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


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.
Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
A
A
Guerrieri-Gonzaga
E
E
Botteri
M
M
Lazzeroni
N
N
Rotmensz
A
A
Goldhirsch
C
C
Varricchio
D
D
Serrano
M
M
Cazzaniga
F
F
Bassi
A
A
Luini
V
V
Bagnardi
G
G
Viale
S
S
Mora
G
G
Bollani
E
E
Albertazzi
B
B
Bonanni
A
A
Decensi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen