scholarly journals Receptor conversion impacts outcomes of different molecular subtypes of primary breast cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110129
Author(s):  
Weipeng Zhao ◽  
Linlin Sun ◽  
Guolei Dong ◽  
Xiaorui Wang ◽  
Yan Jia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Progression ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Primary Tumors ◽  
Therapy Management ◽  
Metastatic Lesions ◽  
Conversion Rates ◽  
Receptor Conversion

Background: Although the conversion of clinically used breast cancer biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) between primary tumors and metastatic lesions is well recognized, data on whether receptor conversion has an effect on therapy management and survival in patients with metastatic breast cancer is limited. This study aimed to investigate the clinical implications of receptor conversion throughout tumor progression. Methods: In total, 2450 patients diagnosed with metastatic breast cancer in Tianjin Medical University Cancer Institute and Hospital were analyzed and 426 female patients with available biopsy results from both primary and metastatic sites were included in this study. We investigated the alteration of ER, PR and HER2 during breast cancer progression and evaluated the therapy management and prognostic value of receptor conversion. Results: The conversion rates of ER, PR, and HER2 between primary tumors and metastasis were 21.1% (McNemar’s test p < 0.001), 33.2% ( p < 0.001), and 11.6% ( p = 0.868), respectively. Evaluation of ER, PR, and HER2 status in multiple consecutive metastases revealed a change in 19.1% ( p > 0.05), 23.5% ( p = 0.021), and 9.8% ( p > 0.05) of patients, respectively. Adjuvant therapy (chemotherapy/endocrine therapy) was related to hormone receptor conversion ( p < 0.05). A statistically significant differential survival associated with hormone receptor (ER/PR) conversion (log-rank p < 0.05) was observed. In the multivariate analysis, ER conversion was an independent influence factor of survival ( p < 0.05). Molecular typing conversion in primary and metastatic lesions also had a significant effect on survival ( p < 0.05). We found that changing treatment based on the receptor conversion could affect clinical outcomes ( p < 0.05). Conclusions: Our findings indicated that receptor conversion during breast tumor progression had a significant effect on survival. Most importantly, our findings proved that patients with receptor conversion benefited from a change in therapy.

scholarly journals Prognostic Value and Influence of Receptor Conversion on Treatment Regimen in Metastatic Breast Cancer at the First Time of Recurrence

2020 ◽  
Vol 43 (11) ◽  
pp. 620-627
Author(s):  
Jiming Shen ◽  
Lu Xu ◽  
Jing Shi ◽  
Lei Zhao ◽  
Sha Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Regimen ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Receptor Status ◽  
Metastatic Lesions ◽  
Receptor Conversion ◽  
First Time

<b><i>Purpose:</i></b> At the first time of metastatic breast cancer recurrence, conversion of the receptors status may occur between primary lesions and metastatic lesions, including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Whether the decision of the treatment regimen is based on the primary receptor status or that of metastatic lesions is still unclear. <b><i>Methods:</i></b> This study enrolled 411 female patients with a diagnosis of metastatic breast cancer at the first time of recurrence to explore the influence of receptor conversion on prognosis prediction and treatment regimen of patients with metastatic breast cancer. <b><i>Results:</i></b> ER and PR changes from negative to positive are both prognostic factors for patients with breast cancer. Patients receiving endocrine therapy showed a better survival after recurrence than those using chemotherapy alone in the ER or PR Prim– Met+ subgroup. Patients in the HER2 Prim– Met+ subgroup using HER2-targeted therapy in multilines showed a post-recurrence survival advantage. In the bone re-biopsy subgroup, the PR change from positive to negative appeared to be more frequent than at other re-biopsy sites. <b><i>Conclusions:</i></b> Patients with metastatic breast cancer should perform re-biopsy to clarify the receptor status of the first metastatic lesions, which may provide clinicians valuable evidence to conduct treatments with higher precision.

scholarly journals Receptor Conversion between Primary Tumors and Distant Metastases in 121 Cases of Metastatic Breast Cancer

2013 ◽  
Vol 04 (02) ◽  
pp. 102-107
Author(s):  
Chaoying Wang ◽  
Lijun Di ◽  
Kun Yan ◽  
Huiping Li ◽  
Guohong Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Primary Tumors ◽  
Receptor Conversion

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals 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

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.

scholarly journals Physical Activity, Weight, and Outcomes in Patients Receiving Chemotherapy for Metastatic Breast Cancer (C40502/Alliance)

2021 ◽  
Author(s):  
Jennifer A Ligibel ◽  
Luke Huebner ◽  
Hope S Rugo ◽  
Harold J Burstein ◽  
Debra L Toppmeyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Body Mass Index ◽  
Metastatic Breast Cancer ◽  
Body Mass ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Hazard Ratio ◽  
First Line ◽  
Risk Of Cancer

Abstract Background Obesity and inactivity are associated with increased risk of cancer related- and overall mortality in breast cancer, but there are few data in metastatic disease. Methods CALGB 40502 was a randomized trial of first-line taxane-based chemotherapy for patients with metastatic breast cancer. Height and weight were collected at enrollment. After 299 patients enrolled, the study was amended to assess recreational physical activity (PA) at enrollment using the Nurses’ Health Study Exercise Questionnaire. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using stratified Cox modeling (strata included hormone receptor status, prior taxane, bevacizumab use, and treatment arm). Results 799 patients were enrolled and at the time of data lock, median follow-up was 60 months. At enrollment, median age was 56.7 years, 73.1% of participants had hormone receptor-positive cancers, 42.6% had obesity, and 47.6% engaged in less than 3 metabolic equivalents of task (MET)-hours of PA/week (&lt;1 hour of moderate PA). Neither baseline body mass index nor PA was statistically significantly associated with PFS or OS, although there was a marginally statistically significant increase in PFS (hazard ratio = 0.83, 95% confidence interval [CI] = 0.79, 1.02; p = .08) and OS (hazard ratio = 0.81, 95% CI = 0.65, 1.02; p = .07) in patients who reported PA greater than 9 MET-hours/week vs 0–9 MET-hours/week. Conclusions In a trial of first-line chemotherapy for metastatic breast cancer, rates of obesity and inactivity were high. There was no statistically significant relationship between body mass index and outcomes. More information is needed regarding the relationship between PA and outcomes.

scholarly journals Olaparib in hormone receptor-positive, HER2-negative metastatic breast cancer with a somatic BRCA2 mutation

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Lee S. Schwartzberg ◽  
Lesli A. Kiedrowski
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Response ◽  
Hormone Receptor ◽  
Brca2 Mutation ◽  
Locally Advanced ◽  
Susceptibility Gene ◽  
Metastatic Breast ◽  
Breast Cancer Susceptibility Gene ◽  
Hormone Receptor Positive

The oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib is approved for the treatment of patients with human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (mBC) and a germline breast cancer susceptibility gene (BRCA) mutation who have been treated with chemotherapy. This case report describes a 63-year-old postmenopausal woman with somatic BRCA2-mutated mBC who responded to olaparib treatment following multiple prior lines of therapy. The patient presented in January 2012 with locally advanced, hormone receptor-positive (HR+), HER2− BC which, despite initial response to neoadjuvant chemotherapy, recurred as bone disease in February 2014, and subsequently skin (June 2016) and liver (October 2016) metastases. A comprehensive 592-gene next-generation sequencing panel (Caris Life Sciences), performed on a skin biopsy, detected a pathogenic frameshift mutation in BRCA2 (H3154fs, c.9460delC), which was not identified in a 28-gene hereditary cancer germline analysis (Myriad Genetics, Inc.), and was therefore considered to be a somatic mutation. In January 2017, cell-free DNA (cfDNA) analysis (Guardant Health, Inc.) confirmed the BRCA2 H3154fs mutation in plasma. After several lines of chemotherapy and endocrine therapy, deriving clinical benefit from eribulin and capecitabine, the disease progressed by October 2017, and olaparib (300 mg orally twice daily) was initiated in January 2018. By April 2018, the liver lesions had shrunk by 80% and a >90% response in multiple skin lesions was noted. Clinical response was maintained for 8 months, followed by progression in the skin in September 2018. Biopsy of recurrent lesions revealed a novel BRCA2 mutation, E3152del (c.9455_9457delAGG), predicted to restore the open reading frame and presumably the mechanism of resistance to olaparib. Further likely resistance mutations were noted in subsequent cfDNA analyses. This case demonstrated a clinical response with olaparib as a later-line therapy for HR+, HER2− mBC with a somatic BRCA2 mutation.

scholarly journals Regulatory T lymphocyte infiltration in metastatic breast cancer—an independent prognostic factor that changes with tumor progression

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jenny Stenström ◽  
Ingrid Hedenfalk ◽  
Catharina Hagerling
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Independent Prognostic Factor ◽  
Primary Tumors

Abstract Background Patients diagnosed with metastatic breast cancer have poor outcome with a median survival of approximately 2 years. While novel therapeutic options are urgently needed, the great majority of breast cancer research has focused on the primary tumor and less is known about metastatic breast cancer and the prognostic impact of the metastatic tumor microenvironment. Here we investigate the immune landscape in unique clinical material. We explore how the immune landscape changes with metastatic progression and elucidate the prognostic role of immune cells infiltrating primary tumors and corresponding lymph node and more importantly distant metastases. Methods Immunohistochemical staining was performed on human breast cancer tissue microarrays from primary tumors (n = 231), lymph node metastases (n = 129), and distant metastases (n = 43). Infiltration levels of T lymphocytes (CD3+), regulatory T lymphocytes (Tregs, FOXP3+), macrophages (CD68+), and neutrophils (NE+) were assessed in primary tumors. T lymphocytes and Tregs were further investigated in lymph node and distant metastases. Results T lymphocyte and Treg infiltration were the most clinically important immune cell populations in primary tumors. Infiltration of T lymphocytes and Tregs in primary tumors correlated with proliferation (P = 0.007, P = 0.000) and estrogen receptor negativity (P = 0.046, P = 0.026). While both T lymphocyte and Treg infiltration had a negative correlation to luminal A subtype (P = 0.031, P = 0.000), only Treg infiltration correlated to luminal B (P = 0.034) and triple-negative subtype (P = 0.019). In primary tumors, infiltration of T lymphocytes was an independent prognostic factor for recurrence-free survival (HR = 1.77, CI = 1.01–3.13, P = 0.048), while Treg infiltration was an independent prognostic factor for breast cancer-specific survival (HR = 1.72, CI = 1.14–2.59, P = 0.01). Moreover, breast cancer patients with Treg infiltration in their distant metastases had poor post-recurrence survival (P = 0.039). Treg infiltration levels changed with metastatic tumor progression in 50% of the patients, but there was no significant trend toward neither lower nor higher infiltration. Conclusion Treg infiltration could have clinical applicability as a prognostic biomarker, deciphering metastatic breast cancer patients with worse prognosis, and accordingly, could be a suitable immunotherapeutic target for patients with metastatic breast cancer. Importantly, half of the patients had changes in Treg infiltration during the course of metastatic progression emphasizing the need to characterize the metastatic immune landscape.

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