Article

Neoadjuvant Chemotherapy Is Associated with Improved Survival Compared with Adjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer Only after Complete Pathologic Response

Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Annals of Surgical Oncology (Impact Factor: 3.93). 07/2011; 19(1):253-8. DOI: 10.1245/s10434-011-1877-y
Source: PubMed

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is known to be chemosensitive. In patients with TNBC, we sought to compare survival outcomes between patients receiving neoadjuvant chemotherapy, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy.
We performed a retrospective chart review and identified 385 patients with stage I-III TNBC who were treated with neoadjuvant or adjuvant chemotherapy between 2000 and 2008. Patients were divided according to receipt of neoadjuvant chemotherapy with pCR, neoadjuvant chemotherapy without pCR, and adjuvant chemotherapy. Data were compared using Fisher's exact test and analysis of variance (ANOVA). Kaplan-Meier curves were generated.
Of 385 patients, 151 (39%) received neoadjuvant chemotherapy and 234 (61%) received adjuvant chemotherapy. Twenty-six (17%) of those patients receiving neoadjuvant chemotherapy had pCR. After controlling for covariates associated with survival in unadjusted tests, patients undergoing neoadjuvant chemotherapy with residual tumor had significantly worse survival compared with patients receiving adjuvant therapy [hazard ratio (HR) = 0.51, P = 0.007] and a trend towards worse survival compared with patients receiving neoadjuvant therapy with pCR (HR = 0.19, P = 0.10).
Although previous clinical trials have not demonstrated a survival difference between patients receiving neoadjuvant versus adjuvant chemotherapy for breast cancer, our study suggests an overall survival benefit in patients with pCR following neoadjuvant chemotherapy compared with patients receiving adjuvant therapy. It is clear that a prospective study needs to be carried out to better elucidate the timing of chemotherapy in patients with TNBC.

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    • "The aim of NAC for breast cancer is to reduce the size of the primary tumor, thereby increasing the likelihood of breast conservation [6], and might allow evaluation of the therapeutic effects that facilitate the strategies of post-operative chemotherapy [7]. Recent studies have demonstrated that the response status after NAC is correlated with improved disease-free survival (DFS) and overall survival (OS) in breast tumors [5,8]. NAC for breast cancer has a pathologic complete response (pCR) rate of approximately 30% [6,9,10] and a clinical complete response (cCR) rate of approximately 60% [10]. "
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    ABSTRACT: Background Neoadjuvant chemotherapy (NAC) is one of the standard care regimens for patients with resectable early-stage breast cancer. It would be advantageous to determine the chemosensitivity of tumors before initiating NAC. One of the parameters potentially compromising such chemosensitivity would be a hypoxic microenvironment of cancer cells. The aim of this study was thus to clarify the correlation between expression of the hypoxic marker carbonic anhydrase-9 (CA9) and chemosensitivity to NAC as well as prognosis of breast cancer patients. Methods A total of 102 patients with resectable early-stage breast cancer was treated with NAC consisting of FEC (5-fluorouracil, epirubicin, and cyclophosphamide) followed by weekly paclitaxel before surgery. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity to NAC and the prognostic potential of CA9 expression were evaluated by immunohistochemistry. Results CA9 positivity was detected in the CNB specimens from 47 (46%) of 102 patients. The CA9 expression in CNB specimens was significantly correlated with pathological response, lymph node metastasis, and lymph-vascular invasion. Multivariate analysis revealed that the CA9 expression in CNB specimens was an independent predictive factor for pathological response. The Kaplan-Meier survival curve revealed a significant negative correlation (p = 0.013) between the disease-free survival (DFS) and the CA 9 expression in resected tissues after NAC. Multivariate regression analyses indicated that the CA9 expression in resected tissues was an independent prognostic factor for DFS. Conclusions CA9 expression in CNB specimens is a useful marker for predicting chemosensitivity, and CA9 expression in resected tissue is prognostic of DFS in patients with resectable early-stage breast cancer treated by sequential FEC and weekly paclitaxel prior to resection.
    Full-text · Article · Jun 2014 · BMC Cancer
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    • "[4], [5] The main aim of NAC is to reduce the size of the primary tumor, increase the likelihood of breast conservation [6], and allow evaluation of the therapeutic effects that facilitate establishment of therapeutic strategies based on the evaluation results [7]. Recent studies have demonstrated that pathologic complete response (pCR) in primary breast tumors after NAC correlates with improved disease-free survival (DFS) and overall survival (OS) [5], [8]. NAC for breast cancer has a pCR rate of approximately 30% [6], [9], [10] and a clinical CR (cCR) rate of approximately 60% [10]. "
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    ABSTRACT: Neoadjuvant chemotherapy (NAC) is a standard care regimen for patients with breast cancer. However, the pathologic complete response (pCR) rate remains at 30%. We hypothesized that a cancer stem cell marker may identify NAC-resistant patients, and evaluated CD133 and ALDH1 as a potential surrogate marker for breast cancer. The aim of this study was to find a surrogate maker to predict chemosensitivity of NAC for breast cancer. A total of 102 patients with breast cancer were treated with NAC consisting of epirubicin followed by paclitaxel. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity and prognostic potential of CD133 or ALDH1 expression was evaluated by immunohistochemistry. Clinical CR (cCR) and pCR rates were 18% (18/102) and 29% (30/102), respectively. Forty-seven (46%) patients had CD133-positive tumors before NAC, and CD133 expression was significantly associated with a low pCR rate (p = 0.035) and clinical non-responders. Multivariate analysis revealed that CD133 expression was significantly (p = 0.03) related to pCR. Recurrence was more frequent in patients with CD133-positive tumors (21/47, 45%) than that in patients with CD133-negative tumors (7/55, 13%). The number of patients with CD133-positive tumors (62%) after NAC was higher than that (46%) before NAC. Furthermore, most patients with CD133-positive tumors before NAC maintained the same status after NAC. CD133 before NAC might be a useful marker for predicting the effectiveness of NAC and recurrence of breast cancer after NAC.
    Full-text · Article · Sep 2012 · PLoS ONE
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    ABSTRACT: With the help of ever more powerful research tools triple-negative breast cancer (TNBC) is slowly yielding its secrets. The neoadjuvant setting gives us the best opportunity to address questions raised by the biologic heterogeneity of the disease, and eventually design individualized treatment plans for patients who are identified as likely to have a suboptimal response to chemotherapy. However, given a plethora of aberrantly activated pathways, exacerbated by its genomic instability, the challenge is to separate what drives the behavior of TNBC from the consequences of that behavior. This article reviews our current understanding of TNBC, including recent efforts to identify clinically relevant subsets of the disease, the role of treatments that exploit defects in DNA repair, including chemotherapeutic agents such as the platinum analogues, and biologic agents such as the poly ADP-ribose polymerases (PARP) inhibitors, and then discusses potential targeted approaches to its treatment, most of which are still early in development.
    No preview · Article · Dec 2012 · Current Breast Cancer Reports
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