Very young women with breast cancer are more likely to benefit from neoadjuvant chemotherapy than older women because of biologic differences in their tumors, German researchers reported at the CTRC-AACR San Antonio Breast Cancer Symposium.
In a meta-analysis of eight neoadjuvant trials involving 8,949 patients (Abstract S3-1), 32 percent of women under age 35 had triple-negative breast cancer—i.e., tumors that are estrogen-receptor negative, progesterone-receptor negative, and HER2-negative—compared with 25 percent of those 36 to 50 and 21 percent of those 51 and older.
The lead investigator, Sibylle Loibl, MD, PhD, Associate Professor of Gynecology at the University of Frankfurt, said that the findings are consistent with clinical observations of more aggressive tumor growth in younger women: “Tumors arising in young women are more aggressive, and triple-negative tumors are aggressive,” she explained.
In the German Breast Group study, 23.6 percent of 704 women younger than 35 achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy, compared with 17.5 percent of 4,167 women age 36 to 50 and 13.5 percent of 4,078 women 51 and older.
The superior pathological complete response rate in the younger women was driven by better pCR rates among patients with triple-negative tumors and among those with luminal-like tumors, Loibl reported.
Among women with triple-negative tumors, the pCR rates were 45 percent for those 35 and younger, 35 percent for those 36 to 50, and 25 percent for those 51 and older.
Among women with luminal-like tumors, the pCR rates were 11 percent for those 35 and younger, eight percent for those 36 to 50, and six percent for those 51 and older.
She said the findings are reassuring for younger women with triple-negative disease: “Some oncologists think younger women don't need chemotherapy, but I think they do. I suggest neoadjuvant chemotherapy for all young women with these cancers, especially those with triple-negative breast cancer. We can tell them that they have an almost 50 percent chance that everything will be gone after treatment.
“Moreover, in contrast to other analyses, we found very young women with luminal-like—i.e., hormone-receptor positive, HER2-negative—tumors benefit from neoadjuvant chemotherapy. As a result, I think young women with luminal-like tumors will be treated more often now with chemo.”
In other findings that would be consistent with having more aggressive disease, the younger women did not fare as well as older women in terms of disease-free survival and local recurrence-free survival rates.
Specifically, the disease-free survival rate was a statistically significant 17 percent worse in women 35 and younger, compared with those 36 to 50. The local recurrence-free survival rate was a statistically significant 26 percent worse in women 35 and younger, compared with those 36 to 50.
There was no difference in disease-free survival rates according to age among those patients who achieved a pathological complete response. However, disease-free survival rates were significantly worse among young women who did not achieve a pCR to neoadjuvant chemotherapy, compared with those who did.
Carlos Arteaga: Support What Is Generally Done at Vanderbilt
Symposium Co-Director Carlos L. Arteaga, MD, PhD, Associate Director of Clinical Research and Director of the Breast Cancer Program at Vanderbilt-Ingram Cancer Center, said that the findings support what is generally done at his institution: “We tend to err on the side of aggressive therapy in younger women,” he said at a news briefing preceding the oral presentation.
But Erica L. Mayer, MD, MPH, Director of Clinical Research at Dana-Farber Cancer Institute, said that that experience is not typical of U.S. medical centers.
In Germany, most patients—regardless of age and tumor subtype—are given neoadjuvant chemotherapy. But in the U.S., its use is generally restricted to academic medical center and clinical trials, she said. “Studies like this are driving an increase in use of neoadjuvant treatment outside of those settings in this country.”
The main reason to give neoadjuvant chemotherapy to these women is to downstage the tumor prior to surgery, she said, noting that there are no targeted agents for triple-negative breast cancer.
Mayer said the German Breast Group should be commended for finding a group of more than 700 breast cancer patients age 35 and younger to study. Noting that the researchers had to comb through the records of almost 9,000 patients to find 704 very young women, she said the findings confirm that breast cancer in these women is biologically different.