Background:

Perou and Serlie's molecular portraits of breast tumors explain the phenotypic heterogeneity of breast cancers by demonstrating diversity in gene expression, and classify tumors into 5 unique subgroups. The commonest breast cancer intrinsic subtype, Luminal A (ER/PR+, HER2-), generally carries a good prognosis with lower incidence of metastatic spread and longer disease free and overall survival compared to non-luminal tumors. Yet within the Luminal A subgroup there appears to be heterogeneous outcome; and debate continues as to the need for adjuvant chemotherapy within this cohort. In the absence of validated molecular predictors of response to chemotherapy, we aimed to assess the outcomes of a large cohort of Luminal A breast cancer patients in order to determine prognostic factors which may guide future treatment strategies for this subgroup.

Methods:

1355 breast cancer patients treated in a tertiary referral symptomatic breast cancer unit, with known molecular subtype, were identified. 965 had Luminal A primary breast tumors, of whom 57% had received adjuvant chemotherapy. Clinicopathological details of all patients were reviewed, including particular details of the chemotherapeutic regimens administered. Current outcome in terms of disease-free (DFS) and overall survival (OS) was determined. Kaplan-Meir & multivariate analyses were performed to identify tumor/patient characteristics indicative of poor response to adjuvant chemotherapy.

Results:

Mean follow-up was 61.3 months. Overall & disease free survival were significantly better for those who received adjuvant chemotherapy (Mean OS: 60 vs. 54 months, p=0.051. DFS: 54 vs. 44 months, P<0.001). Patients whose disease progressed despite chemotherapy had poorer prognostic indicators at the time of diagnosis, compared to their Luminal A counterparts who remained disease free: including significantly greater tumor size (30.34mm vs. 25.0mm, p=0.01), 69% were node positive and 59.4% had stage 3 or 4 disease (chi square<0.001). Of the cohort of Luminal A patients who remained disease free throughout follow-up, 40% had not received adjuvant chemotherapy. Those women who remained disease free despite not receiving systemic chemotherapy had smaller tumors (26mm vs. 31 mm, p=0.021) were generally postmenopausal (80% vs. 56%, P<0.001) and had predominantly node negative (59% vs. 37%, P<0.001) early stage I and II disease (78% vs. 73%, p=0.001), compared to those surviving women who did get chemotherapy.

Conclusion:

Adjuvant chemotherapy is beneficial in the cohort of Luminal A's with advanced disease at diagnosis. However it is critically importance to identify this particular subgroup & spare those with early disease the toxicity of treatment from which they are unlikely to derive further benefit.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-10.