title: Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumors: being younger and getting less benefit from adjuvant tamoxifen treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Breast Surgery, Cancer Hospital/Cancer Institute, Fudan University, 200032 Shanghai, China.
authors.forename: Ke-da
authors.initials: KD
authors.lastname: Yu
authors.forename: Gen-hong
authors.initials: GH
authors.lastname: Di
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Jin-song
authors.initials: JS
authors.lastname: Lu
authors.forename: Kun-wei
authors.initials: KW
authors.lastname: Shen
authors.forename: Guang-yu
authors.initials: GY
authors.lastname: Liu
authors.forename: Zhen-zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhio-ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen