From the Journals

Tamoxifen benefit in lower-risk breast cancer varies by intrinsic subtype



The long-term benefit of adjuvant tamoxifen in lower-risk early breast cancer hinges on intrinsic molecular subtype, finds a secondary analysis of the Stockholm Tamoxifen (STO-3) trial.

“Patients with estrogen receptor (ER)–positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood,” noted the investigators, who conducted the research under senior investigator Linda Lindström, MSc, PhD, department of biosciences and nutrition, Karolinska Institutet, Stockholm.

The STO-3 trial spanned 1976 to 1990 and randomized postmenopausal patients with lymph node–negative breast cancer to receive at least 2 years of adjuvant tamoxifen or no endocrine therapy.

Dr. Lindström and coinvestigators used immunohistochemistry and Agilent microarrays to define tumor molecular subtype. Analyses were based on 462 patients with ER-positive disease: 336 with luminal A subtype tumors and 126 with luminal B subtype tumors.

Results reported in JAMA Oncology showed that the distant recurrence–free interval (DRFI) was significantly better with tamoxifen than with no endocrine therapy in both the luminal A group (P less than .001) and the luminal B group (P = .04).

Among patients given tamoxifen, the 25-year DRFI rate was 87% (95% confidence interval, 82%-93%) for those with luminal A tumors vs. 67% (95% CI, 56%-82%) for those with luminal B tumors. Among patients not given any endocrine therapy, it was 70% (95% CI, 62%-79%) vs. 54% (95% CI, 42%-70%), respectively.

Tamoxifen had a significant DRFI benefit for 15 years after diagnosis in the luminal A group (hazard ratio, 0.57; 95% CI, 0.35-0.94). In contrast, the benefit was significant for only 5 years in the luminal B group (HR, 0.38; 95% CI, 0.24-0.59).

“We conclude that tamoxifen appears to confer a long-term benefit for patients with lymph node–negative, ER-positive, luminal A subtype tumors, and a short-term benefit for patients with luminal B subtype tumors. Given that the risk of distant metastatic disease is low for patients with the luminal A subtype but persists in the long term, whereas the risk for patients with luminal B subtype is higher initially but decreases after 5 years, tamoxifen treatment is beneficial for patients with luminal A or luminal B subtype tumors,” Dr. Lindström and coinvestigators maintained.

“In patients with luminal B subtype, up-front chemotherapy should be discussed and endocrine therapy potentially extended for up to 10 years, particularly in those in the higher risk strata according to other tumor characteristics,” they recommended.

Dr. Lindström disclosed no conflicts of interest. The study was supported by the Swedish Research Council, FORTE, The Gösta Milton Donation Fund, the California Breast Cancer Research Program, The Iris, Stig och Gerry Castenbäcks Stiftelse för Cancerforskning, and Konung Gustaf V:s Jubileumsfond from Radiumhemmets Forskningsfonder.

SOURCE: Yu NY et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1856.

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