p16INK4a Gene Expression, Chemotherapy Toxicity, and Age in Women with Breast Cancer

Project: Research project


Please provide a brief project description in simple language that can be publicly shared on the BCRF website, with donors and in other
communications and releases. Be sure to explain scientific terms and any abbreviations or acronyms and avoid special characters such as Greek
letters. You may type directly into the box provided or cut and paste from a Word document. P16 gene expression, a molecular marker of aging,
increases 10-20 fold between the ages of 20 and 80. Human cells with high p16 expression are less capable of dividing than cells with low
expression. In addition, smoking and lack of exercise increase expression at higher rates than in non-smokers and exercisers. We have shown
that p16 rapidly and irreversibly rises 1-2 fold in circulating immune cells (T-lymphocytes) in the blood in most women receiving standard adjuvant
chemotherapy regimens for breast cancer (Sanoff et al, Journal of the National Cancer Institute, 2014). In addition, our data suggests that patients
with a greater change in p16 levels during chemotherapy are more likely to have greater hematologic toxicity. We hypothesize that patients with
higher levels of cellular p16 protein in their bone marrow stem cells, and cells lining the mouth, esophagus, and stomach, may have greater
toxicity with chemotherapy. This is because after treatment cells with high p16 levels would take longer to replicate as compared to cells with lower
levels. If this is true p16 might prove to be an independent marker that predicts chemotherapy-related toxicity; such information would help tailor
treatment for individual patients. We have also shown that a simple, scalable, walking program in women on aromatase inhibitors is feasible and
well received (Nyrop et al, J Geriatric Oncol, in press). We have preliminary data from an ongoing BCRF supported trial that this walking program
is feasible in older women receiving adjuvant chemotherapy and have opened another trial to test this same walking program in younger women
receiving adjuvant chemotherapy. Last, we have used the data from our BCRF supported projects to apply and successfully be awarded
$1,000,000 grant from the Kay Yow foundation to expand these studies nationally.
Effective start/end date10/1/159/30/16


  • Breast Cancer Research Foundation


p16 Genes
Breast Neoplasms
Gene Expression
Drug Therapy
Adjuvant Chemotherapy
Aromatase Inhibitors
National Cancer Institute (U.S.)
Bone Marrow Cells
Stem Cells
Tissue Donors