Unexpected Results May Push Breast Cancer Research toward More Productive Approaches

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Two recent articles on breast cancer prognostic factors in the Journal of Clinical Oncology “do not jibe with accepted—and profoundly influential—notions of malignant progression,” according to an editorial accompanying the articles in the Journal of Clinical Oncology. One of the articles found that very small tumors with four or more positive lymph nodes may predict for higher breast cancer–specific mortality than larger tumors, suggesting, according to the investigators, “that very small tumor size in the presence of extensive nodal disease may be a surrogate for inherent biologic aggressiveness.” The other article concluded that once there is evidence of lymph node metastasis, the number of positive lymph nodes may not affect prognosis in patients with triple-negative breast cancer.


The study related to tumor size was based on findings from 50,949 female patients identified from SEER registry data and diagnosed between 1990 and 2002 with nonmetastatic T1/T2 invasive breast cancer treated with surgery and axillary lymph node dissection. Tumor size was classified according to the AJCC staging system.

Among patients with four or more positive lymph nodes, those with T1b tumors experienced significantly lower breast cancer–specific mortality relative to patients with T1a tumors (P = .02), the authors reported. Among those with one to three positive lymph nodes, they found no significant difference in breast cancer–specific mortality between patients with T1a tumors and those with T1b or T1c tumors.

“Although the conventional view of cancer spread is that cancer gains metastatic ability through an accumulation of mutations as they grow to large size, we hypothesize that very small cancers with extensive nodal spread represent a subset of cancers where the invasion/metastases pathways are more prominent than those of ‘self-seeding to the primary tumor,’” they wrote.

Triple-negative Population

The other study reviewed 1,711 patients with triple-negative breast cancer diagnosed between 1980 and 2009 at The University of Texas MD Anderson Cancer Center in Houston. The 5-year overall survival rates were 80% for node-negative patients, 65% patients with 1 to 3 positive lymph nodes (N1), 48% for patients with 4 to 9 positive lymph nodes (N2), and 44% patients with 10 positive or more lymph nodes (N3; P < .0001). The 5-year relapse-free survival rates were 67% for N0, 52% for N1, 36% for N2, and 33% for N3 (P < .0001).

“Pairwise comparison by nodal status showed that when comparing N0 with node-positive disease, there was a significant difference in [overall and relapse-free survival] (P < .001 for all comparisons). However, when comparing N1 with N2 and N3 disease regardless of tumor size, there were no significant differences in [overall or relapse-free survival],” the investigators reported.

Clinical Enigmas

“Simple anatomic reasoning—which has led to many advances in clinical oncology but also the clinical enigmas described above—may not be the most productive way forward in understanding the clinical behavior of cancers and hence prognostication,” the editorialists commented. “Elucidating the molecular mechanisms that underlie the biology of individual cancers would seem to be a more useful focus of our attention. Fortunately for us and for our patients, both technical and conceptual improvements are now available and are resulting in headway. These, coupled with insightful clinical observations…herald a future of greater understanding and resulting clinical progress.” ■

Comen EA, et al: J Clin Oncol 29:2610-2612, 2011.
Wo JY, et al: J Clin Oncol 29: 2619-2627, 2011.
Hernandez-Aya LF, et al:  J Clin Oncol 29:2628-2634, 2011.