Geriatric Breast Cancer Tumor Profiles Can Help Plan Treatment

Tumors from elderly breast cancer patients carry unique features compared to their younger counterparts, according to a new study.     

This information is relevant and important to planning patient treatment as well as clinical trial designs.

“This is the largest biomarker analysis on elderly breast tumors to date, which provides information on protein expression, gene amplification, and tremendous amount of mutation data using next-generation sequencing,” lead author Joanne Xiu, PhD, Molecular Science Liaison/Research Scientist at Caris Life Science in Phoenix, said in an interview.

Senior author Paula Pohlmann, MD, MSc, PhD, will present these results at the 2015 American Society of Clinical Oncology (ASCO) Breast Cancer Symposium in San Francisco (Abstract 116).

While the absolute number of geriatric breast cancer patients is increasing, knowledge about the molecular characteristics specific to this patient group is still limited.

“The clinical management of elderly breast cancer patients is very different from younger patients, with the consideration of declining functional status and life expectancy,” said Xiu. “Therefore, the understanding of biomarker profiles in the elderly cohort is important to tailor patient treatment.”

The researchers collected 1189 tumors from breast cancer patients (1168 women, 21 men) with a median age of 75.6 years. The tumors were analyzed by breast biopsy (512) and metastatic site (677).

Of the 1088 tumors with available immunohistochemistries (IHC) of estrogen receptor and progesterone receptor, and IHC and/or fluorescent/chromogenic in-situ hybridization of human epidermal growth factor receptor 2 (HER2), 56% were hormone receptor-positive (HR+)/HER2-, 7% were HR+/HER2+, 32% were triple-negative breast cancer, and 5% were HR-/HER2+.

Overall, 39 of 47 genes sequenced carried mutations. Highest mutation rates were seen in PIK3CA (37%), TP53 (37%), BRCA2 (12%), PTEN (5.8%), AKT1 (4.2%), c-MET (3.9%), ERBB2 (3.5%), BRCA1 (3.3%) and ATM (3.2%).

“Important findings in the study include a lower TOP2A expression and BRCA1 mutation in the geriatric group, supporting a less frequent use of TOP2A inhibitors, including anthracyclines and DNA-damaging agents, including platinums, for elderly patients,” said Xiu.

“Very interestingly, androgen receptor expression in the elderly triple-negative cohort is nearly twice as high as seen in the younger triple-negative cohort. Antiandrogen therapies are under heavy investigations, and the large difference observed could help with the design of such clinical trials.”

In addition, TS, RRM1, and ERCC1 were underexpressed in 69%, 69%, and 53%, respectively, suggesting potential sensitivity to fluoropyrimidines, gemcitabine (Gemzar), and platinums.

“The study shows molecular characteristics of breast cancer that are unique to elderly patients, which reveals therapeutic opportunities that would not have been considered otherwise,” said Xiu. “We believe that all metastatic or aggressive breast tumors taken from elderly patients should be profiled so that the treating physician could make an informed decision on the treatment plan.”