Initiation Of Adjuvant Endocrine Therapy Research Articles

Association between PIK3CA mutations and disease-free survival in patients with HR+, HER2- tumors treated with adjuvant hormonal therapy: A real-world study in Croatia.

e12512 Background: Disease recurrence of early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one-quarter of patients with early disease will present with the disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene have a high prevalence of 30% to 40% in HR+/HER2- advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine this association and impact of PIK3CA mutation status on disease free survival (DFS) in HR+/ HER2- early breast cancer patients. Methods: We conducted a multicentric, retrospective cohort study in five Croatian institutions from July 2020 to December 2021. Study included initially early HR+/HER2- breast cancer patients who have been diagnosed with disease recurrence during adjuvant hormonal treatment or within first six years of follow up. The Cobas PIK3CA Mutation Testing Kit was used for real-time PCR-based amplification and mutation detection on the Cobas z 480 analyzer. We have analyzed differences in DFS from initiation of adjuvant endocrine therapy, using Cox, proportional hazard regression. Results: There was total of 186 patients, out of which 40.9% tested positive for the PIK3CA mutation. Primary and adjuvant treatment and in particular adjuvant endocrine treatment was similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with positive PIK3CA status and with H1047 PIK3CA mutation had significantly lower hazard for disease recurrence in comparison to patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; HR 6.52; 95% CI 1.15; 36.95; p = 0.034 respectively; false discovery rate, FDR < 10%) and higher odds for late recurrence (p = 0.001, FDR < 5%). Conclusions: This study highlights the potential impact of PIK3CA mutations on disease recurrence during/following adjuvant endocrine treatment and by that potentially opens the door for further investigation of possibly more personalized treatment strategies.

Evaluation of recurrence rate in Canadian patients with stage II/III HR+/HER2- early breast cancer in the real-world setting.

e23303 Background: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances. Treatment for this subtype encompasses a multifaceted approach with a curative intent. This real-world evidence study aims to comprehensively analyze the clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer, focusing on recurrence rates after initiation of adjuvant endocrine therapy to identify opportunities for enhancing patient care. Methods: This is a retrospective, longitudinal cohort study involving 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment), with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1996, and May 31st, 2022. We evaluated disease recurrence rates, time to recurrence, and overall survival (OS). Furthermore, the study explored duration of endocrine therapy (ET) in the adjuvant setting. Results: 409 patients received adjuvant ET representing 75.6% of the total cohort, emphasizing the role of ET as standard of care for adjuvant treatment in this patient population. The median duration of adjuvant ET was 4.5 years. In the overall adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the overall patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years. Conclusions: This study marks a pioneering real-world analysis utilizing pan-Canadian EHR data, demonstrating increasing recurrence rates over time in HR+/HER2- early breast cancer. It highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despites adjuvant treatment with ET alone. This indicates the need for more efficacious and tolerable treatment options to reduce short- and long-term recurrence and to prolong survival, not only in the higher risk patient population, but in the overall HR+/HER2- breast cancer patients at increased risk of recurrence.

A randomized trial of the impact of symptom monitoring using an electronic patient-reported outcome app on health-related quality of life in postmenopausal breast cancer patients receiving adjuvant endocrine therapy.

Electronic patient-reported outcomes (ePRO) monitoring is a useful communication tool for cancer patients and healthcare providers. In this study, we examined the impact of symptom monitoring using an ePRO app on quality of life (QoL) in postmenopausal breast cancer patients receiving adjuvant endocrine therapy. The free app "Welby My Carte ONC" was used in the study. Patients with breast cancer starting adjuvant endocrine therapy were randomly assigned in a 1:1 ratio to ePRO monitoring (ONC) and control groups. The ONC group reported five symptoms extracted from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) (insomnia, joint pain, headache, anxiety, and hot flashes) weekly for 3months through the app. Reported symptoms were shared with medical personnel. When serious symptoms were reported, these personnel ascertained the patient's health status and provided advice over the phone. The primary endpoint was QoL measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 3months from enrollment. Differences between groups were tested using analysis of covariance. The study included 125 subjects with mean age of 64years in the ONC group (n = 61) and 63years in the control group (n = 64). In the ONC group, the response rate to PRO-CTCAE was about 70% or higher until week 10. The item missing rate was 0. The ONC group reported more symptoms related to joint pain and insomnia. The difference in FACT-B total score between the groups was -1.55 (95% confidence interval: -5.91, 2.81), indicating no significant difference. Symptom monitoring using ePRO early after initiation of adjuvant endocrine therapy after surgery did not improve QoL of breast cancer patients.

Are breast cancer patients with suboptimal adherence to cardiovascular treatment more likely to discontinue adjuvant endocrine therapy? Competing risk survival analysis in a nationwide cohort of postmenopausal women

BackgroundHigh rates of discontinuation undermine the effectiveness of adjuvant endocrine therapy (AET) among hormone-receptive breast cancer patients. Patient prognosis also relies on the successful management of cardiovascular risk, which affects a high proportion of postmenopausal women. As with AET, adherence with cardiovascular drugs is suboptimal. We examined whether patient adherence with cardiovascular drugs was associated with the rate of AET discontinuation in a French nationwide claims database linked with hospitalisation data.MethodsWe identified postmenopausal women starting AET between 01/01/2016 and 31/12/2020 and taking at least two drugs for the primary prevention of cardiovascular disease (antihypertensive drugs, lipid-lowering drugs and platelet aggregation inhibitors) before AET initiation. Adherence was assessed for each drug class by computing the proportion of days covered. Women were categorised as fully adherent, partially adherent or fully non-adherent with their cardiovascular drug regimen based on whether they adhered with all, part or none of their drugs. AET discontinuation was defined as a 90-day gap in AET availability. Time to AET discontinuation according to levels of cardiovascular drug adherence was estimated using cumulative incidence curves, accounting for the competing risks of death and cancer recurrence. Multivariate cause-specific Cox regressions and Fine-and-Gray regressions were used to assess the relative hazards of AET discontinuation.ResultsIn total, 32,075 women fit the inclusion criteria. Women who were fully adherent with their cardiovascular drugs had the lowest cumulative incidence of AET discontinuation at any point over the 5-year follow-up period. At 5 years, 40.2% of fully non-adherent women had discontinued AET compared with 33.5% of partially adherent women and 28.8% of fully adherent women. Both partial adherence and full non-adherence with cardiovascular drugs were predictors of AET discontinuation in the two models (cause-specific hazard ratios 1.16 [95% CI 1.10–1.22] and 1.49 [95% CI 1.39–1.58]; subdistribution hazard ratios 1.15 [95% CI 1.10–1.21] and 1.47 [95% CI 1.38–1.57]).ConclusionClinicians should be aware that patients who do not adhere with their entire cardiovascular drug regimen are also more likely to discontinue AET. This stresses the importance of integrated care, as suboptimal adherence with both treatment components poses a threat to achieving ideal patient outcomes.

Adjuvant endocrine therapy adherence changes among patients after a virtual behavioral intervention.

12131 Background: Adjuvant endocrine therapy (AET) reduces risk of breast cancer (BC) recurrence; however, adherence is suboptimal and interventions are needed. We conducted a randomized controlled trial of a novel telehealth intervention (STRIDE), which led to improvements in symptom distress, coping, quality of life, and mood. Here we examine which patients had improved adherence following STRIDE by exploring characteristics that may moderate intervention effects. Methods: Women (n = 100) with nonmetastatic BC who reported AET-related distress were randomized to receive STRIDE or a medication monitoring control (MM) between 10/2019-6/2021. STRIDE consisted of six weekly, small-group cognitive behavioral telehealth sessions to enhance symptom management and adherence. All patients stored their AET in electronic MEMS Caps bottles to measure objective adherence. We collected patient characteristics (i.e., months on AET, education) and self-report measures at baseline. Patients completed the Medication Adherence Report Scale (MARS-5) and Cancer Therapy Satisfaction Questionnaire to report adherence behaviors (e.g., “I alter the dose”) and AET perceptions (e.g., convenience, expectations, satisfaction), respectively. We conducted hierarchical linear modeling to test moderators of intervention effects on adherence rates (MEMS Caps) across months 1-3, controlling for ovarian suppression receipt and baseline distress due to group differences/stratification. We report the ‘time X group X moderator’ effects here. Results: Among participants reporting greater difficulty (lower MARS-5) with their AET regimen at baseline, STRIDE participants had greater improvement in adherence over time compared to MM participants ( b= -13.80, SE = 4.56, p < .01). Greater expectations of therapeutic benefit predicted improvements in adherence for STRIDE versus MM participants ( b= 0.25 SE = 0.10, p = .01). Additionally, among participants who reported greater convenience of taking AET ( b= 0.33 SE = 0.17, p = .06), had lower education levels ( b= -4.02, SE = 2.12, p = .06), and had been taking AET for fewer months ( b= -0.43 SE = 0.25, p = .09), STRIDE participants showed adherence increases that approached significance. Other moderators were not significant. Conclusions: STRIDE demonstrated effects of a behavioral intervention on AET adherence. Participants reporting greater difficulty adhering to their AET regimen and who expected more benefit showed improved adherence following STRIDE. Gains in adherence from STRIDE were also more pronounced among those who reported that AET was convenient, started the medication more recently, and had lower levels of education. Patient-level and socioeconomic factors influence response to AET adherence interventions. Clinicians may play a key role in addressing modifiable targets at AET initiation (e.g., logistical barriers, perceived benefit) to enhance adherence. Clinical trial information: NCT03837496 .

Abstract P4-03-18: Group-based trajectories of endocrine therapy adherence and risk of recurrence in a Danish premenopausal breast cancer cohort

Abstract Background: Adjuvant endocrine therapy (AET) approximately halves the risk of recurrence among the two-thirds of premenopausal breast cancer patients whose tumors overexpress the estrogen receptor (ER+). AET is recommended for a minimum five-year duration, but many premenopausal women discontinue AET prematurely. Adherence to AET is dynamic and influenced by many behavioral, societal, clinical, and genetic factors. Describing longitudinal patterns of AET adherence is an important first step towards identifying patients at highest risk of nonadherence–-and therefore recurrence–-who may benefit from adherence-enhancing interventions. We used group-based trajectory models to (1) describe AET adherence patterns, and (2) estimate associations between AET adherence and breast cancer recurrence in a Danish premenopausal, ER+ breast cancer cohort. Methods: Our cohort included 4,487 premenopausal women diagnosed with ER+, stage I–III primary breast cancer registered in the Danish Breast Cancer Group (DBCG) clinical database and treated with AET (2002–2011). We followed all patients from initiation of AET until recurrence, mortality, 10 years of follow-up, another primary malignancy, or the end of available follow-up. We excluded individuals with less than 1.5 years of follow-up as breast cancer recurrences that occur in this time are unlikely to be related to AET. At semi-annual follow-up visits, women were registered as having received (or not) a six-month supply of AET. We created daily indicators to determine if a woman had at least 80% of days covered by an AET fill within each six-month period for the first 4.5 years following AET initiation, yielding 9 variables indicating time-varying adherence. We used these indicators to characterize adherence trajectory groups. We defined recurrence as local, regional or distant metastases or contralateral breast cancer registered in the DBCG using follow-up data through 2017. We fit Cox regression models, adjusted for age and clinical factors, to estimate the association between adherence trajectory groups and recurrence. Results: We identified distinct trajectory groups in the cohort (Table 1)—high adherence (69%), slow decline (23%), and quick decline (8%). Women with quick decline were more likely to have stage I disease, have no positive lymph nodes, to not be treated with chemotherapy, and to have lumpectomy instead of mastectomy when compared to women with high adherence. Compared with high adherence women, the estimated rate of breast cancer recurrence was higher among those with slow decline (HR=1.12, 95%CI=1.04–1.21) and those with quick decline (HR=1.38, 95%CI=1.22–1.56). Conclusions: Group-trajectory modeling facilitated empirical description of AET adherence patterns in a premenopausal breast cancer cohort. As expected, women who more rapidly became AET-nonadherent were at increased risk of breast cancer recurrence compared with those who remained adherent. Future analyses will explore the contribution of specific socioeconomic, genetic, and clinical factors to AET adherence patterns, which will inform the design of interventions to improve AET adherence and reduce recurrence risk in breast cancer patients. Table 1. Trajectory group and the observed proportion of individuals adherent to their adjuvant endocrine therapy (AET) over 4.5 years of follow-up Citation Format: Kirsten M. Woolpert, Julie A. Schmidt, Thomas P. Ahern, Timothy L. Lash, Lindsay J. Collin, Bent Ejlertsen, Deirdre Cronin-Fenton. Group-based trajectories of endocrine therapy adherence and risk of recurrence in a Danish premenopausal breast cancer cohort [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 P4-03-18.

Abstract P3-03-12: Risk of recurrence with adjuvant endocrine therapy in real world patients with hormone receptor positive/human epidermal growth factor receptor-negative early breast cancer: a US database analysis

Abstract Background The recommended 5-10 years of adjuvant endocrine therapy (ET) as standard of care has improved outcomes in patients with HR+/HER2− early breast cancer (EBC); however, risk of recurrence persists. The monarchE study demonstrated improvement in invasive disease-free survival (iDFS) with abemaciclib in node-positive, high-risk EBC, the majority of which were stage III (Johnston SRD, et al. J Clin Oncol. 2021;38:3987); however, monarchE’s relatively short follow-up time to date only allowed for observation of early recurrences—longer follow-up is needed to evaluate late recurrences. Risk of recurrence is a concern for patients with all stages of EBC (Pan H, et al. N Engl J Med. 2017;377:1836). We assessed the risk of recurrence in a real-world setting among patients with stage II-III HR+/HER2− EBC after initiation of adjuvant ET. Methods This was a retrospective analysis of ConcertAI’s deidentified electronic medical records data set among patients treated from January 1, 1995, to April 30, 2021. The cohort included stage II-III patients with HR+/HER2− EBC who underwent surgery and initiated adjuvant ET (if IIIB or IIIC, confirmation was required on residual tumor status). Patients were from academic and community oncology clinics across the US. Data were missing from the database for some variables; thus, percentages may not add up to 100%. iDFS was assessed to determine the risk of disease recurrence, death, or second primary tumor and was defined as the time interval between start of ET and first iDFS event. Kaplan-Meier methods were used to estimate cumulative probabilities of experiencing an iDFS event at 5 and 10 years from the start of ET. Results A total of 3133 patients (98.8% female) with stage II-III HR+/HER2− EBC were included in the analysis. The median follow-up time was 68.1 months. The median age was 59 years; 22.2% of female patients were pre/perimenopausal and 44.7% were postmenopausal; 80.9% of all patients had stage II disease, while 19.1% had stage III disease. In total, 42.1% and 3.7% of those with stage II and III disease had no nodal involvement, respectively. Overall, 51.2% of patients did not receive radiotherapy, and 59.5% of patients did not receive (neo)adjuvant chemotherapy. In the total sample, the 5- and 10-year risk of an iDFS event was 26.1% and 45.0%, respectively. In patients with stage II disease, the 5- and 10-year risks were 22.7% and 40.5%, respectively, and 40.4% and 62.9% among stage III. Conclusions These real-world data demonstrate that the risk of recurrence with adjuvant ET, particularly in those with stage II EBC, is higher than reported in many randomized controlled trials. Importantly, our data show that, in the real-world setting, the stage II population represents a significant proportion of patients (nearly 4 times more than stage III). These findings confirm and underscore the clear unmet need in this population and highlight the need for improved treatment options in this broader EBC population. The NATALEE study will investigate ribociclib + ET in a broad population of patients including stage II and stage III HR+/HER2− EBC with high-risk features, regardless of nodal status. Citation Format: Joyce O’Shaughnessy, Denise Yardley, Lowell Hart, Pedram Razavi, Stephanie L. Graff, Jenifer Wogen, Courtney McDermott, Pierre-Alexandre Dionne, Sina Haftchenary, Purnima Pathak, Sara Tolaney. Risk of recurrence with adjuvant endocrine therapy in real world patients with hormone receptor positive/human epidermal growth factor receptor-negative early breast cancer: a US 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 P3-03-12.

Use of endocrine therapy for estrogen receptor-positive breast cancer among American Indians and Alaska natives.

American Indian/Alaska Native (AI/AN) women with estrogen receptor-positive (ER +) breast cancer have higher mortality compared to non-Hispanic whites (NHW). The purpose of this study is to compare rates of initiation of endocrine therapy (ET) between AI/AN and NHW and further determine survival outcomes for ER + breast cancer. We used the National Cancer Database to identify patients diagnosed with ER + breast cancer, stage I-III, between 2004 and 2017. Multivariable logistic regression was performed to determine factors associated with initiation of adjuvant ET. Overall survival was estimated using the Kaplan-Meier analysis and Cox proportional hazards modeling. We identified a total of 771,619 patients (AI/AN, n = 2473; NHW, n = 769,146). Compared to NHW, AI/AN patients were more likely to live in rural areas, be younger, and have tumors that were higher grade, node positive, and larger. Initiation of adjuvant ET was high in both groups and not significantly different between AI/AN and NHW. Independent predictors of ET initiation included rural location, age, higher tumor grade, node-positive disease, larger tumor size, and progesterone receptor-positive status. Initiation of ET was significantly associated with improved overall survival among all patients. Overall survival was significantly worse among the AI/AN population. AI/AN race was significantly and independently associated with worse overall survival after diagnosis of ER + breast cancer. We did not find a significant difference in the initiation of adjuvant ET between AI/AN and NHW. Exact reasons why AI/AN women with ER + breast cancer have higher mortality rates remain elusive but are probably multifactorial.

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.

An examination of health care utilization during the COVID-19 pandemic among women with early-stage hormone receptor-positive breast cancer

BackgroundWomen undergoing treatment for breast cancer require frequent clinic visits for maintenance of therapy. With COVID-19 causing health care disruptions, it is important to learn about how this population’s access to health care has changed. This study compares self-reported health care utilization and changes in factors related to health care access among women treated at a cancer center in the mid-South US before and during the pandemic.MethodsParticipants (N = 306) part of a longitudinal study to improve adjuvant endocrine therapy (AET) adherence completed pre-intervention baseline surveys about their health care utilization prior to AET initiation. Questions about the impact of COVID-19 were added after the pandemic started assessing financial loss and factors related to care. Participants were categorized into three time periods based on the survey completion date: (1) pre-COVID (December 2018 to March 2020), (2) early COVID (April 2020 – December 2020), and later COVID (January 2021 to June 2021). Negative binomial regression analyses used to compare health care utilization at different phases of the pandemic controlling for patient characteristics.ResultsAdjusted analyses indicated office visits declined from pre-COVID, with an adjusted average of 17.7 visits, to 12.1 visits during the early COVID period (p = 0.01) and 9.9 visits during the later COVID period (p < 0.01). Hospitalizations declined from an adjusted average 0.45 admissions during early COVID to 0.21 during later COVID, after vaccines became available (p = 0.05). Among COVID period participants, the proportion reporting changes/gaps in health insurance coverage increased from 9.5% participants during early-COVID to 14.8% in the later-COVID period (p = 0.05). The proportion reporting financial loss due to the pandemic was similar during both COVID periods (34.3% early- and 37.7% later-COVID, p = 0.72). The proportion of participants reporting delaying care or refilling prescriptions decreased from 15.2% in early-COVID to 4.9% in the later-COVID period (p = 0.04).ConclusionCOVID-19 caused disruptions to routine health care for women with breast cancer. Patients reported having fewer office visits at the start of the pandemic that continued to decrease even after vaccines were available. Fewer patients reported delaying in-person care as the pandemic progressed.

Abstract 15290: Hypertension in Black and White Breast Cancer Survivors: NCT02992730

Introduction: Hypertension (HTN) may increase the risk of cardiovascular (CV) events among breast cancer (BC) survivors, particularly in Black women. Limited information is available about factors associated with the presence of HTN at the time of BC diagnosis among Black versus White women. Methods: In a secondary analysis of data from a longitudinal cohort of Black and White women diagnosed with hormone receptor positive (HR+) BC, post initiation of adjuvant endocrine therapy (AET), medical records were used to determine HTN status and other clinical factors (stage, AET type, CV comorbidities). In the same cohort, psychosocial and quality of life data were collected via surveys. Logistic regression models evaluated factors associated with increased odds of HTN at baseline. Results: Women with BC (n=243) were mostly White (66.7%), mean (SD) aged 61.6 (10.9) years, with borderline obesity (BMI: 29.9 (6.6)). Comorbidities and tamoxifen use were reported by 40.7% and 28.4% of women, respectively. HTN was present in 140 (57.6%) women (38% Black, 62% White). Relative to their White counterparts, Black women with HTN were significantly younger, (61.5 vs. 67.5 years of age, p&lt; 0.01) more overweight (BMI, 32.8 vs 29.3, p =&lt;.01), received chemotherapy more frequently (44.4% vs 22.1%, p &lt;0.01), were more likely to have experienced discrimination (35.2% vs 7%, p &lt;0.01) and more often to possess CV comorbidities (61.1% vs 37.2%, p &lt;0.01). Multivariable logistic regression showed that the odds of having HTN increased significantly with age by 10% per year (OR: 1.10, 95% CI: 1.06-1.14; p&lt;.0001), with Black women having a 2-fold greater risk of having HTN (OR: 2.02, 1.02-4.03; p=.044) than White women. Additionally, a 1-unit increase in BMI was associated with 6% higher odds of having HTN (OR: 1.06, 95% CI: 1.03-1.11; p=0.0390) while Tamoxifen use, presence of CV comorbidities and worse social well-being were not associated with more frequent HTN in women with BC. Conclusions: A high proportion of women diagnosed with HR+ BC have HTN with Black vs White women experiencing more HTN. These results raise the possibility that Black women with BC may benefit from focused HTN management strategies to reduce potential CV events.

Factors influencing the initiation of adjuvant endocrine therapy in patients with estrogen receptor-positive ductal carcinoma in situ: a single institution experience

PurposeThis study evaluates whether race, socioeconomic status, insurance type, oncological provider type, and prior cancer treatment are associated with the suggestion and acceptance of hormonal therapy in patients with estrogen receptor (ER)-positive Ductal carcinoma in situ (DCIS). This study also assesses whether disparities exist pertaining to prescription of such medications.MethodsThis single-center retrospective study included 111 patients diagnosed with DCIS between 2020 and 2021. Data collected included race, type of insurance, prescribing providers, and socioeconomic status. We used zip codes to identify the poverty levels in these areas as published in the United States Census Bureau and stratified the patients into quartiles accordingly. Chi-Square statistics were used to calculate significance levels.ResultsThere was no significant correlation between the intake of hormonal therapy and race (p = 0.60), insurance (p = 0.50), socioeconomic (p = 0.58), or providers (p = 0.99). 79.3% of women were offered endocrine therapy. Of those who were offered endocrine therapy, 70.8% accepted. Of patients not on hormonal therapy, 45.8% were not recommended the medications by their provider, and 54.2% declined treatment when offered.ConclusionIn this study, patients’ demographics and providers were not associated with adjuvant hormonal therapy initiation in DCIS. Our results show that abstaining from endocrine therapy in DCIS patients is both due to lack of provider recommendation and patient rejection of these medications. The wide variation in hormonal therapy treatment among ER-positive DCIS patients suggests a need for improved provider-patient communication regarding the risks and benefits of endocrine therapy in order to ensure a shared decision-making process.

Racial Differences in Patient-Reported Symptoms and Adherence to Adjuvant Endocrine Therapy Among Women With Early-Stage, Hormone Receptor–Positive Breast Cancer

Adjuvant endocrine therapy (AET) reduces breast cancer recurrence, but symptom burden is a key barrier to adherence. Black women have lower AET adherence and worse health outcomes than White women. To investigate the association between symptom burden and AET adherence differences by race. A retrospective cohort study using electronic health records with patient-reported data from a large cancer center in the US. Patients included Black and White women initiating AET therapy for early-stage breast cancer from August 2007 to December 2015 who were followed for 1 year from AET initiation. Sixty symptoms classified into 7 physical and 2 psychological symptom clusters were evaluated. For each cluster, the number of symptoms with moderate severity at baseline, and symptoms with 3-point or greater increases during AET were counted. Adherence was measured as the proportion of days covered by AET during the first-year follow-up. Multivariable regressions for patients' adherence adjusting for race, symptom measures, sociodemographic characteristics, and clinical characteristics were conducted. Kitagawa-Blinder-Oaxaca decomposition was used to quantify racial differences in adherence explained by symptoms and patient characteristics. Analyses were conducted from July 2021 to January 2022. Physical and psychological symptoms at baseline and changes during AET. Among 559 patients (168 [30.1%] Black and 391 [69.9%] White; mean [SD] age 65.5 [12.1] years), Black women received diagnoses younger (mean [SD] age at diagnosis, 58.7 [13.7] vs 68.5 [10.0] years old) than White women, with more advanced stages (30 Black participants [17.9%] vs 31 White participants [7.9%] had stage III disease at diagnosis), and lived in areas with fewer adults attaining high school education (mean [SD], 78.8% [7.8%] vs 84.0% [9.3%]). AET adherence in the first year was 78.8% for Black and 82.3% for White women. Black women reported higher severity in most symptom clusters than White women. Neuropsychological, vasomotor, musculoskeletal, cardiorespiratory, distress, and despair symptoms at baseline and increases during the follow-up were associated with 1.2 to 2.6 percentage points decreases in adherence, which corresponds to 4 to 9 missed days receiving AET in the first year. After adjusting for psychological symptoms, being Black was associated with 6.5 percentage points higher adherence than being White. In this cohort study, severe symptoms were associated with lower AET adherence. Black women had lower adherence rates that were explained by their higher symptom burden and baseline characteristics. These findings suggest that better symptom management with a focus on psychological symptoms could improve AET adherence and reduce racial disparities in cancer outcomes.

Association of Endocrine Therapy Initiation Timeliness With Adherence and Continuation in Low-Income Women With Breast Cancer

Though adjuvant endocrine therapy (AET) has proven efficacy in treating hormone receptor-positive (HR-positive) breast cancer, patient adherence to AET and continuation of treatment as recommended by guidelines remain suboptimal, especially for low-income patients. To quantify timelines for initiating AET and assess their association with short- and long-term adherence and continuation of AET in low-income women with breast cancer. This population-based retrospective cohort study included women younger than 65 years diagnosed with first primary HR-positive breast cancer between January 1, 2007, and December 31, 2013, followed up for 5 years after the first use of AET through December 2018, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Time to initiation (TTI) as days from the date of last treatment (surgery, radiotherapy, or chemotherapy) to the first date of AET prescription fill. The main outcomes were adherence to AET as medication possession ratio of 80% or greater and continuation of AET as no gap in medication supply for at least 90 days. Odds ratios (ORs) of adherence and continuation over 1 to 5 years were estimated using logistic regression adjusted for demographic, clinical, and neighborhood variables. Analyses were performed between September 1, 2020, and May 31, 2022. Among 1711 patients, median TTI was 53 (IQR, 26-117) days. A total of 1029 patients (60.1%) were aged 50 to 64 years old, 1270 (74.2%) were non-Hispanic White, and 1133 (66.2%) were unmarried. In the first year after initiation, 1317 (77.0%) were adherent and 1015 (59.3%) continued AET. Over the full 5 years, 376 (22.0%) were adherent and 409 (23.9%) continued AET. Longer TTI was significantly associated with poorer adherence at every year, with an OR of 0.97 (95% CI, 0.95-0.99) for 1-year adherence and an OR of 0.94 (95% CI, 0.90-0.97) for 5-year adherence per 1-month increase in TTI. Longer TTI was also associated with lower odds of short-term, but not long-term, continuation (OR, 0.97 [95% CI, 0.95-0.99] for 1-year continuation and 0.98 [95% CI, 0.96-0.99] for 2-year continuation). In this cohort study, longer time to AET initiation was associated with lower odds of short-term and long-term adherence to AET in Medicaid-insured patients with breast cancer. Therefore, early interventions targeting treatment initiation timelines may positively impact adherence throughout the course of treatment and, therefore, outcomes.

Factors influencing the initiation of adjuvant endocrine therapy in patients with Estrogen receptor-positive ductal carcinoma in situ: A single institution experience.

e18569 Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal breast cancers. The aim of treatment in DCIS is to prevent local recurrence as almost half of recurrences can be invasive. Few studies have specifically addressed how provider recommendation and patient’s demographic factors contribute to medication initiation in women with DCIS. The objective of this study is to evaluate whether disparities exist pertaining to prescription of adjuvant hormonal therapies. Methods: This single-center retrospective study included 111 patients diagnosed with DCIS between 2020 and 2021. Data collected included race, type of insurance, prescribing providers, and socioeconomic status. We used zip codes to identify the poverty levels in these areas as published in the United States Census Bureau and stratified the patients into quartiles accordingly. Chi-Square statistics were used to calculate significance levels. Results: The average age was 62.8. 63 (56.8%) patients received adjuvant hormonal therapy, and 48 (43.2%) did not. White patients comprised 53.1% of the population, while African Americans were 45%. Among the white patients, 52.5% took hormonal therapy, while 62% of African Americans received hormonal treatment. Majority had Medicare insurance (49.5%), or a commercial insurance (42.3%). 62% of Medicare patients received hormonal therapy and 52.5% of commercial insurance users received adjuvant treatment. 34% lived in areas with the percentage below poverty line greater than 21.9%, 27% lived in areas with the percentage below poverty line between 16.4-21.9%, 38.7% % lived in areas with the percentage below poverty line between 10.6% and 16.4%, and 9% lived in areas with the percentage below poverty line was less than 10.6%. Providers were grouped into either breast oncologist or general oncologists. Breast oncologists prescribed hormonal treatment to 56.8% of their patients, and general oncologists to 56.7% of their patients. There was no statistical significant correlation between the intake of hormonal therapy and race (P = 0.6), insurance (P = 0.5), socioeconomic (P = 0.58) or providers (P = 0.99). Conclusions: In this single-center study, we didn’t find that patients’ demographics or providers influenced the decision to initiate adjuvant hormonal therapy in DCIS.

Adjuvant Hormone Therapy-Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis.

Clinical trials have shown that adjuvant hormone therapy (AHT)-related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11-2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21-1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41-2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39-2.35) or died from cancer (HR, 1.71; 95% CI, 1.37-2.12). AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.

Recurrence risk in early breast cancer as defined by clinicopathologic features.

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p &lt; .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p &lt; .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p &lt; .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p &lt; .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p &lt; .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

Changes in initiation of adjuvant endocrine therapy for breast cancer after state health reform

BackgroundSocioeconomic differences in receipt of adjuvant treatment contribute to persistent disparities in breast cancer (BCA) outcomes, including survival. Adjuvant endocrine therapy (AET) substantially reduces recurrence risk and is recommended by clinical guidelines for nearly all women with hormone receptor-positive non-metastatic BCA. However, AET use among uninsured or underinsured populations has been understudied. The health reform implemented by the US state of Massachusetts in 2006 expanded health insurance coverage and increased the scope of benefits for many with coverage. This study examines changes in the initiation of AET among BCA patients in Massachusetts after the health reform.MethodsWe used Massachusetts Cancer Registry data from 2004 to 2013 for a sample of estrogen receptor (ER)-positive BCA surgical patients aged 20–64 years. We estimated multivariable regression models to assess differential changes in the likelihood initiating AET after Massachusetts health reform by area-level income, comparing women from lower- and higher-income ZIP codes in Massachusetts.ResultsThere was a 5-percentage point (p-value< 0.001) relative increase in the likelihood of initiating AET among BCA patients aged 20–64 years in low-income areas, compared to higher-income areas, after the reform. The increase was more pronounced among younger patients aged 20–49 years (7.1-percentage point increase).ConclusionsThe expansion of health insurance in Massachusetts was associated with a significant relative increase in the likelihood of AET initiation among women in low-income areas compared with those in high-income areas. Our results suggest that expansions of health insurance coverage and improved access to care can increase the number of eligible patients initiating AET and may ameliorate socioeconomic disparities in BCA outcomes.

Initiation and adherence to adjuvant endocrine therapy among urban, insured American Indian/Alaska Native breast cancer survivors.

It has been shown that racial/ethnic disparities exist with regard to initiation of and adherence to adjuvant endocrine therapy (AET). However, the relationship among American Indian/Alaska Native (AIAN) individuals is poorly understood, particularly among those who reside in urban areas. We evaluated whether AET initiation and adherence were lower among AIAN individuals than those of other races/ethnicities who were enrolled in the Kaiser Permanente of Northern California (KPNC) health system. We identified 23,680 patients from the period 1997 to 2014 who were eligible for AET (first primary, stage I-III, hormone receptor-positive breast cancer) and used KPNC pharmacy records to identify AET prescriptions and refill dates. We assessed AET initiation (≥1 filled prescription within 1 year of diagnosis) and AET adherence (proportion of days covered ≥80%) every year up to 5 years after AET initiation. At the end of the 5-year follow-up period, 83% of patients were AET initiators, and 58% were AET adherent. Compared with other races/ethnicities, AIAN women had the second-lowest rate of AET initiation (non-Hispanic Black [NHB], 78.0%; AIAN, 78.6%; Hispanic, 83.0%; non-Hispanic White [NHW], 82.5%; Asian/Pacific Islander [API], 84.7%), the lowest rate of AET adherence after 1 year and 5 years of follow-up (70.3% and 50.8%, respectively), and the greatest annual decline in AET adherence during the 4- to 5-year period of follow-up (a 13.8% decrease in AET adherence [from 64.6% to 50.8%]) after initiation of AET. In adjusted multivariable models, AIAN, Hispanic, and NHB women were less likely than NHW women to be AET adherent. At the end of the 5-year period, total underutilization (combining initiation and adherence) in AET-eligible patients was greatest among AIAN (70.6%) patients, followed by NHB (69.6%), Hispanic (63.2%), NHW (58.7%), and API (52.3%) patients, underscoring the AET treatment gap. Our results suggest that AET initiation and adherence are particularly low for insured AIAN women.

Predicting adjuvant endocrine therapy initiation and adherence among older women with early-stage breast cancer.

The CALGB 9343 trial demonstrated that women age 70 or older with early-stage, estrogenreceptor positive (ER+) breast cancer (BC) may safely forgo radiation therapy (RT) and be treated with breast conserving surgery followed by adjuvant endocrine therapy (AET) alone. However, most patients in this population still undergo RT in part because AET adherence is low. We sought to develop a predictive model for AET initiation and adherence in order to improve decision-making with respect to RT omission. Women ages 70 and older with early-stage, ER + BC were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidities, socioeconomic measures, prescription medications, and demographics were collected as potential predictors. Bivariate analysis was performed to identify factors associated with AET initiation and adherence. Stepwise selection of significant predictors was used to develop logistic regression classifiers for initiation and adherence. Model performance was evaluated using the c-statistic and other measures. 11,037 patients met inclusion criteria. Within the cohort, 8703 (78.9%) patients initiated AET and 6685 (60.6%) were adherent to AET over 1 year. Bivariate predictors of AET initiation were similar to predictors of adherence. The best AET initiation and adherence classifiers were poorly predictive with c-statistics of 0.65 and 0.60, respectively. The best models in the present study were poorly predictive, demonstrating that the reasons for initiation and adherence to AET are complex and individual to the patient, and therefore difficult to predict. Initiation and adherence to AET are important factors in decision-making regarding whether or not to forgo adjuvant RT. In order to better formulate treatment plans for this population, future work should focus on improving individual prediction of AET initiation and adherence.