Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less.
OBJECTIVE
This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of </= 1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone.


METHODS
After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of.05 or less were statistically significant.


RESULTS
XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone; XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of IBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P =.28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P =.039). Survival in the three groups was 93%, 94%, and 93%, respectively (P =.93).


CONCLUSIONS
In women with tumors </= 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, and TAM plus XRT when tumors are ER positive.
Fisher
Bernard
B
National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Division of Pathology, and Breast Committee, Pittsburgh, PA, USA. bernard.fisher@nsabp.org
Bryant
John
J
Dignam
James J
JJ
Wickerham
D Lawrence
DL
Mamounas
Eleftherios P
EP
Fisher
Edwin R
ER
Margolese
Richard G
RG
Nesbitt
Lois
L
Paik
Soonmyung
S
Pisansky
Thomas M
TM
Wolmark
Norman
N
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen