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Improved outcomes for triple negative breast cancer brain metastases patients after stereotactic radiosurgery and new systemic approaches

Mashiach, Elad; Alzate, Juan Diego; De Nigris Vasconcellos, Fernando; Adams, Sylvia; Santhumayor, Brandon; Meng, Ying; Schnurman, Zane; Donahue, Bernadine R; Bernstein, Kenneth; Orillac, Cordelia; Bollam, Rishitha; Kwa, Maryann J; Meyers, Marleen; Oratz, Ruth; Novik, Yelena; Silverman, Joshua S; Harter, David H; Golfinos, John G; Kondziolka, Douglas
PURPOSE/OBJECTIVE:Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS:We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS:Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS:TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.
PMID: 38630386
ISSN: 1573-7373
CID: 5655852

Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies

Mashiach, Elad; Alzate, Juan Diego; De Nigris Vasconcellos, Fernando; Bernstein, Kenneth; Donahue, Bernadine R; Schnurman, Zane; Gurewitz, Jason; Rotman, Lauren E; Adams, Sylvia; Meyers, Marleen; Oratz, Ruth; Novik, Yelena; Kwa, Maryann J; Silverman, Joshua S; Sulman, Erik P; Golfinos, John G; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS:We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS:The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status ( P = .041) and treatment with TT ( P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS ( P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS ( P = .017), triple-negative breast cancer ( P = .002), a Karnofsky Performance Status of <80 at first SRS ( P = .002), and active systemic disease at last follow-up ( P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION/CONCLUSIONS:Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.
PMID: 37581437
ISSN: 1524-4040
CID: 5599542

Heterogeneity of posttraumatic stress, depression, and fear of cancer recurrence in breast cancer survivors: a latent class analysis

Malgaroli, Matteo; Szuhany, Kristin L; Riley, Gabriella; Miron, Carly D; Park, Jae Hyung; Rosenthal, Jane; Chachoua, Abraham; Meyers, Marleen; Simon, Naomi M
PURPOSE/OBJECTIVE:Breast cancer survivors may demonstrate elevated psychological distress, which can also hinder adherence to survivorship care plans. Our goal was to study heterogeneity of behavioral health and functioning in breast cancer survivors, and identify both risk and protective factors to improve targets for wellness interventions. METHODS:Breast cancer survivors (n = 187) consented to complete self-reported psychological measures and to access their medical records. Latent class analysis (LCA) was used to classify heterogeneous subpopulations based on levels of depression, post-traumatic stress, fear of cancer recurrence, cancer-related pain, and fatigue. Multinomial logistic regression and auxiliary analysis in a 3-step modeling conditional approach was used to identify characteristics of the group based on demographics, treatment history and characteristics, and current medication prescriptions. RESULTS:Three subpopulations of breast cancer survivors were identified from the LCA: a modal Resilient group (48.2%, n = 90), a Moderate Symptoms group (34%, n = 65), and an Elevated Symptoms group (n = 17%, n = 32) with clinically-relevant impairment. Results from the logistic regression indicated that individuals in the Elevated Symptoms group were less likely to have a family history of breast cancer; they were more likely to be closer to time of diagnosis and younger, have received chemotherapy and psychotropic prescriptions, and have higher BMI. Survivors in the Elevated Symptoms group were also less likely to be prescribed estrogen inhibitors than the Moderate Symptoms group. CONCLUSIONS:This study identified subgroups of breast cancer survivors based on behavioral, psychological, and treatment-related characteristics, with implications for targeted monitoring and survivorship care plans. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:Results showed the majority of cancer survivors were resilient, with minimal psychological distress. Results also suggest the importance of paying special attention to younger patients getting chemotherapy, especially those without a family history of breast cancer.
PMID: 35224684
ISSN: 1932-2267
CID: 5174072

Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic

Marks, Douglas K; Budhathoki, Nibash; Kucharczyk, John; Fa'ak, Faisal; D'Abreo, Nina; Kwa, Maryann; Plasilova, Magdalena; Dhage, Shubhada; Soe, Phyu Phyu; Becker, Daniel; Hindenburg, Alexander; Lee, Johanna; Winner, Megan; Okpara, Chinyere; Daly, Alison; Shah, Darshi; Ramdhanny, Angela; Meyers, Marleen; Oratz, Ruth; Speyer, James; Novik, Yelena; Schnabel, Freya; Jones, Simon A; Adams, Sylvia
PURPOSE:Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. METHODS:Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality. RESULTS:Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05). CONCLUSION:BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent.
PMID: 35641208
ISSN: 1549-490x
CID: 5235912

Examining the Relationship between Perceived Social and Familial Support and Fear of Cancer Recurrence in Breast Cancer Survivors [Meeting Abstract]

Miron, Carly D.; Malgaroli, Matteo; Szuhany, Kristin; Adhikari, Samrachana; Riley, Gabriella; Chachoua, Abraham; Meyers, Marleen; Rosenthal, Jane; Simon, Naomi M.
ISSN: 1057-9249
CID: 5243052

Barriers and engagement in breast cancer survivorship wellness activities

Szuhany, Kristin L; Malgaroli, Matteo; Riley, Gabriella; Miron, Carly D; Suzuki, Rebecca; Park, Jae Hyung; Rosenthal, Jane; Chachoua, Abraham; Meyers, Marleen; Simon, Naomi M
PURPOSE/OBJECTIVE:Breast cancer survivors may be at risk for increased rates of emotional distress and poorer quality of life. Survivorship care plans (SCPs) promoting wellness activities may support well-being; however, survivors may not receive or engage in their SCPs. This study aimed to assess receipt and participation in SCP activities as well as barriers to engagement amongst breast cancer survivors. METHODS:Breast cancer survivors (n = 187; 99% female, Mean age = 57.7) consented and completed self-reported assessments of SCP recommendations, engagement and interest in wellness activities, and potential barriers to engagement. RESULTS:A minority of participants recalled receiving an SCP (21%). The most physician recommended (62%) and completed (53%) activity was exercise. Interest in adding other wellness activities to the SCP was high, with reported interest levels of approximately 50% for several activities (e.g., mind body, nutrition, psychotherapy interventions). Fully half reported that having a physician-designed plan would influence participation in activities. The most common reported barriers to SCP activity engagement were lack of time (82%), work/school (65%), and lack of information (65%). CONCLUSION/CONCLUSIONS:Few survivors recalled receiving a formal SCP, and lack of information about wellness activities was a commonly reported barrier to participation. Interest in wellness activities was generally high and may indicate the need for more formal prescription or motivation enhancement techniques to promote SCP engagement. There may be a clinical need to emphasize SCP recommendations to enhance recall and increase engagement in wellness activities that may reduce psychological distress and improve quality of life.
PMID: 34095986
ISSN: 1573-7217
CID: 4899592

"Bridge" Neoadjuvant Endocrine Therapy for Early Stage Breast Cancer Patients During COVID-19 at an Academic Hospital in NYC: Lessons Learned and Future Directions

Feinberg, Joshua; Cen, Cindy; Schnabel, Freya; Adams, Sylvia; Plasilova, Magdalena; Yeh, Janet; Meyers, Marleen; Speyer, James; Belenkov, Elliot; Kwa, Maryann; Novik, Yelena; Katz, Elena; Guth, Amber Azniv
ISSN: 2578-9503
CID: 5192472

Nutrition Literacy among Cancer Survivors: Feasibility Results from the Healthy Eating and Living Against Breast Cancer (HEAL-BCa) Study: a Pilot Randomized Controlled Trial

Parekh, Niyati; Jiang, Jieying; Buchan, Marissa; Meyers, Marleen; Gibbs, Heather; Krebs, Paul
Knowledge of nutrition among breast cancer patients is insufficient, despite their motivation to seek valid information about healthy food choices. This study examines the feasibility of nutrition education workshops for cancer survivors, to inform the design of a multi-center intervention. Fifty-nine female English-speaking breast cancer patients, who had completed treatment, were enrolled. Participants were randomized to the intervention or control group. The intervention group attended six nutrition education sessions, and the control group received brochures. Measurements were done at baseline and 3-month follow-up and included the Assessment Instrument for Breast Cancer (NLit-BCa), fruit/vegetable and general health literacy screeners. Height and weight were measured. Changes in nutrition literacy, health literacy, and food intake from baseline to follow-up (within-group change) were calculated for both groups (effect sizes were reported as Cohen's d). Participants were mostly white, with a mean age of 58 years, BMI of 31.6 kg/m2, and had college degrees. Follow-up rates were high (89% = control and 77% = intervention group). At baseline, participants scored high for most NLit-BCa assessment components except food portions in both groups. At the 3-month follow-up, effect sizes (d) on the NLit-BCa ranged from -0.5 to 0.16. The study met its recruitment goals within 6 months. Focus groups indicated that (a) attending six sessions was acceptable, (b) patients found social/emotional support, (c) improvements should include information for special diets and booster sessions. This pilot study suggests that the intervention was acceptable and that scaling up of this intervention is feasible and could provide benefit to breast cancer survivors.
PMID: 28624990
ISSN: 1543-0154
CID: 2604122

Serial immunological parameters in a phase II trial of exemestane and low-dose oral cyclophosphamide in advanced hormone receptor-positive breast cancer

Kwa, Maryann; Li, Xiaochun; Novik, Yelena; Oratz, Ruth; Jhaveri, Komal; Wu, Jennifer; Gu, Ping; Meyers, Marleen; Muggia, Franco; Speyer, James; Iwano, Alyssa; Bonakdar, Maryam; Kozhaya, Lina; Tavukcuoglu, Ece; Budan, Bahar; Raad, Roy; Goldberg, Judith D; Unutmaz, Derya; Adams, Sylvia
BACKGROUND AND PURPOSE: Resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer is a significant challenge. Prior studies have shown that low-dose oral cyclophosphamide can transiently deplete regulatory T cells (Tregs) and improve anti-tumor immunity. We investigated the combination of exemestane with cyclophosphamide in patients with advanced HR-positive breast cancer and assessed changes in circulating immune cell subsets. METHODS: This was a single-arm phase II trial of exemestane with cyclophosphamide in patients with metastatic HR-positive/HER2-negative breast cancer who had progressed on prior endocrine therapy ( NCT01963481). Primary endpoint was progression-free survival (PFS) at 3 months (RECIST 1.1). Secondary objectives included median PFS, objective response rate, duration of response, and safety. Circulating Tregs (FOXP3+Helios+) and other immune cell subsets were monitored during treatment and compared with healthy controls. RESULTS: Twenty-three patients were enrolled. Treatment was well tolerated, without grade 4/5 toxicities. Objective responses were seen in 6/23 patients (26.1%; 95% CI 10.2-48.4%) and were durable (median 11.6 months). Three-month PFS rate was 50.1% (95% CI 33.0-76.0%); median PFS was 4.23 months (95% CI 2.8-11.7). No treatment-related decrease in Tregs was observed. However, elevated baseline levels of Naive Tregs [greater than 2.5 (the median of the naive Tregs)] were associated with relative risk of disease progression or death [hazard ratio 11.46 (95% CI 2.32-56.5)]. In addition, the baseline levels of Naive Tregs (adj-p = 0.04), Memory Tregs (adj-p = 0.003), CD4 + Central Memory T cells (adj-p = 0.0004), PD-1 + CD4 + Central Memory T cells (adj-p = 0.008), and PD-1 + CD4 + Effector Memory T cells (adj-p = 0.009) were significantly greater in the patients than in the healthy controls; the baseline levels of %CD4 + Naive T cells (adj-p = 0.0004) were significantly lower in patients compared with healthy controls (n = 40). CONCLUSION: Treg depletion was not observed with low-dose cyclophosphamide when assessed by the specific marker FOXP3 + Helios +; however, baseline naive Tregs were associated with 3-month PFS. Exemestane/cyclophosphamide combination had favorable safety profile with evidence of clinical activity in heavily pretreated patients.
PMID: 29124456
ISSN: 1573-7217
CID: 2772912

Vinorelbine/cisplatin therapy of locally advanced and metastatic breast cancer: an active regimen [Meeting Abstract]

Hochster H; Wasserheit C; Siddiqui N; Sorich J; Downey A; Wernz J; Oratz R; Meyers M; Moskovits T; Speyer J
Single agent activity of vinorelbine in previously untreated breast cancer and its predictable toxicity make it ideal for combination with cisplatin, a drug we found to be very active in combination with paclitaxel (J Clin Oncol; 14:1993, 1996), but with a high rate of neurotoxicity limiting duration of therapy. Eligibility included: histologically proven locally advanced or metastatic measurable breast cancer, ECOG performance status (PS) of 2 or less, adequate organ function. Cisplatin was given at a dose of 75 mg/m2 on day 1, with vinorelbine 30 mg/m2 days 1 and 8 of a 21 day cycle; day 8 vinorelbine dose was modified for neutropenia and thrombocytopenia. 24 patients (pts) entered the study, of whom 23 were eligible and 1 too early for response evaluation. 20 pts were treated as first line therapy for advanced disease (10 locally advanced and 10 metastatic). 3 pts were treated as second-line therapy for metastatic disease. Median age was 49 (range 32-67), median ECOG PS = 0. Nine pts had prior adjuvant chemotherapy and 8 pts had prior RT. A total of 91 cycles of chemotherapy were given with a median of 3 per pt. Hematological toxicity included leukopenia gr 3 = 4 pts, gr 4 = 2; neutropenia gr 3 = 4, gr 4 = 7 pts; no gr 3 or 4 thrombocytopenia. Non-heme toxicity included: N/V gr 2 = 6 pts, gr 3 = 1; neuropathy gr 1 = 10; gr 2 = 2; renal gr 2 = 1 pt. Responses seen included 2 CRs and 6 PRs (of 9 evaluable) locally advanced, 1 CR and 5 PRs (of 10) in metastatic disease, and 1 CR + 1 PR (of 3) second line therapy. Overall response rate was 73% (4 CR + 12 PR + 4 SD = 18% CR and 55% PR) of 22 evaluable pts. These data suggest that combined vinorelbine/cisplatin therapy is highly active in locally advanced and metastatic breast cancer without the high incidence of dose-limiting neurotoxicity seen in our prior paclitaxel/cisplatin trial. Accrual is continuing to improve the 95% confidence interval. (C) American Society of Clinical Oncology 1997
ISSN: 0736-7589
CID: 6028