P2-12-27: Simply Adding Together the Diameters of Tumor Foci in Patients with Multicentric or Multifocal Disease Does Not Add Any Additional Prognostic Information: An Analysis from NCIC CTG MA.12 Randomized Placebo-Controlled Trial of Tamoxifen after Adjuvant Chemotherapy in Pre-Menopausal Women with Early Breast Cancer.
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AbstractBackground: A common clinical conundrum in breast cancer management is whether pathologic T stage in women with multicentric or multifocal disease should be taken as the diameter of the largest focus or as the sum of all foci in the breast. Most staging systems, such as the American Joint Committee on Cancer (AJCC), simply use the largest tumor focus for staging. We examine here the impact of alternate methods of estimating tumour size including measures of total tumor size, volume and surface area.Materials & Methods: NCIC CTG MA.12 is a randomized placebo-controlled trial of tamoxifen after adjuvant chemotherapy for pre-menopausal women with early breast cancer. Median follow up is 9.7 years. Pathologically reported patient tumor dimensions for up to 3 foci were utilized to examine the effects of tumor size on Breast-Cancer-Free-Interval (BCFI), defined as the time from randomization until recurrence (defined as first local, regional, distant, or contralateral invasive tumor or DCIS). Tumor size was estimated as 1) pathologic T stage as per AJCC criteria; 2) largest dimension of largest tumor focus (cm); 3) sum of largest dimension(s) of tumor foci (cm); 4) sum of surface area(s) of tumor foci (cm2), and 5) sum of volume of tumor foci (cm3). Step-wise forward unstratified Cox regression was used to assess the different effects of tumor size. Results: This study accrued 672 patients, 43% with T1 tumors, 51% with T2 tumors, and 6% with T3/T4 tumors; 25% were node negative and 56% had 1–3 positive lymph nodes. 75% were locally determined to have hormone receptor positive tumors. A higher number of involved lymph nodes was associated with significantly shorter BCFI (p<0.0001). None of pathologic T stage (p=0.14), largest dimension of largest tumor size (p=0.14), sum of largest dimensions of tumor foci (p=0.24), sum of surface area (p=0.38), and sum of volume of foci (p=0.51) were significantly associated with BCFI. Likewise, lymphovascular invasion (p=0.08), grade (p=0.14), nor administration of anthracycline therapy (p=0.08) were associated with BCFI.Discussion: In the MA.12 population of pre-menopausal women randomized to either tamoxifen or placebo, the sole factor significantly associated with BCFI was nodal status. No measure of tumor size in unifocal or multicentric/multifocal tumors impacted BCFI. The findings of this mature data set suggest that simply adding together the diameters of tumors in patients with multicentric or multifocal disease did not add any additional prognostic information.Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-27.
