Post-Treatment Biomarker Changes Improved Breast Cancer Survival

SAN FRANCISCO-About 40% of women experienced a change in at least one biomarker from primary to residual breast cancer after undergoing neoadjuvant chemotherapy, according to the results of a study presented Saturday at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium 2013.

“Changes in ER, PR, and HER2 status between the pretreatment tumor and residual disease after neoadjuvant chemotherapy are not infrequent,” said presenter Napa Parinyanitikul, MD, of the University of Texas MD Anderson Cancer Center. “Patients with any receptor change had a statistically significant improvement in 5-year recurrence-free survival compared to patients without any receptor change.”

Given the heterogeneity of breast cancer, changes in biomarker status are well described in the literature. Dr. Parinyanitikul and colleagues conducted a study of 398 women with breast cancer to explore whether changes in receptor status from primary to residual disease after neoadjuvant chemotherapy had any effect on outcomes.

All patients received neoadjuvant chemotherapy with an anthracycline-based, taxane-based, or anthracycline/taxane-based regimen. In addition, 87.6% of patients with hormone receptor–positive disease received adjuvant endocrine therapy.

The patients were followed for a median of 40 months. During that time 32% of patients died and 41.8% recurred. Between primary and residual disease, 40.7% of women had a change in at least one biomarker status:

• 211 patients were ER-positive; 10.9% changed to ER-negative

• 187 patients were ER-negative; 20.8% changed to ER-positive

• 162 patients were PR-positive; 35.2% changed to PR-negative

• 235 patients were PR-negative; 11.9% changed to PR-positive

• 72 patients were HER2-positive; 40% changed to HER2-negative

• 11 patients were HER2-negative; 3% changed to HER2-positive

When the researchers analyzed the subgroup of the 35 women treated with trastuzumab, 45.7% had a HER2 status change to HER2 negative.

The researchers found that those patients with a change in biomarker status had a statistically significant improvement in recurrence-free survival compared to those without a change (HR = 0.63; 95% CI, 0.44–0.9). The 5-year recurrence-free survival was 63% for women with a biomarker change compared with 48% for patients without a change (P = .003).

No significant difference in 5-year overall survival was found between the two groups (HR = 0.79; 95% CI, 0.53–1.18).

“It is still uncertain if mechanisms for tumor discordance such as tumor heterogeneity, clonal selection, genetic switch, and differential treatment response would be main explanations for the lack of stability in tumor biomarkers,” said Dr. Parinyanitikul. “Further large prospective studies may help to confirm our findings and to determine the impact of biomarker changes in long-term survival outcomes.”