Laura J. van ’t Veer, PhD, Leader of the Breast Oncology Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, commented on the findings.

“These investigators confirm in a robust meta-analysis that neoadjuvant chemotherapy response is different for subgroups identified by standard immunohistochemical markers for estrogen, progesterone receptor, and HER2, and this is helpful. They also showed that we need to further examine the biology of the tumors that arise in younger women,” she said. “I have done much work on the MammaPrint signature in tumors of younger as well as older patients, and we see that age is less of an independent marker in these women, but that the proportion of biological high risk vs low risk varies by age group.”

Dr. van ’t Veer asked the investigators whether they had data on which tumors were screen-detected, but Dr. Loibl said that information is not available on this study population. Dr. van ’t Veer explained that screen-detected cancers in the older women are typically associated with a lower risk of recurrence. “These patients are at ultra-low risk,” Dr. van ’t Veer noted. “When you compare the young women with the older ones, you need to keep this in mind as well,” she suggested.

Alternative Hypotheses

Andrew Seidman, MD, Attending Physician for the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, New York, questioned whether the younger patients got fuller doses of chemotherapy on time and on schedule as compared to older patients. “Data in all subsets of the younger women could be influenced by drug delivery, ie, dose intensity,” he pointed out.

He further offered hypotheses for the finding that pathologic complete responses in estrogen receptor–positive/HER2-negative patients correlated with improved overall survival only in the younger patients, not the older ones. “This leads one to wonder if ovarian failure/amenorrhea/early menopause correlates with improved survival,” he suggested.

“An alternative hypothesis is that luminal A breast cancers in very young patients, as opposed to older patients, have other signaling pathways that are important,” he said, “and these may be perturbed to a greater degree by cytotoxic chemotherapy.” ■

Disclosure: Dr. van ’t Veer is cofounder, stockholder, and part-time employee of Agendia Inc, Irvine, California. Dr. Seidman reported no potential conflicts of interest.