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.
Treatment of hormone receptor‐positive, HER2‐negative early breast cancer should be individualized based on a patient's risk for recurrence. Optimal selection of endocrine therapy, chemotherapy, and emerging targeted agents is driven by risk assessment, tolerability, and consideration for patient preferences.
Purpose
For postmenopausal women with hormone receptor-positive breast cancer, long-term use of aromatase inhibitors (AIs) significantly reduces the risk of cancer recurrence and improves survival. ...Still, many patients are nonadherent due to adverse side effects. We conducted a pilot randomized controlled trial to test the use of a web-based application (app) designed with and without weekly reminders for patients to report real-time symptoms and AI use outside of clinic visits with built-in alerts to patients’ oncology providers. Our goal was to improve symptom burden and medication adherence.
Methods
Forty-four women with early-stage breast cancer and a new AI prescription were randomized to either an App+Reminder (weekly reminders to use app) or an App (no reminders) group. Pre- and post-assessment data were collected from all participants.
Results
Participants in the App+Reminder group had higher weekly app usage rate (74 vs. 38%,
p
< 0.05) during the intervention and reported higher AI adherence at 8 weeks (100 vs. 72%,
p
< 0.05). Symptom burden increase was higher for the App group compared to the App+Reminder group but did not reach statistical significance.
Conclusions
Weekly reminders to use a web-based app to report AI adherence and treatment-related symptoms demonstrated feasibility and improved short-term AI adherence, which may reduce symptom burden for women with breast cancer and a new AI prescription.
Implications for Cancer Survivors
If short-term gains in adherence persist, this low-cost intervention could improve survival outcomes for women with breast cancer. A larger, long-term study should examine if AI adherence and symptom burden improvements persist for a 5-year treatment period.
Despite their anti-tumor efficacy, immune checkpoint inhibitors (ICIs) are associated with a variety of immune-related adverse events (irAEs). Grade ≥ 2 irAEs require ICI discontinuation. The ...decision to resume ICI treatment often remains challenging.
We retrospectively studied 1051 adult patients with stage IV non-small cell lung cancer (NSCLC) treated with ICIs at a single institution between January 2015 and December 2020, and identified 99 (9.4%) patients with grade≥2 irAEs necessitating treatment interruption. Forty patients underwent retreatment (rechallenged group), while 59 discontinued the treatment (discontinued group).
Baseline characteristics of patients in the 2 groups were similar. Initial irAEs were less severe in the rechallenged group. After rechallenging, 24 of 40 (60%) patients had recurrence of the same or de-novo irAEs. Twenty (50%) developed second grade≥ 2 irAEs. No grade 4 irAE or irAE-related death occurred after rechallenging. Using multivariate analysis, no statistically significant differences in overall survival (OS) (HR: 1.10, 95% CI: 0.57-2.15, P = .77) or progression-free survival (PFS) (HR: 0.87, 95% CI: 0.45-1.71, P = .69) were noted between the 2 groups, while the best objective response prior to the initial irAEs was the only variable affecting OS and PFS.
Rechallenge was associated with a relative high risk of second grade≥ 2 irAEs. The risk was less if the initial irAEs were resolved. No differences were seen in survival outcomes of patients who had ICI rechallenge and those who did not. Permanent ICI discontinuation is an appropriate strategy after grade≥ 2 irAEs, especially severe irAEs.
The decision to resume immune checkpoint inhibitor (ICI) treatment often remains challenging after grade ≥2 immune-related adverse events (irAEs). We retrospectively studied the outcomes of ICI rechallenge versus permanent discontinuation in 99 stage IV non-small cell lung cancer (NSCLC) patients. Our finding suggests permanent ICI discontinuation is an appropriate strategy after grade≥2 irAEs.
Symptom burden differences may contribute to racial disparities in breast cancer survival. We compared symptom changes from before to during chemotherapy among women with breast cancer.
This ...observational study followed a cohort of Black and White women diagnosed with Stage I-III, hormone receptor-positive breast cancer from a large cancer center in 2007 to 2015, and reported symptoms before and during chemotherapy. We identified patients who experienced a one-standard deviation (SD) increase in symptom burden after starting chemotherapy using four validated composite scores (General Physical Symptoms, Treatment Side Effects, Acute Distress, and Despair). Kitagawa-Blinder-Oaxaca decomposition was used to quantify race differences in symptom changes explained by baseline characteristics (sociodemographic, baseline scores, cancer stage) and first-line chemotherapy regimens.
Among 1,273 patients, Black women (n = 405, 31.8%) were more likely to report one-SD increase in General Physical Symptoms (55.6% vs. 48.2%, P = 0.015), Treatment Side Effects (74.0% vs. 63.4%, P < 0.001), and Acute Distress (27.4% vs. 20.0%, P = 0.010) than White women. Baseline characteristics and first-line chemotherapy regimens explained a large and significant proportion of the difference in Acute Distress changes (93.7%, P = 0.001), but not General Physical Symptoms (25.7%, P = 0.25) or Treatment Side Effects (16.4%, P = 0.28).
Black women with early-stage breast cancer were more likely to experience significant increases in physical and psychological symptom burden during chemotherapy. Most of the difference in physical symptom changes remained unexplained by baseline characteristics, which suggests inadequate symptom management among Black women.
Future studies should identify strategies to improve symptom management among Black women and reduce differences in symptom burden. See related commentary by Rosenzweig and Mazanec, p. 157.
Objective
Social support is a critical component of breast cancer care and is associated with clinical and quality of life outcomes. Significant health disparities exist between Black and White women ...with breast cancer. Our study used qualitative methods to explore the social support needs of Black and White women with hormone receptor‐positive breast cancer on adjuvant endocrine therapy (AET).
Methods
We conducted four focus group (FG) interviews (N = 28), stratified by race (ie, Black and White) and time on AET. FGs were audiotaped, transcribed, and analyzed according to conventions of thematic analysis.
Results
Participants noted the importance of having their informational and emotional social support needs met by friends and family members. White participants reported support provided by others with breast cancer was crucial; Black women did not discuss other survivors as part of their networks. Notably, both White and Black participants used the FG environment to provide experiential social support to each other.
Conclusions
White participants noted that having other breast cancer survivors in their support network was essential for meeting their social support needs. However, Black participants did not reference other breast cancer survivors as part of their networks. Cancer centers should consider reviewing patients' access to experiential support and facilitate opportunities to connect women in the adjuvant phase.
Immune checkpoint inhibitor (ICI) therapies represent a major advance in treating a variety of advanced-stage malignancies. Nevertheless, only a subset of patients benefit, even when selected based ...on approved biomarkers such as PD-L1 and tumor mutational burden. New biomarkers are needed to maximize the therapeutic ratio of these therapies.
In this retrospective cohort, we assessed a 27-gene RT-qPCR immuno-oncology (IO) gene expression assay of the tumor immune microenvironment and determined its association with the efficacy of ICI therapy in 67 advanced-stage NSCLC patients. The 27-gene IO test score (IO score), programmed cell death ligand 1 immunohistochemistry tumor proportion score (PD-L1 TPS), and tumor mutational burden (TMB) were analyzed as continuous variables for response and as binary variables for one-year progression free survival. The threshold for the IO score was prospectively set based upon a previously described training cohort. Prognostic implications of the IO score were evaluated in a separate cohort of 104 advanced-stage NSCLC patients from The Cancer Genome Atlas (TCGA) who received non-ICI therapy.
The IO score was significantly different between responders or non-responders (p = 0.007) and associated with progression-free survival (p = 0.001). Bivariate analysis established that the IO score was independent of PD-L1 TPS and TMB in identifying patients benefiting from ICI therapy. In a separate cohort of late-stage NSCLC patients from TCGA, the IO score was not prognostic of outcome from non-ICI-treated patients.
This study is the first application of this 27-gene IO RT-qPCR assay in a clinical cohort with outcome data. IO scores were significantly associated with response to ICI therapy and prolonged progression-free survival. Together, these data suggest the IO score should be further studied to define its role in informing clinical decision-making for ICI treatment in NSCLC.
Background
Cancer treatment requires substantial demands on patients and their caregivers. Mobile apps can provide support for self‐management during oncology treatment, but few have been rigorously ...evaluated.
Methods
A 3‐month randomized controlled trial was conducted at a large cancer center to evaluate the efficacy of an app (LivingWith®) that provides self‐management support during cancer treatment on quality of life and health care utilization. Patients in chemotherapy treatment were randomized into the intervention (n = 113) and control group (n = 111). Intervention group participants agreed to use the app weekly for 3 months, and all participants completed a survey at enrollment and after 3 months to evaluate changes in quality of life and health care utilization.
Results
Retention rate was 75.4% with 169 participants completing the follow‐up survey. The intervention group reported 0.74 fewer medical office visits (p = 0.043) and 0.24 fewer visits with a mental health professional (p = 0.061) during the 3 and month intervention compared with controls. There were no significant changes by study group in quality of life, or emergency room and urgent care visits. Among intervention participants, 75.3% reported using the app and on average, used it 11.7 times during the 3‐month intervention. Reasons for not using the app among intervention participants included lack of time, lack of interest in apps, and usability challenges.
Conclusions and Relevance
Apps are inexpensive and scalable tools that can provide additional support for individuals coping with complex cancer treatments. This trial provides evidence that a well‐designed oncology support app used during chemotherapy resulted in fewer clinic visits. Still, nearly a quarter of participants randomized to the intervention arm reported never using the app due to personal preference and usability challenges, which points to future opportunities for calibrating target user population and improving user‐centered design.
Clinicaltrials.gov identifier: NCT04331678.
This randomized controlled trial of oncology patients provides evidence that a well‐designed oncology support mobile app used during chemotherapy resulted in fewer clinic visits.
The phosphatidylinositol-3-kinase (PI3K) pathway is frequently dysregulated in human breast cancer. Approximately 30% of all patients with breast cancer will carry mutations of the PIK3CA gene, which ...encodes the PI3K catalytic subunit isoform p110α. Mutations in PIK3CA have been associated with resistance to endocrine therapy, HER2-directed therapy, and cytotoxic therapy. Early trials of pan-PI3K inhibitors showed little treatment benefit as monotherapy owing to disease resistance arising through enhanced estrogen receptor pathway signaling. Combining PI3K inhibition with endocrine therapy can help overcome resistance. Clinical trials of pan-PI3K inhibitors combined with endocrine therapy demonstrated modest clinical benefits but challenging toxicity profiles, facilitating the development of more selective PI3K-targeting agents. More recent trials of isoform-specific PI3K inhibitors in patients with PIK3CA mutations have shown promising clinical efficacy with a predictable, manageable safety profile. In the present review, we discuss the clinical relevance of mutations of PIK3CA and their potential use as a biomarker to guide treatment choices in patients with HR+ HER2− advanced breast cancer.
To describe real-world treatment patterns/outcomes among patients with HER2+ metastatic breast cancer (MBC).
Real-world treatments and overall survival (OS) were evaluated among adult women diagnosed ...with HER2+ MBC, with and without brain metastases (BMs), between 1 June 2012 and 31 May 2018 using electronic medical records from the Definitive Oncology Dataset.
Among 372 patients, 69% initiated first-line trastuzumab plus pertuzumab-based therapy; many therapy combinations were utilized in the second- to fourth-line. During follow-up (median 24.8 months), 18% of patients died (22% with and 16% without BMs). Mean OS was shortest among patients with BMs at MBC diagnosis in the third- and fourth-line.
OS was poor, and no clear standard of care was observed among patients with HER2+ MBC progressing on trastuzumab-based therapies.
PDF
