PET tracer predicts resistance to hormone therapy for breast cancer

18F-labeled fluoromisonidazole (18F-FMISO) PET/CT can be used during breast cancer treatment planning to predict primary endocrine resistance in estrogen receptor (ER)-positive cancers, according to a study published Feb. 11 in the Journal of Nuclear Medicine.

Approximately 70 percent of breast cancers are hormone-dependent and overexpress hormone receptors, explained Jingyi Cheng, MD, Fudan University Shanghai Cancer Center, Shanghai, China, and colleagues.

“Although endocrine therapy is an effective method to treat (ER)–positive breast cancer, approximately 30 to 40 percent of all hormone receptor–positive tumors display de novo resistance,” they wrote. Patients with primary resistance to hormonal therapy may have their conditions worsen if hormone treatment continues.

“Thus, it is urgent and valuable to find a noninvasive means with the same efficacy as histopathologic marker analysis to predict primary hormonal therapy resistance,” wrote the authors.

Biopsies of metastatic lesions for the purpose of predicting endocrine therapy outcomes in patients with advanced breast cancer can be difficult to obtain, according to Cheng and colleagues. The preoperative endocrine prognostic index, which factors in histopathologic tumor size after three to four months of therapy, nodal status, ER levels and Ki67 protein levels can be used to individualize treatment. Hypoxia is a tumor phenomenon associated with resistance to treatment, and animal studies have shown that 18F-FMISO binding is elevated under hypoxic conditions.

In order to see if 18F-FMISO PET/CT could then be used to predict resistance to hormonal therapy, Cheng and colleagues conducted a prospective study of postmenopausal women with ER-positive breast cancer, stages II-IV, who have never received endocrine therapy. Patients underwent 18F-FDG and 18F-FMISO PET/CT scans before and after treatment, and baseline scans were ultimately obtained for 33 lesions from 16 patients.

Results showed a significantly positive correlation between baseline 18F-FMISO uptake and clinical outcomes after three months of primary endocrine therapy with letrozole, reported the authors. Using a tumor-to-background ratio 4h cutoff of 1.2 or greater allowed for prediction of 88 percent of cases of progressive disease.

“Our study revealed that 18F-FMISO PET/CT is a highly effective method that can accurately predict the clinical efficacy of primary endocrine therapy and has a marginal positive correlation with Ki67 levels,” summed the authors.

They added that the correlation between baseline 18F-FDG uptake and clinical outcome was weak and not statistically significant.

Cheng and colleagues wrote that future studies with more patients will be used to assess the full prognostic value of 18F-FMISO PET/CT performed at baseline.