Low-dose tamoxifen in the treatment of breast ductal intraepithelial neoplasia: results of a large observational study

Ann Oncol. 2010 May;21(5):949-54. doi: 10.1093/annonc/mdp408. Epub 2009 Oct 25.

Abstract

Background: Tamoxifen's cost-benefit ratio for breast ductal intraepithelial neoplasia (DIN) is unclear. Since low-dose tamoxifen showed a favorable modulation of breast cancer biomarkers in phase II trials, a monoinstitutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment was analyzed.

Patients and methods: A total of 309 patients with DIN received low-dose tamoxifen as part of institutional guidelines and were compared with 371 patients with DIN who received no systemic treatment after surgery.

Results: Women with estrogen receptor (ER)/progesterone receptor (PgR) >50% DIN who were not treated had a higher incidence of breast events than women on tamoxifen [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00-3.12] or women with ER/PgR <50% DIN (HR 1.72; 95% CI 1.14-2.58). Among untreated patients with ER >50% DIN, recurrence was higher in PgR > or =50% DIN than in PgR <50% DIN, whereas it was similar among low PgR (<50%) DIN against which tamoxifen had no effect. No difference in endometrial cancer incidence was noted.

Conclusions: High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN, and low-dose tamoxifen appears to be an active treatment. Women with low-expression ER or PgR DIN do not seem to benefit from tamoxifen. A definitive clinical trial is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma in Situ / drug therapy*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Postmenopause
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate
  • Tamoxifen / administration & dosage*
  • Treatment Outcome

Substances

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