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

J Cancer Res Clin Oncol. 2008 Dec;134(12):1347-54. doi: 10.1007/s00432-008-0414-2. Epub 2008 May 17.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Middle Aged
  • Premenopause
  • Prognosis
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Survival Rate
  • Tamoxifen / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen