Estrogen deprivation does not significantly improve pathologic complete response in hormone receptor–positive breast cancer
SAN ANTONIO — The addition of estrogen deprivation to neoadjuvant chemotherapy did not significantly increase pathologic complete response rate among patients with hormone receptor–positive, HER-2–positive breast cancer, according to study results presented at San Antonio Breast Cancer Symposium.
Researchers observed high rates of adverse events with standard neoadjuvant chemotherapy in this trial, but estrogen deprivation did not add to that toxicity.
“We plan to do extensive correlative science studies, evaluation of residual cancer burden, and a more thorough evaluation of pathologic response and long-term outcomes to try to determine if there is a role for estrogen deprivation concurrently with other treatments for HER-2–positive breast cancer,” Mothaffar F. Rimawi, MD, associate professor and medical director at Lester and Sue Smith Breast Cancer, part of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, said during a press conference.
ER–positive, HER-2–positive tumors are less likely than ER–negative/HER-2–positive tumors to respond to dual anti–HER-2 therapy, suggesting the estrogen receptor may serve as a pathway of resistance to this treatment.
In the NRG Oncology/NSABP B-52 trial, Rimawi and colleagues assessed whether concurrent inhibition of ER and HER-2 in addition to chemotherapy would help overcome treatment resistance, thereby increasing pathologic complete response rates.
The analysis included 311 patients with HER-2–positive, ER– or PR–positive invasive breast cancer diagnosed by core needle biopsy. Patients who were clinically node negative were eligible if their tumors were 2 cm or larger; all node-positive patients were eligible. All patients had left ventricular ejection fraction of at least 50% regardless of their testing facility’s lower limit of normal, and they also had adequate organ function.
Nearly half (46%) of patients were aged 49 years or younger. The majority (79%) were white.
“Twenty-six percent of our patients had T3 or T4 disease, and 57% had node-positive disease, so this was a high-risk population,” Rimawi said.
Researchers assigned 154 patients to the TCHP regimen, which consisted of docetaxel, carboplatin and trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech). Treatments were administered every 21 days for six cycles.
The other 157 patients received TCHP plus estrogen deprivation.
Trial protocols required a core biopsy of the primary tumor prior to the third cycle of TCHP. Investigators obtained core biopsies from 103 patients.
At the conclusion of their assigned regimen, patients went on to surgery — either mastectomy or lumpectomy — and axillary staging.
Pathologic complete response rate in the breast and nodes served as the primary endpoint. Researchers established the expected rate of pathologic complete response in the group not treated with estrogen deprivation at 45%, and they powered the study to detect an improvement in pathologic complete response from 45% to 60% with the addition of estrogen deprivation.
Secondary endpoints included pathologic complete response in the breast, clinical complete response and toxicity. Researchers intend to assess two other secondary endpoints — OS and recurrence-free interval — at approximately 8 years after trial initiation, or about 5 years from now.
The addition of estrogen deprivation to neoadjuvant chemotherapy increased pathologic complete response in the breast and nodes in the overall cohort (46% vs. 41%), among premenopausal patients (46% vs. 44%) and among postmenopausal patients (45% vs. 38%). However, none of those differences reached statistical significance.
The addition of estrogen deprivation also increased pathologic complete response in the breast alone among all patients (47% vs. 44%), premenopausal patients (49% vs. 48%) and postmenopausal patients (45% vs. 40%). However, the improvements were not statistically significant.
The addition of estrogen deprivation to chemotherapy did not dramatically increase incidence of adverse events. Researchers reported the same incidence of grade 2 or grade 3 diarrhea (57%) and vomiting (18%) in each treatment group. Patients assigned estrogen deprivation were less likely to experience grade 2 or grade 3 nausea (35% vs. 40%) and dehydration (22% vs. 28%).
Rates of grade 2 or grade 3 anemia (44% vs. 47%), hypokalemia (18% vs. 15%) and febrile neutropenia (7% vs. 5%) were comparable between those assigned the combination and those assigned chemotherapy alone.
“Given the toxicity of standard chemotherapy observed on this trial, findings from NSABP B52 argue quite strongly for a tailored de-escalation approach where toxic treatments are omitted or replaced with less toxic ones without compromising outcomes,” Rimawi said. – by Mark Leiser
Rimawi MF, et al. Abstract S3-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2016; San Antonio.
Disclosure: The NIH and Genentech funded this study. Rimawi reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.