METASTATIC BREAST CANCER PROGNOSIS

NEW YORK (Reuters Health) - In postmenopausal women with hormone receptor-positive invasive breast cancer, the intrinsic subtype is more reflective of outcome than are classical clinical-pathological elements, according to European and U.S. investigators.

As Dr. Alex Prat told Reuters Health by email, "We showed that intrinsic subtype is the most important prognostic factor known to date in the metastatic setting, even more than number or type of metastasis, age, previous treatment, and performance status."

In a June 9 online paper in JAMA Oncology, Dr. Prat, of Vall d'Hebron Institute of Oncology, Barcelona, Spain, and colleagues note that they came to these conclusions after a retrospective analysis of tumor samples from 821 patients with subtype data who had taken part in a clinical trial.

None had had prior therapy for advanced or metastatic disease. They were randomized to letrozole with or without lapatinib, an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor.

Median progression-free survival (PFS) differed across the intrinsic subtypes of clinically HER2-negative disease. For luminal A, this was 16.9 months and for luminal B, it was 11.0 months. With the HER2-enriched subtype, it was 4.7 months and with the basal-like subtype, it was 4.1 months. Corresponding lengths of overall survival were 45, 37, 16 and 23 months.

Only patients with HER2-negative/HER2-enriched disease benefited from lapatinib therapy. Their median PFS was 6.49 months compared to 2.60 months with placebo.

Summing up, Dr. Prat added that he and his colleagues "feel that our findings have potential clinical implications. On one hand, past, current, and future clinical trials cannot ignore the importance of intrinsic biology and will have to take it into account."

"On the other hand," he concluded, "our results suggest that intrinsic biology should be used today to help make treatment decisions regarding chemotherapy versus endocrine therapy in the first-line metastatic setting."

Commenting on the findings by email, Dr. Mitch Dowsett, author of an accompanying editorial, told Reuters Health, "Intrinsic subtyping for characterizing breast cancer has become increasingly frequent for the management of primary breast cancer." This study "shows that the prognostic information from subtyping can also be informative for patients with metastatic disease."

Dr. Dowsett, of Royal Marsden NHS Trust, London, pointed out, "This is a useful advance but it is important to be aware that there are not distinct boundaries between the subtypes of ER+ breast cancer such that oncologists should be circumspect in their clinical application of the information."

GlaxoSmithKline, the Susan G. Komen Foundation, and others supported this research. Four coauthors reported disclosures.