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AACR Special Report: Transforming Cancer Prevention through Precision Medicine and Immune-Oncology

In January of this year, the American Association for Cancer Research (AACR) released a special report outlining its view on how cancer prevention will change in the era of precision medicine and immune-oncology.

The report highlights how emerging technologies, such as next-generation DNA sequencing, computational biology and high-throughput screening for potential new therapies have impacted cancer prevention and how they will shape the future of cancer prevention in the era of precision medicine.

Key advances in breast cancer include:

Identification of genomic patterns (genes that are activated or shut down) in the progression from premalignant to malignant disease.

One example of this is the identification of a genetic pattern shared by both pre-invasive lobular carcinoma in situ (LCIS) and the subsequent invasive lobular cancer (ILC). This work by investigators at Memorial Sloan Kettering Cancer Center has important implications in assessing risk for early prevention.

Further work in this area by BCRF investigator Charles Perou and others identified unique molecular subtypes of invasive lobular breast cancer, the second most prevalent type of invasive breast cancer. This study published last fall in the journal Cell sheds new light on biology of this disease and potential for new therapeutic targets.

These studies lay the groundwork for efforts in the development of genetic profiles for pre-invasive cancers, a sort of “Pre-Cancer Genome Atlas” (PCGA) that can identify the sequence of molecular events in the progression of cancer and enable precision approaches to prevention.

Identification of genomic biomarkers in liquid biopsies. The ability to measure circulating tumor DNA and to isolate single tumor cells in samples of blood has the potential to identify biomarkers for early detection of primary cancers or metastases (cancer spreading), as well as for monitoring patient response to treatment. While still in its infancy, microfluidic technologies and their clinical application are being pursued by several BCRF investigators, including Peter Kuhn and James Hicks, Ben Ho Park, Michael Wigler, Daniel Haber and others.

Characterization of germline (inherited) mutations in cancer predisposition genes. The seminal discoveries that mutations in the BRCA1 and BCRC2 genes result in a deficiency in DNA repair led to new treatment options in BCRA1/2 driven breast cancers, notably the new PARP inhibitors. Subsequent work by BCRF investigator Fergus Couch and others identified genetic modifies of risk in BRCA mutation carriers, leading the way to more personalized risk assessment in this high-risk group. Dr. Couch’s work is part of BCRF’s portfolio totaling more than $7 million dollars in studies of inherited predisposition.

Immunoprevention. Breast cancer immunoprevention, particularly in the form of vaccines, is not as far along as in some other cancers, HPV vaccine for prevention of cervical cancer being a notable example. However, recent developments in immunotherapies such as the new checkpoint (PD1/PDL1) inhibitors that have shown promise in clinical trials are fueling enthusiasm for future immunoprevention strategies.

Genomic technologies have helped in the discovery of unique vaccine targets for cancer prevention, and recent work by Dr. Mary Disis (University of Washington, Seattle) has led to the development of a potential vaccine targeting multiple tumor cell-surface proteins  that are upregulated in high-risk early breast lesions, including ductal carcinoma in situ and atypical hyperplasia. The vaccine will begin testing in Phase I clinical trials this year. Another clinical trial for a vaccine targeting breast cancer stem cells, called STEMVAC, is currently being tested a Phase I clinical trial for the treatment of advanced HER2-negative breast cancer.

BCRF invested more than $6.5 million in 22 cancer immunology-related research projects in 2015.  Work by BCRF investigators including Karen Anderson, Susan Domchek, Leisha Emens and Elizabeth Jaffee, Annette Khaled, Robert Vonderheide, Jedd Wolchok and others continues to inform our understanding of immune-oncology in breast cancer.

Since its inception, BCRF has played a role in every major clinical advancement by supporting the best clinical and basic scientists in the field, fostering collaboration and encouraging innovation.  In 2015, we funded over $6 million in prevention-related studies. With more than $54-million and 240 investigators worldwide this year, BCRF is well positioned to continue to be at the vanguard in advances in breast cancer research.

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