Circulating tumour DNA in metastatic breast cancer to guide clinical trial enrolment and precision oncology: A cohort study

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.

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116 A phase I clinical trial to evaluate the pharmacokinetics, toxicity and dosimetry of 111-indium-labeled human epidermal growth factor in patients with metastatic breast cancer

Radiotherapy and Oncology ◽

10.1016/s0167-8140(05)80277-4 ◽

2005 ◽

Vol 76 ◽

pp. S35

Author(s):

K. Vallis ◽

R. Reilley ◽

D. Scollard ◽

J. Petronis ◽

C. Caldwell ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Metastatic Breast Cancer ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Phase I ◽

Metastatic Breast ◽

Phase I Clinical Trial ◽

Human Epidermal Growth Factor ◽

Epidermal Growth

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Risk of primary gastrointestinal cancers following incident non-metastatic breast cancer: a Danish population-based cohort study

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2020-000413 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000413

Author(s):

Kasper Adelborg ◽

Dóra Körmendiné Farkas ◽

Jens Sundbøll ◽

Lidia Schapira ◽

Suzanne Tamang ◽

...

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Cohort Study ◽

Metastatic Breast Cancer ◽

Stomach Cancer ◽

Metastatic Breast ◽

Population Based ◽

Gastrointestinal Cancers ◽

Increased Risk

ObjectiveWe examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population.DesignUsing population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990–2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs).ResultsAmong 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2–5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6–10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990–2006 and 2007–2017, the 1–10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible.ConclusionBreast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007.

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A phase I clinical trial of bavituximab and paclitaxel in patients with HER2 negative metastatic breast cancer

Cancer Medicine ◽

10.1002/cam4.447 ◽

2015 ◽

Vol 4 (7) ◽

pp. 1051-1059 ◽

Cited By ~ 21

Author(s):

Pavani Chalasani ◽

Marilyn Marron ◽

Denise Roe ◽

Kathryn Clarke ◽

Maria Iannone ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Metastatic Breast Cancer ◽

Phase I ◽

Metastatic Breast ◽

Phase I Clinical Trial

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Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial

Breast Cancer Research and Treatment ◽

10.1007/s10549-018-05070-2 ◽

2018 ◽

Vol 174 (2) ◽

pp. 433-442 ◽

Cited By ~ 17

Author(s):

O. Nanni ◽

◽

D. Amadori ◽

A. De Censi ◽

A. Rocca ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Line Treatment ◽

Phase 2 ◽

First Line ◽

Phase 2 Clinical Trial ◽

Randomized Phase 2 ◽

First Line Treatment

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CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

JCO Precision Oncology ◽

10.1200/po.20.00248 ◽

2021 ◽

pp. 676-686

Author(s):

Mario Hlevnjak ◽

Markus Schulze ◽

Shaymaa Elgaafary ◽

Carlo Fremd ◽

Laura Michel ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Management ◽

Metastatic Breast ◽

Previous Treatment ◽

Progression Free Survival ◽

Tumor Board ◽

Precision Oncology ◽

Whole Genome ◽

Free Survival

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

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