New Approaches Needed for Patients With Locoregional Breast Cancer Progression During Neoadjuvant Systemic Therapy

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Patients with breast cancer who experience disease progression on neoadjuvant systemic therapy tend to have poor survival outcomes, even after surgical management, according to a study presented during the 2021 American Society of Breast Surgeons Annual Meeting.1 Findings from the retrospective analysis showed a median distant disease–free survival and a median overall survival of 14 months and 26 months, respectively, suggesting the need for new treatment approaches in this high-risk patient population.

“Patients with progressive disease on neoadjuvant systemic therapy represent a small proportion of patients with breast cancer who have poor survival outcomes, even after surgical management,” said lead study author, Leisha C. Elmore, MD, MPHS, Breast Surgical Oncology Fellow at The University of Texas MD Anderson Cancer Center, Houston. “The pattern of distant failure, even in the setting of appropriate locoregional tumor control, highlights the need for expanded systemic therapy options, including clinical trials, and careful consideration of the role of surgical management with a multidisciplinary approach to care.”

Leisha C. Elmore, MD, MPHS

Leisha C. Elmore, MD, MPHS

Neoadjuvant systemic therapy is increasingly being utilized for women with breast cancer. This approach has several potential benefits, including downstaging of disease to facilitate less extensive surgical management and assessment of tumor response to therapy, providing a window into the biologic behavior of the tumor.

Although most patients have either a complete or partial response, said Dr. Elmore, a small proportion of patients experience disease progression. Historical data suggest that progressive disease represents 3% to 6% of the neoadjuvant systemic therapy population.

“Given the poor response to medical therapy, patients with progressive disease represent a management challenge, and many of these patients proceed to surgery,” said Dr. Elmore. “The treatment course and clinical outcomes of these patients have not been elaborated in contemporary data.”

Study Methods

For this study, Dr. Elmore and colleagues evaluated the clinical outcomes of patients with locoregional tumor progression during neoadjuvant systemic therapy who were treated with surgery. To accomplish this aim, the researchers queried a prospectively maintained institutional database to extract information on patients with stage I to III breast cancer treated with neoadjuvant therapy between 2005 and 2015. Disease progression—defined as growth of local and/or regional nodal disease or development of new ipsilateral breast or nodal lesions—was determined by radiologic evaluation and/or physical examination.

Primary study endpoints were overall survival and distant disease–free survival. The Kaplan-Meier method was used to determine survival, whereas the Cox proportional hazard regression was utilized to determine factors associated with survival.

Poor Survival Outcomes With Progressive Disease

Of the total 6,362 patients who received neoadjuvant systemic therapy during the study period, 124 patients (1.9%) experienced disease progression, and 84% of these patients went on to receive surgery. Among those treated with surgery, mastectomy was the procedure of choice in 91%, said Dr. Elmore, and a majority of patients had axillary lymph node dissection. A total of 63% of patients received adjuvant radiation therapy.

With a median overall follow-up of 25 months and a median live follow-up of 71 months, median distant disease–free survival was 14 months, and median overall survival was 26 months. According to Dr. Elmore, 69% of patients developed distant metastases, and just 23% of patients were alive without evidence of disease at the end of the study period.

“Compared with those who died during the study period, patients who were alive without evidence of disease at the end of the study were more likely to have T1 disease, non-inflammatory breast cancer, and non–triple-negative breast cancer,” said Dr. Elmore. In addition, she noted that 72.4% of these patients were premenopausal, and 51.7% had clinical N0 disease.

Among patients who were treated with surgery, negative margins were obtained at index operation in 93% of patients. A total of 39% of patients developed locoregional failure, and 64% of patients developed distant metastases during the study period. Median distant disease–free survival was 16 months, and median overall survival was 31 months in patients receiving surgical management.

Subgroup analysis of patients receiving surgical management in the setting of disease progression showed that those with triple-negative breast cancer had significantly worse distant disease–free survival and overall survival than those with hormone receptor–positive and HER2-positive disease. Researchers also noted significant findings with inflammatory breast cancer. Patients with inflammatory breast cancer had significantly worse distant disease–free survival and overall survival when compared with patients who had non-inflammatory breast cancer.

Demographic and Clinical Pathologic Findings

With respect to the study population as a whole, Dr. Elmore noted several “striking” demographic and clinical pathologic findings, including overrepresentation of Black patients. “Although 20% of patients in the study population were Black, only 11.8% of patients diagnosed with breast cancer during the period of study were Black,” said Dr. Elmore.

In addition, the data demonstrated a high prevalence of patients with inflammatory breast cancer, representing 25.8% of all patients with progressive disease. According to Dr. Elmore, inflammatory breast cancer represents 3.6% of all breast cancer diagnoses. In addition, triple-negative breast cancer also appeared to be overrepresented, with 45.2% of patients carrying this diagnosis compared with 12% of all new breast cancer diagnoses.

Finally, Dr. Elmore acknowledged several study limitations. They included its retrospective design and variable chemotherapy combinations.

“Over a 10-year period, there have been changes in systemic therapy protocols, but a shorter time interval would have resulted in a smaller population of patients with limited statistical power,” said Dr. Elmore. “Although our data provide insight into the outcomes of patients with progressive disease, there’s not enough evidence to define optimal management of these patients.” 

DISCLOSURE: Dr. Elmore reported no conflicts of interest.


1. Elmore LC, Kuerer KM, Barcenas CH, et al: Clinical course of breast cancer patients with local regional progression during neoadjuvant systemic therapy. 2021 American Society of Breast Surgeons Annual Meeting. Scientific Session Oral Presentations II. Presented May 2, 2021.