Experts in breast cancer review the case of a 42-year-old woman with grade 2, node-positive invasive ductal carcinoma and discuss updated data from the RxPONDER trial on adjuvant chemotherapy benefit in premenopausal women.
Joyce O’ Shaughnessy, MD: I’d like to go on to the second case and see what you’re doing from a practical standpoint with these patients who fall within the gray zone because we need another clinical trial done to have the answer. But we don’t have the clinical trial yet, so we still have to advise these patients.
She has HR [hormone receptor]–positive high-risk breast cancer. She’s 42 and premenopausal. She has a palpable mass in the upper outer quadrant of her right breast, clinically negative axilla, and biopsy shows grade 2 invasive ductal carcinoma. ER [estrogen receptor] is 100%, PR [progesterone receptor] is 80%, HER2 is 0, and Ki67 is generally low, but it’s noted that there are focal areas of Ki67 up to 20%. There’s no lymphovascular invasion and she doesn’t have a germline mutation. She undergoes bilateral mastectomy, which shows a 2.5 cm grade 2 invasive ductal cancer with 1 of 3 positive axillary lymph nodes, a 5 mm metastasis with no extranodal extension, and clear margins. This is middle-of-the-road biology, but node-positive in a premenopausal patient.
From a practical standpoint, would you send her sample for either 21-gene recurrence score or 70-gene prognostic signature? Would you recommend adjuvant chemotherapy to her? Or might that depend on what a signature showed? What endocrine therapy would you recommend for her? I wanted to show some updated data from RxPONDER that Kevin Kalinsky, MD, MS, [Winship Cancer Institute of Emory University] showed at the 2021 San Antonio Breast Cancer Symposium.
We all recall that patients in RxPONDER were both pre- and postmenopausal with 1 to 3 positive nodes. They’d already had surgery and had a recurrence score of 25 or less. Then they were randomized to endocrine therapy alone vs chemotherapy followed by endocrine therapy. The primary end point was IDFS [invasive disease-free survival]. These are the updated analysis that Kevin Kalinsky convincingly showed at San Antonio. There was no benefit at all in the postmenopausal 1- to 3-node population, with a recurrence score of less than 26. There was no chemotherapy benefit for IDFS or distant relapse-free survival. We had seen it before, and we still see it. We see a 4.9% absolute improvement in IDFS in the premenopausal population and a 2.5% absolute improvement in distant relapse-free survival. This is true whether people have 1 node vs 2 or 3 nodes, or women who have 0 to 13 vs 14 to 25 on the higher end or the lower end. They still get the same benefit from chemotherapy.
There was also an intriguing landmark analysis looking at the 2-year IDFS by regular periods or not. We’re looking at IDFS in the patients on the left randomized to chemotherapy alone—these are the premenopausal women—and on the right, the women randomized to chemotherapy then endocrine therapy. There’s also the women who at 2 years didn’t have menstrual periods in the blue vs those in the red who had resumption of menstrual periods. We can see that in endocrine therapy alone, not having menstrual periods improved IDFS, and the same was true with chemotherapy. Eighty percent of the patients in the chemotherapy group didn’t have periods at 2 years and their outcomes were better. Not menstruating was beneficial to patients. We’ve seen that in other studies in the past.
It raises questions. Sixteen percent of patients—the premenopausal patients—in the RxPONDER trial had an LHRH [luteinizing hormone-releasing hormone] agonist. That’s because the trial was started and mostly enrolled before we had the SOFT and TEXT clinical trial data. By today’s standards, the endocrine therapy wouldn’t be considered optimal for these higher-risk premenopausal patients because most didn’t get an LHRH agonist, so the question is whether the chemotherapy took the place of an LHRH agonist. Many people and I believe NRG Oncology and other cooperative groups are possibly going to collaborate together and do this trial again in the premenopausal population, but this time, the endocrine therapy would include an LHRH agonist. It would be plus-minus chemotherapy, but everybody would get today’s optimal endocrine therapy. We don’t have those data.
Transcript Edited for Clarity