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Slide Show: Highlights From the 2015 ASCO Breast Cancer Symposium

Slide Show: Highlights From the 2015 ASCO Breast Cancer Symposium

  • Slide1: Racial Disparities Among HER2+ Breast Cancer Patients Narrowing--Among women diagnosed with primary HER2-positive (+), estrogen receptor (ER)-negative breast cancer between 2000 and 2012, there were no racial disparities between white and African American women in terms of overall survival. The study analyzed survival by race/ethnicity among 32,597 women diagnosed with HER2+ breast cancer in the the California Cancer Registry. Among those diagnosed with ER+, HER2+ disease, African American women had a higher mortality than white women if diagnosed between 2000 and 2006, but there was no disparity among the women diagnosed between 2007 and 2012. “The era of adjuvant trastuzumab appears to have attenuated the black/white disparity in HER2-positive breast cancer,” the authors concluded.¹ Image Source: Vincent Caggiano MD, Carol Parise, PhD, Sutter Medical Center, Sacramento, Calif.
  • Slide 2: Potential Luminal B Breast Cancer Biomarker--In a retrospective analysis of 200 tumor samples, TOX3 protein was found to be expressed in a significant subset of luminal B breast tumors. Patients with high TOX3 expression had a poorer prognosis (P = .0023). However, there was no association between TOX3 expression and Oncotype Dx recurrence score. A single nucleotide polymorphism within the TOX3 gene, expressed in estrogen receptor (ER)-positive (+) mammary epithelial cells has been previously associated with breast cancer. "The lack of correlation of TOX3 expression and recurrence scores may suggest a facet of the biology of ER+ aggressive cancers that may not be addressed by the Oncotype DX assay,” concluded the study authors.² Image Source: Jenny Hong, MD, Division of Surgical Oncology, Dept. of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles.
  • Slide 3: Clinical Benefit of Retesting for BRCA1, BRCA2 Mutations--Eleven percent (14) of 122 subjects who initially tested negative for a BRCA1 or BRCA2 hereditary mutation tested positive for a pathogenic mutation upon repeat multigene testing. One hundred fifteen patients had a personal history of cancer with a median age of initial diagnosis of 45 years of age; 105 patients had a personal history of breast cancer. The median time between initial testing and retesting was 4 years and median age of patients upon retesting was 54 years of age. All pathological mutations identified are actionable and could impact patient management, and included mutations in the ATM, CHEK2, and PALB2 genes. “This study demonstrates the feasibility and clinical benefit of retesting individuals who previously tested negative for BRCA1/2 mutation,” the authors concluded.³ Image Source: Siddhartha Yadav, MD, Nancy and James Grosfeld Cancer Genetics Center, Beaumont Cancer Institute, Beaumont Health, Royal Oak, Mich.
  • Slide 4: Aromatase Inhibitors and Contralateral Breast Cancer Risk--Adjuvant aromatase inhibitor (AI) therapy may reduce the risk of contralateral breast cancer (CBC) in those women with BRCA-positive (+) disease according to the results of an 812 BRCA+ breast cancer patient analysis. While there is evidence that tamoxifen treatment may reduce CBC risk, this is the first study to examine the connection between AIs and CBC. Of the 812 patients, 700 had estrogen receptor-positive tumors and 68 (8.7%) were diagnosed with contralateral breast cancer. Compared to BRCA-negative patients, patients with either BRCA1+ or BRCA2+ tumors had a higher risk of developing CBC (hazard ratio [HR] of 2.49, P = .013 for BRCA1+ and HR of 1.97, P = .036 for BRCA2+ patients). Those patients who received an AI had a reduced risk of CBC (HR of 0.42, P = .01) compared to those who did not receive an AI.⁴ Image Source: San Francisco - 2015 Breast Cancer Symposium; ASCO/Scott Morgan 2015.
  • Slide 5: Variability of Responses to PARP Inhibitors Among Breast Cancer Cell Lines--At least three different poly ADP ribose polymerase (PARP) inhibitors—veliparib, olaparib, and BMN673 are currently being tested in clinical trials for breast cancer. Saima Noor Hassan, MD, and her colleagues are developing a triple-negative breast cancer cell line-based assay to assess which breast cancer subtypes are more likely to respond to PARP inhibitors. Thus far, of the eight cell lines tested, the three PARP inhibitors exhibited a range of responses to each cell line. BMN 673 had the highest potency with half maximal inhibitory concentrations (IC50) in the nanomolar range, while IC50 values of olaparib and veliparib were in the micromolar range. The researchers are currently further improving their cell death DNA damage response score, which is able to distinguish which BRCA-wild type cell lines could be more responsive to either PARP inhibitor monotherapy or combination therapies.⁵ Image Source: San Francisco - 2015 Breast Cancer Symposium; ASCO/Scott Morgan 2015.
  • Slide 6: Extended Adjuvant Therapy With Neratinib for HER2+ Breast Cancer Patients--Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improved invasive disease-free survival (iDFS) in patients with HER2-positive (+) breast cancer who have been pretreated with trastuzumab (Herceptin) adjuvant therapy for one year. The study sought to understand whether additional therapy with neratinib after standard trastuzumab plus chemotherapy adjuvant therapy for women at high risk of relapse would improve outcomes. Women with local, early-stage, HER2+ disease were randomized one-to-one to either an oral daily dose of neratinib or placebo. Of a total of 2,840 patients in the intent to treat cohort, neratinib lowered the risk of death from invasive breast cancer by 33% compared to placebo (hazard ratio of 0.67).⁶ Image Source: San Francisco - 2015 Breast Cancer Symposium; ASCO/Scott Morgan 2015.
References: 
  1. Caggiano V, Parise C. Racial/ethnic disparities in HER2-positive breast cancer in the era of adjuvant trastuzmab. Presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium; Abstract 139.
  2. Hong JJ, Seksenyan A, Yuan X. et al. TOX3 as a novel biomarker in luminal B breast cancer. Presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium; Abstract 130.
  3. Yadav S, Fulbright J, Dreyfuss H,  et al. Outcomes of retesting BRCA-negative patients using multigene panels. Presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium; Abstract 23.
  4. Shafaee MN, Gutierrez-Barrera AM, Lin HL, Arun B. Aromatase inhibitors and the risk of contralateral breast cancer in BRCA mutation carriers. Presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium; Abstract 3.
  5. Hassan SN, Esch A, Heiser L, Gray JW. Biological indicators of response and resistance to PARP inhibition in BRCA wild-type breast cancer. Presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium; Abstract 125.
  6. Chan A, Martin M, Von Minckwitz G. et al. Invasive disease-free survival benefit following neratinib as extended adjuvant therapy in centrally-confirmed HER2+ early-stage breast cancer: The ExteNET phase III randomized placebo-controlled trial. Presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium; Abstract 117.

 

 

 

 

 

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