No survival benefit from adding adjuvant chemotherapy to endocrine therapy in older women with a genomic grade index high-risk ER-positive, HER2-negative breast cancer

Findings from ASTER 70s, a phase III randomized superiority study conducted on women 70 years or older "with a genomic grade index (GGI) high-risk oestrogen receptor (ER)-positive, HER2-negative breast cancer" identified no statistically significant effect of adding adjuvant chemotherapy to the prescribed treatment plan.  While the authors od this study admit that more evidence of genomic profiling is needed to determine "whether chemotherapy is necessary for older patents with ER-positive tumours", ASTER 70s has provided little evidence on the benefit of adjuvant chemotherapy for older breast cancer patients. 

To read more about this study, click here. 

Sources mentioned: 

• Brain E, Mir O, Bourbouloux E, et al. for the GERICO&UCBG/Unicancer. Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial . The Lancet 2025;406(10502):p489-500.
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• Linn SC, Hilbers FS. Balancing quality and quantity of life in older patients with breast cancer . The Lancet 2025;406(10502):P422-424.

Analysis identifies 50 new genomic regions associated with kidney cancer risk

 A new genomic study conducted at the National Cancer Institute has identified "50 new areas across the genome that are associated with the risk of developing kidney cancer."  Study data from this data will be used to establish a polygenic risk score, looking at known kidney cancer risk factors, including high blood pressure, smoking, and high body-mass index. 

To read more about this study, click here. 

Source mentioned: Purdue MP, Dutta D, Machiela MJ, et al. Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions. Nature Genetics. April 26, 2024. DOI: 10.1038/s41588-024-01725-7.

Colon cancer linked to mouth bacteria

 A new study, recently published in Nature indicates that Fusobacterium nucleatum, bacteria found in the mouth is linked to colon cancer.  Fusobacterium nucleatum, "associated with dental plaque and gingivitis."  While more evidence linking this bacterium to colon cancer is required (the Nature study was conducted on 100 colon cancer patients), the study authors "envision developing a vaccine against the Fusobacterium nucleatum", using an approach similar to the HPV vaccine. 

To read more about this study, click here. 

First report from the cancer program of the 100,000 genomes project

 The first report from the 100,000 Genomes Cancer Program, consisting of an analysis of whole-genome sequencing from 13,800 solid tumours was recently published in Nature Medicine.  As discussed in the report, comprehensive tumour profiling "will enable further refinement of prognostic and predictive molecular markers, not only with combinations of different genomic alterations, but beyond genomics, including emerging technologies to expand the reach of precision oncology to improve cancer outcomes." 

To learn more about the 100,000 genomes project, click here. 

Source mentioned: 

Sosinsky A., Ambrose J, Cross W, et al. Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme. Nature Medicine; Published online 11 January 2024. DOI: https://doi.org/10.1038/s41591-023-02682-0

First prospective description of familial EGFR-mutated lung cancer

A prospective cohort study, conducted at the Dana-Farber Cancer Institute in Boston has confirmed the existence "of an underappreciated syndrome of familial EGFR-mutated lung cancer predisposition which is characterized by development of lung adenocarcinomas harbouring an atypical spectrum of somatic EGFR mutations and high prevalence of lung nodules in germline carriers without a lung cancer diagnosis."   The study team further describes how cancer genomics has aided in the treatment of non-small cell lung cancer, including an understanding of inherited risk in lung cancer patients who have never smoked.  

To learn more about this study, click here. 

Source mentioned: Oxnard GR, Chen R, Pharr JC, et al. Germline EGFR mutations and familial lung cancer. JCO; Published online 14 August 2023. DOI: 10.1200/JCO.23.01372

NCI unveils comprehensive proteogenomic dataset to help cancer researchers unravel molecular mysteries

 The National Institutes of Health (NIH) is releasing data, via the National Cancer Institute (NCI) "that standardizes genomic, proteomic, imaging, and clinical data from individual studies of more than 1,000 tumors across 10 cancer types."  The purpose of this pan-cancer proteogenomic dataset is to speed up cancer research via sharing of data, namely cancer mutations and protein modifications.  Proteomics data can be accessed via the Proteomic Data Commons at https://pdc.cancer.gov/pdc/cptac-pancancer. Genomic and transcriptomic data can be accessed via the Genomic Data Commons at https://portal.gdc.cancer.gov and the Cancer Data Service at https://dataservice.datacommons.cancer.gov/.

Sources mentioned: 

1. Li Y, Dou Y, Leprevost FDV, et al. Proteogenomic data and resources for pan-cancer analysis. Cancer Cell. August 14, 2023. DOI: 10.1016/j.ccell.2023.06.009.

2. Geffen Y, Anand S, Akiyama Y, et al. Pan-Cancer analysis of post-translational modifications reveals shared patterns of protein regulation. Cell. August 14, 2023. DOI: 10.1016/j.cell.2023.07.013.

3. Li Y, Dou Y, Leprevost FDV, et al. Pan-Cancer proteogenomics connects oncogenic drivers to functional states. Cell. August 14, 2023. DOI: 10.1016/j.cell.2023.07.014.

Helicobacter Pylori infection modifies the risk of gastric cancer associated with germline pathogenic variants in homologous recombination genes

A joint Japanese and Australian cohort study, led by the RIKEN Center for Integrative Medical Sciences in Yokohama, indicated that "pathogenic variants and Helicobacter pylori infection interacted to markedly increase the risk of gastric cancer..."   According to lead researcher Dr. Yukihide Momozawa, evaluation and eradication of Helicobacter pylori is of particular importance in individuals "known to carry a pathogenic variant in a homologous recombinant gene."  

To read more about this study, click here. 

Sources mentioned: 

• Usui Y, Taniyama Y, Endo M, et al. Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. N Engl J Med 2023;388:1181-1190.
• Müller A, He J. A Double Whammy on Gastric Cancer Risk. N Engl J Med 2023;388:1225-1229.

Similarity of molecular portraits in synchronous bilateral breast cancers could be influenced by common environmental factors

 A recent study conducted within the Translational Research Department, Institut Curie, Universite de Paris, found that in breast cancer patients, "immune infiltration was not determined purely by local tumour microenvironment properties, but was different according to the subtype of the contralateral tumour."  The study further unveiled that 5% of patients with bilateral breast cancers carry BRCA1 or BRCA2 mutations; from the 17575 patients listed in the Institut Curie clinical databases, only 2.3% (404) patients had synchronous bilateral breast cancers.  

To read more about this study, click here. 

Source mentioned: Hamy A-S, Abécassis J, Driouch K, et al. Evolution of synchronous female bilateral breast cancers and response to treatment. Nature Medicine; Published online 6 March 2023. DOI: https://doi.org/10.1038/s41591-023-02216-8

Large genomic analysis identifies persistent tumour mutational burden associated with immunotherapy response

Findings from a recently completed genomic analysis published in Nature Medicine indicates that "a high persistent TMB [tumour mutational burden], a biologically relevant measure of tumour foreignness within the overall TMB, represents an 'uneditable' target set for adaptive immune responses and may function as an intrinsic driver of sustained immunologic tumour control that cannot be readily bypassed by neoantigen loss via chromosomal deletions during cancer evolution."  Following an extensive evaluation of mutations across 31 tumour types amongst 9,242 patients, along with 8 patient cohorts (total of 524 patients) diagnosed with non-small-cell lung cancer, melanoma, mesothelioma, and head and neck cancer patients, the study team discovered that "mutations in single-copy regions and those present in multiple copies per cell constitute a pTMB...linked with response to immune checkpoint blockade. 

To read more about this study, click here. 

Source mentioned: Niknafs N, Balan A, Cherry C, et al. Persistent mutation burden drives sustained anti-tumor immune responses. Nature Medicine; Published online 26 January 2023. DOI: https://doi.org/10.1038/s41591-022-02163-w

New trial alert: Marathon of Hope Cancer Centres Network Study for Ontario (MOHCCN-O)

 The Marathon of Hope Cancer Centres Network (MOHCCN), is presently recruiting cancer patients for its new study focusing on "evolving technologies such as genomics and artificial intelligence to study cancer so that the right treatment can be given to the right patient, at the right time."  Sponsored by the University Health Network in Toronto, and involving a collaboration between the Princess Margaret Hospital, the Ontario Institute for Cancer Research, and the Terry Fox Research Institute, this observational study,  over a 5-year period, aims to develop standard practices "to create a unique shareable dataset of molecular imaging, clinical, and health outcome information on Canadian cancer cases." 

To learn more about this trial and the MOHCCN, click here. 

Origins of lung cancer in never smokers

 A new study lead by researchers at the National Cancer Institute (NCI) has conducted a genomic analysis of lung cancer in individuals who have never smoked, determining that "a majority of these tumors arise from the accumulation of mutations caused by natural processes in the body."  The epidemiologic study, conducted a genomic analysis on 232 non-smoker patients with a non-small call lung cancer diagnosis, revealing 3 cancer subtypes categorized by musical names according to number of genomic changes in the tumors.  The "piano" subtype had the least number of mutations, with "mezzo-forte" exhibiting chromosomal changes, and "forte" showcasing "whole-genome doubling, a genomic changes that is often seen in lung cancers in smokers." 

To read more about this study, click here. 

Source mentioned: 

Zhang T, Joubert P, Ansari-Pour N, et al. Genomic and evolutionary classification of lung cancer in never smokers. Nature Genetics. Sept 6, 2021. DOI: 10.1038/s41588-021-00920-0.

Genomics could improve treatment of pancreatic cancer

Researchers at the University of Pittsburgh have analyzed genomes of 3,600 pancreatic tumours worldwide in an effort to diagnose pancreatic cancer at earlier stages and thus increase odds of survival.  According to study lead author Dr. Aatur Singh, "every pancreatic cancer is different.  Developing a molecular profile of each patient's tumor could help determine best treatments." 


To read more about this study, click here.

Test helps identify thyroid nodules that don’t require surgery

Researchers in JAMA Oncology, found that a test measuring genomic changes in tissue samples taken from the thyroid can help identify which patients likely need diagnostic surgery for thyroid cancer and which do not. When a suspicious small growth or lump (called a nodule) is found in the thyroid, doctors perform a fine-needle biopsy so that the cells can be examined by a pathologist.

To read more about this study, click here.

Asbestos-associated genome-wide DNA methylation changes in lung cancer

An Epub ahead of print article published July 19, 2017 in the International Journal of Cancer follows up on previous studies correlating exposure to asbestos and lung cancer.  The current study, a cooperative endeavour between researchers in Finland, France, and Lithuania, reveals "distinctive DNA methylation changes" after a comparison of lung tissue from asbestos-exposed and non-exposed patients (primarily smokers).

 The abstract of this study can be found here.

The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein

Rockefeller University investigators identify a key anti-cancer protein - the study was recently published. Please read more from the Journal of Cell Biology here.

Study reveals how ionising radiation damages DNA and causes cancer

From this study, researchers from the Wellcome Trust Sanger Institute and their collaborators have been able to identify in human cancers two characteristic patterns of DNA damage caused by ionising radiation. These fingerprint patterns may now enable doctors to identify which tumours have been caused by radiation, and investigate if they should be treated differently.

Read more here.

Study mentioned:
S. Behjati and G. Gundem et al. (2016) Mutational signatures of ionizing radiation in second malignancies. Nature Communications DOI: ncomms12605

Regulations issued by FDA for next-generation sequencing use

The utilization of next-generation sequencing (NGS)—which can examine millions of DNA variants at one time—is now being regulated. The FDA has released 2 draft guidances regarding the use of these NGS-based tests, which can be used to inform risk and treatment decisions across multiple tumor types.

The first draft guidance, titled, “Use of Standards in FDA’s Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases” provides recommendations for designing, developing, and validating NGS-based tests for rare hereditary disease.

The second draft guidance, titled, “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics” describes an approach wherein test developers may rely on clinical evidence from FDA-recognized public genome databases to support clinical claims for their tests and provide assurance of accurate clinical interpretation of genomic test results.

The guidances are part of the of the FDA’s engagement in the Precision Medicine Initiative (PMI), created by the White House in early 2015.

“Targeting the right treatments to the right patients at the right time is the goal of the President’s Precision Medicine Initiative,” said FDA commissioner Robert Califf, MD, in a statement. “Soon, patients will have a much more complete picture of their health than in the past, informed by their genetic and genomic makeup.

Read more here.

Patient-derived tumour xenograft models encyclopedia

Researchers from the Novartis Institutes for BioMedical Research established 1,075 patient-derived tumour xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, they performed in vivo compound screens to assess the population responses to 62 treatments across six indications. They demonstrated both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. Read more here.

AACR releases 2015 cancer progress report: Transforming lives through precision medicine

The American Association for Cancer Research (AACR) has released its fifth Cancer Progress Report, a comprehensive summary of the current status of cancer research and treatment. Read more here.

Genomic profiling of cancer of unknown primary site

Genomic profiling of cancer of an unknown primary site (CUP) found at least one clinically relevant genomic alteration in most of the samples tested, an indication of potential to influence and personalise therapy for this type of cancer, which responds poorly to classical chemotherapy, according to a study published online on February 12 by JAMA Oncology. Read more here.