Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: Results of the International Breast Cancer Study Group (IBCSG) Trial VI

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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Clinical update: Impact of Adjuvant Therapy on Quality of Life in Women with Node Positive Operable Breast Cancer. Hurny, C., Bernhard, J., Coates, A.S., Castiglione-Gertsch, M., Peterson, H.F.et al. for the International Breast Cancer Study Group (1996)347, No. 9011, 1279–1284.

Psycho-Oncology ◽

10.1002/(sici)1099-1611(199703)6:1<78::aid-pon9259>3.0.co;2-# ◽

1997 ◽

Vol 6 (1) ◽

pp. 78-78

Author(s):

William Breitbart ◽

Ann Cull ◽

Donna Greenberg

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Adjuvant Therapy ◽

Operable Breast Cancer ◽

Study Group ◽

Cancer Study ◽

Node Positive ◽

Cancer Study Group ◽

Breast Cancer Study

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Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor–Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00

Journal of Clinical Oncology ◽

10.1200/jco.2015.65.6595 ◽

2016 ◽

Vol 34 (28) ◽

pp. 3400-3408 ◽

Cited By ~ 41

Author(s):

Marco Colleoni ◽

Kathryn P. Gray ◽

Shari Gelber ◽

István Láng ◽

Beat Thürlimann ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Hormone Receptor ◽

Low Dose ◽

Phase Iii ◽

Study Group ◽

Cancer Study ◽

Node Positive ◽

Cancer Study Group ◽

Breast Cancer Study

Purpose To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. Patients and Methods International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor– and progesterone receptor–negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. Results After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). Conclusion CM maintenance did not produce a significant reduction in DFS events in hormone receptor–negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.

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