Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

AbstractCirculating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.

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Randomized phase-II evaluation of letrozole plus dasatinib in hormone receptor positive metastatic breast cancer patients

npj Breast Cancer ◽

10.1038/s41523-019-0132-8 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 3

Author(s):

Devchand Paul ◽

Svetislava J. Vukelja ◽

Frankie Ann Holmes ◽

Joanne L. Blum ◽

Kristi J. McIntyre ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Kinase Inhibitor ◽

Acquired Resistance ◽

Metastatic Breast ◽

Progression Free Survival ◽

Therapy Resistance ◽

Breast Cancer Patients ◽

Er Positive

Abstract The non-receptor tyrosine kinase Src activation plays a role in the malignant progression of breast cancer, including development of endocrine therapy resistance and survival of bone metastases. This study investigated whether adding Src kinase inhibitor dasatinib to aromatase inhibitor (AI) therapy improved outcomes in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC). Postmenopausal patients with ER-positive, HER2-negative MBC (0–1 prior chemotherapies and no prior AI for MBC) were eligible for this non-comparative, parallel group, phase-II study. Patients were randomized to letrozole (2.5 mg/day PO) alone or with dasatinib (100 mg/day PO). Patients with disease progression on letrozole alone could crossover to dasatinib plus continued letrozole. The primary endpoint was clinical-benefit-rate (CBR; complete response + partial response + stable disease ≥6 months). A total of 120 patients were randomized. The CBR of 71% (95% CI 58–83%) was observed with letrozole + dasatinib versus the projected CBR of the combination of 56%. The CBR of 66% (95% CI 52–77%) with letrozole alone also exceeded the projected CBR of 39% with letrozole alone. The CBR was 23% in the crossover arm of letrozole plus dasatinib in patients progressing on letrozole alone. Median progression-free survival with the combination was 20.1 months and 9.9 months with letrozole alone. Letrozole plus dasatinib was well tolerated, although 26% of patients required dasatinib dose reductions. In this non-comparative phase-II trial, the CBR of 71% and the median PFS of 20.1 months with letrozole + dasatinib are encouraging and suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.

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Abstract P1-01-01: Circulating tumor cell number and CTC-endocrine therapy index predict clinical outcomes in ER positive metastatic breast cancer patients: Results of the COMETI Phase 2 trial

10.1158/1538-7445.sabcs16-p1-01-01 ◽

2017 ◽

Cited By ~ 4

Author(s):

C Paoletti ◽

MM Regan ◽

MC Liu ◽

PK Marcom ◽

LL Hart ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Tumor Cell ◽

Metastatic Breast ◽

Circulating Tumor Cell ◽

Cell Number ◽

Phase 2 ◽

Breast Cancer Patients ◽

Phase 2 Trial ◽

Er Positive

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Degree of Early Estrogen Response Predict Survival after Endocrine Therapy in Primary and Metastatic ER-Positive Breast Cancer

Cancers ◽

10.3390/cancers12123557 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3557

Author(s):

Masanori Oshi ◽

Yoshihisa Tokumaru ◽

Fernando A. Angarita ◽

Li Yan ◽

Ryusei Matsuyama ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Endocrine Therapy ◽

Patient Compliance ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Gene Set ◽

Estrogen Response ◽

Er Positive

Endocrine therapy is the gold-standard treatment for ER-positive/HER2-negative breast cancer. Although its clear benefit, patient compliance is poor (50–80%) due to its long administration period and adverse effects. Therefore, a predictive biomarker that can predict whether endocrine therapy is truly beneficial may improve patient compliance. In this study, we use estrogen response early gene sets of gene set enrichment assay algorithm as the score. We hypothesize that the score could predict the response to endocrine therapy and survival of breast cancer patients. A total of 6549 breast cancer from multiple patient cohorts were analyzed. The score was highest in ER-positive/HER2-negative compared to the other subtypes. Earlier AJCC stage, as well as lower Nottingham pathological grade, were associated with a high score. Low score tumors enriched only allograft rejection gene set, and was significantly infiltrated with immune cells, and high cytolytic activity score. A low score was significantly associated with a worse response to endocrine therapy and worse survival in both primary and metastatic breast cancer patients. The hazard ratio was double that of ESR1 expression. In conclusion, the estrogen response early score predicts response to endocrine therapy and is associated with survival in primary and metastatic breast cancer.

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Tolerance of concurrent CDK inhibitor and radiation therapy in metastatic breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12598 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12598-e12598

Author(s):

Arnaud Beddok ◽

Alexandre Arsene-Henry ◽

Baptiste Porte ◽

Kim Cao ◽

Nathaniel Scher ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Metastatic Breast Cancer ◽

Brain Lesion ◽

Metastatic Breast ◽

Progression Free Survival ◽

Late Toxicity ◽

Breast Cancer Patients ◽

Number Of Patients ◽

Er Positive

e12598 Background: Palbociclib, a small-molecule inhibitor of cyclin-dependent kinases (CDK4 and CDK6), combined with letrozole increases progression-free survival among patients with previously untreated ER-positive, HER2 negative advanced breast cancer. The purpose of our study was to retrospectively evaluate the tolerance of the concomitant association of Palbociclib and radiation therapy (RT) at Curie Institute. Methods: Between April 2017 and August 2019, 30 women with ER-positive, HER2 negative metastatic breast cancer received locoregional (LR) and/or symptomatic irradiation at a metastatic site concurrently with Palbociclib at a daily dose of 125 mg, from d1 to d21 every 28 days. Palbociclib was always associated with endocrine therapy: letrozole (with or without an LHRH analogue) or fulvestrant. Thirty-five sites were irradiated: nine patients received post-operative locoregional RT, including the chest wall or breast and lymph node areas, and 26 sites of metastases were irradiated: 17 at the spine, 7 peripheral skeletal lesions, 1 brain lesion and 1 choroidal lesion. The dose prescribed for locoregional mammary radiotherapy was 50 Gy in 25 fractions and varied for the treatment of metastatic sites: 20 Gy in 5 fractions (n = 13), 30 Gy in 10 fractions (n = 10) and 8 Gy in 1 fraction (n = 2). The brain metastasis was stereotactically treated (1 fraction of 18 Gy). The primary endpoint was toxicity scored according to the common terminology criteria for NCI adverse events, version v5.0. Results: Mean number of days of Palbociclib during RT was 8.8 days (range, 1 to 24 days). The most common acute toxicities were dermatitis (12/35, including 2 grade 2) and neutropenia (12/35, including 9 grade 2). Palbociclib had to be stopped during the RT of two patients (2/30): one patient treated locoregionally (bilateral breast and lymph nodes irradiation) developed a grade 3 dermatitis and febrile neutropenia, another treated locoregionally developed grade 2 dysphagia. After a median follow-up since the end of RT of 17 months (6 – 31 months, SD 8), none of the patients have so far exhibited late toxicity. Conclusions: Concomitant administration of palbociclib with RT was reasonably well tolerated in our series of 30 patients. Given this experience, palbociclib should not be discontinued during radiation therapy. Nevertheless, our findings should be confirmed in prospective registration studies collecting larger number of patients.

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Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2– Metastatic Breast Cancer Patients: What Is the Better Choice?

Oncology ◽

10.1159/000521252 ◽

2021 ◽

Author(s):

Alessandra Fabi ◽

Mariangela Ciccarese ◽

Sinome Scagnoli ◽

Michelangelo Russillo ◽

Francesco Schettini ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Metastatic Breast ◽

Progression Free Survival ◽

Subsequent Treatment ◽

Second Line ◽

Breast Cancer Patients ◽

Third Line ◽

Metastatic Sites

Background: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). Objectives: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. Methods: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. Results: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. Conclusions: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

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Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920987651 ◽

2021 ◽

Vol 13 ◽

pp. 175883592098765

Author(s):

Raffaella Palumbo ◽

Rosalba Torrisi ◽

Federico Sottotetti ◽

Daniele Presti ◽

Anna Rita Gambaro ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Endocrine Therapy ◽

Real World ◽

Hormone Receptor ◽

Metastatic Breast ◽

Progression Free Survival ◽

Her2 Receptor ◽

Treatment Line ◽

Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

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