Redrawing the Lines: The Next Generation of Treatment in Metastatic Breast Cancer

2019 ◽  
pp. e8-e21 ◽  
Author(s):  
Marie-France Savard ◽  
Omar Khan ◽  
Kelly K. Hunt ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Mammalian Target Of Rapamycin ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Careful Consideration ◽  
Locoregional Therapy ◽  
Immune Checkpoints ◽  
Novel Treatments

Although not considered curative in nature, new therapeutic advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. This article discusses the state-of-the-art and emerging therapeutic options for management of MBC. BC systemic therapy targets multiple key pathways, including estrogen receptor signaling, HER2 signaling, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Other therapeutic strategies include targeting DNA repair, inhibiting immune checkpoints, and developing antibody-drug conjugates. Although surgery historically was reserved for palliation of symptomatic, large, or ulcerating masses, some data suggest a possibly expanding role for more aggressive locoregional therapy in combination with systemic therapy. As technology develops, biomarker-specific, line-agnostic, and receptor-agnostic treatment strategies will redraw the current lines of MBC care. However, tumor heterogeneity remains a challenge. To effectively reshape our approach to MBC, careful consideration of the patient perspective, the costs and value of novel treatments, and accessibility (especially in developing countries) is paramount.

Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108)

2022 ◽  
Author(s):  
Seema A. Khan ◽  
Fengmin Zhao ◽  
Lori J. Goldstein ◽  
David Cella ◽  
Mark Basik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Primary Site ◽  
Locoregional Control ◽  
Locoregional Therapy

PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

scholarly journals Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

Breast Cancer ◽  
2021 ◽  
Author(s):  
Takamichi Yokoe ◽  
Sasagu Kurozumi ◽  
Kazuki Nozawa ◽  
Yukinori Ozaki ◽  
Tetsuyo Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

scholarly journals FDG PET/CT for prognostic stratification of patients with metastatic breast cancer treated with first line systemic therapy: Comparison of EORTC criteria and PERCIST

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0199529 ◽  
Author(s):  
Edouard Depardon ◽  
Salim Kanoun ◽  
Olivier Humbert ◽  
Aurélie Bertaut ◽  
Jean-Marc Riedinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Fdg Pet ◽  
Metastatic Breast ◽  
First Line ◽  
Pet Ct ◽  
Eortc Criteria ◽  
Prognostic Stratification ◽  
Fdg Pet Ct

scholarly journals Could Primary Tumor Resection Improve Survival in Metastatic Breast Cancer?

2021 ◽  
Vol 9 (07) ◽  
pp. 422-428
Author(s):  
Rafaela Aparecida Dias de Oliveira ◽  
Lyvia Aparecida Dias de Oliveira ◽  
Marília Davoli Abella Goulart ◽  
Maria Clara Faustino Linhares
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Tumor Resection ◽  
Free Survival

Introduction: In advanced breast cancer, local treatment is considered palliative. However, although there are some polemic opinions about the surgical treatment, some of the latest studies have emphasized that in advanced cases primary tumor resection (PTR) is related to better outcomes. This review aims to evaluate how resection of the original tumor impacts women with metastatic breast cancer, considering the most recent studies about this subject. Methods: The search was performed in MEDLINE, Scopus, PMC, Current Contents and Wiley Online Library databases; 23 articles - from 2016 to 2019 - were selected and 11 were included in this review. As inclusion criteria were considered: studies presenting outcomes about resection of the primary tumor, comparison between chemotherapy/ hormone therapy/ targeted cancer therapies and surgical intervention, studies published from 2016 to 2019 and available in English, Spanish or Portuguese. We excluded those which did not approach PTR, did not present outcomes of interest (progression-free survival comparison between PTR and systemic therapy) or only discussed systemic therapy, as well as those published before 2016. Results: It was reported in 6 studies that progression-free survival is better on those who underwent surgery. PTR was also related to longer median overall survival in women submitted to surgery, up to 16 months higher when compared to the ones who were not. Enhanced survival even pertained to surgical groups regardless of tumor size.  Conclusion: Based in the analysis, PTR in metastatic breast cancer can be related to higher overall survival.

scholarly journals Changes in Overall Survival Over Time for Patients With de Novo Metastatic Breast Cancer

2021 ◽  
Author(s):  
Toshiaki Iwase ◽  
Tushaar Vishal Shrimanker ◽  
Ruben Rodriguez-Bautista ◽  
Onur Sahin ◽  
Anjali James ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
De Novo ◽  
Metastatic Breast ◽  
Locoregional Therapy ◽  
Cancer Center ◽  
Her2 Positive ◽  
Time Periods ◽  
Over Time

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P &amp;lt;.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

scholarly journals Locoregional Surgery in Metastatic Breast Cancer: Do Concomitant Metabolic Aspects Have a Role on the Management and Prognosis in this Setting?

2020 ◽  
Vol 10 (4) ◽  
pp. 227
Author(s):  
Maria Ida Amabile ◽  
Federico Frusone ◽  
Alessandro De Luca ◽  
Domenico Tripodi ◽  
Giovanni Imbimbo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Medical Treatment ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Treatment Decision ◽  
Careful Consideration ◽  
Level Of Evidence ◽  
Systemic Treatments ◽  
Metastatic Setting

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient’s global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.

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