Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

PURPOSE: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. METHODS: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. RESULTS: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. CONCLUSION: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. CLINICAL TRIAL REGISTRATION: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).

Leveraging Mobile Health to Improve Capecitabine Adherence Among Women With Breast Cancer: A Pilot Randomized Controlled Trial.

PURPOSE: Oral capecitabine improves convenience compared to intravenous therapies but presents monitoring challenges. We conducted a randomized pilot trial to evaluate a mobile health intervention to remotely monitor capecitabine adherence and patient-reported outcomes (PROs) among women with breast cancer. METHODS: Patients with breast cancer prescribed capecitabine, an oral chemotherapy with a complex, cyclical regimen, were randomly assigned to enhanced usual care (EUC) or PRO arm. Participants were asked to use a smart pill bottle to measure adherence (timing and dose) and complete baseline and 90-day follow-up surveys. PRO participants received text messages for missed or incorrect doses and weekly text-based symptom assessments, and their oncologists received alerts for severe symptoms or missed doses. We compared nonadherence (<80%) and changes from enrollment to follow-up on reported physical and mental health quality-of-life scores and number of severe symptoms by study arm. RESULTS: Overall, 32 women were randomly assigned (17 EUC and 15 PRO): 28 (87.5%) received the intervention and 24 (78.1%) completed the follow-up survey. Among participants who received the intervention, PRO participants responded to 83.3% of symptom questions; 7.7% of PRO participants were nonadherent compared with 40.0% of EUC participants (P = .049). Among those who completed the follow-up survey, 12.5% of PRO participants had reductions in their mental health composite scores compared with 69.2% of EUC participants (P = .011); 10% of PRO participants had more severe symptoms at follow-up compared with 57.1% of EUC participants (P = .019). CONCLUSION: A mobile health intervention using text message reminders and symptom assessments improved medication adherence and mental health quality-of-life scores and lowered symptom burden of patients with breast cancer prescribed capecitabine. Future work should evaluate the longer-term impacts of this intervention.

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer.

PURPOSE: Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting. METHODS: The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P. RESULTS: Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years). Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC. Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62). The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = .23). The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations. CONCLUSION: The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.

High tumor infiltrating lymphocytes are significantly associated with pathological complete response in triple negative breast cancer treated with neoadjuvant KEYNOTE-522 chemoimmunotherapy.

INTRODUCTION: For patients with locally advanced triple negative breast cancer (TNBC), the standard of care is to administer the KEYNOTE-522 (K522) regimen, including chemotherapy and immunotherapy (pembrolizumab) given in the neoadjuvant setting. Pathological complete response (pCR) is more likely in patients who receive the K522 regimen than in patients who receive standard chemotherapy. Studies have shown that pCR is a strong predictor of long-term disease-free survival. However, factors predicting pCR to K522 are not well understood and require further study in real-world populations. METHODS: We evaluated 76 patients who were treated with the K522 regimen at our institution. Twenty-nine pre-treatment biopsy slides were available for pathology review. Nuclear grade, Nottingham histologic grade, Ki-67, lymphovascular invasion, and tumor infiltrating lymphocytes (TIL) were evaluated in these 29 cases. For the cases that did not have available slides for review from pre-treatment biopsies, these variables were retrieved from available pathology reports. In addition, clinical staging, race, and BMI at the time of biopsy were retrieved from all 76 patients' charts. Binary logistic regression models were used to correlate these variables with pCR. RESULTS: At the current time, 64 of 76 patients have undergone surgery at our institution following completion of K522 and 31 (48.4%) of these achieved pCR. In univariate analysis, only TIL was significantly associated with pCR (p = 0.014) and this finding was also confirmed in multivariate analysis, whereas other variables including age, race, nuclear grade, Nottingham grade, Ki-67, lymphovascular invasion, BMI, pre-treatment tumor size, and lymph node status were not associated with pCR (p > 0.1). CONCLUSION: Our real-world data demonstrates high TIL is significantly associated with pCR rate in the K522 regimen and may potentially serve as a biomarker to select optimal treatment. The pCR rate of 48.4% in our study is lower than that reported in K522, potentially due to the smaller size of our study; however, this may also indicate differences between real-world data and clinical trial results. Larger studies are warranted to further investigate the role of immune cells in TNBC response to K522 and other treatment regimens.

Correlation of HER2 Protein Level With mRNA Level Quantified by RNAscope in Breast Cancer.

Trastuzumab deruxtecan (T-DXd) has been approved by the US Food and Drug Administration (FDA) to treat patients with metastatic HER2-positive and HER2-low breast cancer, and clinical trials are examining its efficacy against early-stage breast cancer. Current HER2 immunohistochemical (IHC) assays are suboptimal in evaluating HER2-low breast cancers and identifying which patients would benefit from T-DXd. HER2 expression in 526 breast cancer tissue microarray (TMA) cores was measured using the FDA-approved PATHWAY and HercepTest IHC assays, and the corresponding RNA levels were evaluated by RNAscope. HER2 protein levels by regression analysis using a quantitative immunofluorescence score against cell line arrays with known HER2 protein levels determined by mass spectrometry were available in 48 of the cores. RNAscope was also performed in 32 metastatic biopsies from 23 patients who were subsequently treated with T-DXd, and the results were correlated with response rate. HER2 RNA levels by RNAscope strongly correlated with HER2 protein levels (P < .0001) and with HER2 IHC H-scores from the PATHWAY and HercepTest assays (P < .0001). However, neither protein levels nor RNA levels significantly differed between cases scored 0, ultralow, and 1+ by PATHWAY and HercepTest. The RNA levels were significantly higher (P = .030) in responders (6.4 ± 8.2 dots/cell, n = 12) than those in nonresponders (2.6 ± 2.2, n = 20) to T-DXd. RNAscope is a simple assay that can be objectively quantified and is a promising alternative to current IHC assays in evaluating HER2 expression in breast cancers, especially HER2-low cases, and may identify patients who would benefit from T-DXd.

Impact of BMI in Patients With Early Hormone Receptor-Positive Breast Cancer Receiving Endocrine Therapy With or Without Palbociclib in the PALLAS Trial.

PURPOSE: BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. METHODS: Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. RESULTS: Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). CONCLUSION: This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.

Improving palbociclib adherence among women with metastatic breast cancer using a CONnected CUstomized Treatment Platform: A pilot study.

OBJECTIVE: To pilot test a mobile health intervention using a CONnected CUstomized Treatment Platform that integrates a connected electronic adherence monitoring smartbox and an early warning system of non-adherence with bidirectional automated texting feature and provider alerts. METHODS: In total, 29 adult women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer and a prescription for palbociclib were asked to complete a survey and participate in a CONnected CUstomized Treatment Platform intervention, including use of a smartbox for real-time adherence monitoring, which triggered text message reminders for any missed or extra dose, and referrals to (a) participant's oncology provider after three missed doses or an episode of over-adherence, or (b) a financial navigation program for any cost-related missed dose. Use of smartbox, number of referrals, palbociclib adherence, CONnected CUstomized Treatment Platform usability measured by System Usability Scale, and changes in symptom burden and quality of life were assessed. RESULTS: Mean age was 57.6 and 69% were white. The smartbox was used by 72.4% of participants, with palbociclib adherence rate of 95.8%±7.6%. One participant was referred to oncology provider due to missed doses and one was referred to financial navigation. At baseline, 33.3% reported at least one adherence barrier including inconvenience to get prescription filled, forgetfulness, cost, and side effects. There were no changes in self-reported adherence, symptom burden or quality of life over 3 months. CONnected CUstomized Treatment Platform usability score was 61.9 ± 14.2. CONCLUSION: The CONnected CUstomized Treatment Platform interventions is feasible, resulting in a high palbociclib adherence rate without any decline in overtime. Future efforts should focus on improving usability.

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

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

A Discordant Pattern of Uptake on 68 Ga-PSMA PET/CT Versus 18 F-Fluciclovine PET/CT in Radiation-Induced Hepatitis : Implications for Early Postradiotherapy Imaging-Based Response Assessment.

ABSTRACT: A 62-year-old woman with right-sided invasive lobular breast carcinoma completed external beam radiotherapy 6 weeks before undergoing a 68 Ga-PSMA PET/CT and 18 F-fluciclovine PET/CT scan as part of an ongoing clinical trial (NCT04750473) assessing the performance of these molecular imaging modalities in invasive lobular breast carcinoma. The 68 Ga-PSMA PET/CT demonstrated a band-like area of increased radiotracer uptake in the dome of the right lobe of the liver anteriorly, whereas 18 F-fluciclovine PET/CT done a day later revealed photopenia in the corresponding area of the liver. The external beam radiotherapy plan confirmed that the radiotherapy field overlaid the region of the hepatic discordant radiotracer uptake on the PET/CT scans.

Predicting outcomes in female germ cell tumors using a modified International Germ Cell Cancer Collaborative Group classification system to guide management.

OBJECTIVE: We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and assessed it in female patients with germ cell tumors (GCTs). We sought to validate these modified IGCCCG (mIGCCCG) models in a new cohort. METHODS: We queried institutional databases for female patients with GCTs treated at Memorial Sloan Kettering Cancer Center from 1/1/1990-6/1/2020. The mIGCCCG model classifies patients with non-dysgerminomas as good, intermediate, or poor risk based on tumor markers using male IGCCCG cutoffs and absence/presence of non-pulmonary/peritoneal visceral metastasis. In dysgerminomas, good- and intermediate-risk groups are defined by absence/presence of non-pulmonary/peritoneal visceral metastasis. Progression-free survival (PFS) and overall survival (OS) were estimated for each group in the validation and combined original and validation cohorts. Associations between individual clinical factors and outcomes were evaluated. RESULTS: Among 183 female patients with GCTs, clinical characteristics and outcomes were similar between the original (n = 93) and validation (n = 90) cohorts. In multivariable models, higher stage, older age, and non-dysgerminoma histology predicted worse PFS and OS (p < 0.05). Among 162 patients who received chemotherapy, preoperative and pre-chemotherapy mIGCCCG models were significantly associated with PFS and OS (p < 0.001 for all groups). With the preoperative model, 3-year PFS rates were 94%, 76%, and 50% in the good-, intermediate-, and poor-risk patients, respectively; OS rates were 96%, 86%, and 52%, respectively. Even within stage groups, mIGCCCG risk classifications were associated with clinical outcomes. CONCLUSIONS: A female-specific mIGCCCG risk model effectively stratifies patients and should be incorporated into clinical trials.

A Tale of 3 Tracers: Contrasting Uptake Patterns of 18F-Fluciclovine, 68Ga-PSMA, and 18F-FDG in the Uterus and Adnexa.

ABSTRACT: A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.

Percutaneous CT-Guided Cryoneurolysis of the Intercostobrachial Nerve for Management of Postmastectomy Pain Syndrome.

PURPOSE: To evaluate the feasibility, safety, and efficacy of intercostobrachial nerve (ICBN) cryoneurolysis for pain control in patients with postmastectomy pain syndrome (PMPS). MATERIALS AND METHODS: Fourteen patients with PMPS were prospectively enrolled into this clinical trial after a positive response to a diagnostic computed tomography (CT)-guided percutaneous block of the ICBN. Participants subsequently underwent CT-guided percutaneous cryoneurolysis of the same nerve and were observed on postprocedural Days 10, 90, and 180. Pain scores, quality-of-life measurements, and global impression of change values were recorded before the procedure and at each follow-up point using established validated outcome instruments. RESULTS: Cryoneurolysis of the ICBN was technically successful in all 14 patients. The mean pain decreased significantly by 2.1 points at 10 days (P = .0451), by 2.4 points at 90 days (P = .0084), and by 2.9 points at 180 days (P = .0028) after cryoneurolysis. Pain interference with daily activities decreased significantly by 14.4 points after 10 days (P = .0161), by 16.2 points after 90 days (P = .0071), and by 20.7 points after 180 days (P = .0007). There were no procedure-related adverse events. CONCLUSIONS: Cryoneurolysis of the ICBN in patients with PMPS was technically feasible and safe and resulted in a significant decrease in postmastectomy pain for up to 6 months in this small cohort.

Recurrent uterine inflammatory myofibroblastic tumor previously managed as leiomyosarcoma has sustained response to alectinib.

Soft tissue sarcomas encompass a wide range of histologic subtypes with varied clinical implications. The incorporation of comprehensive genetic profiling into clinical practice is refining our ability to make these distinctions in diagnosis to better reflect prognosis and clinical behavior of a tumor. In this report, we describe a case of recurrent inflammatory myofibroblastic tumor (IMT) of the uterus, initially diagnosed and managed as leiomyosarcoma. At the time of recurrence, the patient was found to have a TNS1-ALK rearrangement and was treated successfully with alectinib, a second-generation anaplastic lymphoma kinase (ALK)-inhibitor. She had a complete response by imaging six months after initiation of alectinib and remains without evidence of disease at 36 months follow-up. Pathology review in the setting of her known ALK fusion and the 2020 update to the World Health Organization Classification of Female Genital Tumors led to a change in diagnosis from leiomyosarcoma to IMT. Our case highlights the role of molecular testing in the diagnosis and management of uterine mesenchymal tumors and the efficacy of alectinib in this ALK-rearranged recurrent IMT of the uterus. Care must be taken to differentiate between IMT and other uterine mesenchymal tumors as this distinction can impact prognosis and management. Furthermore, this case adds to the growing body of evidence supporting the paradigm shift toward developing molecularly targeted therapies rather than disease site-specific treatments, especially in cases of recurrence as recommended by the National Comprehensive Cancer Network.

Study Protocol: Efficacy and Safety of Radioembolization (REM) as an Early Modality (EM) Therapy for Metastatic Breast Cancer (BR) to the Liver with Y90 (REMEMBR Y90).

PURPOSE: The primary objective of the REMEMBR Y90 study is to evaluate the efficacy of Yttrium-90 (Y90) radioembolization in patients with breast cancer metastases to the liver as a 2nd or 3rd line treatment option with systemic therapy by assessing liver-specific and overall progression-free survival. Secondary objectives include quality of life, overall survival benefit, and toxicity in relation to patients' tumor biology. MATERIALS AND METHODS: This trial is a multi-center, prospective, Phase 2, open-label, IRB-approved, randomized control trial in the final phases of activation. Eligible patients include those over 18 years of age with metastatic breast cancer to the liver with liver-only or liver-dominant disease, and history of tumor progression on 1-2 lines of chemotherapy. 60 patients will be randomized to radioembolization with chemotherapy versus chemotherapy alone. Permissible regimens include capecitabine, eribulin, vinorelbine, and gemcitabine within 2 weeks of enrollment for every patient. Patients receiving radioembolization will receive lobar or segmental treatment within 1-6 weeks of enrollment depending on their lesion. After final radioembolization, patients will receive clinical and imaging follow-up every 12-16 weeks for two years, including contrast-enhanced computed tomography or magnetic resonance imaging of the abdomen and whole-body positron emission tomography/computed tomography. DISCUSSION: This study seeks to elucidate the clinical benefit and toxicity of Y90 in patients with metastatic breast cancer to the liver who are receiving minimal chemotherapy. Given previous data, it is anticipated that the use of Y90 and chemotherapy earlier in the metastatic disease course would improve survival outcomes and reduce toxicity. LEVEL OF EVIDENCE: Level 1b, Randomized Controlled Trial. TRIAL REGISTRATION NUMBER: NCT05315687 on clinicaltrials.gov.

Evaluating the Effectiveness of a Telehealth Cancer Genetics Program: A BRCA Pilot Study.

INTRODUCTION: Ashkenazi Jewish (AJ) individuals face a 1 in 40 (2.5%) risk of having a BRCA mutation, which is 10 times the general population risk. JScreen launched the PEACH BRCA Study, a telehealth-based platform for BRCA education and testing, with the goal of creating an effective model for BRCA testing in low-risk AJ individuals who do not meet national testing criteria. Other goals were to determine the rate of BRCA mutations in this group, to assess the adequacy of screening for the 3 common AJ founder mutations only, and to assess satisfaction with the telehealth model to help inform a national launch of a broader cancer genetic testing program. METHODS: Criteria for participation included those who were AJ, resided in the metro-Atlanta area, were aged 25 and older, and had no personal or close family history of BRCA-related cancers. Pre-test education was provided through a video and written summary, followed by complimentary BRCA1/2 sequencing and post-test genetic counseling. Participants responded to pre- and post-test surveys, which assessed knowledge and satisfaction. Those who were not eligible to participate were sent genetic counseling resources and later surveyed. RESULTS: Five hundred one participants were tested and the results included 4 positives (0.8% positivity rate), 494 negatives, and 3 variants of uncertain significance. Overall satisfaction with the study process was high (96.9/100), knowledge about BRCA was high (97.5% of participants passed a pre-test knowledge quiz), and satisfaction with pre- and post-test education was high (97.9% of participants were satisfied with the pre-test video and written summary, and 99.5% felt that their post-test genetic counseling session was valuable). Many participants expressed interest in receiving broader cancer testing. CONCLUSIONS: The BRCA founder mutation rate in a low-risk AJ population was significantly lower than the previously established AJ rate of 1 in 40. It was also determined that a telehealth model for a cancer genetics program is effective and acceptable to the population tested. This study established interest in broader cancer genetic testing through a telehealth platform and suggested that testing may be successful in the Jewish community at a national level and potentially in other populations, provided that patient education and genetic counseling are adequately incorporated.

Are we closer to being able to select patients with node-positive hormone receptor-positive breast cancer who can safely omit chemotherapy?

The treatment of hormone receptor-positive, HER2-negative breast cancer has become increasingly individualized, thanks to the development of genomic testing. Gene expression assays provide clinicians and patients with both prognostic and predictive information regarding breast cancer recurrence risk and potential benefit of chemotherapy. While the ability to tailor therapy based on clinicopathologic and genomic factors has enabled a growing number of women to forego chemotherapy, several questions remain regarding how best to apply genomic assay results across varying subgroups of women. Here, we review the role of genomic assays for patients with both lymph node-negative and lymph node-positive breast cancer, and how these assays may help us more precisely select patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer with or without lymph node involvement who can safely omit chemotherapy in the future.

Utility of Oncotype DX score in clinical management for T1 estrogen receptor positive, HER2 negative, and lymph node negative breast cancer.

BACKGROUND: The management of estrogen receptor positive (ER+)/HER2- and lymph node (LN) negative breast cancers can be influenced by Oncotype DX recurrence score (RS) in the USA. However, the benefit of RS in T1 tumors (≤ 1 cm) is not clear. METHODS: We retrieved 199 T1 ER+/HER2-/LN- breast cancer diagnosed between 1993 and 2016 that had undergone RS testing. The median follow-up time was 51 months. We examined the disease-free survival (DFS) and distant metastasis and their association with RS and other clinicopathologic features. RESULTS: Of the 199 cases, 40 were T1a (≤ 0.5 cm) and 159 were T1b (> 0.5 cm to 1 cm) tumors. In the 40 T1a tumors, 11 would benefit from chemotherapy by the TAILORx study results. Of these T1a tumors, 36 were Nottingham grade 1/2, 3 were grade 3, and 1 was microinvasive carcinoma; 2 (5%) had local recurrence and 1 (2.5%) had distant metastasis to the bone. The only patient with T1a tumor (Nottingham grade 3, RS = 42) and distant metastasis to bone had received adjuvant chemotherapy. In the 159 T1b tumors, 25 would benefit chemotherapy by the TAILORx results. Of the T1b tumors, 149 were Nottingham grade 1/2 and 10 were grade 3. Nine (5.7%) had local recurrence and 2 (1.3%) had distant metastasis to bone and mediastinum, respectively. The two T1b tumors with distant metastasis had a RS 20 and Nottingham grade 2, and RS 27 and Nottingham grade 3, respectively. Both patients received adjuvant chemotherapy. In multivariate analysis of the entire cohort (T1a and T1b tumors), Nottingham tumor grade and receiving chemotherapy were significantly associated with DFS. In univariate analysis of the entire cohort, Nottingham tumor grade, receiving adjuvant chemotherapy, and RS were significantly associated with distant metastasis. CONCLUSION: This study demonstrates that the metastatic rate of T1a and T1b ER+/HER2-/LN- breast cancer is very low. Patients with low grade (1 or 2), T1a ER+/HER2-/LN- breast cancer may not need RS for treatment decision-making; however, in patients with high-grade T1a or T1b ER+/HER2-/LN- breast cancer, RS analysis should be strongly considered.

Pilot Feasibility Study of a Video Intervention to Educate Patients with Breast Cancer About Clinical Trials.

The purpose of this project was to develop and test the feasibility and preliminary efficacy of a video about cancer clinical trials (CCTs) developed for breast cancer patients. We developed 2 brief 7-min videos that focused on breast cancer patients describing their experiences participating in CCTs, supplemented with doctors and research staff explaining key research concepts. One video was culturally tailored to Black patients and the other to White patients. To assess feasibility study, participants and their care providers completed a survey to evaluate their satisfaction with the video. Eligibility criteria for the study included ≥ 21 years of age, English-speaking, no prior experience participating in a CCT, and being potentially eligible for breast CCT enrollment. Preliminary efficacy was evaluated with a pretest-posttest design using a single item asking about intent to enroll in a clinical trial. The mean age of the patient sample (n = 50) was 53.0 years, and 50.0% were Black. Participants reported that the video was in the right length, useful, and easy to understand. Providers' evaluation (n = 5) revealed that viewing the video helped prepare patients for further CCT discussion. Preliminary efficacy showed no statistically significant difference in participant interest in CCT enrollment pre- and post-video. Changes in patients' intent in enrollment were associated with age and education. Culturally adapted video interventions can be helpful in supporting both patients and providers throughout the CCT education process but additional work is needed to improve enrollment into clinical trials.

Correlates of financial toxicity in adult cancer patients and their informal caregivers.

BACKGROUND: Financial toxicity is commonly reported by cancer patients, but few studies have assessed caregiver perceptions. We aimed to validate the modified Comprehensive Score for Financial Toxicity (COST) in cancer caregivers, identify factors associated with financial toxicity in both patients and caregivers, and assess the association of caregiver financial toxicity with patient and caregiver outcomes. METHODS: Using a convenience sampling method, 100 dyads of adult cancer patients and a primary caregiver visiting outpatient oncology clinics (Jan-Sep 2019) were recruited. We assessed the internal consistency and convergent and divergent validity of the modified COST. Multivariable analyses identified correlates of financial toxicity. Association of financial toxicity with care non-adherence, lifestyle-altering behaviors (e.g., home refinance/sale, retirement/saving account withdrawal), and quality of life (QOL) was investigated. RESULTS: Recruited patient vs. caregiver characteristics were as follows: mean age: 60.6 vs. 56.5; 34% vs. 46.4% female; 79% vs. 81.4% white. The caregiver COST measure demonstrated high internal consistency (Cronbach α = 0.91). In patients, older age (B, 0.3 [95% CI, 0.1-0.4]) and higher annual household income (B, 14.3 [95% CI, 9.3-19.4]) correlated with lower financial toxicity (P < 0.05). In caregivers, lower patient financial toxicity (B, 0.4 [95% CI, 0.2-0.6]) and cancer stages 1-3 (compared to stage 4) (B, 4.6 [95% CI, 0.4-8.8]) correlated with lower financial toxicity (P < 0.05). Increased caregiver financial toxicity correlated with higher care non-adherence in patients, increased lifestyle-altering behaviors, and lower QOL in patients and caregivers (P < 0.05). CONCLUSION: The COST measure can also be used to assess caregiver financial toxicity. Caregivers' financial toxicity was associated with negative outcomes for both dyad members.