Risk Factors for Locoregional Recurrence Among Breast Cancer Patients: Results From International Breast Cancer Study Group Trials I Through VII

2003 ◽  
Vol 21 (7) ◽  
pp. 1205-1213 ◽  
Author(s):  
A. Wallgren ◽  
M. Bonetti ◽  
R.D. Gelber ◽  
A. Goldhirsch ◽  
M. Castiglione-Gertsch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Vascular Invasion ◽  
Risk Groups ◽  
Study Group ◽  
Node Negative ◽  
Node Positive ◽  
Cancer Study Group ◽  
Breast Cancer Study ◽  
Node Positive Disease

Purpose: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. Patients and Methods: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months’ duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. Results: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. Conclusion: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.

Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.

1992 ◽  
Vol 10 (7) ◽  
pp. 1049-1056 ◽  
Author(s):  
B A Gusterson ◽  
R D Gelber ◽  
A Goldhirsch ◽  
K N Price ◽  
J Säve-Söderborgh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Study Group ◽  
Primary Tumors ◽  
Node Negative ◽  
Cancer Study ◽  
Node Positive ◽  
Cancer Study Group ◽  
Breast Cancer Study ◽  
Prognostic Importance

PURPOSE To evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer. PATIENTS AND METHODS Primary tumors from 1,506 breast cancer patients (760 node-negative and 746 node-positive) who were treated in the International (Ludwig) Breast Cancer Study Group Trial V were studied. Node-negative patients were allocated randomly to either a single cycle of perioperative chemotherapy (PeCT) or no adjuvant treatment, and node-positive patients received either a prolonged chemotherapy (with tamoxifen for postmenopausal patients) or a single perioperative cycle. RESULTS Tumors from 16% of the node-negative patients and 19% of the node-positive patients were found to be c-erbB-2-positive. In both groups c-erbB-2 positivity correlated with negative progesterone receptors (PR), negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were all negative, and, thus support the view that such tumors represent a defined subtype of breast carcinoma. The expression of c-erbB-2 was prognostically significant for node-positive but not for node-negative patients. However, in both subgroups, the prognostic significance was greater for patients who had received more adjuvant therapy. For node-positive patients, the effect of prolonged-duration therapy on disease-free survival (DFS) was greater for patients without c-erbB-2 overexpression (hazards ratio [HR], = 0.57; 95% confidence interval [CI], 0.46 to 0.72) than for those with c-erbB-2 overexpression (HR, 0.77; 95% CI, 0.51 to 1.16). Similarly, for node-negative patients, the effect of PeCT on DFS was greater for those without c-erbB-2 overexpression (HR, 0.82; 95% CI, 0.61 to 1.09) than for those with c-erbB-2 overexpression (HR, 1.22; 95% CI, 0.66 to 2.25). CONCLUSION We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.

Prognostic importance of thymidylate synthase expression in early breast cancer.

1997 ◽  
Vol 15 (5) ◽  
pp. 1923-1931 ◽  
Author(s):  
B C Pestalozzi ◽  
H F Peterson ◽  
R D Gelber ◽  
A Goldhirsch ◽  
B A Gusterson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Thymidylate Synthase ◽  
Early Stage ◽  
Node Negative ◽  
Node Positive ◽  
Cancer Study Group ◽  
Breast Cancer Study ◽  
Prognostic Importance ◽  
Disease Free ◽  
Worse Prognosis

PURPOSE To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. PATIENTS AND METHODS The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. RESULTS High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease-free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P < .01 for DFS; P < .01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. CONCLUSION In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

scholarly journals Patterns of Recurrence and Outcome According to Breast Cancer Subtypes in Lymph Node–Negative Disease: Results From International Breast Cancer Study Group Trials VIII and IX

2013 ◽  
Vol 31 (25) ◽  
pp. 3083-3090 ◽  
Author(s):  
Otto Metzger-Filho ◽  
Zhuoxin Sun ◽  
Giuseppe Viale ◽  
Karen N. Price ◽  
Diana Crivellari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Study Group ◽  
Luminal A ◽  
Node Negative ◽  
Cancer Study ◽  
Cancer Study Group ◽  
Breast Cancer Study ◽  
Viii And Ix ◽  
Over Time

Purpose To retrospectively evaluate the pattern of recurrence and outcome of node-negative breast cancer (BC) according to major subtypes. Patients and Methods In all, 1,951 patients with node-negative, early-stage BC randomly assigned in International Breast Cancer Study Group Trials VIII and IX with centrally reviewed pathology data were included. BC subtypes were defined as triple negative (TN; n = 310), human epidermal growth factor receptor 2 (HER2) positive (n = 369), and hormone receptor positive with high (luminal B–like [LB-like]; n = 763) or low (luminal A–like [LA-like]; n = 509) proliferative activity by Ki-67 labeling index. BC-free interval (BCFI) events were invasive BC recurrence in local, contralateral breast, nodal, bone, or visceral sites. Time to first site–specific recurrence was evaluated by using cumulative incidence and competing risks regression analysis. Results Median follow-up was 12.5 years. The 10-year BCFI was higher for patients with LA-like (86%) BC compared with LB-like (76%), HER2 (73%), and TN (71%; P < .001) BC. TN and HER2 cohorts had higher hazard of BCFI event in the first 4 years after diagnosis (pre-trastuzumab). LB-like cohorts had a continuously higher hazard of BCFI event over time compared with LA-like cohorts. Ten-year overall survival was higher for LA-like (89%) compared with LB-like (83%), HER2 (77%), and TN (75%; P < .001) BC. LB-like subtypes had higher rates of bone as first recurrence site than other subtypes (P = .005). Visceral recurrence as first site was lower for the LA-like subgroup, with similar incidence among the other subgroups when treated with chemotherapy (P = .003). Conclusion BC subtypes have different distant recurrence patterns over time. Defining different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of clinical studies.

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