Gene Marker may Predict Breast Cancer Response to Tamoxifen

The gist: Oncologists can sometimes check a patient’s tumor for specific genetic mutations that indicate how well different treatment options might work. Researchers recently discovered a genetic mutation found in some breast cancer tumors that could help oncologists predict how well the drug tamoxifen will work for a patient with ER-positive breast cancer. Further studies are needed to explore just how useful the discovery might be.

“Researchers have identified genes that may help predict whether a patient with estrogen receptor (ER)-positive breast cancer is likely to benefit from tamoxifen therapy, according to a study published in the July 15 issue of Cancer Research.

“Hendrika M. Oosterkamp, M.D., of The Netherlands Cancer Institute in Amsterdam, and colleagues conducted a large-scale loss-of-function genetic screen in ZR-75-1 luminal breast cancer cells to identify candidate genes for tamoxifen resistance.

“The researchers found that loss of function in the deubiquitinase USP9X prevented proliferation arrest by tamoxifen, but not by the ER downregulator fulvestrant. RNAi-mediated attenuation of USP9X stabilized ERα on chromatin in the presence of tamoxifen, and this caused a global activation of ERα-responsive genes driven by tamoxifen. A gene signature defined by differential expression after USP9X attenuation in the presence of tamoxifen was used to identify patients with ERα-positive breast cancer experiencing a poor outcome after adjuvant therapy with tamoxifen. Correlation of the gene signature with survival was not observed in patients with breast cancer who did not receive endocrine therapy.

” ‘Overall, our findings identify a gene signature as a candidate biomarker of response to tamoxifen in breast cancer,’ the authors write.”


Palbociclib Plus Letrozole Extended PFS in Metastatic Breast Cancer

“The addition of palbociclib to letrozole during first-line treatment significantly extended PFS in post-menopausal patients with ER-positive, HER-2–negative advanced breast cancer, according to final results of a randomized, open-label, phase 2 trial presented at the American Association for Cancer Research annual meeting.

“Palbociclib (PD-0332991, Pfizer), an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, prevents DNA synthesis by blocking cell cycle progression. Results of preclinical studies showed HR-positive breast cancer cells are dependent on CDK-4/6 for growth, and a phase 1 study showed the combination of palbociclib and the antiestrogen drug letrozole appeared to be a safe, effective combination.”

Editor’s note: “PFS” stands for “progression-free survival.” It refers to a period of time in which a cancer patient does not experience worsening of his/her disease. In the clinical trial described here, a combination of two drugs —palbociclib and letrozole—extended PFS for some people with ER-positive, HER-2-negative advanced breast cancer.