Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumors: being younger and getting less benefit from adjuvant tamoxifen treatment

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Abstract
Most breast cancer patients with estrogen receptor-negative/progesterone receptor-positive (ER−/PgR+) tumors are premenopausal cases, with few alternatives of adjuvant endocrine therapy but tamoxifen (TAM). The efficacy of adjuvant TAM on ER−/PgR+ patients is still controversial. In this study, we evaluated the efficacy of adjuvant TAM on patients with ER−/PgR+ tumors. Among all 1,836 consecutive patients with operable primary breast cancer, 798 cases were with ER+/PgR+ tumors and 205 with ER−/PgR+ tumors. By sub-grouping the patients according to ER/PR phenotypes and whether the patients had been treated with adjuvant TAM therapy or not, we investigated the differences of survivals between groups. Patients with ER−/PgR+ tumors were younger than those with ER+/PgR+ tumors (P = 0.021), and were mainly premenopausal (P = 0.013). ER−/PgR+ patients were related to more involved lymph nodes and later stage. In the absence of TAM treatment, ER+/PgR+ group had a similar survival to ER−/PgR+ group in terms of 5-year disease-free survival (DFS), as well as overall survival (OS). After TAM treatment, both groups had increased survival rates comparing with the baseline of non-TAM-treated groups. Moreover, significant survival differences were then observed between TAM-treated ER+/PgR+ group and TAM-treated ER−/PgR+ group either in DFS (P = 0.016) or OS (P = 0.007). Of the TAM-treated patients, by sub-dividing the chemotherapy-treated population into CMF (cyclophosphamide, methotrexate and 5-fluorouracil) group and CA(E)F (cyclophosphamide, doxorubicin/epirubicin and 5-fluorouracil) group, we found that ER−/PgR+ group got more benefits from CMF regimen than from CA(E)F. Subpopulation treatment effect pattern plot (STEPP) analysis showed that the ER−/PgR+ group had an obvious worse survival than ER+/PgR+ group in younger patients (<55 years). Axillary lymph nodes involvement was the only independent prognostic factor for ER−/PgR+ group. Our results indicate that patients with ER−/PgR+ tumors are mainly premenopausal and young. Although patients with ER−/PgR+ tumors are generally considered as candidates for endocrine therapy clinically, the ER−/PgR+ group gains less benefits from adjuvant TAM treatment than ER+/PgR+ group.

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