Estrogen-Receptor Status and Outcomes of Modern Chemotherapy for Patients With Node-Positive Breast Cancer

Abstract

Context-Breast cancer estrogen-receptor status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy.Objective-Compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative versus ER-positive tumors.Design-Trial data from the Cancer and Leukemia Group B and U.S. Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models.Setting-Randomized trials comparing (1): three regimens of cyclophosphamide, doxorubicin, and fluorouracil; (2) three doses of doxorubicin concurrent with cyclophosphamide, with/without subsequent paclitaxel; (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also three-week versus two-week cycles.Patients-Total of 6644 node-positive breast cancer patients receiving adjuvant treatment. Main Outcome Measures-Disease-free and overall survival.Results-For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21, 25 and 23 percent in the three studies, respectively, and 55 percent comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9, 12, and 8 percent in the three studies, and 26 percent overall. The overall mortality rate reductions associated with chemotherapy improvements were 55 and 23 percent among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8 percent more ER-negative patients survived to 5 years

Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944)

“…Overall, the hazard of dying was highest in the first 5 years after diagnosis and we found that hormone receptor status was predictive of outcome: having no recurrence in the first 5 years was a much stronger predictor of long-term outcome in patients whose tumors were hormone receptor negative that in patients whose tumors were hormone receptor positive. An analysis of trial data from the Cancer and Leukemia Group B and the US Breast Cancer Intergoup, also supports the good prognosis of persons surviving beyond 5 years and the relationship of hormone receptor status to response to therapy [44]. In that analysis, patients who had hormone receptor negative tumors had better rates of response to chemotherapy and the risk of recurrent breast cancer was highest in the first three years of follow-up.…”

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

“…In the entire HE10/97 trial, the hazard of death was significantly reduced when patients with negative hormonal receptor status were treated with paclitaxel. There is evidence that ER positivity may represent a negative predictive factor for the response to chemotherapy in breast cancer (Berry et al, 2006). In our patient cohort, performing an exploratory analysis based on ER status, no significant HER2/paclitaxel interaction was found in either ER-positive or ER-negative patients.…”

Clinicopathological Features in Bilateral Breast Cancer

“…The response rate to first-line palliative chemotherapy in the MC group was higher (p<0.0001). Inverse relation between hormone receptor expression rate and chemotherapy response is known (Berry et al, 2006). The weaker HR expression than those of synchronous tumors in MC, can explain the higher response rate to chemotherapy.…”