Adjuvant Chemotherapy with Clear Lymph Nodes (Stage I)

The benefits of chemotherapy are the same for node negative women as node positive, but the absolute advantages are smaller. (In other words if the odds of a cure are already very high, the benefits from chemotherapy may be quite small as in the B20 trail below the survival from adding chemotherapy to Tamoxifen wnet up from 94% to 96%.) Premenopausal women benefit the most from chemotherapy, and in fact postmenopausal women whose tumors are sensitive to estrogen (estrogen receptor +) may do just as well with Tamoxifen which is less toxic. A recent trial in postmenopausal women  with ERP+ tumors and node metastases reported 5 year survival as: Tamoxifen alone (80%) and Tamoxifen + CMF (82%). J Clin Onc 1997;15:2302. The 10 year results for node negative women who are considered high risk (i.e. ERP negative or ERP+ but tumors larger than 3 cm was reported and showed a survival benefit, especially in the premenopausal women:)
 

10 Year Survival Benefits in Women with Negative Lymph Nodes Given Adjuvant Chemotherapy

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Intergroup Study, High Risk (ERP - or ERP + T > 3cm)
Mansour. J Clin Onc 1998;16:3486

 
So there is a survival advantage for using chemotherapy, but it may be quite small for tumors that are small (2 cm or less.) The results for the ERP- cancers by tumor size are noted (DFS = disease free survival, or alive with no relapse and OS = overall survival from Mansour. J Clin Onc 1998;16:3486)

Results in ERP - Tumors (Node Negative)
Tumor Size DFS DFS OS OS
  control chemo control chemo
1 - 2 cm 71.4% 77.1% 85.5% 85.7%
2 - 3cm 61.8% 76.4% 70.3% 89.2%
3cm + 65.9% 67.9% 71.6% 76.6%

Fisher recently (Journal of the National Cancer Institute, Vol. 93, No. 2, 112-120, January 17, 2001) reviewed all the NSABP trials for node negative breast cancers with small (1cm or less) cancers and published the following data:

8 Year Results from NSABP for Stage I Cancers with Small (1cm or less) Primaries
ERP (-) Surgery Alone S + ChemoRx  
DFS 81% 90%  
OS 93% 91%  
ERP (+) Surgery Alone S + Tamoxifen S + T + chemotherapy
DFS 86% 93% 95%
OS 90% 92% 97%


Studies  Using Chemotherapy for Stage I Breast Cancer
J Clin Oncol 1998 Nov;16(11):3486-92

Survival advantage of adjuvant chemotherapy in high-risk node-negative breast cancer: ten-year analysis--an intergroup study.

Mansour EG,

Case Western Reserve University,

Preliminary analysis showed that adjuvant chemotherapy is effective in improving disease-free survival (DFS) among high-risk breast cancer patients. This report updates the analysis of the high-risk group and reports the results of the low-risk group. Patients who had undergone a modified radical mastectomy or a total mastectomy with low-axillary sampling, with negative axillary nodes and either an estrogen receptor-negative (ER-) tumor of any size or an estrogen receptor-positive (ER+) tumor that measured > or = 3 cm (high-risk) were randomized to receive six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or no further treatment. Patients with ER+ tumors less than 3 cm (low-risk) were monitored without therapy. RESULTS: DFS and overall survival (OS) at 10 years were 73% and 81%, respectively, among patients who received chemotherapy, as compared with 58% and 71% in the observation group. Chemotherapy was beneficial for patients with large tumors, both ER+ and ER-, showing a 10-year DFS of 70% versus 51 % and OS of 75% versus 65%.. Ten-year survival was 77% among low-risk patients, 85% among premenopausal patients, and 73% in the postmenopausal group. CONCLUSION: The observed 37% reduction in risk of recurrence and 34% reduction in mortality risk at 10 years, associated with a 15.4% absolute benefit in disease-free state and 10.1% in survival, reaffirm the role of adjuvant chemohormonal therapy in the management of high-risk node-negative breast cancer. Tumor size remains a significant prognostic factor associated with recurrence and survival in the low-risk group.

N Engl J Med 1989 Feb 23;320(8):473-8

A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors.

Fisher B, No survival advantage was observed with this therapy as compared with no postoperative therapy during four years of follow-up (87 percent vs. 86 percent; P = 0.8). However, there was a significant prolongation of disease-free survival among women who received this therapy as compared with those who did not (80 percent vs. 71 percent; P = 0.003).

N Engl J Med 1989 Feb 23;320(8):479-84

A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.

Fisher B

National Surgical Adjuvant Breast and Bowel Project (NSABP) Headquarters, Pittsburgh, PA 15261.

We conducted a randomized, double-blind, placebo-controlled trial of postoperative therapy with tamoxifen (10 mg twice a day) in 2644 patients with breast cancer, histologically negative axillary nodes, and estrogen-receptor-positive (greater than or equal to 10 fmol) tumors. No survival advantage was observed during four years of follow-up (92 percent for placebo vs. 93 percent for tamoxifen). There was a significant prolongation of disease-free survival among women treated with tamoxifen, as compared with those receiving placebo (83 percent vs. 77 percent). This advantage was observed in both the patients less than or equal to 49 years old (P = 0.0005) and those greater than or equal to 50 (P = 0.0008), particularly in the former, among whom the rate of treatment failure was reduced by 44 percent. Multivariate analysis indicated that all subgroups of patients benefited. Tamoxifen significantly reduced the rate of treatment failure at local and distant sites, tumors in the opposite breast, and the incidence of tumor recurrence after lumpectomy and breast irradiation.

JNatl Cancer Inst Monogr 1992;(11):105-16

Systemic therapy in node-negative patients: updated findings from NSABP clinical trials. National Surgical Adjuvant Breast and Bowel Project.

Fisher B. In trial B-13, 737 women with estrogen receptor (ER)-negative tumors treated by sequential methotrexate and fluorouracil (MTX----5-FU) followed by leucovorin were compared with a control group treated by surgery alone. Findings for all patients through 5 years of follow-up indicate a 27% reduction in treatment failure as a result of MTX-5-FU (76% vs 67%). A 69% reduction in mortality resulting from MTX----5-FU was observed in the older group (95% vs 84%). Trial B-14 compared placebo with tamoxifen (TMX) in 2844 patients with ER-positive tumors. As originally reported, findings through 5 years of follow-up indicate a significant reduction (36%) in treatment failure as a result of the TMX (82% vs 72%). Improvement in DFS was highly significant in both age groups. In patients 49 years old or younger, there was a 44% reduction in DFS (81% vs 66%) and, in those 50 years old or more, a 31% reduction (82% vs 74%).

J Clin Oncol 1996 Jul;14(7):1982-92

Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13

Fisher B, A significant benefit in overall DFS (74% v 59%) was demonstrated at 8 years in all B-13 patients who received M-->F (69% v 56%] in those <or= 49 years of age, and (81% v 63%] in those >or= 50 years). A survival advantage was evident in older patients (89% v 80% ).

J Natl Cancer Inst 1997 Nov 19;89(22):1673-82

Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer.

Fisher B, The B-20 study of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was conducted to determine whether chemotherapy plus tamoxifen would be of greater benefit than tamoxifen alone in the treatment of patients with axillary lymph node-negative, estrogen receptor-positive breast cancer. Through 5 years of follow-up, chemotherapy plus tamoxifen resulted in significantly better disease-free survival than tamoxifen alone (90% for MFT versus 85% for tamoxifen; 89% for CMFT versus 85% for tamoxifen). A similar benefit was observed in both distant disease-free survival (92% for MFT versus 87% for tamoxifen; 91% for CMFT versus 87% for tamoxifen) and survival (97% for MFT versus 94% for tamoxifen; 96% for CMFT versus 94% for tamoxifen.

N Engl J Med 1989 Feb 23;320(8):485-90

Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study.

Mansour EG, The patients were considered at high risk for recurrence because they had either an estrogen-receptor-negative tumor of any size or an estrogen-receptor-positive tumor at least 3 cm in diameter with no histopathological evidence of axillary-node involvement. The overall disease-free survival among patients treated with the four-drug regimen was 84 percent, as compared with 69 percent for the control group, at a median follow-up of three years (P = 0.0001). A treatment benefit was also observed in premenopausal and postmenopausal patients as well as in patients with estrogen receptor-positive or with estrogen-receptor-negative tumors.

Ann Oncol 1996 Jul;7(5):481-5

Adjuvant cyclophosphamide, methotrexate and fluorouracil in node-negative and estrogen receptor-negative breast cancer. Updated results.

Zambetti M, At 12 years after surgery treatment outcome was significantly superior for patients given adjuvant CMF. Three relapse-free survival rate was 71% versus 43% and total survival was 80%  versus 50% respectively.

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