Extensive review of patient records by a research team at the University of Texas MD Anderson Cancer Center in Houston, under Dr. Napa Parinyanitikul, suggested that changing receptor status on breast cancer patients during neo-adjuvant therapy can significantly improve the prognosis of cancer. Data suggested that an improvement in the overall survival status (OS) and better 5-year prognosis was associated with changes in the receptor status of estrogen, progesterone, or HER2.
The results of the analysis presented at the Breast Cancer Symposium suggested that a decrease of ≥20% in the concentration of estrogen receptor is associated with higher RFS and OS. While discussimg the results of the review, Parinyanitikul explained that during neo-adjuvant therapy, approximately 40% of patients reported a change in the status of receptor. She commented:
“Changes in ER [estrogen], PR [progesterone], and HER2 status between the pretreatment tumor and residual disease after neoadjuvant chemotherapy are not infrequent. The frequency of biomarker change is even higher when anti-HER2 therapy is incorporated for patients with HER2-positive disease.”
Previously a number of studies have reported changes in the status of receptors in residual and primary breast cancers. Parinyanitikul explained that the discordance rates are fairly high (43% for HER2 status and 51% for hormone receptors). However, it is still unclear if the discordance rates influence the outcome (so far the results of most evaluations are mixed).
“It is still uncertain if the mechanisms for tumor discordance — such as tumor heterogeneity, clonal selection, genetic switch, and differential treatment response — would be the main explanations for the lack of stability in tumor biomarkers.”
Details of the study:
The University of Texas MD Anderson Cancer Center’s Dr. Parinyanitikul identified and isolated 2058 breast cancer patients who received neoadjuvant chemotherapy at MD Anderson during 1992 to 2012. Analysis revealed that 398 patients still reported residual disease after the completion of therapy. The research team determined their ER, PR, and HER2 status at the beginning and after the completion of treatment regimen.
The patients received anthracycline- or taxane-based chemotherapeutic drugs alone or in combination. Patients with hormone receptor-positive disease were also given adjuvant endocrine therapy and 87.6% of the sample successfully completed the endocrine regimen. During the entire study period, Parinyanitikul and colleagues determined biomarker status for each patient and observed the change in receptor status before and after neoadjuvant therapy.
Read more about biomarkers at BioNews Texas
The entire sample was labeled according to the hormonal status (ER, PR, and HER2) and was further categorized into 4 classes:
1. Stable positive
2. Change from positive to negative,
3. Change from negative to positive
4. Stable negative.
Results of Analysis:
During the study period, each patient had a median follow-up period of 40 months. The research team investigated and compared the receptor status with 5-year RFS and OS. The results suggested:
– Mortality of 32% (128 patients)
– Recurrence in 41.8% (167 patients)
The analysis of primary tumor of biomarker status suggested:
– Hormone receptor-positive primary tumor in 113 (48%) cases
– Triple negative primary tumor in 93 (39%) cases
– HER2-positive primary tumor in 30 (13%) cases
The study of residual tumors also presented noticeable changes all three biomarkers:
– 80 patients with residual disease were hormone-receptor positive (corresponds to 51%)
– 42 patients with residual disease were HER2-positive (corresponds to 27%)
– 35 patients with residual disease were triple negative (corresponds to 22%).
The patients who reported change in the status of receptor suggested a 5-year overall survival rate of 73% as opposed to 63% in those with no changes in the receptor status. The 5-year RFS also suggested positive results (63%) in those who had change in receptor status as opposed to 48% with no change in the receptor status.
Similarly, a decrease in the receptor concentration of <20% in primary ER-positive tumors suggested a worst prognosis (5-year OS of 73%, 5- year RFS value of 59%) as opposed to 5-year OS of 87% and 5- year RFS value of 71% in primary ER-positive tumors with receptor concentration of ≥20%).
At the Breast cancer Symposium, the audience and panels of speakers suggested a further need for collecting more information regarding the types and frequency of biomarkers required for the treatment of breast cancer. Speakers also discussed in great detail how receptor status data can influence clinical decision making.