Abstract P5-13-01: Patterns of Breast Cancer Relapse According to Breast Cancer Subtypes in Lymph Node-Negative Breast Cancer — Results from International Breast Cancer Study Group Trials VIII and IX

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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Site of Primary Tumor Has a Prognostic Role in Operable Breast Cancer: The International Breast Cancer Study Group Experience

Journal of Clinical Oncology ◽

10.1200/jco.2005.06.052 ◽

2005 ◽

Vol 23 (7) ◽

pp. 1390-1400 ◽

Cited By ~ 57

Author(s):

Marco Colleoni ◽

David Zahrieh ◽

Richard D. Gelber ◽

Stig B. Holmberg ◽

Jan E. Mattsson ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Axillary Lymph Node ◽

Study Group ◽

Axillary Lymph ◽

Node Negative ◽

Cancer Study ◽

Cancer Study Group ◽

Breast Cancer Study ◽

Significant Difference

Purpose Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease. Patients and Methods Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years. Results A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS). Conclusion Tumor site has a significant prognostic utility, especially for axillary lymph node–negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.

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Chemoendocrine Compared With Endocrine Adjuvant Therapies for Node-Negative Breast Cancer: Predictive Value of Centrally Reviewed Expression of Estrogen and Progesterone Receptors—International Breast Cancer Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2007.10.6393 ◽

2008 ◽

Vol 26 (9) ◽

pp. 1404-1410 ◽

Cited By ~ 72

Author(s):

Giuseppe Viale ◽

Meredith M. Regan ◽

Eugenio Maiorano ◽

Mauro G. Mastropasqua ◽

Rastko Golouh ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Predictive Value ◽

Study Group ◽

Node Negative ◽

Cancer Study ◽

Cancer Study Group ◽

Node Negative Breast Cancer ◽

Breast Cancer Study ◽

Low Levels

Purpose To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer. Patients and Methods International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology. Results Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX. Conclusion Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER.

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Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer

Annals of Oncology ◽

10.1093/annonc/mdq735 ◽

2011 ◽

Vol 22 (10) ◽

pp. 2216-2226 ◽

Cited By ~ 30

Author(s):

P. Karlsson ◽

Z. Sun ◽

D. Braun ◽

K.N. Price ◽

M. Castiglione-Gertsch ◽

...

Keyword(s):

Breast Cancer ◽

Long Term Results ◽

Study Group ◽

Node Negative ◽

Cancer Study Group ◽

Node Negative Breast Cancer ◽

Breast Cancer Study ◽

Premenopausal Patients ◽

Group Trial

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Radiation Oncologists’ Approach to Internal Mammary Lymph Node Radiotherapy in Breast Cancer: The Turkish Society for Radiation Oncology Breast Cancer Study Group (TROD 06-005 Survey Study)

Cancer Management and Research ◽

10.2147/cmar.s327666 ◽

2021 ◽

Vol Volume 13 ◽

pp. 7203-7212

Author(s):

Ayfer Ay Eren ◽

Mehmet Fuat Eren

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Radiation Oncology ◽

Survey Study ◽

Study Group ◽

Internal Mammary Lymph Node ◽

Cancer Study Group ◽

Breast Cancer Study ◽

Internal Mammary ◽

Turkish Society

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

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.7.1049 ◽

1992 ◽

Vol 10 (7) ◽

pp. 1049-1056 ◽

Cited By ~ 555

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2003.03.130 ◽

2003 ◽

Vol 21 (7) ◽

pp. 1205-1213 ◽

Cited By ~ 197

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.

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