Re: Jean Ann - Tamoxifen

[Guest guest]

Ann - found an article for you to read. The charts did not come out

right on the email....you can see this article at

http://www.medscape.com/medscape/cno/1999/SABCS/Story.cfm?story_id=949

22nd Annual San Breast Cancer Symposium

Day 1 - December 8, 1999

New Insights Into Adjuvant Therapy in Node-Negative Breast Cancer

Author: Edith A., MD

Writer: L. Plante, PharmD

In today's opening session at the 22nd annual Breast Cancer Symposium, 2

important papers with implications for the adjuvant therapy of node-negative

breast cancer were presented.

Utility of Tamoxifen Depends on Tumor Hormone-Receptor Status

In the first abstract presentation, Dr. L Hutchins of the Southwest Oncology

Group Operations Office, San , Texas presented data evaluating whether

the addition of tamoxifen was superior to chemotherapy alone in patients with

high-risk, node-negative breast cancer irrespective of tumor-receptor

status.[1] These data were derived from an intergroup trial that enrolled

2691 high-risk node-negative women (out of the total cohort of 4406 patients

enrolled in the study). Patients were considered to be at high risk for

recurrence if they had any of the following characteristics: tumor >/= 2cm,

hormone receptor-negative, > 7% S-phase for diploid tumors of any size, or >

4.4% S-phase for aneuploid tumors of any size. High-risk patients were

randomized to receive either CMF or CAF chemotherapy +/- 5 years of tamoxifen

treatment. The disease-free survival (DFS) was 88% in the chemotherapy plus

tamoxifen group and 82% in the chemotherapy alone group (P= .007). Similarly,

overall survival (OS) was significantly better with the addition of tamoxifen

to the chemotherapy (94% vs 92%, respectively, P= .02) when all patients were

considered. However, no benefit was demonstrated for patients with estrogen

receptor (ER)-negative disease. The table below summarizes some of these

data:

Hormone Receptor-Positive Hormone Receptor-Negative

Chemo

n = 763 Chemo + Tam

n = 768 Chemon

n = 584 Chemo + Tam

n = 576

DFS 83% 88% 86% 83%

OS 92% 94% 91% 89%

Chemo = chemotherapy, tam = tamoxifen, all P values nonsignificant

Further subset analysis demonstrated that the addition of adjuvant tamoxifen

led to a worse outcome in the premenopausal hormone receptor-negative

subgroup, with a DFS of 88% in the chemotherapy group and 82% in the

chemotherapy plus tamoxifen group (P= .05). No benefit was seen with the

addition of tamoxifen in the premenopausal hormone receptor-positive and

postmenopausal hormone receptor-negative subgroups.

In conclusion, this study demonstrated improved outcomes in the hormone

receptor-positive patients, with the majority of the effect seen in the

postmenopausal patients. The subset analysis brought up the possibility that

tamoxifen does not help postmenopausal patients with hormone

receptor-negative breast cancer and that it may be harmful in premenopausal

women with hormone receptor-negative disease.

Prognosis of Patients With Small Primary Breast Tumors

In probably one of the most important presentations of the meeting, Dr.

Tan-Chiu of the National Surgical Adjuvant Breast and Bowel

Project, Pittsburgh, Pennsylvania presented data on the prognosis of patients

with small primary breast tumors (defined as tumors </= 1 cm).[2] The data

were derived from a combined analysis of 5 node-negative NSABP studies. The

number and overall schema of the 5 trials included are:

B-06: mastectomy vs lumpectomy plus radiation therapy (RT) in ER-positive and

ER-negative patients

B-13: surgery vs methotrexate plus 5-fluorouracil (5-FU) in ER-negative

patients

B-14: placebo vs tamoxifen in ER-positive patients

B-19: methotrexate plus 5-FU vs cyclophosphamide, methotrexate, 5-FU

B-20: methotrexate plus 5-FU vs tamoxifen vs cyclophosphamide, methotrexate,

5-FUf and tamoxifen

Data on 1260 patients were presented. About 60% of patients had tumors that

measured 1 cm, and about 40% had smaller tumors. Two hundred thirty-six

patients were ER-negative and 1024 were ER-positive.

The 8-year relapse-free survival (RFS) and OS were analyzed on the basis of

ER status and type of systemic therapy administered. Some of the data are

summarized in the table below:

ER-Negative ER-Positive

Surgery

n = 61 Surgery + Chemo

n = 174 Surgery

n = 264 Surgery + Chemo

n = 539 Surgery + Chemo + Tam

n = 219

RFS 79% 90% 86% 92% 94%

OS 93% 91% 90% 92% 97%

The analysis of this provocative report demonstrated an improvement in RFS

with the addition of chemotherapy in patients with ER-negative tumors. Also,

a benefit was seen with the addition of tamoxifen (or even tamoxifen +

chemotherapy) in patients with ER-positive small tumors. However, no

statistical analyses were provided. Therefore, although there were numerical

differences in RFS and OS, it will be important to await a peer-reviewed

publication or follow-up that reports whether any of these differences are

statistically significant before reaching any conclusions or recommending

routine adjuvant systemic therapy for patients with node-negative cancer and

</= 1 cm tumor size.

References

Hutchins L, Green S, Radvin P, et al. CMF versus CAF +/- tamoxifen in

high-risk node-negative breast cancer patients and a natural history

follow-up study in low-risk node-negative patients. Program and abstracts of

the 22nd Annual San Breast Cancer Symposium; December 8-11, 1999; San

, Texas. Abstract 1.

Tan-Chiu E, Dignam J, Fisher B, et al. Prognosis of node-negative breast

cancer patients with small (< 1 cm) tumors: The NASBP experience from

protocols B-06, B-13, B-14, B-19, and B-20. Program and abstracts of the 22nd

Annual San Breast Cancer Symposium; December 8-11, 1999; San ,

Texas. Abstract 3.