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Moderately expressed protein carried poor prognosis for breast cancer
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The prognosis for breast cancer after surgery is adverse when a key protein is expressed moderately and without amplification of its associated oncogene, according to study results.
HER-2 testing in patients with operable breast cancer identifies candidates for adjuvant anti-HER-2 therapy. HER-2 tumors express different levels of the HER-2 protein. This can influence a prognosis, according to background information provided by researchers.
For the current study, Valentina Rossi, MD, of Piedmont Foundation for Oncology at the Institute for Cancer Research and Treatment in Candiolo, Italy, and colleagues compared the clinical outcomes of operable patients with breast cancer stratified according to a common HER-2 testing algorithm.
Researchers evaluated 1,150 women who underwent surgery for early breast cancer from June 1996 to September 2009. The median age of patients was 58 years.
Researchers determined HER-2 by using the HercepTest (Dako, Glostrup) and by fluorescence in situ hybridization testing when needed.
HER-2 status was 0 for 40% of patients (n=457), +1 for 39% of patients (n=454), 2+/HER-2– for 10% (n=116) and HER-2– for 11% (n=123).
“Compared with patients who had tumors with HER-2 scores of 0 and 1+, those with a HER-2 2+/HER-2¯ tumor status tended to have larger tumors at diagnosis, more frequently had high-grade tumors, higher Ki-67 expression and more extensive axillary lymph node involvement,” Rossi and colleagues wrote.
In total, 254 DFS events were registered at a median overall follow-up duration of 60 months (5 to 175 months). HER-2+/HER-2– status showed a time-dependent effect on the DFS probability. The initial advantage worsened every year by a factor of 1.649, according to study results.
Researchers found that HER-2 2+/HER-2– tumors carry a prognosis that is worse than tumors with no or weak HER-2 expression.
“In the absence of adjuvant anit-HER-2 therapy, the prognosis of these patients is significantly better than that of patients with HER-2+ tumors in the initial 4 to 5 years of follow-up, but worsens with longer follow-up,” Rossi and colleagues wrote.
Rossi and colleagues recommended further testing to build on the study findings. Confirmation is needed to determine whether patients with more moderate HER-2 levels would benefit from treatments similar to those received by patients with higher HER-2 and HER-2/neuoncogene amplification levels, they said.
“These findings suggest rethinking HER-2 status with respect to prediction of trastuzumab-related benefit in patients with early breast cancer and also, in our opinion, prognostic terms,” Filippo Montemurro, MD, of the unit of investigative clinical oncology and division of medical oncology at the Institute for Cancer Research and Treatment in Torino, Italy, said in a press release.
Disclosure: Montemurro reports serving on scientific advisory boards for AstraZeneca, GlaxoSmithKline and Roche.
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