SAN FRANCISCO – A change in the status of any breast cancer tumor biomarker after neoadjuvant therapy was independently associated with a 37% decreased likelihood of recurrence in 5 years, a multivariate analysis showed.
The subtyping of breast cancer by receptor status changed in 41% of 398 samples between the initial tumor and residual disease after neoadjuvant chemotherapy.
In patients with any change in the status of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), after neoadjuvant chemotherapy, 63% were relapse free 5 years later as compared with 48% of patients with no receptor change, a significant difference.
Dr. Napa Parinyanitikul
Overall survival at 5 years, however, did not differ significantly based on receptor status change, Dr. Napa Parinyanitikul and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology. At 5 years, 73% of patients with a receptor status change and 63% with no change were alive.
The study analyzed data on patients treated at her institution in 1992-2012 who had tumor biomarker results from pretreatment biopsies and from samples of residual disease after neoadjuvant chemotherapy. Most patients in the study were white, with clinical stage II or III disease.
Of the tumors, 49% were hormone receptor–positive and HER2 negative; 18% were HER2 positive, and 33% were negative for all three receptors (triple-negative breast cancer). Neoadjuvant chemotherapy consisted of a taxane-based regimen in 10%, an anthracycline-based regimen in 19%, an anthracycline/taxane-based regimen in 71%, and trastuzumab-based chemotherapy in 49%. The 88% of patients with hormone receptor-positive disease received adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor.
After a median of 40 months of follow-up, 32% of women had died and 42% had a recurrence of breast cancer, reported Dr. Parinyanitikul, a fellow at the University of Texas MD Anderson Cancer Center, Houston.
The likelihood of receptor status changes differed significantly by the subtype of breast cancer. Of hormone receptor–positive cancers, 51% had a change in receptor status, compared with 27% of HER2-positive cancers and 22% of triple-negative breast cancers.
Other factors did not significantly affect the likelihood of receptor status change, including patient age or race, histology, tumor stage or grade, the presence of lymphovascular invasion, or the class of neoadjuvant chemotherapeutic agents.
Of ER-positive tumors, 11% changed to ER negative after neoadjuvant chemotherapy; of ER-negative tumors, 21% changed to ER positive. Of the PR-positive tumors, 35% changed to PR-negative; of PR-negative tumors, 12% changed to PR positive. Of HER2-positive tumors, 40% changed to HER2 negative; of HER2-negative tumors, 3% changed to HER2 positive. Among 35 patients treated with trastuzumab, the HER2 status changed in 16 (46%).
Patients who had tumors with an ER-negative status that did not change had the worst 5-year rates for overall survival (47%) and relapse-free survival (40%), compared with patients whose tumors had an ER-positive status did not change (81% overall survival and 63% relapse-free survival), patients whose ER status changed from positive to negative (67% and 66% survival rates, respectively), and patients whose ER status changed from negative to positive (75% and 59%, respectively).
Similarly, patients who had PR-negative tumors whose status did not change had significantly lower rates of overall survival (51%) and relapse-free survival (41%), compared with patients whose PR-positive tumor status did not change (87% and 67%, respectively), those who changed from PR positive to PR negative (78% and 73%, respectively), and patients whose PR-negative status changed to PR positive (69% and 55%, respectively).
Changes or lack of change in HER2 subgroups were not significantly associated with varying outcomes.
The investigators also looked at the absolute percent changes in ER or PR status using cutoffs in 10% increments from 10% to 50%. The 5-year overall survival rate was significantly greater in ER-positive patients who had at least a 20% change in ER status, compared with those with less than a 20% change (87% vs. 73%, respectively). The 5-year relapse-free survival rate also was significantly greater if the ER status changed by at least 20% (71%), compared with smaller ER changes (59%).
Of cancers that were hormone receptor–positive and HER2 negative before neoadjuvant chemotherapy, 20% changed to HER2-positive or triple-negative breast cancer after treatment, 12% of tumors that had been HER2 positive changed to triple negative tumors, and 2% of triple negative breast cancers changed to HER2-positive after treatment. These changes produced only one significant effect on outcomes: 5-year overall survival rates were significantly lower in patients who changed from HER2-positive to triple-negative breast cancer (23%), compared with those whose HER2-positive cancer did not change to triple negative (71%).