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Medical Crossfire®: Establishing the Role of Predictive Biomarkers and Testing Strategies for Breast Cancer Management PER Pulse™ Recaps

PER Pulse Recap

PER Pulse™ Recap


1 of 3
PER Pulse™ Recap

Overview of Tumor Molecular Profiling in Breast Cancer

This first of 3 PER Pulse™ Recaps focuses on the evolution of the molecular assessment of breast cancer, beginning with ASCO-CAP guideline recommendations. Preanalytic, analytic, and postanalytic variables may all be sources of variability, and these guidelines help to optimize assessment, including guidance regarding the appropriate handling of tissue specimens.1,2 Specific parameters and algorithms regarding immunohistochemistry assessment of estrogen receptor [ER], progesterone receptor [PR], and HER2 are also provided in these guidelines, which may help to inform decisions, particularly in the case of equivocal reporting. All breast tumors should receive this testing, including metastatic tumors.

Molecular assessment continues to evolve with the inclusion of biomarkers in the American Joint Committee on Cancer 8th edition guidance on breast cancer evaluation. The evidence to support the inclusion of biomarkers has come from multiple studies, including a study of 3327 patients with breast cancer from The University of Texas MD Anderson Cancer Center,3 as well as an analysis performed by Dr David Winchester of 238,265 women diagnosed with invasive breast cancer in the National Cancer Database.4 The new prognostic group staging assessment incorporates traditional TNM factors as well as expanded nonanatomic factors such as tumor grade, HER2 status, ER status, and PR status.5 This new system and results from prognostic studies such as TAILORx may help to personalize breast cancer staging and prognosis.5,6

For additional commentary about these topics and others, visit www.gotoper.com to access more resources.

References

  1. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118-145.
  2. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013. doi: 10.1200/JCO.2013.50.9984.
  3. Mittendorf EA, Chavez-MacGregor M, Vila J, et al. Bioscore: a staging system for breast cancer patients that reflects the prognostic significance of underlying tumor biology. Ann Surg Oncol. 2017 Jul 9. doi: 10.1245/s10434-017-6009-x.
  4. Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer – major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290-303. doi: 10.3322/caac.21393.
  5. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized“ approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi: 10.3322/caac.21388.
  6. Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005-2014. doi: 10.1056/NEJMoa1510764.

2 of 3
PER Pulse™ Recap

Personalizing Care by Integrating Advances in Biomarkers

This second of 3 PER Pulse™ Recaps focuses on the potential for integration of biomarker assessment in clinical practice. Determination of the presence of actionable biomarkers is a key component of establishing personalized care; not all tumors have mutations, and not all mutations have a targeted therapy.1 Clinical decision making may be guided by germline and tumor genomic profiles. Two key areas where biomarkers have been studied are triple-negative breast cancer, where BRCA mutations have been studied, as well as estrogen receptor [ER]-positive breast cancer, where a variety of somatic mutations have been studied.2,3

PARP inhibitor therapy is a key class of treatment that has been shown to be influenced by BRCA mutation status in trials of patients with ovarian cancer. Although PARP inhibitor therapy has not yet been approved in breast cancer, recent studies have examined the efficacy of PARP inhibitors in patients with germline BRCA mutations. In the recent OlympiAD study, patients with HER2-negative breast cancer treated with prior anthracycline/taxane treatment and a deleterious or suspected germline BRCA mutation were randomized to olaparib or standard chemotherapy.2 Patients in the olaparib arm had a greater median PFS (7.0 versus 4.2 months), with a hazard ratio for disease progression/death of 0.58.2

In patients with ER-positive breast cancer, endocrine therapy alone or in combinations with CDK4/6 inhibitor therapy is often used.4 A variety of somatic tests, including the implications of ESR1 mutations on treatment efficacy, have been studied in this patient population.3 Genomic profiling may help to guide sequencing decisions for these and other patients.3

For additional commentary about these topics and others, visit www.gotoper.com to access more resources.

References

  1. Shah SP, Roth A, Goya R, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486(7403):395-399. doi: 10.1038/nature10933.
  2. Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523-533. doi: 10.1056/NEJMoa1706450.
  3. Fribbens C, O’Leary B, Kilburn L, et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34(25):2961-2968. doi: 10.1200/JCO.2016.67.3061.
  4. NCCN Clinical Practice Guidelines in Oncology – Breast Cancer. Version 2.2017. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

3 of 3
PER Pulse™ Recap

Tumor Testing Strategies: Current and Future Roles

This third of 3 PER Pulse™ Recaps focuses on the current state of tumor-testing strategies and recent advancements that may shape clinical practice for patients with breast cancer. The concept of personalized breast cancer relies on the identification of molecular profiles associated with therapeutic benefits, enabling selection of patients whose outcomes may be improved with specific therapies.1 There are limitations to the application of precision medicine in breast cancer, which are addressed by the faculty.2

Advancements in testing technology may have the potential to guide therapy selection. Currently, there is no standard of care recommendation for next generation sequencing and proteomic testing. Circulating tumor cells and circulating tumor DNA may have potential applications for patients with breast cancer.3,4 Tumor genotyping (by tissue or blood) has been utilized for selection of matched therapy in clinical trials. Monitoring of tumor mutations by circulating tumor DNA can provide early evidence of pharmacodynamics effect related to matched targeted therapy, but clinical utility has not yet been established. Tumor genotyping may provide insight into tumor changes over time, which may help to guide subsequent lines of therapy.

For additional commentary about these topics and others, visit www.gotoper.com to access more resources.

References

  1. André F, Bachelot T, Commo F, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicenter, prospective trial (SAFIR01/UNICANCER). Lancet Oncol. 2014;15(3):267-274. doi: 10.1016/S1470-2045(13)70611-9.
  2. Arnedos M, Vicier C, Loi S, et al. Precision medicine for metastatic breast cancer—limitations and solutions. Nat Rev Clin Oncol. 2015;12(12):693-704. doi: 10.1038/nrclinonc.2015.123.
  3. Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4(6):650-661. doi: 10.1158/2159-8290.CD-13-1014.
  4. Malvarosa G, Spring L, Juric D, et al. Comparison of genotyping results from tissue and circulating DNA (ctDNA) in patients with metastatic breast cancer. 2016 San Antonio Breast Cancer Symposium. Abstract P1-05-05.
PER® Practice Pulse
Practice Pattern Questions
How often do you attend society oncology/hematology meetings? (ASCO, ASH, SABCS)
Practice Pattern Questions
What is the most significant barrier to implementing new information in your clinical practice?






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