Primary Systemic Therapy of Breast Cancer

Abstract

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer. The Oncologist 2006;11:574-589 Learning ObjectivesAfter completing this course, the reader will be able to:1. Describe the rationale for using primary systemic therapy (PST) in the treatment of nonmetastatic breast cancer.2. Discuss the pathologic complete response (pCR) rate as a surrogate marker of PST benefit.3. Select the most appropriate regimen for a patient with breast cancer considered for PST.4. Explain the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients.Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.

Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk, locally advanced prostate cancer

“…21 As an example of how the regimen and duration of therapy impacts pCR, in trials of neoadjuvant for breast cancer, 4 cycles of chemotherapy reportedly achieves pCR ranging from 4% to 13%. 27 With the addition of sequential therapy to a noncross-resistant regimen and up to 6 months of therapy, the pCR rate was reported to be 26% to 31%. 27 The pathologic outcome and surgical morbidity in the current study were similar to other high-risk series.…”

“…27 With the addition of sequential therapy to a noncross-resistant regimen and up to 6 months of therapy, the pCR rate was reported to be 26% to 31%. 27 The pathologic outcome and surgical morbidity in the current study were similar to other high-risk series. 8,21 In this study, 1 patient experienced rectal injury, which is similar to the rate of 4.2% reported from a similar series of high-risk patients without preoperative therapy.…”

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

“…The BEvacizumab and Trastuzumab Adjuvant Therapy in HER-2-Positive Breast Cancer trial is a multicenter phase III randomized adjuvant trial comparing chemotherapy plus trastuzumab with chemotherapy plus trastuzumab and the anti-VEGF ligand bevacizumab [352]. No efficacy data are available at this time.…”

Neutrophil–Lymphocyte Ratio Predicts Response to Chemotherapy in Triple-Negative Breast Cancer

“…Neoadjuvant chemotherapy (nac) has become the standard treatment in locally advanced breast cancer. It can render surgically inoperable tumours operable or can downstage a primary tumour, allowing for breast-conserving surgery in patients who might have needed a mastectomy at initial diagnosis 5,6 . Several randomized clinical trials have demonstrated no difference in long-term outcome between patients who receive nac and those who receive adjuvant chemotherapy 7,8 .…”