Prognostic Factors in Patients with Stage II/III Breast Cancer Treated with Adjuvant Extension of Neoadjuvant Chemotherapy: A Retrospective Cohort Study with Ten-Years of Follow-Up Data

Abstract

PurposeThe aim of this retrospective study was to identify the reliable long term prognostic factors in patients with stage II/III breast cancer who were treated with an adjuvant extension of neoadjuvant chemotherapy (NC).MethodsWomen under the age of 70-years, with previously untreated clinical stage II and III breast cancer, were treated with NC, which was comprised of three cycles of FEC (5-FU, epirubicin, and cyclophosphamide every 3 weeks) or MMM (methotrexate, mitoxantrone, and mitomycin-C every 3 weeks) with an adjuvant extension of three cycles of the same regimen.ResultsCumulative 10-years disease-free survival (DFS) was 87.3% for patients with a good response and 55.5% for patients with no response (p=0.032); 92.9% for node negative patients, 75.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). Cumulative 10-years overall survival (OS) was 89.1% for patients with good response and 55.5% for patients with no response (p=0.024); 95.2% for node negative patients, 80.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). No significant difference was observed in DFS and OS between the FEC and MMM treated groups.ConclusionBased on a review of data with a long follow-up, only the clinical response to NC and the absolute number of metastatic axillary lymph node identified at surgical staging were independent predictors of both DFS and OS in patients with stage II/III breast cancer patients treated with adjuvant extension of NC.

Estrogen Enhances the Expression of the Multidrug Transporter Gene ABCG2—Increasing Drug Resistance of Breast Cancer Cells through Estrogen Receptors

“…Mitoxantrone (MX), a synthetic anthracenedione, has attained clinical approval and has been routinely used alone or in combination for the treatment of breast cancers [ 7 , 8 ]. The anti-neoplastic activity of MX is believed to be related to its ability to bind DNA and inhibit DNA topoisomerase II, an essential enzyme in DNA synthesis and meiotic division which is highly expressed in cancer cells [ 9 ].…”

Gene Silencing of FANCF Potentiates the Sensitivity to Mitoxantrone through Activation of JNK and p38 Signal Pathways in Breast Cancer Cells

“…MX is known to stabilize topoisomerase (Topo) II-DNA complexes, to induce crosslinks and double-strand breaks (DSBs) in DNA, and to cause breakdown of the transcription and replication [25] . MX is used routinely in combination with other anticancer drugs as neoadjuvant chemotherapy in the treatment of breast cancers [26] , [27] , [28] . It is known that a defect in DNA repair underlies the sensitivity of cancer cells to chemotherapeutic drugs.…”

Treatment outcome in patients with stage III breast cancer treated with neoadjuvant chemotherapy

“…In a recent study, Zhang et al (7) investigated axillary nodal staging in stage II/III breast cancer after NAC. The authors observed that the ypN staging adjusted by pCR following NAC may predict differential DFS.…”

“…Our results suggested that the Ki-67 labeling index and the number of involved ALNs are prognostic predictors in stage III breast cancer. In a recent study, Zhang et al ( 7 ) investigated axillary nodal staging in stage II/III breast cancer after NAC. The authors observed that the ypN staging adjusted by pCR following NAC may predict differential DFS.…”

“…According to the databases of the American Cancer Society ( 1 ), the five-year overall survival (OS) rates for stage III breast cancer are 67% in stage IIIA and 41–49% in stage IIIB–IIIC. A number of prognostic factors for NAC have been correlated with OS and disease free survival (DFS) in locally advanced breast cancer, such as the triple-negative type, the human epidermal growth factor receptor 2 (HER2)-enriched type (hormone receptor negative/HER2 positive type) ( 2 , 3 ), a pathological complete response (pCR) ( 4 , 5 ) and the number of involved axillary lymph nodes (ALNs) at surgical staging ( 6 , 7 ). However, only a small number of studies have investigated the prognostic indicators that are associated with long-term survival in pts with stage III breast cancer treated with NAC.…”