), ER 1-10% and/or PR 1-10% (HR-Low), ER >11-30% and/or PR>11-30% (HR-Int), ER> 30% and/or PR > 30% (HR-High). Those with undocumented HR status (3%) or without curative intent surgery (5%) were excluded. The primary outcome was pathologic complete response (pCR) by HR expression in those undergoing neoadjuvant chemotherapy. Key secondary objectives included assessment of clinicopathologic characteristics and practice patterns. The categorical variables were compared between the four groups using a Chi-square test. Age was compared using a Kruskal-Wallis test. Results: Out of 104,205 incident cases, 2541 (2.4%) were HR-Low and 1241 (1.2%) were HR-Int. Significant differences were found between HR groups with higher grade, clinical stage, and Ki-67 in HR-Low vs. HR-Int or HR-High groups (Table 1). Patients with HR-Low and HR-Int BC were more likely to receive chemotherapy than HR-High (74%, 70% vs. 20%; p < 0.001) and the use of adjuvant endocrine therapy correlated with HR expression. Only half of patients in the HR-Low group received any endocrine therapy compared to higher rates in the HR-Int and HR-High groups (52% vs. 74%, 92%; p< 0.001). pCR rates in those receiving neoadjuvant chemotherapy were significantly different by HR status, with higher pCR rates in HR-Low vs. HR-High groups (p< 0.001) (Table 2). NAC utilization significantly differed between groups. A higher proportion of patients with HR-Low BC received NAC than other HR-positive groups (p < 0.001). Additionally, there was an increased use of NAC in patients with HR-Low BC treated at academic vs. community cancer centers (p< 0.001). Conclusions: This is one of the largest real-world analyses comparing key differences in biology and practice patterns of HR-Low, HER2-negative BC. Consistent with prior studies, we report HR-Low BC to be a rare and distinct subtype with higher pCR rates compared to HR-High BC. Practice patterns show wide variability in utilization of neoadjuvant chemotherapy and endocrine therapy for these patients. Future studies should address this disparity and enhance representation of patients with HR-Low BC in clinical trials to improve long-term outcomes. Table 1: Patient demographics Table 2: Neoadjuvant chemotherapy response amongst differing HR expression levels Citation Format: Dionisia Quiroga, Michael Grimm, Julie Stephens, Kai Johnson, Nicole Williams, Preeti K. Sudheendra, Mathew A. Cherian, Daniel Stover, Ashley C. Pariser, Margaret Gatti-Mays, Robert Wesolowski, Jose G. Bazan, Sasha Beyer, Ko Un Park, Bridget Oppong, Bhuvaneswari Ramaswamy, Julia White, Sachin R. Jhawar, Sagar Sardesai. Impact of low hormone receptor expression on neoadjuvant chemotherapy response and patterns of care in early-stage HER2-negative breast cancer: a US National Cancer Database analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-17.

Abstract B086: Barriers to use of adjuvant endocrine therapy among Black women with breast cancer: A qualitative investigation

Abstract Post-operative or adjuvant endocrine therapy (AET) is the mainstay of treatment for hormone receptor-positive (HR+) breast cancer. When taken daily for 5-to-10 years, AET improves the time to disease recurrence and overall survival rates. However, past work has shown that Black women are less likely to begin prescribed AET treatments and less likely to take these medications as directed, often discontinuing treatment early. For hormone receptor-positive (HR+) breast cancer, rates of death from breast cancer are higher than those of similar White women. This study investigates the patient-, provider-, and practice-level barriers to AET initiation and adherence faced by Black women with the ultimate goal of developing an intervention to address these barriers. This study consists of qualitative semi-structured interviews with two populations, Black breast cancer survivors with HR+ breast cancer who were prescribed AET and cancer care providers (including medical doctors and advance-practice providers). All participants were recruited from the same comprehensive cancer center with a dedicated breast cancer clinic. Data collection is ongoing; thus far, the sample includes fifteen interviews with breast cancer survivors and nine with providers. Participants were asked about the barriers to care they (or their patients) face, their (or their patients’) perception of AET, and their views of possible interventions to improve clinical practices related to AET initiation and adherence. Preliminary findings include differences in perceived barriers to care between Black women and their providers. Providers understood barriers to AET initiation and adherence as minimal compared to other treatments, in terms of cost, toxicity, and burden of care. Meanwhile, patients understood the cost of the treatment as very high, largely due to side-effect. While the price of the medications were not a common barrier, the side effects (including brain fog, bone aches, fatigue, and depression) impact patients’ interpersonal relationships, employment, and/or ability to perform care work for family members, were seen as a heavy burden. In addition, patient interviews showed a need for higher quality education regarding how AET therapy works and its importance in preventing recurrence. While providers described the myriad ways in which they educate their patients about AET and its importance in breast cancer care, patients interviewed described gaps in their knowledge related to how AET works and why it is an essential aspect of their care. These findings point to a need for reframing barriers to breast cancer care for providers and the implementation of new clinical procedures to address and rectify racial disparities in AET use. Citation Format: Hayden J. Fulton, Dannelle R. Charles, Kimberley T. Lee. Barriers to use of adjuvant endocrine therapy among Black women with breast cancer: A qualitative investigation [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B086.

Patient experiences and views on pharmaceutical care during adjuvant endocrine therapy for breast cancer: A qualitative study.

The use of adjuvant endocrine therapy (AET) after primary treatment of hormone receptor-positive breast cancer reduces the risk of recurrence and mortality. However, non-adherence is still common. Limited consideration has been given to how users deal with AET and the role of pharmaceutical care. Therefore, this study aims to obtain insight into the needs and wishes of women using AET regarding pharmaceutical care and eHealth. This is a qualitative explorative study comprising semi-structured interviews (n = 16) and a focus group (n = 5) among women who use or used AET after primary early-stage breast cancer (EBC) treatment using a thematic analysis approach. Three themes emerged from the interviews and focus group: (1) experiences with AET use, (2) experiences with provided information and (3) needs and wishes regarding pharmaceutical care. Most women were highly motivated to use AET and indicated to have received useful information on AET. However, many expressed a strong need for more elaborate tailored and timely provided information on AET. They acknowledged the accessibility of pharmacists but reported that currently, pharmacists are hardly involved in AET care. Several women considered eHealth useful to obtain counselling and reliable information. Women need more comprehensive information and follow-up in primary setting after initial cancer treatments. A more elaborate role for the pharmacy and eHealth/mHealth, especially with regard to counselling on side effects and side effect management, could potentially improve pharmaceutical care.

Health-Related Quality of Life in Women With Breast Cancer Undergoing Treatment With Hormonal Therapy - A Review Study.

This review aimed to analyze the significance and impact of health-related quality of life (QoL) in women with breast cancer undergoing treatment with hormonal therapy. This study developed a comprehensive, structured, systematic search strategy to identify literature related to health and QoL in breast cancer patients undergoing treatment with hormonal therapy. The search was conducted for published literature indexed in PubMed (Medline), Cancer Lit, CINAHL, Google Scholar, and Web of Science between 2010 and 2020. Patients associated with the study of QoL reported some difficulties in terms of depression, anxiety, chronic fatigue, sleep problems, pain, sexual dysfunction and sleep disorders. Endocrine-related symptoms did not fluctuate between interventions and remained unchanged in all groups. The evaluation of FACT-G scores (physical well-being subscale) showed statistically significant differences among participants receiving anastrozole versus tamoxifen and exemestane. It can be concluded that the QoL of postmenopausal women with breast cancer is affected by the long-term use of adjuvant endocrine therapy, with difference reported associated with the different therapies. However, further efforts are required to improve QoL instruments and the quantitative evaluation of QoL data for patients receiving adjuvant ET.

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

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

A look at current and potential treatment approaches for hormone receptor-positive, HER2-negative early breast cancer.

The heterogeneity of hormone receptor (HR)-positive, HER2-negative early breast cancers reinforces the importance of individualized, risk-adapted treatment approaches. Numerous factors contribute to the risk for recurrence, including clinical tumor features, individual biomarkers, and genomic risk. Current standard approaches for patients with HR-positive, HER2-negative, early stage disease focus on endocrine therapy and chemotherapy. The specific treatment regimen and duration of adjuvant therapy should be selected based on accurate risk assessment, tolerability of available therapies, and consideration for patient preferences. For patients with high-risk features, such as highly proliferative tumors, large tumor size, and significant nodal involvement, the risk for recurrence remains clinically significant despite appropriate adjuvant treatment with current standards of care. This has driven investigation into novel treatment approaches, including the addition of cyclin-dependent kinase 4 and 6 inhibitors to adjuvant endocrine therapy. Cyclin-dependent kinase 4 and 6 inhibition has demonstrated significant efficacy in patients with high-risk, HR-positive, HER2-negative, nonmetastatic breast cancer and now offers a new strategy to greatly improve outcomes in this difficult to treat patient population.; LAY SUMMARY: Hormone receptor (HR)-positive, HER2-negative early breast cancers are highly diverse and need to be managed differently for individual patients. The use of adjuvant endocrine therapy and chemotherapy should be driven by a patient's risk for recurrence, preferences, and risk for side effects. Patients with high-risk tumors have a persistently elevated risk for recurrence despite current standards of care. Emerging cyclin-dependent kinase 4 and 6 inhibitors are highly effective when added to endocrine therapy in high-risk, HR-positive early breast cancer and have the potential to improve patient outcomes in this difficult to treat patient population.

Abstract OT2-02-01: Utilization of patient reported outcomes generated by electronic medical record and smart pill bottles with follow up telehealth encounters to improve adherence to adjuvant endocrine therapy in breast cancer patients

Abstract Background: The use of adjuvant endocrine therapy (ET) in the form of tamoxifen (TAM) or an aromatase inhibitor (AI) for up to 10 years is the standard of care (SOC) for women with hormone receptor positive (HR+) breast cancer (BC). These agents can reduce recurrence by 30-50% and reduce mortality by approximately 1/3 irrespective of the use of chemotherapy (CT). Many women have difficulty with long-term compliance and persistence due to side effects and may ultimately self-discontinue. In the EBCTCG meta-analysis, evaluating 20 separate trials of adjuvant TAM for 5 years versus no adjuvant TAM, there was an estimated 80% adherence. Other BC trials have demonstrated lower adherence to TAM, dropping to 50% by years 4-5. Additionally, within the first year, discontinuation rates have been reported to be as high as 20-23%. In this investigator-initiated clinical trial we aim to evaluate the utility of one of two interventions a) serial electronic medical record (EPIC) generated patient (pt) reported outcomes (PRO)and pt surveys, OR b) a smart pill bottle, in increasing adherence to adjuvant ET over a 12-month interval during the first 4 years of adjuvant ET. The study also includes research-specific Telehealth (TH) visits when indicated in response to reports of increased toxicity or non-compliance. Methods: This is the Phase II, randomized, open-label, three-arm, multi-site study that will randomize 285 pts ≥18 years of age with stage 0-III HR+ BC in a 1:1:1 fashion with 95 patients in each arm. Arm A includes standard of care (SOC) quarterly visits (in-person or TH) with the treating provider during 12 months follow-up. Arm B is SOC quarterly visits during 12 months follow up, 18 electronic surveys every 3 weeks in between the SOC visits. Arm C is SOC quarterly visits during for 12 months follow up and use of electronic smart pill bottle with daily reminders to take ET. Primary Objective is to evaluate if the intervention of utilization of automated PROs and follow up TH encounters or the utilization of Smart Pill Bottles and follow up TH encounters can improve patient adherence with adjuvant ET within 12 months of study participation during the first 4 years of ET. The secondary objective is to evaluate if these interventions can improve quality of life and decrease side effects of adjuvant ET. The trial is open with 119 patients enrolled at the time of this abstract submission. ClinicalTrials.gov Identifier: NCT04054557 Citation Format: Utilization of patient reported outcomes generated by electronic medical record and smart pill bottles with follow up telehealth encounters to improve adherence to adjuvant endocrine therapy in breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-02-01.

The role of the clinical pharmacist in guiding adjuvant hormonal therapy in patients with breast cancer.

Breast cancer is the most prevalent type of cancer among women, affecting about 2.1 million worldwide and is responsible for the highest number of cancer-related deaths among women. Approximately 80% of breast cancers express on the surface of hormone receptor cells, such as progesterone and estrogen. In these cases, Adjuvant Hormonal Therapy (AHT) is indicated for a period of five to ten years and consists of taking a daily oral pill. The two most used drugs in AHT are tamoxifen and Aromatase Inhibitors. One of the issues most faced by individuals who are subjected to long periods of treatment is the lack of medication adherence and, consequently, therapeutic inefficiency. It is believed that the monitoring by the pharmacist can contribute to the reduction of errors inherent to the medication, making the treatment more effective and improving the patient's quality of life. The present study aimed to know the perception of patients who live with breast cancer and who do AHT in relation to the educational performance of the clinical pharmacist. This is a qualitative, descriptive and exploratory study, carried out from March to October 2020, with 15 women undergoing treatment at the oncology unit of a tertiary-care hospital in south of Brazil. The data were obtained through a semi-structured interview using an instrument composed of two parts, one referring to the characterization of the participants and the other with the guiding question of the research: "How do you perceive the role of the pharmacist in relation to the guidelines for the use of adjuvant hormonal therapy?". The method of theoretical saturation was used to perform the sample closure and the thematic analysis was used to analyze the data. The participants were between 32 and 74 years old, seven were on tamoxifen therapy and eight on anastrozole, ten were on the first year of treatment, two on the second and three on the third year. The themes that emerged were: pharmacist-patient interaction as a safety factor in hormone therapy; role of the pharmacist in the development of strategies for self-management of the patients during hormone therapy; and, challenges for the pharmacist in relation to hormone therapy through continued guidance. It was evident that the pharmacist's educational action encouraged the participants to carry out the treatment in a more confident and assertive manner according to their particularities and beliefs.

Both "Vitamin L for Life" and "One Milligram of Satan": A Multi-Perspective Qualitative Exploration of Adjuvant Endocrine Therapy Use after Breast Cancer.

Adjuvant endocrine therapy (AET) is recommended after hormone receptor-positive breast cancer to reduce risk of recurrence, but adherence is sub-optimal in many women. Behavioral interventions have been ineffective in improving adherence rates to AET. This qualitative descriptive study investigates factors that support women in AET use and suggestions for interventions to improve AET use and management. Interviews with women who persisted with AET (n = 23), women who discontinued AET (n = 15), and healthcare providers (HCPs; oncologists, oncology residents, and pharmacists; n = 9) were conducted, transcribed, and described using thematic analysis. Data collection stopped once saturation occurred (i.e., no new codes or themes emerged during interviews). Two researchers created codes and developed themes in an iterative process; a third researcher verified the representativeness of final themes. This study was approved by the Health Research Ethics Board of Alberta (ID: HREBA.CC-17-0513). Women who persisted described being prepared for side effects and having self-management strategies, strong rationale for AET use, supportive HCPs, and available resources as relevant factors. Women who discontinued described feeling overwhelmed by side effects, information needs, drawbacks of AET, helpful/unhelpful experiences with HCPs, and contextual factors as relevant to their discontinuation. HCPs described health system-related and patient-related barriers, side effect management, and patient-provider interactions as relevant to supporting AET use. The considerable overlap in themes among the three groups suggests broad recognition of salient factors relevant to AET use and that associated strategies to improve use may be acceptable to patients and providers alike. Factors supporting AET use could include the following: education (which may be necessary but insufficient), developing a strong personal rationale for use, being prepared for side effects, having side effect management strategies, reciprocal communication between patients and HCPs, and accessible resources.

Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer.

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.

Abstract PS9-26: Pelvic floor disorders and quality of life among breast cancer survivors

Abstract Introduction: Approximately 25% of women in the United States experience a symptomatic pelvic floor disorder such as urinary incontinence, pelvic organ prolapse, anal incontinence, and sexual dysfunction. Aspects associated with breast cancer treatment such a chemotherapy, oophorectomy/ovarian suppression, and endocrine therapy may predispose women to pelvic floor disorders. The prevalence of pelvic floor disorders among breast cancer survivors has been cited at 18%, but unpublished cross-sectional data suggests the prevalence may be much higher. In this study, 8.5% - 11.5% of participants experienced prolapse symptoms, 56.2% experienced anal incontinence symptoms, and 43.3% - 51.2% experience urinary incontinence symptoms. While pelvic floor dysfunction is associated with lower quality of life, it is unknown if breast cancer survivors with pelvic floor disorders experience decreased quality of life. The primary aim of this study was to assess if breast cancer survivors with pelvic floor disorders experience lower quality of life. Methods: Women 18 years or older who were previously treated for breast cancer and who were enrolled in a cancer research registry were invited to complete the Pelvic Floor Distress Inventory 20 (PFDI-20), the Female Sexual Function Index (FSFI), and the Short Form 12. Demographic and clinical data were abstracted from the research registry. A participant was considered eligible for the study if she had enrolled in the cancer registry and completed all core questions (i.e. demographics, cancer diagnosis, cancer treatment, endocrine therapy, medical/surgical history, and risk factors). As per standard PFDI-20 reporting, presence of a symptom was defined as answering a 1, 2, 3, or 4 to a question, while presence of a bothersome symptom was defined as answering a 2, 3, or 4. A score of 26 or less on the FSFI was considered indicative of sexual dysfunction. Results: A total of 634 women were considered eligible for enrollment in the study. 445 were able to be contacted, and 410 women agreed to participate in the study. Of those, 303 returned the PFDI-20 questionnaire and FSFI questionnaire, and 264 returned the SF-12 for response rates of 74% and 64%, respectively. Overall, higher scores on the PFDI-20 was associated with lower scores on both the physical and mental components of the SF-12 (Rho = -0.298, p = <.0001; Rho = -0.202, p = .0009, respectively). When the PFDI-20 was broken into subscores, higher POPDI scores (prolapse) was associated with lower physical component scores but not lower mental component scores. Higher CRADI scores (anal incontinence) and UDI-6 scores (urinary incontinence) were associated with lower physical and mental scores. Neither overall FSFI scores or subset domain scores were associated with lower physical or mental component scores of the SF-12. In linear regression analysis, PFDI summary score remained statistically significantly related to both mental and physical component subscores after controlling for age, race, stage of breast cancer, time since diagnosis, and use of adjuvant endocrine therapy. FSFI scores were related to age and endocrine therapy use, but were not related to SF-12 scores. Conclusion: Among a subset of breast cancer survivors, pelvic disorders including pelvic organ prolapse, urinary incontinence, and anal incontinence exist, and these disorders are associated with decreased mental wellbeing. All pelvic floor disorders except pelvic organ prolapse were associated with decreased physical wellbeing. None of the domains of female sexual dysfunction were associated with decreased physical or mental wellbeing among breast cancer survivors. A subset of breast cancer survivors experiences bothersome pelvic floor disorders and thus screening for these disorders can increase referrals to appropriate treatment and complement survivorship care to enhance overall quality of life. Citation Format: Jon F Pennycuff, Felice Yang, Tania Lobo, Caroline Jackman, Colleen McGuire, Ami Chitalia, Kristi Graves. Pelvic floor disorders and quality of life among breast cancer survivors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-26.

Use of Adjuvant Endocrine Therapy Among Post-Menopausal Breast Cancer Patients in Malaysia.

ContextGlobally, breast cancer is the most common cancer affecting women, and adjuvant endocrine therapy (AET) is part of its treatment modality, which improves patients’ outcome. However, there are concerns on side effects related to its use, which may affect treatment adherence.PurposeThis study was conducted to explore attitude and practice on using AET among breast cancer patients in Malaysia.Patients and MethodsPostmenopausal breast cancer patients on at least 3 months of AET attending the outpatient oncology clinic at a tertiary care hospital were interviewed. Patients underwent in-depth interviews exploring their attitude and practices while on AET using a semi-structured interview guide. The interviews were transcribed verbatim and analyzed using thematic analysis.ResultsThere were four main themes for attitude toward the use of AET: 1) benefits of using AET, 2) concerns on taking AET, 3) beliefs on alternative treatment, and 4) beliefs toward the doctor. For practice, six themes were obtained: 1) correct use of AET, 2) appointment adherence, 3) information-seeking behavior, 4) counseling services obtained, 5) experienced side effects of AET, and 6) usage of complementary and alternative medicines.ConclusionSeveral themes concerning attitude and practice of breast cancer patients receiving AET were identified, which may be addressed during treatment consultations in clinical practice.

Ductal carcinoma in situ in patients younger than 30years: differences in adjuvant endocrine therapy and outcomes.

To use the National Cancer Database to assess treatment patterns in very young women with ductal carcinoma in situ (DCIS) given their propensity for higher risk features and increased risk of recurrence. We used the NCDB to identify female patients who underwent surgery for a first cancer diagnosis of DCIS within three different age groups: ≤30, 31-50, and >50. Demographic information, tumor characteristics, and initial treatment patterns were characterized and compared. Univariable and multivariable logistic regression of individuals with hormone-receptor-positive disease who underwent breast-conserving surgery (BCS) was conducted to assess for group differences in adjuvant endocrine therapy utilization. Survival analysis was conducted via Kaplan-Meier method and Cox regression. We identified 236,832 patients meeting inclusion criteria. Individuals in the youngest group were more likely to be a minority, had better Charlson-Deyo scores, lived further from their treatment facility, and were less often insured. This group also had more unfavorable tumor features and were more likely to undergo bilateral mastectomy. In subgroup analysis of patients with hormone-receptor-positive disease who underwent BCS, the youngest group was significantly less likely to have received endocrine therapy. There was also a trend toward worse overall survival in the youngest group. We report differences in demographics, tumor characteristics, and treatment of very young women with DCIS. Given the known reduction in recurrence with use of adjuvant endocrine therapy, there may be room for increasing therapy rates or otherwise altering guidelines for treatment of young women with hormone-receptor-positive DCIS who undergo BCS.

Improving Adherence to Adjuvant Hormonal Therapy Among Disadvantaged Women Diagnosed with Breast Cancer in South Carolina: Proposal for a Multimethod Study.

BackgroundCurrent clinical guidelines recommend that hormone receptor–positive breast cancer survivors take adjuvant hormonal therapy (AHT) for 5 to 10 years, following the end of definitive treatment. However, fewer than half of patients adhere to the guidelines, and suboptimal adherence to AHT is associated with an increased risk of breast cancer mortality. Research has extensively documented sociodemographic and disease-specific factors associated with adherence to AHT, but very little evidence exists on behavioral factors (eg, knowledge, patient-provider communication) that can be modified and targeted by interventions.ObjectiveThe goal of this study is to develop and test a theory-based, multilevel intervention to improve adherence to AHT among breast cancer survivors from racially and socioeconomically disadvantaged backgrounds (eg, Medicaid-insured). The specific aims are to (1) explore multilevel (eg, patient, health care system) factors that influence adherence to AHT; (2) develop a theory-based, multilevel intervention to improve adherence to AHT; and (3) pilot test and evaluate the intervention developed in Aim 2.MethodsFor Aim 1, we will recruit breast cancer survivors and health care professionals to participate in semistructured interviews to gain their perspectives about barriers and facilitators to AHT use. We will conduct a directed content analysis of the Aim 1 qualitative interview data. For Aim 2, we will integrate Aim 1 findings and current literature into the design of a multilevel intervention using an Intervention Mapping approach. For Aim 3, we will recruit Medicaid-insured breast cancer survivors to assess the feasibility of the pilot intervention.ResultsFrom May 2016 to July 2018, we completed interviews with 19 breast cancer survivors and 23 health care professionals in South Carolina. We will conduct a directed content analysis of the qualitative interview data. Results from this analysis will be used, in combination with current literature, to design (Aim 2) and pilot test a theory-based multilevel intervention (Aim 3) in Summer 2021. Results of the pilot are expected for Fall 2021.ConclusionsThis study will provide a deeper understanding of how to improve adherence to AHT, using a novel and multilevel approach, among socioeconomically disadvantaged breast cancer survivors who often experience disproportionate breast cancer mortality.International Registered Report Identifier (IRRID)DERR1-10.2196/17742