Young Women With Breast Cancer Were More Likely Than Older Women to Respond to Neoadjuvant Chemotherapy

This abstract will be presented at a press conference hosted by Carlos L. Arteaga, M.D. associate director for clinical research and director of the Breast Cancer Program at Vanderbilt Ingram Cancer Center, on Thursday, Dec. 6 at 7:30 a.m. CT in Room 217 A-C of the Henry B. Gonzales Convention Center. Reporters who cannot attend in person can call in using the following information:• U.S./Canada (toll free): 1 (800) 446-2782• International (toll call): 1 (847) 413-3235

Newswise — SAN ANTONIO — Women with breast cancer aged 35 or younger were more likely than older women to achieve a pathological complete response after neoadjuvant chemotherapy, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“Young women with breast cancer are rare, and some data indicate that their prognosis is worse than it is for older women,” said Sibylle Loibl, M.D., Ph.D., an associate professor at the University of Frankfurt in Germany. “This is not only because their tumors tend to be more aggressive, but because breast tumors that arise in women who are young seem to be a special biological entity.”

Loibl and colleagues evaluated data from eight German studies that included 8,949 women with operable or locally advanced, nonmetastatic breast cancer who were treated with neoadjuvant chemotherapy. The researchers compared pathological complete response and disease-free survival for the subgroup of 704 women aged 35 or younger to those of older women. The subgroup of younger women included a greater proportion of triple-negative breast cancer cases and a smaller proportion of luminal A-type breast cancer cases than in the group of women aged older than 35 (26 percent versus 19 percent and 21 percent versus 27 percent for triple-negative and luminal A-type, respectively).

The pathological complete response rate was significantly higher in very young women — 23.6 percent compared with 15.7 percent among older women. Through further analysis, the researchers found this difference was isolated to women with triple-negative breast cancer and luminal-like breast cancer.

They found no difference in disease-free survival according to age among those patients who achieved a pathological complete response. However, disease-free survival was significantly worse among young women who did not achieve a pathological complete response.

In addition, tumor biology seemed to play an important role, especially in young women, for predicting pathological complete response and survival, according to Loibl. Age, but not pathological complete response, predicted disease-free survival in women with luminal A-type cancer. However, the worst disease-free survival rate was among women with this type of cancer who were younger than 35 and did not achieve a pathological complete response. The best disease-free survival rate was among women younger than 35 who did achieve a pathological complete response.

“The most surprising finding was that young women with a luminal-type tumor — hormone receptor-positive and HER2-negative — who achieved a pathological complete response had a better survival rate than the patients with nonpathological complete response,” Loibl said. “This is not true for other age groups, which indicates that breast cancer in the young — even when a luminal-type breast cancer — is chemosensitive.”

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The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Abstract:Publication Number: S3-1

Title: Neoadjuvant Chemotherapy in the very young 35 years of age or younger

Sibylle Loibl1, Christian Jackisch2, Stephan Gade1, Michael Untch3, Stefan Paepke4, Sherko Kuemmel5, Andreas Schneeweiss6, Christian Jackisch7, Jens Huober8, Jörn Hilfrich9, Claus Hanusch10, Bernd Gerber11, Holger Eidtmann12, Carsten Denkert13, Serban-Dan Costa14, Jens-Uwe Blohmer15, Valentina Nekljudova1, Keyur Mehta1 and Gunter von Minckwitz1. 1German Breast Group, Neu-Isenburg; 2Klinikum Offenbach; 3Helios Kliniken Berlin; 4University Muenchen; 5Kliniken Essen Mitte; 6University Heidelberg; 7Klinikum Offenbach; 8Uni Duesseldorf; 9Eilenriedeklinik Duessldorf; 10Rotkreuzklinikum Muenchen; 11University Rostock; 12University Kiel; 13Charite Berlin; 14University Magdeburg and 15Sankt Gertrauden Berlin.

Body: Background: In young women the course of breast cancer (BC) tends to be more aggressive. In several trials young age at diagnosis was an independent predictive factor for pathological complete response (pCR) after neoadjuvant chemotherapy. Here we investigate especially the rare entity of very young women at age 35 years or younger.

Methods: 8949 patients from 8 neoadjuvant German studies with operable or locally advanced, non-metastatic breast cancer and follow-up were included (for details see von Minckwitz G et al, BCRT 2010 and NEJM 2012). A subgroup of 704 patients of age 35 years or younger was analyzed. All patients with endocrine responsive disease received adjuvant endocrine therapy according to institutional standard. We compared pathological complete remission rate (pCR) defined as ypT0, ypN0 and disease free survival rate (DFS) of this very young group with older patients in total and in different histopathological subgroups (as defined previously by von Minckwitz J Clin Oncol 2012).

Results: From 8949/6561 had known ER, PR, HER2 and grading. There were less Luminal A and more TNBC in the very young women compared to the one >35 years of age: Luminal A: 131 (21%) vs. 2251 (27%); Luminal B HER2-: 50 (8%) vs. 783 (10%); Luminal B HER2+: 103 (17%) vs. 989 (14%); HER2+/HR-: 72 (11%) vs. 739 (10%); TNBC: 164 (26%) vs. 1415 (19%). The pCR rate was significantly higher in the very young than in the group older than 35 years (23.6% vs. 15.7.%; p<0.0001). However, this difference was confined to the TNBC subgroup (45% vs. 31%; OR 1.85; 95%CI [1.33-2.56]; p<0.001). Only in the triple negative cohort age had independent predictive factors for achieving a. pCR. Compared to patients >35 years, in the very young only hormone receptor status and grading had independent predictive information for pCR but not T-stage and nodal-stage. No difference in DFS according to age was seen when the patients had a pCR. Non-pCR patients had a significantly worse DFS when they were very young (DFS HR: 1.35; p=0.001). Adjusting for T-stage, nodal-stage, age and pCR; within the TNBC pCR but not age had independent prognostic information for DFS (pCR: HR: 0.18 [95%CI 0.13-0.16]; p<0.0001; age HR: 1.06 [95%CI 0.74-1.51]; p=0.77); within the Luminal A group age but not pCR had independent prognostic information for DFS (age: HR 2.5 [95% CI 1.6-3.9] p<0.001; pCR: HR 0.72 [95%CI 0.37-1.41] p=0.34). In the Luminal A group the worst DFS was seen in the group <=35years/no-pCR and the best DFS in the <=35 years with pCR (log rank p=0.27; HR 0.05 wide CI due to small sample size; p=0.5).

Conclusion: Very young women are more likely to achieve a pCR after neoadjuvant chemotherapy. This effect is driven mainly by triple negative BC, which is more common in the very young. Age did not influence DFS in TNBC when a pCR was achieved. It can be hypothesized that the very young pts with Luminal A tumors benefit from a pCR, whereas overall pCR is not a predictor in the Luminal A subgroup.