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Impact of Chemotherapy Sequencing on Local-Regional Failure Risk in Breast Cancer Patients Undergoing Breast-Conserving Therapy

Mittendorf, Elizabeth A. MD*; Buchholz, Thomas A. MD; Tucker, Susan L. PhD; Meric-Bernstam, Funda MD*; Kuerer, Henry M. MD, PhD*; Gonzalez-Angulo, Ana M. MD§; Bedrosian, Isabelle MD*; Babiera, Gildy V. MD*; Hoffman, Karen MD; Yi, Min MD, PhD*; Ross, Merrick I. MD*; Hortobagyi, Gabriel N. MD; Hunt, Kelly K. MD*

doi: 10.1097/SLA.0b013e3182805c4a

Objective: This study was performed to evaluate long-term local-regional control rates after breast-conserving therapy (BCT) for patients undergoing surgery before or after neoadjuvant chemotherapy.

Methods: There were 2983 patients who underwent segmental mastectomy with whole-breast irradiation from 1987 to 2005. Clinicopathological and outcome data were reviewed, and comparisons were made between those undergoing surgery before and those undergoing surgery after neoadjuvant chemotherapy.

Results: There were 2331 patients (78%) who underwent surgery first and 652 (22%) received neoadjuvant chemotherapy. Patients receiving neoadjuvant chemotherapy had more advanced disease at baseline and more adverse clinicopathological features. The 5- and 10-year local-regional recurrence (LRR)-free survival rates were 97% [95% confidence interval (CI), 96–98) and 94% (95% CI, 93–95) for surgery first and 93% (95% CI, 91–95) and 90% (95% CI, 87–93) after neoadjuvant chemotherapy (P < 0.001). However, there were no differences in LRR-free survival rates when comparing the presenting clinical stage (P = NS). Of 607 patients presenting with clinical stage II/III disease, chemotherapy downstaged 313 patients (52%) to pathological stage 0/I disease; 294 (48%) had residual stage II/III disease. In multivariate analysis, an age less than 50 years, clinical stage III, grade 3, estrogen receptor (ER)-negative disease, estrogen receptor-positive disease without receipt of endocrine therapy, lymphovascular invasion, multifocal disease on pathology, and close/positive margins were associated with LRR. Use of neoadjuvant chemotherapy was not significant when added to the model. Adjusting for adverse factors, there were no differences in LRR between patients who underwent surgery before and those who underwent neoadjuvant chemotherapy after surgery.

Conclusions: LRR after BCT is driven by tumor biology and disease stage. Appropriately selected patients can achieve high rates of local-regional control with BCT with either upfront surgery or surgery after neoadjuvant chemotherapy.

We show that appropriately selected patients can achieve high rates of local-regional control with breast-conserving therapy (BCT) with either upfront surgery or surgery after neoadjuvant chemotherapy. Local-regional recurrence after BCT is driven by biological factors, not the sequencing of treatment.

Departments of *Surgical Oncology

Radiation Oncology

Bioinformatics and Computational Biology

§Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Reprints: Elizabeth A. Mittendorf, MD, or Kelly K. Hunt, MD, Department of Surgical Oncology, Unit 1484, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Houston, TX 77030. E-mail: or

Presented in part at the ASCO Breast Cancer Symposium, San Francisco, CA, September 8–10, 2011.

Supported by the National Institutes of Health through MD Anderson's Cancer Center Support grant CA01667233.

Disclosure: The authors declare no conflicts of interest.

© 2013 Lippincott Williams & Wilkins, Inc.