• Oncology Clinical Trials
• Breast Cancer
• Adjuvant/Neoadjuvant Therapy

Evidence suggests that breast cancer in younger women may be clinically and etiologically distinct from older women [Bleyer A et al. Nat Rev Cancer 2010]. Breast cancer in young women demonstrates a worse prognosis and a more aggressive phenotype, higher proportions of high-grade and later-stage tumors, lower estrogen receptor (ER) positivity, and, in some studies, higher expression of human epidermal growth factor receptor 2 (HER2) [Bleyer A et al. Nat Rev Cancer 2010; Gnerlich JL et al. J Am Coll Surg 2009]. While some studies point to a unique breast cancer biology in young women, others have illustrated that the aggressive nature is the result of higher frequencies of aggressive breast cancer subtypes among younger patients. Sibylle Loibl, MD, PhD, German Breast Group, Neu-Isenburg, Germany, presented data on the response to neoadjuvant chemotherapy in women with breast cancer who are aged ≤35 years compared with older women.

The meta-analysis included 8949 patients with operable or locally advanced nonmetastatic breast cancer from 8 neoadjuvant German studies with follow-up. Patients were categorized into 3 age groups: ≤35 (n=704), 36 to 50 (n=4167), and ≥51 years (n=4078). All patients with endocrine responsive disease received adjuvant endocrine therapy. Subgroup analyses were conducted defined by hormone receptor (HR) and HER2 status.

Breast cancer subtype distribution was found to differ according to patient age group. Triple-negative breast cancer (TNBC) was more common in patients aged ≤35 than patients aged >35 years (26% vs 19%). In contrast, HR-positive/HER2-negative breast cancer was more common in patients aged >35 years compared with patients aged ≤35 years (37% vs 29%). HER2-positive tumors were similar in both age groups regardless of HR status.

The overall pathologic complete response (pCR) rate (defined as ypT0, ypN0) was significantly higher in patients aged ≤35 compared with patients aged ≥51 years (23% vs 13%; p=0.002; Figure 1). The only subgroups with pCR rates that were statistically higher for patients aged ≤35 years compared with patients aged ≥51 years were HR-positive/HER2-negative (11% vs 6%; p=0.013) and TNBC (45% vs 25%; p=0.004).

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Figure 1.

pCR Rates Overall and in Subgroups.

*HR and HER2-status not available for all patients. HER2=human epidermal growth factor receptor 2; HR=hormone receptor; TNBC=triple-negative breast cancer.Reproduced with permission from S Loibl, MD, PhD.

The pCR rate was an independent predictor of disease-free survival (DFS) when the analysis was adjusted for age, tumor size, nodal status, histological type, grading, and clinical trial. DFS was significantly inferior in patients aged ≤35 compared with patients in the 36 to 50 (p=0.031) and the ≥51 year age groups (p=0.022). The difference was greater between age groups in patients who did not achieve pCR; patients aged ≤35 years had a 25% higher risk of relapse compared with the 36 to 50 (p=0.002) and ≥51 year age groups (p=0.001). In contrast to previous studies, patients aged ≤35 years with HR-positive/HER2-negative breast cancer who achieved a pCR had a better DFS compared with patients in the same age group who did not achieve pCR. Local recurrence-free survival was also significantly inferior in patients aged ≤35 years compared with patients in the 36 to 50 (p=0.017) and ≥51 years age groups (p=0.00018). Overall survival was not significantly different between the 3 age groups.

These results are retrospective and provided support to the hypothesis that breast cancer might be biologically different in very young women and the higher likelihood of achieving a pCR in young patients is driven mainly by TNBC subgroup.

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